PReD-Bench/PRed-Bench huggingface dataset:
Prognostic significance of MYCN related genes in pediatric neuroblastoma: a study based on TARGET and GEO datasets
Authors: Liangpu Xu
Ji Zhang
Xinrui Wang
Haiwei Wang
Hua Cao
Journal: BMC pediatrics (2020)
Discipline: CLINICAL MEDICINE
Keywords: E2F1; EIF4G1; GEO; MYCN; Pediatric neuroblastoma
Affiliations: Medical Research Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China. ., Medical Research Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China., State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China. .

Abstract:  Background: Neuroblastoma patients with MYCN amplification are associated with poor prognosis. However, the prognostic relevance of MYCN associated genes in neuroblastoma is unclear. Methods: The expression profiles of MYCN associated genes were identified from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. Enriched transcription factors and signaling pathways were determined using gene set enrichment analysis (GSEA). Kaplan-Meier plotter was used to identify the prognostic relevance of MYCN associated genes. Multivariate cox regression and Spearman's correlation were used to determine the correlation coefficients of MYCN associated genes. Results: In TARGET and GSE85047 datasets, neuroblastoma patients with MYCN amplification were associated with worse prognosis. Transcription factor MYC was positively associated with MYCN amplification in GSEA assay. We identified 13 MYC target genes which were increased in neuroblastoma patients with MYCN amplification in TARGET, GSE19274 and GSE85047 datasets. Moreover, six out of the 13 MYC target genes ARMC6, DCTPP1, EIF4G1, ELOVL6, FBL and PRMT1 were associated with adverse prognosis in TARGET and GSE85047 datasets. Transcription factor E2F1 was up-regulated by MYCN amplification and associated with the poor prognosis of neuroblastoma. Furthermore, RPS19 in ribosome signaling pathway was also associated with MYCN amplification and correlated with the poor prognosis of neuroblastoma. At last, we showed that most of MYCN target genes were correlated with each other. However, EIF4G1 was an independent prognostic marker. And the prognostic effects of the combination of MYCN amplification and EIF4G1 expression were more significant than MYCN or EIF4G1 alone. Conclusions: MYCN target genes ARMC6, DCTPP1, EIF4G1, ELOVL6, FBL, PRMT1, E2F1 and RPS19 had significant prognostic effects in pediatric neuroblastoma. And neuroblastoma patients without MYCN amplification and low EIF4G1 expression had best prognosis. 

Retracted: No

PubPeer comments:
 The authors should specify the gene set they chose for GSEA in the  Method part. ,
MiR-155 inhibits proliferation, invasion and migration of melanoma via targeting CBL
Authors: Q-Q Wang
L-X Meng
H Li
H-X Chen
J-B Song
Y Li
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: malignant melanoma; miR-155; CBL; proliferation; migration
Affiliations: Department of Dermatology, People's Hospital of Rizhao Affiliated to Jining Medical University, Rizhao, China. .

Abstract:  Objective: Malignant melanoma (MM), the deadliest form of skin malignancy, is a highly aggressive and malignant tumor with an increasing incidence rate in recent years. Increasing evidence suggested that dysfunctions of microRNAs (miRNAs) may play an important role in human tumors. However, the effect of miR-155 on malignant melanoma cell migration and invasion remains largely elusive. This research was designed to evaluate the potential function of miR-155 and CBL (Casitas B-lineage lymphoma) in malignant melanoma. Patients and methods: Quantitative Real-time polymerase chain reaction (qRT-PCR) was utilized to detect miR-155 and CBL expression in malignant melanoma tissues and cell lines. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to examine the regulation of miR-155 in melanoma proliferation. Transwell assay was carried out to detect the effect of miR-155 on the MM cell migration and invasion. Luciferase assay and biological analysis were used to predict and determine the target gene of miR-155. Results: miR-155 was down-regulated in malignant melanoma tissues and cell lines. Ectopic expression of miR-155 could inhibit migration and invasion in malignant melanoma cells. What's more, we found that CBL was a new target of miR-155. Additionally, CBL was negatively associated with miR-155 in malignant melanoma and overexpression of CBL attenuated miR-155-mediated inhibition on MM cell migration and invasion. Conclusions: miR-155 inhibited malignant melanoma proliferation, migration and invasion. And high CBL expression was observed in MM tissues. This newly identified miR-155/CBL axis may provide new insight into the pathogenesis of malignant melanoma. 

