PReD-Bench/PRed-Bench huggingface dataset:
pecific nutrient combination effects on tax, NF- κB and MMP-9 in human T-cell lymphotropic virus -1 positive malignant T-lymphocytes
Authors: Rania Azar
Mona Diab-Assaf
Steve Harakeh
Mourad Assidi
Aleksandra Niedzwiecki
Esam Azhar
Mathias Rath
Taha Kumosani
Mohammed H Alqahtani
Elie Barbour
Ghazi A Damanhouri
Ahmed Al-Hejin
Muhammad Abu-Elmagd
Journal: BMC Cancer (2015)
Discipline: CLINICAL MEDICINE
Keywords: Adult T-cell Leukemia; ATL; HTLV-1; Tax; NF-κB

Abstract:  Background: Adult T-cell Leukemia (ATL) is a disease with no known cure. The disease manifests itself as an aggressive proliferation of CD4+ cells with the human T-cell Lymphotropic virus type 1 (HTLV-1). The leukemogenesis of the virus is mainly attributed to the viral oncoprotein. Tax activates the Nuclear Factor kappa B (NF-κB) which stimulates the activity and expression of the matrix metalloproteinase-9 (MMP-9). The objective of this study was to investigate the efficacy of a specific nutrient synergy (SNS) on proliferation, Tax expression, NF-κB levels as well as on MMP-9 activity and expression both at the transcriptional and translational levels in two HTLV-1 positive cell lines, HuT-102 and C91-PL at 48h and 96h of incubation. Cytotoxicity of Epigallocatechin-3-gallate (EGCG) was assayed using CytoTox 96 Non-radioactive and proliferation was measured using Cell Titer96TM Nonradioactive Cell Proliferation kit (MTT- based assay). Enzyme linked immunosorbant assay (ELISA) and electrophoretic mobility shift assay (EMSA) were used to assess the effect of SNS on NF-κB mobility. Zymography was used to determine the effects of SNS on the activity and secretion of MMP-9. The expression of MMP-9 was done using RT-PCR at the translational level and Immunoblotting at the transcriptional level. Results: A significant inhibition of proliferation was seen in both cell lines starting at a concentration of 200μg/ml and in a dose dependent manner. SNS induced a dose dependent decrease in Tax expression, which was paralleled by a down-regulation of the nuclearization of NF-κB. This culminated in the inhibition of the activity of MMP-9 and their expression both at the transcriptional and translational levels. Conclusions: The results of this study indicate that a specific nutrient synergy targeted multiple levels pertinent to the progression of ATL. Its activity was mediated through the NF-κB pathway, and hence has the potential to be integrated in the treatment of this disease as a natural potent anticancer agent. 

Retracted: No

PubPeer comments:
 Figure 4 may include some repeated bands. Could the authors please check? *** ![file] *** Closeup 1 ![file] *** Closeup 2 ![file] ,
Research on the role of GLP-2 in the central nervous system EPK signal transduction pathway of mice with vascular dementia
Authors: Z Liu
M-X Chang
C-L Chi
Y Huang
H Wang
S-A Zhang
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: GLP-2; EPK; signal transduction pathway; mice; vascular dementia
Affiliations: Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. .

Abstract:  Objective: To investigate the role of Glucagon-like peptide-2 (GLP-2) in the central nervous system eukaryotic protein kinase (EPK) signal transduction pathway of mice with vascular dementia. Materials and methods: We take the 3-week-old mice raised in the laboratory as the object of study in this research and then divide them into four groups in random, including sham operation group, control group, GLP-2 group, and GLP-2+ERK (extracellular-signal-regulated kinase) inhibitor intervention group, with 30 in each group. The step-down test, water-maze test, electron microscopy observation, immunohistochemical method, and Western-blotting are adopted to investigate the role of GLP-2 in the central nervous system EPK signal transduction pathway of mice with vascular dementia. Results: The step-down test, as well as the water-maze learning and memory test, shows that the mice injected with GLP-2 in the experiment group have their learning and memory ability improved significantly when compared with other three groups, which is greatly different from that of other three groups (p &lt; 0.05); the electron microscopy observation shows that the injection of GLP can partially reverse the reduction of vesicles while ERK inhibitor removes the said protection; the immunohistochemical result and image analysis result show that the EPK expression quantity in GLP-2 group has no significant difference from that of other three groups (p &gt; 0.05). However, the content of pi-EPK in the GLP-2 group is significantly higher than that in VD group and GLP-2+PD98095 group and is significantly different from them (p &lt; 0.05), and such result is in line with the result of Western-blotting. Conclusions: GLP can influence the change in hippocampus cells extensions and finally influence their cognitive function by activating the EPK signal transduction pathway of hippocampal neuron in the central nervous system. 

Retracted: No

PubPeer comments:
 A possible duplication in Figure 3 was pointed out to me by a reader. The panels in A look unexpectedly similar to panels in B, with the exception of the inset graph. ![file] , 
 Some important details appear to be missing from the Methods. * Which type of mice have been used in this study? * Did the authors obtain approval by an animal ethics board at the appropriate institute? I cannot seem to find a statement about that. The paper appears to involve rather invasive surgery on the mice. *  The step-down test and water-maze test have been carried out on the survival mice - how many mice survived the procedures described in the paper? ![file] ,
Food odors trigger Drosophila males to deposit a pheromone that guides aggregation and female oviposition decisions
Authors: Katharine A Prokop-Prigge
Christopher J Potter
George Preti
Chun-Chieh Lin
Journal: eLife (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: D. melanogaster; aggregation; neuroscience; olfaction; oviposition
Affiliations: The Solomon H Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, United States., Monell Chemical Senses Center, Philadelphia, United States., Department of Dermatology, School of Medicine, University of Pennsylvania, Philadelphia, United States.

