PReD-Bench/PRed-Bench huggingface dataset:
Insulin receptor substrate 1 is a target for the pure antiestrogen ICI 182,780 in breast cancer cells
Authors: M Salerno
L Mauro
S Ando
E Surmacz
D Sisci
M A Guvakova
Journal: International Journal of Cancer (1999)
Discipline: CLINICAL MEDICINE
Keywords: ICI 182,780; insulin-like growth factor; breast cancer cells; IGF-IR; signal transduction
Affiliations: Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Abstract:  The pure antiestrogen ICI 182,780 inhibits insulin-like growth factor (IGF)-dependent proliferation in hormone-responsive breast cancer cells. However, the interactions of ICI 182,780 with IGF-I receptor (IGF-IR) intracellular signaling have not been characterized. Here, we studied the effects of ICI 182,780 on IGF-IR signal transduction in MCF-7 breast cancer cells and in MCF-7-derived clones overexpressing either the IGF-IR or its 2 major substrates, insulin receptor substrate 1 (IRS-1) or src/collagen homology proteins (SHC). ICI 182,780 blocked the basal and IGF-I-induced growth in all studied cells in a dose-dependent manner; however, the clones with the greatest IRS-1 overexpression were clearly least sensitive to the drug. Pursuing ICI 182,780 interaction with IRS-1, we found that the antiestrogen reduced IRS-1 expression and tyrosine phosphorylation in several cell lines in the presence or absence of IGF-I. Moreover, in IRS-1-overexpressing cells, ICI 182,780 decreased IRS-1/p85 and IRS-1/GRB2 binding. The effects of ICI 182,780 on IGF-IR protein expression were not significant; however, the drug suppressed IGF-I-induced (but not basal) IGF-IR tyrosine phosphorylation. The expression and tyrosine phosphorylation of SHC as well as SHC/GRB binding were not influenced by ICI 182,780. In summary, downregulation of IRS-1 may represent one of the mechanisms by which ICI 182,780 inhibits the growth of breast cancer cells. Thus, overexpression of IRS-1 in breast tumors could contribute to the development of antiestrogen resistance. 

Retracted: No

PubPeer comments:
 Figure 2B. IRS-1 panels much more similar than you would expect even though the cells are different. https: imgur.com MVuduOq , 
 2020 correction. https: doi.org 10.1002 ijc.33274 u201cInsulin receptor substrate 1 is a target for the pure antiestrogen ICI 182,780 in breast cancer cells.u201d Salerno M, Sisci D, Mauro L, Guvakova MA, Ando S, Surmacz E. Int J Cancer. 1999, 81(2):299u2010304. In the Western Blot in Figure 2B of the aboveu2010mentioned manuscript, the bands for IRSu20101 in MCFu20107 IGFu2010IR and MCFu20107 cells look very similar. The authors are unable to retrieve the original data due to the time that has elapsed; therefore, duplication of the bands in question can neither be proven nor disproven. Given that the experiments presented in this manuscript have been performed in 1998 or earlier and logistic conditions are very different now, the editors consider that a reu2010performance of the experiments would not be appropriate. The authors stand by the conclusions of the paper. ,
Long noncoding RNA FAM201A mediates the metastasis of lung squamous cell cancer via regulating ABCE1 expression
Authors: B Ma
Z-X Qiao
W He
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; FAM201A; lung squamous cell carcinoma; metastasis; molecular mechanism
Affiliations: Department of Thoracic Surgery, General Hospital of Ningxia Medical University, Yinchuan, China. .

Abstract:  Objective: Long noncoding RNA (lncRNA) family with sequence similarity 201-member A (FAM201A) is a novel lncRNA promoting the development of various cancers. However, the biological function of FAM201A on the metastasis of lung squamous cell carcinoma (LSCC) remains unknown. The aim of this study was to explore the molecular mechanism of FAM201A and its target protein in advanced LSCC. Patients and methods: Quantitative Polymerase Chain Reaction (qPCR) was applied to evaluate FAM201A expression in lung cancer tissues. The impact of high FAM201A expression on the overall survival in patients with lung cancer was tested using the log-rank test. The relevance between aberrant FAM201A and clinicopathological characteristics in patients with lung cancer was analyzed using the Chi-square tests. Cell proliferation was assayed using the Cell Counting Kit-8 (CCK-8) and a transwell assay, and the mice xenograft models were applied to determine the promoting effects of FAM201A on LSCC in vitro and in vivo. The underlying regulatory mechanism was explored through RNA transfection, qPCR, and Western blotting. The correlation between ATP-binding cassette transporter E1 (ABCE1) and FAM201A expression was verified using Spearman's correlation coefficient. Results: FAM201A is aberrantly elevated in tissues from patients with non-small cell lung cancer. High levels of FAM201A expression were more likely to present in patients with squamous type, M1 stage, and inferior overall survival. Differential expression was found between non-metastatic and metastatic squamous carcinoma, but not in adenocarcinoma. FAM201A knockdown inhibits cell proliferation, migration, and invasion of LSCC cells in vitro, and represses tumor growth in vivo. Furthermore, ABCE1 in LSCC cells was downregulated by silencing FAM201A. The tissue level of ABCE1 was positively correlated with FAM201A expression in patients with LSCC. Conclusions: FAM201A may markedly induce migration and invasion of LSCC, resulting in the M1 stage and poor survival. These findings suggest the FAM201A-ABCE1 axis as a novel therapeutic target in LSCC. 