Retracted: No

PubPeer comments:
 1) The authors used cancer cell lines and they claim that they have examined the patterns and consequences of the expression of miRNA182-5p in the context of CML progression. How does this study explain the CML progression - unless they have done analysis on patients before CML even starts. This is a false claim. 2) They have used human patient samples here. Bone marrow from CML patients was isolated and mononuclear cells were separated from the whole blood by Ficoll Histo-paque density gradient method. I could not find the  IRB details and ethics approval . Please show me where this is stated. I am sorry, if I missed out. Please highlight where this is. I wonder how the journal editor reviewers missed this, if the ethical approval details are not provided. 3) If you use blood and bone marrow from the CML patients, it is not studying cancer progression. Hope the senior authors know what cancer progression means. ,
H-Ras nanocluster stability regulates the magnitude of MAPK signal output
Authors: Barak Rotblat
John F Hancock
Galit Elad-Zefadia
Yoel Kloog
Sarah J Plowman
Liron Belanis
Hong Liang
Roni Haklai
Journal: PLoS ONE (2010)
Discipline: Multidisciplinary
Keywords: H-Ras; MAPK; Galectin-1; plasma membrane; nanoclusters
Affiliations: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Abstract:  H-Ras is a binary switch that is activated by multiple co-factors and triggers several key cellular pathways one of which is MAPK. The specificity and magnitude of downstream activation is achieved by the spatio-temporal organization of the active H-Ras in the plasma membrane. Upon activation, the GTP bound H-Ras binds to Galectin-1 (Gal-1) and becomes transiently immobilized in short-lived nanoclusters on the plasma membrane from which the signal is propagated to Raf. In the current study we show that stabilizing the H-Ras-Gal-1 interaction, using bimolecular fluorescence complementation (BiFC), leads to prolonged immobilization of H-Ras.GTP in the plasma membrane which was measured by fluorescence recovery after photobleaching (FRAP), and increased signal out-put to the MAPK module. EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Taken together these data demonstrate that the magnitude of the signal output from a GTP-bound H-Ras nanocluster is proportional to its stability. 

Retracted: No

PubPeer comments:
 Figure 4A. Gal-1 panel. Vertical, straight right edge band middle lane. None of the bands in the other panels have vertical, straight edges. ![file] ,
Aldose reductase inhibitor Epalrestat alleviates high glucose-induced cardiomyocyte apoptosis via ROS
Authors: X Wang
F Yu
W-Q Zheng
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: aldose reductase inhibitor; high glucose; cardiomyocyte apoptosis; oxidative stress; nitric oxide synthase
Affiliations: Department of Pharmacy, Weihai Central Hospital, Weihai, China. .

Abstract:  Objective: To clarify the role of aldose reductase inhibitor (ARI) in the high glucose-induced cardiomyocyte apoptosis and its mechanism. Materials and methods: In this study, H9c2 cardiomyocytes were employed as objects, high-glucose medium as stimulus, and ARI Epalrestat as a therapeutic drug. The cell apoptosis and activity changes of nitric oxide synthase (NOS), NO, and reactive oxygen species (ROS) were evaluated via Hoechst staining, enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and Western blotting. In addition, the mitochondrial membrane potential was measured via fluorescence counting. Results: Epalrestat inhibited the activity of AR to improve high glucose-induced oxidative stress in cardiomyocytes, weaken ROS activity, relieve the inhibition on NO activity, alleviate mitochondrial membrane potential damage, reduce the level of high glucose-induced cardiomyocyte apoptosis, and suppress the expression and activity of Caspase-3, thereby preventing high glucose-induced cardiomyocyte apoptosis. Conclusions: ARI protects against high glucose-induced cardiomyocyte apoptosis. 

Retracted: No

PubPeer comments:
 Concern about Figures 5 (Immunohistochemistry of caspase-3), 6 (inducible nitric oxide syn- thase), and 7 (NFkB). Some of the panels appear to overlap, although they represent different proteins and different groups of rats. * Figure 5A, 6A, 6D, 7A, and 7D might all be showing the same sample, since they all are connected through overlaps. Shown with pink, orange, lime, and brown boxes. * Figure 5B, 6B, 7B all appear to show an area of overlap. Shown with red boxes. * Figure 6C and 7C also appear to show an area of overlap. Shown with yellow boxes. ![file] , 
 July 2021 retraction: https: link.springer.com article 10.1007%2Fs11033-021-06475-x  The editors have retracted this article. Concerns were raised regarding a number of figures, specifically: Figures 5A, 6A, 7A and 7D appear to be part of one sample; Figures 5B, 6B and 7B appear to have overlapping sections; Figures 6C and 7C appear to have overlapping sections. Additionally, the article shows significant overlap with a number of previously published articles [1,2,3]. The editors therefore no longer have confidence in the reliability of the data reported in the article. The authors have not responded to correspondence regarding this retraction notice. I reported these issues to the journal in November 2019. The journal did not notify me of this retraction. ,
LINC01116 promotes the progression of epithelial ovarian cancer via regulating cell apoptosis
Authors: Y-N Fang
H Li
J-L Wu
Z-L Huang
W-B Tan
L Wang
Q-G Zhang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: LINC01116; epithelial ovarian cancer; biological function; proliferation; invasion
Affiliations: Department of Obstetrical, The First People's Hospital of Jining, Jining, China. .

Abstract:  Objective: To explore the biological function of LINC01116 in epithelial ovarian cancer (EOC) and its underlying mechanism. Patients and methods: The expression level of LINC01116 in 60 EOC tissues, 30 normal ovarian tissues and EOC cells were detected by qRT-PCR (quantitative real-time polymerase chain reaction). Disease-free survival (DFS) and overall survival (OS) of enrolled EOC patients were recorded. The correlation between LINC01116 expression, DFS and OS of EOC patients was analyzed using ROC curve. Influencing factors for DFS and OS were analyzed by univariable and multivariable Cox regression model. For in vitro experiments, the effect of LINC01116 knockdown on proliferation, invasion and apoptosis of EOC cells were detected by CCK-8 (cell counting kit-8), transwell assay and flow cytometry, respectively. Protein expressions of apoptosis-related genes in EOC cells transfected with pc-DNA-LINC01116 or si-LINC01116 were detected by Western blot. Results: LINC01116 was overexpressed in EOC tissues than that of paracancerous tissues. DFS and OS in EOC patients with higher expression of LINC01116 were remarkably shorter than those with lower expression. FIGO (International Federation of Gynecology and Obstetrics) clinical stage and LINC01116 expression were the independent factors that affected DFS and OS of EOC patients. Besides, LINC01116 expression was positively correlated to the diagnostic sensitivity of EOC patients. In vitro experiments found that LINC01116 overexpression promoted proliferation and invasion of EOC cells. Overexpressed LINC01116 resulted in upregulated Bcl-2, and downregulated cleaved Caspase-3 and cleaved Caspase-9 in EOC cells. Conclusions: Overexpressed LINC01116 promotes EOC progression via increasing proliferation and migration, and inhibiting cell apoptosis. 