Abstract:  Animals use olfactory cues for navigating complex environments. Food odors in particular provide crucial information regarding potential foraging sites. Many behaviors occur at food sites, yet how food odors regulate such behaviors at these sites is unclear. Using Drosophila melanogaster as an animal model, we found that males deposit the pheromone 9-tricosene upon stimulation with the food-odor apple cider vinegar. This pheromone acts as a potent aggregation pheromone and as an oviposition guidance cue for females. We use genetic, molecular, electrophysiological, and behavioral approaches to show that 9-tricosene activates antennal basiconic Or7a receptors, a receptor activated by many alcohols and aldehydes such as the green leaf volatile E2-hexenal. We demonstrate that loss of Or7a positive neurons or the Or7a receptor abolishes aggregation behavior and oviposition site-selection towards 9-tricosene and E2-hexenal. 9-Tricosene thus functions via Or7a to link food-odor perception with aggregation and egg-laying decisions. 

Retracted: No

PubPeer comments:
 Concern about Figure 5D, bottom panel. Some areas appear to be visible multiple times, as highlighted by me with boxes of the same color. ![file] , 
 Figure 6C. In the middle panel, some areas appear to be visible multiple times, as highlighted by me with boxes of the same color. ![file] , 
 An update on Figure 5D, the one marked above in comment #1 for possible duplicated areas in one of the panels. That panel also looks similar to Figure 2C in Komi Koukoura Komi et al. Microbes and Infection (2014) DOI: 10.1016 j.micinf.2014.10.010. Pink, light blue, and purple boxes show areas that look similar between these two photos. The position of the Leptospira bacteria, however, is different. Could the authors please explain what happened here? ![file] , 
 #3 Thank you for bringing this issue to our attention. We are checking the data and will contact the journal for advice. , 
 Figure 1D. ![file] Figure 4 from [Haiyan Dong et al, 2008] ![file] Much more similar than expected. ,
Machine learning. Clustering by fast search and find of density peaks
Authors: Alex Rodriguez
Alessandro Laio
Journal: Science (2014)
Discipline: Multidisciplinary
Keywords: Cluster analysis; classification; similarity; density; distance
Affiliations: SISSA (Scuola Internazionale Superiore di Studi Avanzati), via Bonomea 265, I-34136 Trieste, Italy.

Abstract:  Cluster analysis is aimed at classifying elements into categories on the basis of their similarity. Its applications range from astronomy to bioinformatics, bibliometrics, and pattern recognition. We propose an approach based on the idea that cluster centers are characterized by a higher density than their neighbors and by a relatively large distance from points with higher densities. This idea forms the basis of a clustering procedure in which the number of clusters arises intuitively, outliers are automatically spotted and excluded from the analysis, and clusters are recognized regardless of their shape and of the dimensionality of the space in which they are embedded. We demonstrate the power of the algorithm on several test cases. 

Retracted: No

PubPeer comments:
 This is a really nice technique, and the article explains it clearly. ,
Effects of losartan on the collagen degradative enzymes in hypertrophic and congestive types of cardiomyopathic hamsters
Authors: N Makino
K Masutomo
M S Fushiki
Journal: Molecular and Cellular Biochemistry (2001)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AT1 receptor blockade; losartan; extracellular matrix degradation; Bio 14.6; Bio 53.58
Affiliations: Department of Molecular and Cellular Biology Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.

Abstract:  The present study was undertaken to determine the effects of AT1 receptor blockade which occurred in response to losartan, on the extracellular matrix (ECM) degradation process in the Bio 14.6 (n = 12) and Bio 53.58 (n = 12) strains which are referred as models of hypertrophic and dilated cardiomyopathy, respectively. The administration of losartan (30 mg/kg/day) in hamsters from 10-20 weeks of age reduced the accumulation of the left ventricular collagen matrix in both of the Bio 14.6 and the Bio 53.58 strains. According to the RT-PCR, the levels of mRNA for matrix metalloproteinase (MMP) and the tissue inhibitor of MMP (TIMP) were examined. MMP-1, -2, -3, and -9 were more enhanced in both myopathic strains than in the control F1beta, strains. With losartan, the levels of MMP-1, -2, -9, TIMP-1 and -2 decreased in the both strains but those for MMP-3 did not in Bio 14.6 strains. TIMP-3 and -4 mRNA levels did not change in any of the experimental hamsters, whether treated or untreated with losartan. The Western blots also showed similar observations in the both strains as seen in mRNA expressions although MMP-2 in the Bio 53.58 strains did not differ between treated and untreated with losartan. Although losartan has an inhibitory effect on collagen accumulation in the development of cardiomyopathy, MMPs (-1, -2, -9) and TIMPs (-1, -2) seem to be susceptible to responding to losartan in Bio cardiomyopathic hamsters. 