Retracted: No

PubPeer comments:
 This paper appears to belong to the  Golden Arches paper set, reported here: https: scienceintegritydigest.com 2020 07 02 the-golden-arches-paper-set These papers all appear to share the same photos of tumors, colony formation assays, and transwell experiments. Here is an comparisosn of this paper s transwell photos shown in Figure 3 and those shown in Figure 2 of Yong Liu et al., OncoTargets and Therapy 2020:13 745u2013755, DOI: 10.2147 ott.s236162. Boxes of the same color show images that look very similar. ![file] ,
The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells
Authors: Li-Hua Xu
Mengfeng Li
Hamid Band
Ling Zhang
Xing Zhang
Qing-Hua Shi
Li-Wu Fu
Wen-Lin Huang
Wan-Li Liu
Yi-Xin Zeng
Yan Feng
Chun-Ping Yu
Vimla Band
Qing-Li Kong
Tie-Bang Kang
Mu-Sheng Zeng
Li-Juan Hu
Jun Li
Yun-Fei Xia
Man-Zhi Li
Li-Bing Song
Sai Wah Tsao
Wen-Ting Liao
Journal: Journal of Clinical Investigation (2009)
Discipline: CLINICAL MEDICINE
Keywords: Bmi-1; nasopharyngeal carcinomas; epithelial-mesenchymal transition (EMT); motility; invasiveness
Affiliations: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Abstract:  The polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is dysregulated in various cancers, and its upregulation strongly correlates with an invasive phenotype and poor prognosis in patients with nasopharyngeal carcinomas. However, the underlying mechanism of Bmi-1-mediated invasiveness remains unknown. In the current study, we found that upregulation of Bmi-1 induced epithelial-mesenchymal transition (EMT) and enhanced the motility and invasiveness of human nasopharyngeal epithelial cells, whereas silencing endogenous Bmi-1 expression reversed EMT and reduced motility. Furthermore, upregulation of Bmi-1 led to the stabilization of Snail, a transcriptional repressor associated with EMT, via modulation of PI3K/Akt/GSK-3beta signaling. Chromatin immunoprecipitation assays revealed that Bmi-1 transcriptionally downregulated expression of the tumor suppressor PTEN in tumor cells through direct association with the PTEN locus. This in vitro analysis was consistent with the statistical inverse correlation detected between Bmi-1 and PTEN expression in a cohort of human nasopharyngeal carcinoma biopsies. Moreover, ablation of PTEN expression partially rescued the migratory/invasive phenotype of Bmi-1-silenced cells, indicating that PTEN might be a major mediator of Bmi-1-induced EMT. Our results provide functional and mechanistic links between the oncoprotein Bmi-1 and the tumor suppressor PTEN in the development and progression of cancer. 

Retracted: No

PubPeer comments:
 Supplementary Figure 6A contains two images which share multiple sets of similar regions, however, these two images are not identical. ![file] , 
 Fig. 3A. More similar than expected. ![file] ,
Interleukin 6 regulates the expression of programmed cell death ligand 1 in thyroid cancer
Authors: Chen-Tian Shen
Guo-Qiang Zhang
Hong-Jun Song
Zhong-Ling Qiu
Hui-Zhen Zhang
Qiong Jiao
Quan-Yong Luo
Journal: Cancer science (2021)
Discipline: CLINICAL MEDICINE
Keywords: IL-6; PD-L1; mechanism; regulation; thyroid cancer.
Affiliations: Department of Nuclear Medicine Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China, Department of Pathology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China

Abstract:  Programmed cell death ligand 1 (PD-L1), inducing T cell exhaustion to facilitate immune escape of tumor cells, is upregulated by interleukin 6 (IL-6) in T cell lymphoma and ovarian cancer. The purpose of this study is to investigate the expression of IL-6 and PD-L1 in thyroid cancer, and whether IL-6 regulates PD-L1 expression. As a result, IL-6 and PD-L1 were highly expressed in thyroid cancer tissues. Multivariate logistic analysis showed that tumor size, distant metastasis, and risk stratification were significantly associated with IL-6 expression (P &lt; .05), and multifocality, lymph node metastasis, distant metastasis, risk stratification, and IL-6 expression were identified as the independent predictors of PD-L1 expression (P &lt; .05). The invasiveness of thyroid cancer was significantly enhanced after IL-6 treatment or PD-L1 overexpression. PD-L1 positive rate correlated with IL-6 expression in cancer tissues (P &lt; .001), and after IL-6 treatment, the PD-L1 expression in TPC-1 and BCPAP significantly increased. The mitogen-activated protein kinase pathway (MAPK) and the Janus-activated kinase (JAK)-signal transducers and activators of transcription 3 (STAT3) signaling pathways were activated by IL-6, and the IL-6-induced PD-L1 expression decreased after treatment with these two signaling pathway inhibitors. Knockdown of transcription factors c-Jun and stat3 suppressed the expression of PD-L1 induced by IL-6, and these two factors could bind to PD-L1 gene promoter directly and promote its transcription. It is concluded that IL-6 and PD-L1 are overexpressed in thyroid cancer and are related to tumor invasiveness. IL-6 upregulates PD-L1 expression through the MAPK and JAK-STAT3 signaling pathways, which function via transcription factors c-Jun and stat3. 