Retracted: No

PubPeer comments:
  EOC patients treated in The First Peopleu2019s Hospital of Jining from **July 2012 to July 2017** were enrolled. Fig 1B,C.  DFS in epithelial ovarian cancer patients with higher expression of LINC01116 was remarkably shorter than those with lower expression . ...  OS in epithelial ovarian cancer patients with higher expression of LINC01116 was remarkably shorter than those with lower expression . ![file] In a paper published in early 2018, the authors followed their patients survival through ten years, i.e. to the date range **June 2022 to July 2027**. ,
Retracted Article: Kinetic and mechanistic studies on adsorption of Cu(ii) in aqueous medium onto montmorillonite K10 and its modified derivative
Authors: Himani Medhi
Krishna G. Bhattacharyya
Journal: New Journal of Chemistry (2017)
Discipline: CHEMISTRY
Keywords: Copper removal; Adsorption technique; Clay minerals; Montmorillonite K10; Tetramethylammonium cations
Affiliations: Department of Chemistry, Gauhati University, Guwahati-781014, India

Abstract: Copper is a widely used metal and known as a micronutrient; however, it is poisonous to the living organisms and has a permissible concentration of 1.3 mg L\u22121 in aqueous solutions. Thus, it is necessary to provide a suitable, environmentally friendly, and cost-effective copper removal process to save the world. The adsorption technique has been found to be an effective method for the treatment and removal of copper from aqueous solutions. Clays and clay minerals are naturally abundant adsorbents used in this field from very early days. The commercially available montmorillonite K10 clay mineral is modified via intercalation with tetramethylammonium cations to enhance its characteristic properties. The materials are characterized via CEC, FTIR, XRD, TGA-DTG, BET N2-adsorption, and SEM-EDX measurements, and their adsorption capacities for Cu(II) removal from a water system are investigated. Cu(II) adsorption study shows an increase in adsorption capacity from 41.71 to 96.31 mg g\u22121 after modification of Mt, and at pH 7.0, the Cu(II) removal capacity reaches up to 99.40%. The kinetics study and statistical analysis shows pseudo-second order kinetics as the best fit model for Cu(II) adsorption controlled by more than one mechanism. Thermodynamic study shows the endothermic and spontaneous nature of Cu(II) adsorption with higher affinity towards the TMA-Mt surface. The isotherm study shows the Langmuir maximum adsorption capacity of Mt and TMA-Mt to be 450.45 and 925.93 mg g\u22121, respectively, for Cu(II) removal from a water system.

Retracted: Yes

PubPeer comments:
  Fig.9. SEM micrographs of ... TMA-Mt (c) ![file] , 
 Retracted t06 Apr 2020: https: doi.org 10.1039 D0NJ90041A  The Royal Society of Chemistry hereby wholly retracts this New Journal of Chemistry article due to concerns with the reliability of the data in the published article.  There are repeating motifs within the TEM image in Fig. 9c, which indicates that this image has been manipulated.  There are unexpected similarities in the 4000u20133500 cmu22121 and 2000u20131250 cmu22121 regions of the FTIR spectra in Fig. 14a and b (purple u201cafteru201d spectra).  Given the significance of the concerns about the validity of the data, the findings presented in this paper are no longer reliable. Himani Medhi and Krishna G. Bhattacharyya were informed about the retraction of the article but did not respond.  Signed: Andrew Shore, Executive Editor, New Journal of Chemistry  Date: 12th March 2020 ,
RETRACTED ARTICLE: The amine-catalysed Suzuki–Miyaura-type coupling of aryl halides and arylboronic acids
Authors: Fu-Yue Liu
Zhong-Lin Liu
Qi Zhang
Hai-Zhu Yu
Wei-Jun Chang
Ying Lv
Hua-Jian Xu
Lei Xu
Jian-Jun Dai
Jun Xu
Journal: Nature Catalysis (2021)
Discipline: CHEMISTRY
Keywords: Suzuki-Miyaura coupling; organocatalytic; aryl halides; arylboronic acids; amines

Abstract: Suzuki–Miyaura coupling is a practical and attractive carbon\u2212carbon bond formation reaction due to its high efficiency and wide functional group compatibility, but its industrial applications are limited because it is typically catalysed by expensive palladium-containing transition-metal complexes. Here we show a robust and chemoselective organocatalytic Suzuki\u2212Miyaura-type coupling of aryl halides with arylboronic acids catalysed by amines. The utility and scope of this reaction were demonstrated by the synthesis of several commercially relevant small molecules and a selection of derivatives of pharmaceutical drugs. The coupling of aryl halides and arylboronic acids is generally performed by metal-catalysed Suzuki–Miyaura reactions while metal-free approaches remain elusive. Here an organocatalytic approach based on amine catalysts is introduced for the preparation of commercially relevant asymmetric biaryls.