Retracted: No

PubPeer comments:
 Figures 2A, 3A, 4A. * Red, blue, green, and pink boxes: Some panels look more similar to each other than expected. Part of a set of 60+ papers reported to the journal in October 2015 with a friendly reminder in 2017. In the past five years, the journal did not correct or retract a single paper from this set. ![file] ,
Functional division of substrate processing cofactors of the ubiquitin-selective Cdc48 chaperone
Authors: Stefan Jentsch
Sebastian Rumpf
Journal: Molecular Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ubiquitin-dependent protein degradation; Cdc48; Ufd2; Ufd3; Otu1
Affiliations: Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.

Abstract:  Ubiquitin-dependent protein degradation usually involves escort factors that target ubiquitylated substrates to the proteasome. A central element in a major escort pathway is Cdc48, a chaperone-like AAA ATPase that collects ubiquitylated substrates via alternative substrate-recruiting cofactors. Cdc48 also associates with Ufd2, an E4 multiubiquitylation enzyme that adds further ubiquitin moieties to preformed ubiquitin conjugates to promote degradation. Here, we show that E4 can be counteracted in vivo by two distinct mechanisms. First, Ufd3, a WD40 repeat protein, directly competes with Ufd2, because both factors utilize the same docking site on Cdc48. Second, Cdc48 also binds Otu1, a deubiquitylation enzyme, which disassembles multiubiquitin chains. Notably, Cdc48 can bind Otu1 and Ufd3 simultaneously, making a cooperation of both inhibitory mechanisms possible. We propose that the balance between the distinct substrate-processing cofactors may determine whether a substrate is multiubiquitylated and routed to the proteasome for degradation or deubiquitylated and/or released for other purposes. 

Retracted: No

PubPeer comments:
 Fig. 1A u2013 much more similar than expected. Could author check please? ![file] ,
Calreticulin exposure dictates the immunogenicity of cancer cell death
Authors: Grégoire Mignot
François Ghiringhelli
Theoharis Panaretakis
Jean-Luc Perfettini
Michel Obeid
Noelia Casares
Guido Kroemer
Peter van Endert
Antoine Tesniere
Nathanael Larochette
Mauro Piacentini
Gian Maria Fimia
Maria Castedo
Didier Métivier
Laurence Zitvogel
Fabiola Ciccosanti
Lionel Apetoh
Journal: Nature Medicine (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Anthracyclin; immunogenic cell death; calreticulin; dendritic cells; protein phosphatase 1/GADD34 complex
Affiliations: INSERM U848, 39 Rue Camille-Desmoulins, F-94805 Villejuif, France.

Abstract:  Anthracyclin-treated tumor cells are particularly effective in eliciting an anticancer immune response, whereas other DNA-damaging agents such as etoposide and mitomycin C do not induce immunogenic cell death. Here we show that anthracyclins induce the rapid, preapoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knockdown of CRT suppressed the phagocytosis of anthracyclin-treated tumor cells by dendritic cells and abolished their immunogenicity in mice. The anthracyclin-induced CRT translocation was mimicked by inhibition of the protein phosphatase 1/GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase 1/GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anticancer immune responses and delineate a possible strategy for immunogenic chemotherapy. 

Retracted: No

PubPeer comments:
 Figure 3e. Immunoblot. Background right lane CRT panel has different quality than background middle and left lanes. There are only 3 lanes. ![file] , 
 There are some unexpectedly similar features between two panels in figure 3a. ![file] ,
Ligation of intersphincteric fistula tract (LIFT) in treatment of anal fistula: An updated systematic review, meta-analysis, and meta-regression of the predictors of failure
Authors: Sualeh Muslim Khan
Adeyinka Adejumo
Sameh Hany Emile
Oyintonbra Koroye
Journal: Surgery (2020)
Discipline: CLINICAL MEDICINE
Keywords: Ligation of intersphincteric fistula tract; success rates; complication rates; predictors; failure
Affiliations: Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Mansoura University, Egypt. Electronic address: ., Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan., Division of General Surgery, Department of Surgery, Federal Medical Center, Keffi, Nigeria., Department of Surgery, Niger Delta University, Amassoma, Nigeria.

Abstract:  Background: Ligation of intersphincteric fistula tract has gained increasing popularity as a sphincter-sparing technique for complex anal fistula. The present review aimed to investigate the pooled success and complication rates of ligation of intersphincteric fistula tract in the published literature and to explore the risk factors for failure after ligation of intersphincteric fistula tract. Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature search was conducted. Electronic databases were searched in the period of January 2007 through April 2019 for studies that assessed the outcome of the ligation of intersphincteric fistula tract procedure. The main outcomes of the review were the pooled success and complication rates of ligation of intersphincteric fistula tract, predictors of failure after ligation of intersphincteric fistula tract, operation time, hospital stay, and how failures were managed. Results: Twenty-six studies comprising 1,378 patients (996 male) were included in this review. The mean age of patients was 42.3 ± 4.2 years. The weighted mean rate of success was 76.5%. The median follow-up duration was 16.5 months. The weighted mean complication rate was 13.9%. The most common complication was wound dehiscence. Fecal incontinence was recorded in 1.4% of patients. Factors that were statistically significantly associated with failure after the ligation of intersphincteric fistula tract procedure were horseshoe fistulas, fistulas associated with Crohn's disease, and those with a history of previous fistula surgery. Conclusion: The pooled success and complication rates of the ligation of intersphincteric fistula tract procedure were about 76% and 14%, respectively. Horseshoe fistulas, Crohn's disease, and previous fistula surgery were identified as predictors for failure after ligation of intersphincteric fistula tract procedure. 