Retracted: No

PubPeer comments:
 Fig6-A:duplicate image ![file] , 
 Thanks for your comment! We have checked the images in Figure 6A, and indeed we made a mistake. The raw experimental data of cell lines TPC-1 and BCPAP were processed prior to paper submission, with corresponding images and data processing date as proof. However, when arranging the whole picture of Figure 6, since several images were opened at the same time, the image of TCP-1 was repeatedly moved into Figure 6A twice, while the result of BCPAP was omitted. We will email the editor to correct the error. We apologize for this issue. And thank you very much for reminding. The revised Figure 6A is as shown below.**** ![file] ,
Cell Cycle Genes Are Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma
Authors: Chen Qi
Li Dongen
Yang Liang
Jiang Jianshuai
Li Jia
Xu Liping
Journal: BioMed Research International (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell cycle pathway genes; hepatocellular carcinoma; gene expression; diagnostic; prognostic
Affiliations: Department of Hepatobiliary Pancreatic Surgery, Ningbo First Hospital, Ningbo, Zhejiang Province, China, Department of Breast and Thyroid, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

Abstract:  Background: The cell cycle pathway genes are comprised of 113 members which are critical to the maintenance of cell cycle and survival of tumor cells. This study was performed to investigate the diagnostic and prognostic values of cell cycle gene expression in hepatocellular carcinoma (HCC) patients. Methods: Clinical features and cell cycle pathway gene expression data were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Differentially expressed genes (DEGs) were determined by the student t-test between HCC and noncancerous samples. Kaplan-Meier survival, univariate, and multivariate survival analyses and validation analysis were performed to characterize the associations between cell cycle gene expression and patients' overall survival and recurrence-free survival. Results: 47 and 5 genes were significantly upregulated and downregulated genes in HCC samples, respectively. The high expression of BUB3, CDK1, and CHEK1 was associated with increased mortality (adjusted P value = 0.04, odds ratio (OR): 1.89 (95% confidence interval (CI): 1.04-3.46); adjusted P value = 0.02, OR: 2.06 (95% CI:1.15-3.75); and adjusted P value = 0.04, OR: 1.84 (%95 CI: 1.03-3.32), respectively). The expression of PTTG2 and RAD21 was significantly associated with cancer recurrence (adjusted P value = 0.01, OR: 2.17 (95% CI: 1.24-3.86); adjusted P value = 0.03, OR: 1.88[95% CI:1.08-3.28], respectively), while the low expression of MAD1L1 was associated with cancer recurrence (adjusted P value = 0.03, OR: 0.53 (%95 CI: 0.3-0.93)). Conclusions: The present study demonstrated that BUB3, CDK1, and CHEK1 may serve as a prognostic biomarker for HCC patients. PTTG2, RAD21, and MAD1L1 expression is a major factor affecting the recurrence of HCC patients. 

Retracted: No

PubPeer comments:
 Table 2 seems to have some data anomalies. Similar to the image issues expressed by an overlapping author group here: https: pubpeer.com publications 6A12D08C3B890539A14F2044D59569 *** ![file] ,
MicroRNA-494 acts as a tumor suppressor in pancreatic cancer, inhibiting epithelial-mesenchymal transition, migration and invasion by binding to SDC1
Authors: Chun-Bo Li
Xiong Tao
Ying Yang
Chang-Miao Wang
Journal: International Journal of Oncology (2018)
Discipline: CLINICAL MEDICINE
Keywords: Pancreatic cancer; microRNAs; epithelial-mesenchymal transition; invasion; syndecan 1
Affiliations: Department of General Surgery, Τhe First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China

Abstract:  Pancreatic cancer (PC) is the fourth most common cause of cancer‑related mortality in the industrialized world. Emerging evidence indicates that a variety of microRNAs (miRNAs or miRs) are involved in the development of PC. The aim of the present study was to elucidate the mechanisms through which miR‑494 affects the epithelial‑mesenchymal transition (EMT) and invasion of PC cells by binding to syndecan 1 (SDC1). PC tissues and pancreatitis tissues were collected, and the regulatory effects of miR‑494 on SDC1 were validated using bioinformatics analysis and a dual‑luciferase report gene assay. The cell line with the highest SDC1 expression was selected for use in the following experiments. The role of miR‑494 in EMT was assessed by measuring the expression of SDC1, E‑cadherin and vimentin. Cell proliferation was assessed using a cell counting kit (CCK)‑8 assay, migration was measured using a scratch test, invasion was assessed with a Transwell assay and apoptosis was detected by flow cytometry. Finally, a xenograft tumor model was constructed in nude mice to observe tumor growth in vivo. We found that SDC1 protein expression was significantly higher in the PC tissues. SDC1 was verified as a target gene of miR‑494. The SW1990 cell line was selected for use in further experiments as it had the lowest miR‑494 expression and the highest SDC1 expression. Our results also demonstrated that miR‑494 overexpression and SDC1 silencing significantly decreased the mRNA and protein expression of SDC1 and vimentin in SW1990 cells, while it increased E‑cadherin expression and apoptosis, and inhibited cell growth, migration, invasion and tumor growth. On the whole, the findings of this study demonstrated that miR‑494 is able to downregulate SDC1 expression, thereby inhibiting the progression of PC. These findings reveal a novel mechanism through which miR‑494 affects the development of PC and may thus provide a basis for the application of miR‑494 in pancreatic oncology. 