Retracted: Yes

PubPeer comments:
 Retracted, December 2021: https: www.nature.com articles s41929-021-00726-7  We wish to retract this article as we can no longer claim that the observed reactivity for the Suzuki-Miyaura-type coupling of aryl halides and arylboronic acids is attributed to the amine organocatalyst. Efforts from different laboratoriesu2014published in the form of Matters Arising articles1,2,3u2014have pointed to the fact that the reaction is catalyzed by residual palladium impurity contained in the amine. We have performed a series of validation experiments confirming that during the synthesis of the amine, stable palladium complexes are formed, which could not be completely removed by column chromatography. Moreover, the ICP-MS method we used could not completely digest the residual palladium. Such factors led us to misjudge the nature of the catalyst. We are very grateful to the authors of the Matters Arising articles for raising these issues. We sincerely apologize to the scientific community for any confusion arising from our publication. All authors agree with this retraction. This article on Retraction Watch gives some background: https: retractionwatch.com 2021 12 28 highly-professional-but-the-process-seems-to-take-a-long-time-is-this-the-best-way-to-correct-the-record ,
Intermolecular disulfide bond in the dimerization of S-periaxin mediated by Cys88 and Cys139
Authors: Yemei Ren
Yawei Shi
Yan Yang
Journal: Acta biochimica et biophysica Sinica (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: S-periaxin; bimolecular fluorescence complementation analyses; cysteine; dimer; intermolecular disulfide bond.

Abstract:  Periaxin is expressed in mammalian Schwann cells and lens fiber cells, and has been identified in a screen for cytoskeleton-associated proteins. Charcot-Marie-Tooth 4F is caused by losses or mutations of theperiaxingene. Theperiaxingene encodes two protein isoforms, namely, L-periaxin and S-periaxin.S-periaxin contains 147 amino acid residues and has an N-terminal PDZ domain. In this paper, S-periaxin was reported to be homodimerized through the formation of intermolecular disulfide bonds with its Cys88 and Cys139 residues under mild oxidation conditions. The covalent dimer of S-periaxin was also observed by western blot analysis and bimolecular fluorescence complementation analyses. S-periaxin dimerization formation could be regulated by cellular redox fluctuations. These results offer a possible mechanism to the formation of periaxin complexes, improvement of complex stability, and establishment of a link between the extracellular matrix and the cytoskeleton. 

Retracted: No

PubPeer comments:
 ![file] , 
 Also Fig 1C shows unnatural background features. ![file] ,
Epstein–Barr Virus nuclear antigen 1 (EBNA1) confers resistance to apoptosis in EBV-positive B-lymphoma cells through up-regulation of survivin
Authors: Sabyasachi Haldar
Mariusz A Wasik
Qiliang Cai
Jaap Middeldorp
Subhash C Verma
Jie Lu
Masanao Murakami
Erle S Robertson
Rajeev Kaul
Journal: Virology (2011)
Discipline: MICROBIOLOGY
Keywords: Resistance; apoptosis; tumorigenic process; EBV; gamma-herpesvirus
Affiliations: Department of Microbiology and Tumor Virology Program, Abramson Comprehensive Cancer Center, School of Medicine, University of Pennsylvania, 202E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.

Abstract:  Resistance to apoptosis is an important component of the overall mechanism which drives the tumorigenic process. EBV is a ubiquitous human gamma-herpesvirus which preferentially establishes latent infection in viral infected B-lymphocytes. EBNA1 is typically expressed in most forms of EBV-positive malignancies and is important for replication of the latent episome in concert with replication of the host cells. Here, we investigate the effects of EBNA1 on survivin up-regulation in EBV-infected human B-lymphoma cells. We present evidence which demonstrates that EBNA1 forms a complex with Sp1 or Sp1-like proteins bound to their cis-element at the survivin promoter. This enhances the activity of the complex and up-regulates survivin. Knockdown of survivin and EBNA1 showed enhanced apoptosis in infected cells and thus supports a role for EBNA1 in suppressing apoptosis in EBV-infected cells. Here, we suggest that EBV encoded EBNA1 can contribute to the oncogenic process by up-regulating the apoptosis suppressor protein, survivin in EBV-associated B-lymphoma cells. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar and different than you would expect. https: imgur.com DCbyAD0 , 
 Last author appears to be on the editorial board of this journal: https: www.sciencedirect.com journal virology about editorial-board ,
Bone morphogenetic protein 15 (BMP15) acts as a BMP and Wnt inhibitor during early embryogenesis
Authors: Ali H Brivanlou
Elisa Di Pasquale
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bone morphogenetic protein 15; BMP15; TGFbeta superfamily; Smad1/5/8 pathway; Wnt pathway
Affiliations: Molecular Embryology Laboratory, The Rockefeller University, New York, New York 10065, USA.