Retracted: No

PubPeer comments:
 ![file] ,
miR-218 suppresses cardiac myxoma proliferation by targeting myocyte enhancer factor 2D
Authors: Junwei Zhang
Yanyu Wang
Xinge Shi
Yongsheng Wang
Quanxing Cao
Pingshuan Dong
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Cardiac myxoma; MEF2D; proliferation; tumorigenicity; cell cycle progression
Affiliations: Department of Cardiovascular Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China., Department of Cardiology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.

Abstract:  Cardiac myxoma is the most common type of human heart tumor, yet the molecular mechanism is still poorly understood. In the present study, we found that the level of myocyte enhancer factor 2D (MEF2D), a key regulatory protein for cardiac development, was elevated in specimens of cardiac myxoma, and was positively associated with the proliferation of myxoma cells. MEF2D suppression reduced the proliferation of myxoma cells and its tumorigenicity. Cell cycle progression was also inhibited by MEF2D suppression. miR-218, which is downregulated in myxoma, suppressed MEF2D expression by targeting its mRNA 3'UTR. Altogether, we found that miR-218/MEF2D may be an effective target for myxoma treatment. 

Retracted: No

PubPeer comments:
 Fig 2C.  Cardiac myxoma cells were transfected with MEF2D siRNA or control (50 nM). Twenty-four hours later, MEF2A, MEF2C and MEF2D proteins were determined by immunoblot analysis. ![file] For comparison: Fig 6 A,B from [Zhao, Liu Li (2015)] .  A549 cells were treated with OA at 15, 30, or 60 lg ml-1 for 48 h (a), or at 30 lg ml-1 for 24, 48, or 72 h . ![] That thread links to other manifestations. ,
Upregulation of miR-34a by diallyl disulfide suppresses invasion and induces apoptosis in SGC-7901 cells through inhibition of the PI3K/Akt signaling pathway
Authors: Xiefu Zhang
Yanwei Ye
Yang Fu
Guanghui Liu
Guojun Wang
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: apoptosis; diallyl disulfide; gastric cancer; invasion; microRNA-34a

Abstract:  Diallyl disulfide (DADS) exerts anticarcinogenic activity in various types of cancer. However, the mechanism underlying its anticarcinogenic activity remains to be elucidated. The aim of the present study was to explore the mechanism of the anticarcinogenic activity of DADS in gastric cancer (GC). The expression levels of microRNA (miR)-34a in GC and normal tissues were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of miR-34a was also measured using RT-qPCR in SGC-7901 cells following treatment with DADS. In addition, the effect of DADS on the invasion capability of SGC-7901 cells was observed in the presence of miR-34a or anti-miR-34a using a Matrigel invasion assay. Furthermore, in identical conditions, the apoptosis of SGC-7901 cells was observed using flow cytometry. Finally, the present study investigated the effects of DADS and miR-34a on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in vitro. The level of miR-34a in GC tissues was reduced compared with that in adjacent normal tissues (P&lt;0.05). Treatment with DADS upregulated miR-34a expression in SGC-7901 cells (P&lt;0.05). In the Matrigel invasion assay, DADS inhibited the invasive capability of SGC-7901 cells (P&lt;0.05 vs. control), which was improved by overexpression of miR-34a (P&lt;0.01 vs. control) but reduced by downregulation of miR-34a (P&lt;0.05 vs. DADS treatment group). Furthermore, DADS induced apoptosis of SGC-7901 cells (P&lt;0.05 vs. control); and DADS and miR-34a synergistically enhanced apoptosis of SGC-7901 cells (P&lt;0.01 vs. control). In addition, DADS and miR-34a inhibited the expression levels of phosphorylated (p)-PI3K and p-Akt (P&lt;0.05 vs. control). By contrast, downregulation of miR-34a alleviated the decrease in p-PI3K and p-Akt expression induced by DADS (P&lt;0.05 vs. DADS treatment group). Cell viability was reduced with increasing concentrations of DADS, however, DADS did not affect cell viability following inhibition of the PI3K/Akt signaling pathway. In conclusion, DADS suppresses invasion and induces apoptosis of SGC-7901 cells by upregulation of miR-34a, via inhibition of the PI3K-Akt signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 2. I will let ImageTwin.io do the talking here. ![file] , 
 We found the problem several years ago, and we have already sent the correction to the Editor on July 2017. , 
 Dear Dr. Wang, Could you please clarify exactly what happened here? How could these images end up with so many duplicated parts? A correction is usually done in case of a small error, such as inserting the same image twice by accident. This problem appears to be of larger concern than that. ,
Linc00152 promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma
Authors: Xing Qiu Liang
Xin Deng
Yi Feng Pan
Xiao Fang Zhao
Jian Liang
Ran Chen
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: EZH2; Epithelial-mesenchymal transition; HBx; Linc00152; ：Hepatocellular carcinoma.
Affiliations: Infectious Diseases Laboratory, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China., Department of Gastroenterology, the first affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China., Hepatobiliary Intestine Research Center, XiangYa School of Medicine, Central South University, Changsha, China., Infectious Diseases Laboratory, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China. Electronic address: .