Retracted: No

PubPeer comments:
 ![file] , 
 ![file] , 
 #1 I have taken the liberty of extending the comparison between Fig 3A from  Cytochrome P4503A: evidence for mRNA expression and catalytic activity in rat brain [(Yadav et al 2006)] ; and Fig 4 from the present paper. ![file] ,
MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression
Authors: Zhongling Zhang
Huifan Liu
Xing Li
Juanjuan Bai
Journal: Cancer Biomarkers (2015)
Discipline: CLINICAL MEDICINE
Keywords: Malignant melanoma (MM); cancer biomarker; invasion and metastasis; miR-365; neuropilin1 (NRP1)

Abstract:  Objective: The role of miR-365 in cancer cells seemed controversial in previous studies. We thereby in this article aimed to define the role of miR-365 in malignant melanoma (MM) pathogenesis. Methods: We detected miR-365 expression in malignant melanoma cell lines and then investigated the effects of miR-365 on the metastasis and malignancy of melanoma cells. The correlation between miR-365 level and NRP1 (neuropilin1) was further investigated in clinical malignant melanoma specimens. Results: MiR-365 was strongly down-regulated in malignant melanoma (MM) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of MM. We also found that ectopic expression of miR-365 inhibited MM cell proliferation and MM metastasis in vitro and in vivo. We further identified a novel mechanism of miR-365 to suppress MM growth and metastasis. NRP1 was proved to be a direct target of miR-365, using luciferase assay and western blot. NRP1 over-expression in miR-365 expressing cells could rescue invasion and growth defects of miR-365. In addition, miR-365 expression inversely correlated with NRP1 protein levels in MM. Conclusion: Our data suggest that miR-365 functions as a tumor suppressor in MM development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for MM. 

Retracted: No

PubPeer comments:
 It looks like this paper has been published elsewhere... https: pubmed.ncbi.nlm.nih.gov 26191184 https: pubmed.ncbi.nlm.nih.gov 26406949 , 
 As Parsonsia Longipetiolata pointed out, this paper is almost indistinguishable from [ MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression ] by the same authors (2015). ![file] ,
Synergistic Microbicidal Effect of Auranofin and Antibiotics Against Planktonic and Biofilm-Encased S. aureus and E. faecalis
Authors: Linying Zhou
Zhen Luo
Yong Wu
Lanlan Xu
Shijia Li
Pengfei She
Lihua Chen
Yiqing Liu
Journal: Frontiers in Microbiology (2019)
Discipline: MICROBIOLOGY
Keywords: Enterococcus faecalis; Staphylococcus aureus; auranofin; biofilm; combination therapy
Affiliations: Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, China.