Abstract:  Bone morphogenetic protein 15 (BMP15) belongs to an unusual subgroup of the transforming growth factor beta (TGFbeta) superfamily of signaling ligands as it lacks a key cysteine residue in the mature region required for proper intermolecular dimerization. Naturally occurring BMP15 mutation leads to early ovarian failure in humans, and BMP15 has been shown to activate the Smad1/5/8 pathway in that context. Despite its important role in germ cell specification, the embryological function of BMP15 remains unknown. Surprisingly, we find that during early Xenopus embryogenesis BMP15 acts solely as an inhibitor of the Smad1/5/8 pathway and the Wnt pathway. BMP15 gain-of-function leads to embryos with secondary ectopic heads and to direct neural induction in intact explants. BMP15 inhibits BMP4-mediated epidermal induction in dissociated explants. BMP15 strongly inhibits BRE response induced by BMP4 and blocks phosphorylation and activation of Smad1/5/8 MH2-domain. Mechanistically, BMP15 protein specifically interacts with BMP4 protein, suggesting inhibition upstream of receptor binding. Loss-of-function experiments using morpholinos or a naturally occurring human BMP15 dominant-negative mutant (BMP15-Y235C) leads to embryos lacking head. BMP15-Y235C also eliminates the inhibitory activity of BMP15 on BRE (BMP-responsive element). Finally, we show that BMP15 inhibits the canonical branch of the Wnt pathway, upstream of beta-catenin. We, thus, demonstrate that BMP15 is necessary and sufficient for the specification of dorso-anterior structures and highlight novel mechanisms of BMP15 function that strongly suggest a reinterpretation of its function in ovaries specially for ovarian failure. 

Retracted: No

PubPeer comments:
 ![file] Undeclared splicing site in Fig 4, could the author show the original data? ,
Identification of seven novel mutations in ABCD1 by a DHPLC-based assay in Italian patients with X-linked adrenoleukodystrophy
Authors: Carlo Piantadosi
Diego Colabianchi
Natalia Cannelli
Roberto Cotrufo
Serafina Salvati
Lucilla Attori
Giorgia Montagna
Clarice Patrono
Marco Cappa
Filippo M Santorelli
Antonella Di Biase
Mariarosa A B Melone
Journal: Human mutation (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: X-linked adrenoleukodystrophy; ABCD1 gene; mutations; molecular screening; denaturing high-performance liquid chromatography (DHPLC)
Affiliations: Molecular Medicine and Endocrinology, IRCCS Bambino Gesù Children's Hospital, Rome.

Abstract:  We report the molecular findings in 14 patients (12 families) with X-linked adrenoleukodystrophy (X-ALD, MIM# 300100), a well-defined peroxisomal disorder attributed to mutations in the ABCD1 gene on chromosome Xq28. With the aims of determining the spectrum of mutations and developing an efficient molecular genetic test for analysis of at-risk women whose carrier status is unknown, and to offer molecular confirmation of their status to obligate heterozygotes, regardless of their clinical status, we carried out molecular screening by setting up a denaturing high-performance liquid chromatography (DHPLC)-based protocol. We identified eleven hemizygous base changes in ABCD1, including seven new mutations (c.145underscore;146ins4, c.264C&gt;G, c.919C&gt;T, c.994C&gt;T, c.1027G&gt;A, c.1508T&gt;C, and c.1540A&gt;C, resulting in the p.Pro193fs, p.Cys88Trp, p.Gln307X, p.Gln332X, p.Gly343Ser, p.Leu503Pro, and p.Ser514Arg changes, respectively). Adding new variants to the repertoire of ABCD1 mutations in X-ALD, our data provide an efficient, cost-effective, and reliable DHPLC detection protocol for mutation screening of X-ALD families. 

Retracted: Yes

PubPeer comments:
 Figure 2. Much more similar than you would expect. https: imgur.com bstrMLk , 
 #1 Figure 2 continued. Much more similar than you would expect. https: imgur.com nCWkKMM ,
Autophagic Markers in Chordomas: Immunohistochemical Analysis and Comparison with the Immune Microenvironment of Chordoma Tissues
Authors: Jean Marc Dumollard
Cédric Barrey
Maroa Dridi
Jean Michel Prades
Michel Péoc&#x27;h
François Vassal
Timothée Jacquesson
Georgia Karpathiou
David Meyronet
Emmanuel Jouanneau
Lila Krebs-Drouot
Jean Boutonnat
Journal: Cancers (2021)
Discipline: CLINICAL MEDICINE
Keywords: ATG16L1; CD8; LC3B; M6PR; PD-L1
Affiliations: Pathology Department, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France., Pathology Department, University Hospital of Grenoble, 38700 Grenoble, France., Neurosurgery Department, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France., Department of Neurosurgery B, Neurological Hospital Pierre Wertheimer, 69500 Lyon, France., Department of Spine Surgery, P Wertheimer Hospital, Hospices Civils de Lyon, Claude Bernard University, Lyon 1, 69100 Lyon, France., Head and Neck Surgery Department, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France.