Abstract:  Background: The X protein (HBx) plays as a key role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. The study aimed to figure out the role of Linc00152 in hepatocellular carcinoma (HCC) and the association between the expression levels of Linc00152 and HBx. Methods: QRT-PCR assays were applied to analyzed the expression levels of Linc00152 and HBx. Kaplan-Meier survival curve was performed to identify the association between LINC00152 and the over survival time (OS) in HCC patients. Cell growth and invasion ability was evaluated by CCK8 cell proliferation and transwell invasion assays. Western-blot analysis was detected the protein expression. RNA immunoprecipitation (RIP), RNA-pull down and chromatin Immunoprecipitation (ChIP) assays was also been carried out. Results: We demonstrated that LINC00152 expression in hepatocellular carcinoma (HCC) patients was significantly higher compared with adjacent non-tumour tissues and positively correlated with tumor size, HBV infection (HBsAg) and tumor number. Patient with hepatitis B virus (HBV) infection HCC was higher expression than that without HBV. Furthermore, the expression levels of Linc00152 were positively correlated with HBx expression in HCC tissues and higher Linc00152 expression levels were correlated with poor prognosis of HCC patients. In vitro, Linc00152 was up-regulated in Huh-7 and SM7721 cells after overexpression of HBx and down-regulated after silencing HBx. Furthermore, silencing Linc00152 suppressed the cell proliferation and invasion. Moreover, we found that Linc00152 inhibited the E-cadherin expression via interacting with EZH2 and promoted the Epithelial-mesenchymal transition (EMT) phenomenon in HCC cells. Conclusions: These results suggested that HBx enhanced LINC00152 expression and inhibition of LINC00152 could provide a therapeutic target for HCC. 

Retracted: No

PubPeer comments:
 ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ,
Overcoming remyelination failure in multiple sclerosis and other myelin disorders
Authors: Emily P Harrington
Mark R Kotter
David H Rowitch
Robin J M Franklin
Stephen P J Fancy
Jeffrey K Huang
Chao Zhao
Journal: Experimental Neurology (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Axons; degeneration; myelin disorders; multiple sclerosis; remyelination
Affiliations: Department of Pediatrics, Eli and Edyth Broad Institute for Stem Cell Research and Regeneration Medicine and Howard Hughes Medical Institute, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Abstract:  Protecting axons from degeneration represents a major unmet need in the treatment of myelin disorders and especially the currently untreatable secondary progressive stages of multiple sclerosis (MS). Several lines of evidence indicate that ensuring myelin sheaths are restored to demyelinated axons, the regenerative process of remyelination, represents one of the most effective means of achieving axonal protection. Remyelination can occur as a highly effective spontaneous regenerative process following demyelination. However, for reasons that have not been fully understood, this process is often incomplete or fails in MS. Recognizing the reasons for remyelination failure and hence identifying therapeutic targets will depend on detailed histopathological studies of myelin disorders and a detailed understanding of the molecular mechanisms regulating remyelination. Pathology studies have revealed that chronically demyelinated lesions in MS often fail to repair because of a failure of differentiation of the precursor cell responsible for remyelination rather than a failure of their recruitment. In this article we review three mechanisms by which differentiation of precursor cells into remyelinating oligodendrocytes are regulated-the Notch pathway, the Wnt pathway and the pathways activated by inhibitor of differentiation in myelin debris-and indicate how these might be pharmacologically targeted to overcome remyelination failure. 

Retracted: No

PubPeer comments:
 In Figure 1A, a micrographs (bottom, 5dpl, SC) has been duplicated from a previous publication (Fancy SP et al., 2009; Genes Dev. 23(13); Figure 2C; 10dpl, SC). The other duplication and flipping in Figure A is ok since this is a review article. ![file] ,
Transcriptional diversification and functional conservation between DELLA proteins in Arabidopsis
Authors: Miguel A Blázquez
Javier Gallego-Bartolomé
Jaime A Marín
Eugenio G Minguet
Salomé Prat
David Alabadí
Journal: Molecular Biology and Evolution (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Plasticity; Robustness; Signaling pathways; Genetic redundancy; Arabidopsis
Affiliations: Instituto de Biología Molecular y Celular de Plantas (UPV-Consejo Superior de Investigaciones Científicas), Universidad Politécnica de Valencia, Valencia, Spain.

Abstract:  Plasticity and robustness of signaling pathways partly rely on genetic redundancy, although the precise mechanism that provides functional specificity to the different redundant elements in a given process is often unknown. In Arabidopsis, functional redundancy in gibberellin signaling has been largely attributed to the presence of five members of the DELLA family of transcriptional regulators. Here, we demonstrate that two evolutionarily and functionally divergent DELLA proteins, RGL2 and RGA, can perform exchangeable functions when they are expressed under control of the reciprocal promoter. Furthermore, both DELLA proteins display equivalent abilities to interact with PIF4 and with other bHLH transcription factors with a reported role in the control of cell growth and seed germination. Therefore, we propose that functional diversification of Arabidopsis DELLA proteins has largely relied on changes in their gene expression patterns rather than on their ability to interact with different regulatory partners, model also supported by a clustering analysis of DELLA transcript profiles over a range of organs and growth conditions that revealed specific patterns of expression for each of these genes. 