Abstract:  Methicillin-resistant/susceptible Staphylococcus aureus (MRSA/MSSA) and Enterococcus faecalis strains are often found in community- and hospital-acquired infections. The single use of conventional antibiotics hardly completely kills the bacterial cells of interest, especially in the form of biofilms. Thus, drug repurposing and antimicrobial combination are promising ways to solve this problem. Antimicrobial susceptibility assays against cocci in a suspension and in a biofilm mode of growth were performed with broth microdilution methods. Checkerboard assays and the cutaneous mouse infection model were used to examine the activity of auranofin and conventional antibiotics alone and in combination. In the present study, auranofin possesses potent antimicrobial activities against both planktonic cells and biofilms with minimum inhibitory concentrations ranging 0.125-0.5 mg/L. Auranofin in combination with linezolid or fosfomycin showed synergistic antimicrobial activities against S. aureus MSSA and MRSA both in vitro and in vivo. Similarly, auranofin also behaved synergistic effect with chloramphenicol against E. faecalis. Additionally, auranofin improved the antibiofilm efficacy of chloramphenicol and linezolid, even on the biofilms grown on a catheter surface. Though, S. epidermidis showed significant susceptibility to AF treatment, no synergistic antimicrobial effects were observed with antibiotics we tested. In all, the use of a combination of auranofin with linezolid, fosfomycin, and chloramphenicol can provide a synergistic microbicidal effect in vitro and in vivo, which rapidly enhances antimicrobial activity and may help prevent or delay the emergence of resistance. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have a duplicated image. *** ![file] , 
 Thank you for your reminder! We are really sorry that we misused the Figure of Ctrl. group in Figure 2A. for our careless after we checked the raw data. And we revised it, please see the attached image: ![file] Meanwhile, we are writing a Corrigendum to the Frontiers in microbiology at the same time! ,
Tectorigenin Attenuates Palmitate-Induced Endothelial Insulin Resistance via Targeting ROS-Associated Inflammation and IRS-1 Pathway
Authors: Ling Zhou
Xiao-Lan Cheng
Min-Jian Qin
Qi Wang
Yong Qin
Kang Liu
Guo-Yong Xie
Xue-Jiao Gao
Dong-Yan Zhang
Bao-Lin Liu
Xiao-Ying Qin
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Tectorigenin; endothelial dysfunction; insulin resistance; inflammation; ROS production
Affiliations: Department of Resource Science of Traditional Chinese Medicines, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Abstract:  Tectorigenin is a plant isoflavonoid originally isolated from the dried flower of Pueraria thomsonii Benth. Although its anti-inflammatory and anti-hyperglycosemia effects have been well documented, the effect of tectorigenin on endothelial dysfunction insulin resistance involved has not yet been reported. Herein, this study aims to investigate the action of tectorigenin on amelioration of insulin resistance in the endothelium. Palmitic acid (PA) was chosen as a stimulant to induce ROS production in endothelial cells and successfully established insulin resistance evidenced by the specific impairment of insulin PI3K signaling. Tectorigenin effectively inhibited the ability of PA to induce the production of reactive oxygen species and collapse of mitochondrial membrane potential. Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation. Tectorigenin also can inhibit inflammation-stimulated IRS-1 serine phosphorylation and restore the impaired insulin PI3K signaling, leading to a decreased NO production. These results demonstrated its positive regulation of insulin action in the endothelium. Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta. These findings suggested that tectorigenin could inhibit ROS-associated inflammation and ameliorated endothelial dysfunction implicated in insulin resistance through regulating IRS-1 function. Tectorigenin might have potential to be applied for the management of cardiovascular diseases involved in diabetes and insulin resistance. 

Retracted: No

PubPeer comments:
 Figure 1, bottom part. * Blue boxes: The 0.1 and 1 uM Tectorigenin panels look very similar. ![file] , 
 Figure 7. * Red boxes: The ET-1 panel in Figure 7A looks very similar to the VCAM-1 panel in Figure 7B. The actin panels also look similar but that is expected. ![file] ,
Downregulation of lncRNA MEG3 attenuates high glucose-induced cardiomyocytes injury by inhibiting mitochondria-mediated apoptosis pathway
Authors: X Geng
W-W Zhang
W-Q Zhang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; MEG3; cardiomyocytes; high glucose; apoptosis
Affiliations: Department of Cardiology, Dezhou People's Hospital, Dezhou, China. .

Abstract:  Objective: The aim of the present work was to investigate the effects and mechanisms of long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) in cardiomyocytes injury and apoptosis induced by high glucose (HG) in vitro. Materials and methods: HG-induced rats' cardiomyocytes with si-MEG3 transfection were constructed. Cell viability and lactate dehydrogenase (LDH) level were examined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and LDH assay kits, respectively. Cardiomyocytes apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining. The expressions of Bcl-2, Bax, cleaved caspase-9 and cleaved caspase-3 proteins were determined by Western blot. The expression of lncRNA MEG3 was measured by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Results: Our results indicated that the expression of MEG3 was significantly upregulated in HG-treated cardiomyocytes. The downregulation of MEG3 could attenuate cardiomyocytes injury and apoptosis by decreasing the Bax/Bcl-2 ratio, cleaved caspase-9 and cleaved caspase-3 expression. Conclusions: The downregulation of MEG3 could attenuate cardiomyocytes injury and apoptosis induced by HG. The molecular mechanism was associated with the inhibition of the mitochondria-mediated apoptosis pathway. 

Retracted: No

PubPeer comments:
 Figure 3.  Downregulation of MEG3 inhibited HG-induced cardiomyocytes apoptosis. Cardiomyocytes apoptosis were stained by TUNEL. I have a concern with the HG-si-NC image. ![file] ,
Rigid and non-rigid registration of polarized light imaging data for 3D reconstruction of the temporal lobe of the human brain at micrometer resolution
Authors: Roland Eils
Sharib Ali
Karl Rohr
Stefan Wörz
Markus Axer
Katrin Amunts
Journal: NeuroImage (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: 3D reconstruction; Canonical correlation transform; Hippocampus; Human brain; Image registration
Affiliations: Dept. of Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, BIOQUANT, IPMB, University of Heidelberg, Germany; German Cancer Research Center (DKFZ), Germany. Electronic address: ., Dept. of Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, BIOQUANT, IPMB, University of Heidelberg, Germany; German Cancer Research Center (DKFZ), Germany., Institute of Neuroscience and Medicine 1, Research Centre Jülich, Germany; Cécile and Oskar Vogt Institute of Brain Research, Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Germany., Institute of Neuroscience and Medicine 1, Research Centre Jülich, Germany.