Abstract:  Chordomas are notably resistant to chemotherapy. One of the cytoprotective mechanisms implicated in chemoresistance is autophagy. There are indirect data that autophagy could be implicated in chordomas, but its presence has not been studied in chordoma tissues. Sixty-one (61) chordomas were immunohistochemically studied for autophagic markers and their expression was compared with the expression in notochords, clinicopathological data, as well as the tumor immune microenvironment. All chordomas strongly and diffusely expressed cytoplasmic p62 (sequestosome 1, SQSTM1/p62), whereas 16 (26.2%) tumors also showed nuclear p62 expression. LC3B (Microtubule-associated protein 1A/1B-light chain 3B) tumor cell expression was found in 44 (72.1%) tumors. Autophagy-related 16‑like 1 (ATG16L1) was also expressed by most tumors. All tumors expressed mannose-6-phosphate/insulin-like growth factor 2 receptor (M6PR/IGF2R). LC3B tumor cell expression was negatively associated with tumor size, while no other parameters, such as age, sex, localization, or survival, were associated with the immunohistochemical factors studied. LC3B immune cell expression showed a significant positive association with programmed death-ligand 1 (PD-L1)+ immune cells and with a higher vascular density. ATG16L1 expression was also positively associated with higher vascular density. Notochords (n = 5) showed different immunostaining with a very weak LC3B and M6PR expression, and no p62 expression. In contrast to normal notochords, autophagic factors such as LC3B and ATG16L1 are often present in chordomas, associated with a strong and diffuse expression of p62, suggesting a blocked autophagic flow. Furthermore, PD-L1+ immune cells also express LC3B, suggesting the need for further investigations between autophagy and the immune microenvironment. 

Retracted: No

PubPeer comments:
 Figure 1E. Much more similar than you would expect. https: imgur.com JvwfHOJ ,
Cationic transfersomes based topical genetic vaccine against hepatitis B
Authors: Amit K Goyal
Kapil Khatri
Praveen K Dubey
Prem N Gupta
S P Vyas
Amit Rawat
Sunil Mahor
Journal: International journal of pharmaceutics (2007)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: DNA vaccines; transcutaneous immunization; cationic transfersomes; topical delivery; hepatitis B surface antigen
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, MP 470003, India.

Abstract:  DNA vaccines have been shown to elicit both cellular and humoral immune responses and to be effective in a variety of preclinical bacterial, viral, and parasitic animal models. We have recently described a needle-free method of vaccination, transcutaneous immunization, based on topical application of vaccine antigens on intact skin using a novel carrier system, namely transfersomes. In the present study, a novel modified version of transfersomes, i.e., cationic transfersomes for topical DNA vaccine delivery has been developed. Cationic transfersomes composed of cationic lipid DOTMA and sodium deoxycholate as constitutive lipids were prepared and optimized for their size, shape, zeta potentials, deformability and loading efficiency. Plasmid DNA encoding hepatitis B surface antigen (HBsAg) was loaded in the cationic transfersomes using charge neutralization method. The immune stimulating activity was studied by measuring serum anti-HBsAg titer and cytokines level (IL-2 and IFN-gamma) following topical applications of plasmid DNA loaded cationic transfersomes in Balb/c mice and results were compared with naked DNA applied topically as well as naked DNA and pure recombinant HBsAg administered intramuscularly. Results revealed that DNA loaded cationic transfersomes elicited significantly (*P&lt;0.05) higher anti-HBsAg antibody titer and cytokines level as compared to naked DNA. It was also observed that topical application of DNA loaded cationic transfersomes elicited a comparable serum antibody titer and endogenous cytokines levels as produced after intramuscular recombinant HBsAg administration. The study signifies the potential of cationic transfersomes as DNA vaccine carriers for effective topical immunization. 

Retracted: No

PubPeer comments:
  Fig. 1. Transmission electron microscopic image of DNA loaded cationic transfersomes. Two of the cationic transfersomes are the same. Areas of background repeat. ![file] , 
 #1 At right, Fig 1 from [Tiwari et al (2009)] ,  Transmission electron photomicrograph of [A] conventional liposomes [B] gel core liposomes. Rotated through 180 deg. ![file] ,
A high-content, high-throughput siRNA screen identifies cyclin D2 as a potent regulator of muscle progenitor cell fusion and a target to enhance muscle regeneration
Authors: Jonathan Yang
Thomas Caldwell
Refik Kayali
Carmen Bertoni
Michael V Khanjyan
Journal: Human Molecular Genetics (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: muscle progenitor cells; regeneration; high-throughput screening; myogenesis; cyclin D2
Affiliations: Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095, USA.

Abstract:  Cell-mediated regenerative approaches using muscle progenitor cells hold promises for the treatment of many forms of muscle disorders. Their applicability in the clinic, however, is hindered by the low levels of regeneration obtained after transplantation and the large number of cells required to achieve an effect. To better understand the mechanisms that regulate the temporal switch of replicating muscle progenitor cells into terminally differentiated cells and to develop new strategies that could enhance muscle regeneration, we have developed and performed a high-throughput screening (HTS) capable of identifying genes that play active roles during myogenesis. Secondary and tertiary screens were used to confirm the effects of RNAi in vitro and in vivo and to select for candidate hits that significantly increase regeneration into skeletal muscles. Downregulation of cyclin D2 (CCND2) was shown to dramatically enhance myogenic differentiation of muscle progenitor cells and to induce a robust regeneration after cell transplantation into skeletal muscles of dystrophin-deficient mice. Protein interaction network and pathway analysis revealed that CCND2 directly interacts with the cyclin-dependent kinase Cdk4 to inhibit phosphorylation of the retinoblastoma protein (pRb), thus blocking the activation of the myogenic switch during fusion. These studies identify CCND2 as a new key regulator of terminal differentiation in muscle progenitor cells and open new possibilities for the treatment of many forms of muscle disorders characterized by impaired regeneration and loss of muscle mass. 