Retracted: No

PubPeer comments:
 Figure 7A, much more similar than expected (red boxes). Could the authors please check? ![file] ,
Nuclear targeting of protein phosphatase-1 by HIV-1 Tat protein
Authors: Sergei Nekhai
Tatyana Ammosova
Angela Jackson
William Southerland
Bart Lesage
Mathieu Bollen
Victor R Gordeuk
Fatah Kashanchi
Monique Beullens
Marina Jerebtsova
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HIV-1; Tat protein; transcription; CDK9/cyclin T1; protein phosphatase-1 (PP1)
Affiliations: Center for Sickle Cell Disease, Howard University, Washington, DC 20059, USA.

Abstract:  Transcription of human immunodeficiency virus (HIV)-1 genes is activated by HIV-1 Tat protein, which induces phosphorylation of the C-terminal domain of RNA polymerase-II by CDK9/cyclin T1. We previously showed that Tat-induced HIV-1 transcription is regulated by protein phosphatase-1 (PP1). In the present study we demonstrate that Tat interacts with PP1 and that disruption of this interaction prevents induction of HIV-1 transcription. We show that PP1 interacts with Tat in part through the binding of Val36 and Phe38 of Tat to PP1 and that Tat is involved in the nuclear and subnuclear targeting of PP1. The PP1 binding mutant Tat-V36A/F38A displayed a decreased affinity for PP1 and was a poor activator of HIV-1 transcription. Surprisingly, Tat-Q35R mutant that had a higher affinity for PP1 was also a poor activator of HIV-1 transcription, because strong PP1 binding competed out binding of Tat to CDK9/cyclin T1. Our results suggest that Tat might function as a nuclear regulator of PP1 and that interaction of Tat with PP1 is critical for activation of HIV-1 transcription by Tat. 

Retracted: No

PubPeer comments:
 Figure 3A appears to have a repeated image. *** ![file] , 
 Dear Actinopolyspora Biskrensis, Thank you very much for pointing out the referred mistake in our manuscript. We revisited our original preparation files and found that the photo for miR-200b-3p in Figure 3A for 24 h time point was accidentally reused for miR-429-5p. We had kept all original image data and have identified the correct photo for miR-429-5p at 24 h time point. We are sorry for this mistake, which was caused by our carelessness. We will contact Oncotarget and provide a revised Figure 3 as erratum. Thank you again and we will try best to avoid such mistake in future.! ![file] Reference record # 1: Original data saved in our computer file folder. ![file] Reference record #2: Original and correct image data file for miR-429-5p at 24 h time point. , 
 I would also note for other readers that this group appears to have more than a [dozen papers] with similar concerns. ,
Overexpression of Rho GDP-dissociation inhibitor alpha is associated with tumor progression and poor prognosis of colorectal cancer
Authors: Liang Zhao
Jianming Li
Yanqing Ding
Yawei Liu
Hui Wang
Journal: Journal of Proteome Research (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: GDP dissociation inhibitors; Rho GTPases; tumor progression; metastasis; RhoGDI
Affiliations: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China, Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China, State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China, and Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

Abstract:  The GDP dissociation inhibitors (GDIs) are pivotal regulators of Rho GTPases, which are essential for tumor progression, particularly in the area of metastasis. One member of GDIs was identified as RhoGDI (Rho GDP-dissociation inhibitor alpha, or RhoGDIalpha), but little is known about this protein in tumors. In this study, we used comparative proteomic analysis to show that RhoGDI is markedly up-regulated in metastatic colorectal cancer (CRC). The elevated level of RhoGDI protein in metastatic CRC was confirmed by Western blot at the tissue ( n = 24) and cell ( n = 6) levels. Further, we analyzed RhoGDI protein expression in 126 clinicopathologically characterized CRC cases by immunohistochemistry. Statistical analysis showed that there were significant differences of RhoGDI overexpression in patients categorized according to tumor invasion ( p = 0.018), lymph node metastasis ( p = 0.001) and clinical stage ( p = 0.009). A trend was also identified between high expression of RhoGDI and shorter overall survival ( p = 0.013). In the present work, we also analyzed the effect of RhoGDI on CRC cell line. Gene transfection-mediated overexpression of RhoGDI in HT29 cells, containing a low detectable level of endogenous RhoGDI, resulted in a significant increase in cell proliferation and motility in vitro. These data suggest that RhoGDI may promote CRC progression and metastasis by stimulating tumor cell growth and migration. 

Retracted: No

PubPeer comments:
 WB bands were reused in two separate papers by the same author group. ![file] , 
 WB bands were reused in these two papers. ![file] ,
lncRNA MEG3 had anti-cancer effects to suppress pancreatic cancer activity
Authors: Jiaqiang Zhang
Qian Zhan
Baiyong Shen
Chenghong Peng
Lei Gu
Minmin Shi
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: AKT; Bax; Bcl-2; Cyclin D1; MEG 3
Affiliations: Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China; Research Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China., Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China; Research Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. Electronic address: .