Abstract:  To understand the spatial organization as well as long- and short-range connections of the human brain at microscopic resolution, 3D reconstruction of histological sections is important. We approach this challenge by reconstructing series of unstained histological sections of multi-scale (1.3μm and 64μm) and multi-modal 3D polarized light imaging (3D-PLI) data. Since spatial coherence is lost during the sectioning procedure, image registration is the major step in 3D reconstruction. We propose a non-rigid registration method which comprises of a novel multi-modal similarity metric and an improved regularization scheme to cope with deformations inevitably introduced during the sectioning procedure, as well as a rigid registration approach using a robust similarity metric for improved initial alignment. We also introduce a multi-scale feature-based localization and registration approach for mapping of 1.3μm sections to 64μm sections and a scale-adaptive method that can handle challenging sections with large semi-global deformations due to tissue splits. We have applied our registration method to 126 consecutive sections of the temporal lobe of the human brain with 64μm and 1.3μm resolution. Each step of the registration method was quantitatively evaluated using 10 different sections and manually determined ground truth, and a quantitative comparison with previous methods was performed. Visual assessment of the reconstructed volumes and comparison with reference volumes confirmed the high quality of the registration result. 

Retracted: No

PubPeer comments:
 2017 correction http: www.impactjournals.com oncotarget index.php?journal=oncotarget page=article op=view path[]=18923 , 
null, 
null, 
 Note: This article has been corrected. Please see the link below: https: www.oncotarget.com article 18923 ,
Spontaneous human adult stem cell transformation
Authors: Javier Garcia-Castro
Alison C Lloyd
Antonio Bernad
Daniel Rubio
María C Martín
Juan C Cigudosa
Ricardo de la Fuente
Journal: Cancer Research (2005)
Discipline: CLINICAL MEDICINE
Keywords: Human adult stem cells; therapeutic approaches; clinical trials; safety; transformation
Affiliations: Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, UAM Campus de Cantoblanco, Darwin, 3 E-28049 Madrid, Spain.

Abstract:  Human adult stem cells are being evaluated widely for various therapeutic approaches. Several recent clinical trials have reported their safety, showing them to be highly resistant to transformation. The clear similarities between stem cell and cancer stem cell genetic programs are nonetheless the basis of a recent proposal that some cancer stem cells could derive from human adult stem cells. Here we show that although they can be managed safely during the standard ex vivo expansion period (6-8 weeks), human mesenchymal stem cells can undergo spontaneous transformation following long-term in vitro culture (4-5 months). This is the first report of spontaneous transformation of human adult stem cells, supporting the hypothesis of cancer stem cell origin. Our findings indicate the importance of biosafety studies of mesenchymal stem cell biology to efficiently exploit their full clinical therapeutic potential. 

Retracted: No

PubPeer comments:
null, 
null, 
 As of 27th March 2021 cited 1385 times according to google scholar. https: scholar.google.co.uk scholar?q=bernad+lloyd hl=en as_sdt=0%2C5 as_ylo=2011 as_yhi=2021 Spontaneous human adult stem cell transformation u2026, R de la Fuente, JC Cigudosa, AC Lloyd, A Bernad - Cancer research, 2005 - AACR Human adult stem cells are being evaluated widely for various therapeutic approaches. Several recent clinical trials have reported their safety, showing them to be highly resistant to transformation. The clear similarities between stem cell and cancer stem cell genetic u2026 Cited by 1385 ,
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice
Authors: Audra L Clos
Rakez Kayed
Urmi Sengupta
Cristian A Lasagna-Reeves
George R Jackson
Diana L Castillo-Carranza
Journal: Molecular neurodegeneration (2011)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: neurofibrillary tangles; tau oligomers; Alzheimer's disease; neurotoxic; memory consolidation
Affiliations: George P, and Cynthia Woods Mitchell Center for Neurodegenerative Diseases, Departments of Neurology, and Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, TX 77555-1045, USA. .

Abstract:  Background: The correlation between neurofibrillary tangles of tau and disease progression in the brains of Alzheimer's disease (AD) patients remains an area of contention. Innovative data are emerging from biochemical, cell-based and transgenic mouse studies that suggest that tau oligomers, a pre-filament form of tau, may be the most toxic and pathologically significant tau aggregate. Results: Here we report that oligomers of recombinant full-length human tau protein are neurotoxic in vivo after subcortical stereotaxic injection into mice. Tau oligomers impaired memory consolidation, whereas tau fibrils and monomers did not. Additionally, tau oligomers induced synaptic dysfunction by reducing the levels of synaptic vesicle-associated proteins synaptophysin and septin-11. Tau oligomers produced mitochondrial dysfunction by decreasing the levels of NADH-ubiquinone oxidoreductase (electron transport chain complex I), and activated caspase-9, which is related to the apoptotic mitochondrial pathway. Conclusions: This study identifies tau oligomers as an acutely toxic tau species in vivo, and suggests that tau oligomers induce neurodegeneration by affecting mitochondrial and synaptic function, both of which are early hallmarks in AD and other tauopathies. These results open new avenues for neuroprotective intervention strategies of tauopathies by targeting tau oligomers. 