Retracted: No

PubPeer comments:
 ![file] ,
Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1
Authors: Kevin J Fitzgerald
Jason Moffat
Nada Y Kalaany
Deanna M Stevens
Aurora A Burds
David A Guertin
David M Sabatini
Michael Brown
Carson C Thoreen
Journal: Developmental cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mTOR; mTORC1; mTORC2; mLST8; raptor
Affiliations: Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, Massachusetts 02141, USA.

Abstract:  The mTOR kinase controls cell growth, proliferation, and survival through two distinct multiprotein complexes, mTORC1 and mTORC2. mTOR and mLST8 are in both complexes, while raptor and rictor are part of only mTORC1 and mTORC2, respectively. To investigate mTORC1 and mTORC2 function in vivo, we generated mice deficient for raptor, rictor, or mLST8. Like mice null for mTOR, those lacking raptor die early in development. However, mLST8 null embryos survive until e10.5 and resemble embryos missing rictor. mLST8 is necessary to maintain the rictor-mTOR, but not the raptor-mTOR, interaction, and both mLST8 and rictor are required for the hydrophobic motif phosphorylation of Akt/PKB and PKCalpha, but not S6K1. Furthermore, insulin signaling to FOXO3, but not to TSC2 or GSK3beta, requires mLST8 and rictor. Thus, mTORC1 function is essential in early development, mLST8 is required only for mTORC2 signaling, and mTORC2 is a necessary component of the Akt-FOXO and PKCalpha pathways. 

Retracted: No

PubPeer comments:
 Figure 5E appears to show some sharp background transitions around some of the fluorescent cells. Shown with pink arrows. Image contrast adjusted to bring out details. There might be a perfectly acceptable technical explanation for this (although it is unexpected that these areas differ between images). Could authors comment, please? ![file] ![file] , 
 Fig 5: I agree with the Callinectes bocourti s concerns. Additionally, also in Figure 5E, a similar difference in the background can be observed in the wt panel after increasing brightness. ![file] Fig 6: Possible *horizontal* splice. Could authors clarify this please? ![file] ,
Effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells
Authors: Jin-Ye Fu
Ze-Ming Zhao
Cun-Qiu Chen
Yue-Zu Fan
Journal: World Journal of Gastroenterology (2005)
Discipline: CLINICAL MEDICINE
Keywords: norcantharidin; proliferation; invasion; GBC-SD cells; anticancer mechanism
Affiliations: Department of General Surgery, Tongji Hospital of Tongji University, 389 Xincun Road, Shanghai 200065, China. .

Abstract:  Aim: To investigate the effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells in vitro and its anticancer mechanism. Methods: Human gallbladder carcinoma GBC-SD cells were cultured by cell culture technique. The growth and the invasiveness of GBC-SD cells in vitro were evaluated by the tetrazolium-based colorimetric assay and by the Matrigel experiment and the crossing-river test. Expression of PCNA, Ki-67, MMP2 and TIMP2 proteins of GBC-SD cells was determined by streptavidin-biotin complex method. Results: In vitro norcantharidin inhibited the growth and proliferation of GBC-SD cells in a dose- and time-dependent manner, with the IC50 value of 56.18 microg/mL at 48 h. Norcantharidin began to inhibit the invasion of GBC-SD cells at the concentration of 5 microg/mL, and the invasive action of GBC-SD cells was inhibited completely and their crossing-river time was prolonged significantly at 40 microg/mL. After treatment with norcantharidin, the expression of PCNA, Ki-67, and MMP2 was significantly decreased. With the increase in TIMP2 expression, the MMP2 to TIMP2 ratio was decreased significantly (P&lt;0.05). Conclusion: Norcantharidin inhibits the proliferation and growth of human gallbladder carcinoma cells in vitro at relatively low concentrations by inhibiting PCNA and Ki-67 expression. Its anti-invasive activity may be the result of decrease in MMP2 to TIMP2 ratio and reduced cell motility. 

Retracted: No

PubPeer comments:
 Several figures and tables in this paper appear similar or identical to those in an older paper by the same authors, i.e. Yue-Zu Fan et al., Hepatobiliary Pancreat Dis Int 2004; 3:603-607, PMID:15567755. This paper does not appear to be listed in the References. Figures 1A and 1B of the 2004 paper (top) compared to Figures 1 and 2 of this 2005 paper (below): ![file] Figures 2 and 3 of the 2004 paper (top left) compared to Figures 3 and 4 of this 2005 paper (right and below), with the same overlap as noticed for the 2004 paper marked in red. ![file] Table 1 of the 2004 paper (left) compared to Table 1 of this 2005 paper (right): ![file] ,
Knockdown of long noncoding RNA SNHG7 inhibits the proliferation and promotes apoptosis of thyroid cancer cells by downregulating BDNF
Authors: C Li
B-L Huo
Y-H Wang
G Ma
W Cao
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNAs; SNHG7; thyroid cancer; qRT-PCR; clinicopathological factors
Affiliations: Department of Oncology Surgery, Shaanxi Provincial People's Hospital, China. .