Abstract:  Aim: The aim of this study was to explain the mechanism of lncRNA MEG 3 in pancreatic cancer. Methods: We were collecting 30 pancreatic cancer patients, taking the sample from these patients. We measured the PI3K protein expressions from 30 patients by IHC and WB methods and MEG 3 expression by RT-PCR, and analyzed the relationship between PI3K protein expression and pancreatic cancer patients' clinical pathology and the correlation between lncRNA MEG 3 and PI3K. In the cell experiment, PANC-1 cells were divided into three groups: NC, BL and lncRNA groups, after treatment,we measured cell proliferation rate of 3 groups by MTT methods, evaluated cell apoptosis and cell cycle using flow cytometry, tested the invasion cells and migrate rate of 3 groups by transwell and wound healing assays. Results: Compared with carcinoma adjacent tissue, The PI3K protein expression of pancreatic cancer tissue were significantly up-regulation (P&gt;0.05). MEG 3 gene expression was negatively correlated with PI3K expression. The MEG 3 was negatively correlated with tumor size, Metastasis and Vascular invasion in pancreatic cancer (P&lt;0.05, respectively). In the cell experiment, The cell proliferation and apoptosis rates of lncRNA group were significantly difference compared with NC group (P&lt;0.05, respectively), and the G1 phase rate of lncRNA group was higher than NC group (P&lt;0.05). The invasion cells and wound healing rate were significantly reduced in lncRNA group than those in NC group (P&lt;0.05, respectively). Conclusion: MEG 3 over-expressing had anti-cancer effects to suppress pancreatic cancer activity by regulation PI3K/AKT/Bcl-2/Bax/Cyclin D1/P53 and PI3K/AKT/MMP-2/MMP-9 signaling pathways. 

Retracted: No

PubPeer comments:
 Fig 5 has an overlap, although the color background is different between the 2 images ![file] ,
A simple technique for the prediction of interacting proteins reveals a direct Brn-3a-androgen receptor interaction
Authors: Daniel C Berwick
James K J Diss
David S Latchman
Vishwanie S Budhram-Mahadeo
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: multiprotein complexes; interactors; Brn-3a; androgen receptor; transcription factors
Affiliations: Medical Molecular Biology Unit, University College London Institute of Child Health, London, UK. 

Abstract:  The formation of multiprotein complexes constitutes a key step in determining the function of any translated gene product. Thus, the elucidation of interacting partners for a protein of interest is of fundamental importance to cell biology. Here we describe a simple methodology for the prediction of novel interactors. We have applied this to the developmental transcription factor Brn-3a to predict and verify a novel interaction between Brn-3a and the androgen receptor (AR). We demonstrate that these transcription factors form complexes within the nucleus of ND7 neuroblastoma cells, while in vitro pull-down assays show direct association. As a functional consequence of the Brn-3a-AR interaction, the factors bind cooperatively to multiple elements within the promoter of the voltage-gated sodium channel, Nav1.7, leading to a synergistic increase in its expression. Thus, these data define AR as a direct Brn-3a interactor and verify a simple interacting protein prediction methodology that is likely to be useful for many other proteins. 

Retracted: No

PubPeer comments:
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 The top secret UCL report on the Masteru2019s laboratory gone rogue was recently leaked to the Telegraph **Leading university embroiled in major research scandal** https: www.telegraph.co.uk education 2018 05 16 one-britains-leading-universities-embroiled-majorresearch-scandal *u201cbut in seven others, it concluded there was evidence of fraud.u201d* Since this JBC paper is neither included in the three new retractions, nor in the three new stealth corrections, it surely has presented no evidence of fraud to the three appointed investigators. With hindsight, it is a pity that this paperu2019s Western UCL Blots (WUBs) were marked up several years ago, before the JBC Data Integrity Manager had come into existence. Because, based on recent form, the DIM would decide for herself on the fraud issue and would not rely on the conclusions of the three wise men. Apart from anything else, the DIM might have better image archives for the WUBs than does UERP (UCL, Europe s Research Powerhouse). , 
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 https: www.theguardian.com science 2019 jul 01 research-misconduct-claim-upheld-against-former-head-of-ucl-lab https: www.buzzfeednews.com article peteraldhous david-latchman-scientific-misconduct ,
Transplantation of HGF gene-engineered skeletal myoblasts improve infarction recovery in a rat myocardial ischemia model
Authors: Shu-Ling Rong
Xu-Jiong Li
Zhuo-Hui Song
Bao Li
Lu-Hua Cui
Cui-Ying Zhang
Xiao-Lin Wang
Xiao-Feng He
Hui-Jin Du
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: Skeletal myoblast transplantation; myocardial infarction; gene engineering; angiogenic growth factors; hepatocyte growth factor (HGF)
Affiliations: Department of Cardiology, Heping Hospital and Institute of cardiovascular disease, Changzhi Medical College, Changzhi, China., Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China., Department of Pediatrics, Heping Hospital and Institute of cardiovascular disease, Changzhi Medical College, Changzhi, China., Department of Physiology, Changzhi Medical College, Changzhi, China., Department of Research, Heping Hospital, Changzhi Medical College, Changzhi, China.