Retracted: No

PubPeer comments:
 unexpected 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. ,
Placental Pathology in COVID-19
Authors: Jeffery A Goldstein
Elisheva D Shanes
Emily S Miller
Hooman A Azad
Leena B Mithal
Sebastian Otero
Journal: American journal of clinical pathology (2020)
Discipline: CLINICAL MEDICINE
Keywords: COVID-19; Coronavirus; Decidual arteriopathy; Intervillous thrombi; Maternal vascular malperfusion
Affiliations: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL., Department of Pediatrics, Division of Infectious Diseases, Ann and Robert H. Lurie Children's Hospital of Chicago and Feinberg School of Medicine, Northwestern University, Chicago, IL., Feinberg School of Medicine, Northwestern University, Chicago, IL., Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Abstract:  Objectives: To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy. Methods: Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. Results: Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased.The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. Conclusions: Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology. 

Retracted: No

PubPeer comments:
 Excellent, wide ranging piece, resonant across all public services. , 
 Outstanding article with significant policy implications beyond the UK, especially in PIIGS economy - Portugal, Ireland, Italy, Greece and Span who have also suffered from austerity. ,
Comparison of the metastasis-inducing protein S100A4 (p9ka) with other prognostic markers in human breast cancer
Authors: S De Silva Rudland
J H Winstanley
A M Platt-Higgins
C A Renshaw
P S Rudland
C R West
R Barraclough
Journal: International Journal of Cancer (2000)
Discipline: CLINICAL MEDICINE
Keywords: S100A4; breast cancer; prognostic significance; tumour variables; patient survival
Affiliations: School of Biological Sciences, University of Liverpool, Liverpool, United Kingdom.

Abstract:  Our aim was to compare the occurrence and prognostic significance over 14-20 years of immunocytochemically detected S100A4 and other tumour variables in primary tumours from 349 patients with operable breast cancer. For a cut-off of 1% staining of the malignant cells, the antibody to S100A4 stains positively 56% of the carcinomas. There was a significant association of staining for S100A4 with tumours fixed to the chest wall, staining for c-erbB-2, c-erbB-3, pS2, cathepsin D and, inversely, at borderline levels with staining for estrogen receptor. Using Wilcoxon statistics in univariate analyses, staining for S100A4, nodal status, tumour class, histological grade and staining for c-erbB-2, p53 were associated negatively and staining for estrogen receptor, progesterone receptor were associated positively with patient survival times. The survival times of patients with S100A4-negative carcinomas with or without one of the other tumour variables showed no significant differences, whilst those of patients with S100A4-positive carcinomas showed significant differences in a negative or a positive way. Multivariate regression analysis for 137 patients showed that staining for S100A4 is most highly correlated with patient deaths, but involved lymph nodes, fixed tumours, high histological grade and staining for progesterone receptor were also significant independent prognostic variables. Our results suggest that in this set of patients, the tumour variable most tightly correlated with patient death is S100A4. 

Retracted: No

PubPeer comments:
 Figure 1. https: imgur.com 2lefJsy ,
Exosomes derived from human umbilical cord blood mesenchymal stem cells improve hepatic ischemia reperfusion injury via delivering miR-1246
Authors: Jiangming Chen
Lei Liu
Kun Xie
Fubao Liu
Journal: Cell Cycle (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Exosomes; hepatic injury; ischemia/reperfusion injury.
Affiliations: Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Abstract:  The purpose of this study was to explore the associated mechanism by which MSCs-derived exosomes exerted protective effect in hepatic ischemia/reperfusion injury (IRI). Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs)-derived exosomes were administrated into LO2 cells exposed to hypoxia/reoxygenation (H/R) and mice subjected to IRI. Cell viability was assessed by CCK-8 assay. Apoptosis was analyzed by flow cytometry and TUNEL staining. The expression of miR-1246 and Wnt/β-catenin pathway-related proteins was detected by quantitative real-time PCR (qRT-PCR) and western blotting. The concentration of pro-inflammatory cytokines was determined by ELISA. Luciferase activity assay was performed to confirm the interaction between miR-1246 and glycogen synthase kinase 3β (GSK3β). Hepatic function was assessed by determining serum alanine amino transferase (ALT) and aspartate amino transferase (AST) levels. Histological changes were observed using hematoxylin-eosin (H&amp;E) staining. MiR-1246 was significantly downregulated in H/R-treated LO2 cells. Treatment with exosomes derived from hUCB-MSCs led to miR-1246 upregulation. Furthermore, hUCB-MSCs-derived exosomes induced anti-apoptotic and pro-survival effects in LO2 cells and ameliorated IRI-induced hepatic dysfunction in mice, while treatment of exosomes from miR-1246 inhibitor-transfected hUCB-MSCs showed opposite effect, which was mediated by regulating GSK3β-Wnt/β-catenin pathway. Collectively, hUCB-MSCs-derived exosomes alleviated hepatic IRI by transporting miR-1246 via regulating GSK3β-mediated Wnt/β-catenin pathway. 