Abstract:  Objective: Recently, long noncoding RNAs (lncRNAs) have got much attention for their role in tumor progression. LncRNA small nucleolar RNA host gene 7 (SNHG7) was studied in this research to identify how it affects the development of thyroid cancer (TC). Patients and methods: SNHG7 expression was detected by quantitative Real-time polymerase chain reaction (qRT-PCR) in both TC cells and tissue samples. Pearson's Chi-square test was used to determine the association of SNHG7 expression with several clinicopathological factors. Moreover, colony formation assay, cell proliferation and cell apoptosis assay were conducted. In addition, by performing qRT-PCR and Western blot assay, the underlying mechanism was explored. Results: SNHG7 expression level was higher in TC samples than that in corresponding ones. The SNHG7 expression was associated with tumor size and TNM stage. Moreover, TC cell proliferation was inhibited, and TC cell apoptosis was induced after SNHG7 was knocked down in vitro. Moreover, the mRNA and protein expressions of brain-derived neurotrophic factor (BDNF) were downregulated after knockdown of SNHG7. Furthermore, the expression level of BDNF was positively related to the expression of SNHG7 in TC tissues. Conclusions: These results suggested that knockdown of SNHG7 could inhibit TC cell proliferation and induce cell apoptosis via downregulating BDNF, which might be a potential therapeutic target in TC. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. ,
Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery
Authors: Jittima Chatchawalsaisin
Poj Kulvanich
Chutima Sinsuebpol
Journal: Drug Design Development and Therapy (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Salmon calcitonin; chitosan; mannitol; nanoparticles; pulmonary delivery
Affiliations: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Road, Bangkok, Thailand.

Abstract:  Purpose: The aim of the present study was to prepare inhalable co-spray dried powders of salmon calcitonin loaded chitosan nanoparticles (sCT-CS-NPs) with mannitol and investigate pulmonary absorption in rats. Methods: The sCT-CS-NPs were prepared by the ionic gelation method using sodium tripolyphosphate (TPP) as a cross-linking polyion. Inhalable dry powders were obtained by co-spray drying aqueous dispersion of sCT-CS-NPs and mannitol. sCT-CS-NPs co-spray dried powders were characterized with respect to morphology, particle size, powder density, aerodynamic diameter, protein integrity, in vitro release of sCT, and aerosolization. The plasmatic sCT levels following intratracheal administration of sCT-CS-NPs spray dried powders to the rats was also determined. Results: sCT-CS-NPs were able to be incorporated into mannitol forming inhalable microparticles by the spray drying process. The sCT-CS-NPs/mannitol ratios and spray drying process affected the properties of the microparticles obtained. The conformation of the secondary structures of sCTs was affected by both mannitol content and spray dry inlet temperature. The sCT-CS-NPs were recovered after reconstitution of spray dried powders in an aqueous medium. The sCT release profile from spray dried powders was similar to that from sCT-CS-NPs. In vitro inhalation parameters measured by the Andersen cascade impactor indicated sCT-CS-NPs spray dried powders having promising aerodynamic properties for deposition in the deep lung. Determination of the plasmatic sCT levels following intratracheal administration to rats revealed that the inhalable sCT-CS NPs spray dried powders provided higher protein absorption compared to native sCT powders. Conclusion: The sCT-CS-NPs with mannitol based spray dried powders were prepared to have appropriate aerodynamic properties for pulmonary delivery. The developed system was able to deliver sCT via a pulmonary route into the systemic circulation. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Enhanced anti-tumor and anti-metastasis therapy for triple negative breast cancer by CD44 receptor-targeted hybrid self-delivery micelles
Authors: Qin He
Bing Xiang
Man Li
Yashi Wang
Zhirong Zhang
Kebai Ren
Yang Long
Yiliang Yang
Journal: International Journal of Pharmaceutics (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Anti-metastasis; CD44; Hyaluronic acid; Multiphase; Targeting.
Affiliations: Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China., Department of Hematology, Hematology Research Laboratory, West China Hospital of Sichuan University, Chengdu 610041, People's Republic of China. Electronic address: ., Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address: .

Abstract:  Tumor growth and metastasis are multistep processes regulated by multiple signaling pathways. The successful treatment of cancer largely depends on the ability to inhibit metastatic process. Multiphase inhibition of metastasis is a promising approach. Here, we described a targeting delivery system which was constructed by mixing hyaluronic acid-d-α-tocopheryl succinate (HA-TOS, HT) and low molecular weight heparin-TOS (LMWH-TOS, LT) to form a stable hybrid micelle (HT-LT), encapsulating chemotherapeutic drug doxorubicin (DOX). The prepared HT-LT NPs was about 125 nm in diameter with high drug encapsulation rate and continuous drug release behavior. We confirmed that HT-LT NPs exhibited an effective targeting ability both in vitro and in vivo using a 4T1 model that was attributed to HA binding to CD44 receptors. In addition, HT-LT NPs acted on different phases of the invasion-metastasis cascade and inhibited tumor cell migration and invasion, thus inhibiting tumor metastasis. This combinatorial strategy provided an alternative approach for triple negative breast cancer therapy. 

Retracted: No

PubPeer comments:
 The first column of images in Figure 2A appear to be repetitive. I believe the second column of Figure 2A may include some overlapping images, which the authors may wish to investigate as well, and Figure 5 appears to suffer from the same issues. I did not care to also document those. *** ![file] ,