Abstract:  Background: Skeletal myoblast transplantation seems a promising approach for the repair of myocardial infarction (MI). However, the low engraftment efficacy and impaired angiogenic ability limit the clinical efficiency of the myoblasts. Gene engineering with angiogenic growth factors promotes angiogenesis and enhances engraftment of transplanted skeletal myoblasts, leading to improved infarction recovery in myocardial ischemia. The present study evaluated the therapeutic effects of hepatocyte growth factor (HGF) gene-engineered skeletal myoblasts on tissue regeneration and restoration of heart function in a rat MI model. Methods and results: The skeletal myoblasts were isolated, expanded, and transduced with adenovirus carrying the HGF gene (Ad-HGF). Male SD rats underwent ligation of the left anterior descending coronary artery. After 2 weeks, the surviving rats were randomized into four groups and treated with skeletal myoblasts by direct injection into the myocardium. The survival and engraftment of skeletal myoblasts were determined by real-time PCR and in situ hybridization. The cardiac function with hemodynamic index and left ventricular architecture were monitored; The adenovirus-mediated-HGF gene transfection increases the HGF expression and promotes the proliferation of skeletal myoblasts in vitro. Transplantation of HGF-engineered skeletal myoblasts results in reduced infarct size and collagen deposition, increased vessel density, and improved cardiac function in a rat MI model. HGF gene modification also increases the myocardial levels of HGF, VEGF, and Bcl-2 and enhances the survival and engraftment of skeletal myoblasts. Conclusions: HGF engineering improves the regenerative effect of skeletal myoblasts on MI by enhancing their survival and engraftment ability. 

Retracted: No

PubPeer comments:
 In Figure 4e, a micrograph has been duplicated, rotated, modified and presented as something else. ![file] ,
Chronic ethanol exposure increases the binding of HuR to the TNFalpha 3'-untranslated region in macrophages
Authors: Enzo Cocuzzi
Maria Hatzoglou
Laura E Nagy
Megan R McMullen
Journal: Journal of Biological Chemistry (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Tumor necrosis factor alpha; TNFalpha; ethanol-induced liver disease; lipopolysaccharide; macrophages
Affiliations: Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106-4906, USA.

Abstract:  Tumor necrosis factor alpha (TNFalpha) expression is a key mediator of ethanol-induced liver disease. Increased lipopolysaccharide (LPS)-stimulated TNFalpha expression in macrophages after chronic ethanol feeding is associated with a stabilization of TNFalpha mRNA (Kishore, R., McMullen, M. R., and Nagy, L. E. (2001) J. Biol. Chem. 276, 41930-41937). Here we show that the 3'-UTR of murine TNFalpha mRNA was sufficient to mediate increased LPS-stimulated expression of a luciferase reporter in RAW 264.7 macrophages after chronic ethanol exposure. Further, we show that HuR, a nuclear/cytoplasmic shuttling protein, which binds to TNFalpha mRNA, is required for increased expression of TNFalpha after chronic ethanol. In Kupffer cells, HuR was primarily localized to the nucleus and then translocated to the cytosol in response to LPS in both pair- and ethanol-fed rats. After chronic ethanol feeding, HuR quantity in the cytosol was greater, both at baseline and in response to LPS, compared with pair-fed controls. Using RNA gel shift assays, we found that LPS treatment increased HuR binding to the 65-nucleotide A + U-rich element of the TNFalpha 3'-UTR by 2-fold over baseline in Kupffer cells from pair-fed rats. After chronic ethanol feeding, HuR binding to the TNFalpha A + U-rich element was increased by more than 5-fold at baseline and in response to LPS, compared with pair-fed controls. Down-regulation of HuR expression by RNA interference prevented the chronic ethanol-induced increase in expression of luciferase reporters containing the TNFalpha 3'-UTR. Taken together, these data demonstrate that increased binding of HuR to the TNFalpha 3'-UTR contributes to increased LPS-stimulated TNFalpha expression in macrophages after chronic ethanol exposure. 

Retracted: No

PubPeer comments:
 There is an undeclared splicing site in Fig. 2B ![file] ,
Epstein-Barr virus-encoded EBNA1 regulates cellular gene transcription and modulates the STAT1 and TGFbeta signaling pathways
Authors: S E Stewart
W Wei
C W Dawson
J D O&#x27;Neil
V H J Wood
L S Young
Journal: Oncogene (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Epstein-Barr virus; EBNA1; transcription; cellular genes; STAT1
Affiliations: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK.

Abstract:  The Epstein-Barr virus (EBV)-encoded EBNA1 protein is expressed in all virus-associated tumors where it plays an essential role in the maintenance, replication and transcription of the EBV genome. Transcriptional profiling of EBNA1-expressing carcinoma cells demonstrated that EBNA1 also influences the expression of a range of cellular genes including those involved in translation, transcription and cell signaling. Of particular interest was the ability of EBNA1 to enhance expression of STAT1 and sensitize cells to interferon-induced STAT1 activation with resultant enhancement of major histocompatibility complex expression. A negative effect of EBNA1 on the expression of TGFbeta1-responsive betaig-h3 and PAI-1 genes was confirmed at the protein level in EBV-infected carcinoma cells. This effect resulted from the ability of EBNA1 to repress TGFbeta1-induced transcription via a reduction in the interaction of SMAD2 with SMAD4. More detailed analysis revealed that EBNA1 induces a lower steady-state level of SMAD2 protein as a consequence of increased protein turnover. These data show that EBNA1 can influence cellular gene transcription resulting in effects that may contribute to the development of EBV-associated tumors. 

Retracted: No

PubPeer comments:
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 I independently came across another possible issue with images in this paper. Figure 5a appears to include a repeated image, marked with red boxes. I adjusted the exposure and contrast in various ways and am unable to see any differences between the two. *** ![file] ,