Retracted: No

PubPeer comments:
 The electron microscopy image presented in Figure 1 is not very convincing. It can also be just an artefact. Without immuno staining I assume it is an artefact. In addiion, the Western immunoblot of CD63 in Figure 1 is questionable due to it appearance. Immunoblotting of CD63 always gives a smear, not a clear thin band like the one presented here. In your flow cytometry results (Figure 2 and 3), many of the cells have negative values. Can you please explain why? ![file] ,
Blood Culture–Negative Endocarditis, Morocco
Authors: Najma Boudebouch
Salma Fadili
Pierre-Edouard Fournier
M&#x27;hammed Sarih
Zahira Zouizra
Drissi Boumzebra
Hamid Amarouch
Didier Raoult
Badie Azamane Mahadji
Abdelfattah Chakib
Journal: Emerging infectious diseases (2017)
Discipline: IMMUNOLOGY
Keywords: Bartonella quintana; Casablanca; Marrakech; Morocco; bacteria

Abstract:  We investigated the microorganisms causing blood culture-negative endocarditis (BCNE) in Morocco. We tested 19 patients with BCNE by serologic methods, molecular methods, or both and identified Bartonella quintana, Staphylococcus aureus, Streptococcus equi, and Streptococcus oralis in 4 patients. These results highlight the role of these zoonotic agents in BCNE in Morocco. 

Retracted: No

PubPeer comments:
 The authors describe a study done in Morocco in patients. Authors mentioned that, during June 1, 2009u2013September 1, 2010, they *prospectively included all patients with BCNE seen in 3 health centers in the Morocco regions of Casablanca and Marrakech*. In the paper, the authors did not mention the ethical approval process. This is quite surprising considering the [Editor s Policy] : *when studies involve human participants, authors are responsible for including a statement that those studies have been approved by the appropriate institutional or national research ethics committee and have been performed in accordance with the ethical standards noted in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards*. Furthermore, the [Editor s Policy] mentions *Emerging Infectious Diseases follows the ICMJE recommendations for Protection of Research Participants*. With regards to prospective study, ICMJE requires that - *the patient (or parent or guardian) gives written informed consent* - *All authors should seek approval to conduct research from an independent local, regional, or national review body (e.g., ethics committee, institutional review board)* Otherwise, in accordance with Helsinki Declaration, ethics approval must occur before the recruitment of participants. Considering: - the study is a prospective study, - Blood sample have been taken in Morocco to be exported in France, It would be in the interest of the readers and the public: - to detail the ethical process (dates and approvals number of the ethics committee approval in Morocco and in France, names of the ethics committee) - to describe how the participant consent has been obtained. Could the authors elaborate on this matter ? ,
A Smart Multifunctional Nanoparticle for Enhanced Near-Infrared Image-Guided Photothermal Therapy Against Gastric Cancer
Authors: Xiaoming Zheng
Bo Wei
Xudong Zhu
Dongbing Ding
Hongbo Wei
Jun Shao
Shengxue Hu
Rongpu Liang
Journal: International Journal of Nanomedicine (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: gastric cancer; indocyanine green; nanoparticle; near-infrared imaging; photothermal therapy.
Affiliations: Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People's Republic of China., College of Biological Science and Engineering, Fuzhou University, Fujian, 350108, People's Republic of China.

Abstract:  Background: Surgery is considered to be a potentially curative approach for gastric cancer. However, most cases are diagnosed at a very advanced stage for the lack of typical symptoms in the initial stage, which makes it difficult to completely surgical resect of tumors. Early diagnosis and precise personalized intervention are urgent issues to be solved for improving the prognosis of gastric cancer. Herein, we developed an RGD-modified ROS-responsive multifunctional nanosystem for near-infrared (NIR) imaging and photothermal therapy (PTT) against gastric cancer. Methods: Firstly, the amphiphilic polymer was synthesized by bromination reaction and nucleophilic substitution reaction of carboxymethyl chitosan (CMCh) and 4-hydroxymethyl-pinacol phenylborate (BAPE). Then, it was used to encapsulate indocyanine green (ICG) and modified with RGD to form a smart multifunctional nanoparticle targeted to gastric cancer (CMCh-BAPE-RGD@ICG). The characteristics were determined, and the targeting capacity and biosafety were evaluated both in vitro and in vivo. Furthermore, CMCh-BAPE-RGD@ICG mediated photothermal therapy (PTT) effect was studied using gastric cancer cells (SGC7901) and SGC7901 tumor model. Results: The nanoparticle exhibited suitable size (≈ 120 nm), improved aqueous stability, ROS-responsive drug release, excellent photothermal conversion efficiency, enhanced cellular uptake, and targeting capacity to tumors. Remarkably, in vivo studies suggested that CMCh-BAPE-RGD@ICG could accurately illustrate the location and margin of the SGC7901 tumor through NIR imaging in comparison with non-targeted nanoparticles. Moreover, the antitumor activity of CMCh-BAPE-RGD@ICG-mediated PTT could effectively suppress tumor growth by inducing necrosis and apoptosis in cancer cells. Additionally, CMCh-BAPE-RGD@ICG demonstrated excellent biosafety both in vitro and in vivo. Conclusion: Overall, our study provides a biocompatible theranostic nanoparticle with enhanced tumor-targeting ability and accumulation to realize NIR image-guided PTT in gastric cancer. 

Retracted: No

PubPeer comments:
 Two images in Figure 8F appear to overlap. *** ![file] ,