PReD-Bench/PRed-Bench huggingface dataset:
The unfolded-protein-response sensor IRE-1Œ± regulates the function of CD8Œ±+ dendritic cells
Authors: Iris Delrue
Eef Parthoens
Bart N Lambrecht
Jessica Vetters
Eik Hoffmann
Fabiola Osorio
Yvan Saeys
Simon J Tavernier
Riet De Rycke
Liesbet Martens
Sophie Janssens
Philippe Pouliot
Takao Iwawaki
Journal: Nature Immunology (2014)
Discipline: IMMUNOLOGY
Keywords: unfolded protein response; endoplasmic reticulum stress; immune system; dendritic cells; IRE-1Œ±
Affiliations: 1] Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium. [2] GROUP-ID Consortium, Ghent University and University Hospital, Ghent, Belgium. [3] Department of Respiratory Medicine, Ghent University, Ghent, Belgium. [4]., 1] GROUP-ID Consortium, Ghent University and University Hospital, Ghent, Belgium. [2] Unit of Molecular Signal Transduction in Inflammation, VIB Inflammation Research Center, Ghent, Belgium., 1] Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium. [2] GROUP-ID Consortium, Ghent University and University Hospital, Ghent, Belgium. [3] Department of Respiratory Medicine, Ghent University, Ghent, Belgium., Microscopy Core Facility, VIB Inflammation Research Center, Ghent, Belgium., Advanced Scientific Research Leaders Development Unit, Gunma University, Gunma, Japan., 1] Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium. [2] GROUP-ID Consortium, Ghent University and University Hospital, Ghent, Belgium. [3] Department of Respiratory Medicine, Ghent University, Ghent, Belgium. [4] Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands. [5].

Abstract:  The role of the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress in homeostasis of the immune system is incompletely understood. Here we found that dendritic cells (DCs) constitutively activated the UPR sensor IRE-1Œ± and its target, the transcription factor XBP-1, in the absence of ER stress. Loss of XBP-1 in CD11c+ cells led to defects in phenotype, ER homeostasis and antigen presentation by CD8Œ±+ conventional DCs, yet the closely related CD11b+ DCs were unaffected. Whereas the dysregulated ER in XBP-1-deficient DCs resulted from loss of XBP-1 transcriptional activity, the phenotypic and functional defects resulted from regulated IRE-1Œ±-dependent degradation (RIDD) of mRNAs, including those encoding CD18 integrins and components of the major histocompatibility complex (MHC) class I machinery. Thus, a precisely regulated feedback circuit involving IRE-1Œ± and XBP-1 controls the homeostasis of CD8Œ±+ conventional DCs. 

Retracted: No

PubPeer comments:
 A concurrent paper on this topic should be consulted - Guth et al (2021) Contribution to the ongoing discussion on fluoride toxicity . This concludes that  the totality of evidence does not support the notion that fluoride should be considered a human developmental neurotoxicant at current exposure levels in European countries. And it argues that the calculated benchmark in Grandjean et al (2021)  should be treated with caution. ,
WITHDRAWN: COVID-19 related acute decline in paediatric admissions in Malta, a population-based study
Authors: Yana Marie Dimech
Neil Grech
Sophie Degiorgio
John Xuereb
Victor Grech
Journal: Early Human Development (2020)
Discipline: CLINICAL MEDICINE
Keywords: Article withdrawal; Author; Editor; Publisher; Elsevier Policy
Affiliations: Department of Paediatrics, Mater Dei Hospital, L-Imsida, Malta. Electronic address: ., Department of Medicine, Mater Dei Hospital, L-Imsida, Malta., Department of Paediatrics, Mater Dei Hospital, L-Imsida, Malta.

Abstract:  This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal. 

Retracted: No

PubPeer comments:
 **Retracted** in March 2021: https: doi.org 10.1016 j.earlhumdev.2020.105251  *This article has been withdrawn at the request of the author(s) and or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https: www.elsevier.com about our-business policies article-withdrawal* The background for this and other retractions of the same author(s) has been covered by Retraction Watch: https: retractionwatch.com 2021 03 31 beam-us-up-elsevier-pulls-26-covid-19-papers-by-researcher-with-a-penchant-for-star-trek ,
Hypoxia inducible factor 1Œ± promotes survival of mesenchymal stem cells under hypoxia
Authors: Xiaodan Jiang
Zhongfei Zhang
Zhiming Feng
Tian Hua
Bingke Lv
Feng Li
Jie Fang
Limin Xu
Chengmei Sun
Jianbang Han
Journal: American journal of translational research (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hypoxia inducible factor 1Œ±; apoptosis; hypoxia; mesenchymal stem cell; p53.
Affiliations: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.

Abstract:  Mesenchymal stem cells (MSCs) are ideal materials for cell therapy. Research has indicated that hypoxia benefits MSC survival, but little is known about the underlying mechanism. This study aims to uncover potential mechanisms involving hypoxia inducible factor 1Œ± (HIF1A) to explain the promoted MSC survival under hypoxia. MSCs were obtained from Sprague-Dawley rats and cultured under normoxia or hypoxia condition. The overexpression vector or small interfering RNA of Hif1a gene was transfected to MSCs, after which cell viability, apoptosis and expression of HIF1A were analyzed by MTT assay, flow cytometry, qRT-PCR and Western blot. Factors in p53 pathway were detected to reveal the related mechanisms. Results showed that hypoxia elevated MSCs viability and up-regulated HIF1A (P &lt; 0.05) as previously reported. HIF1A overexpression promoted viability (P &lt; 0.01) and suppressed apoptosis (P &lt; 0.001) under normoxia. Correspondingly, HIF1A knockdown inhibited viability (P &lt; 0.05) and promoted apoptosis (P &lt; 0.01) of MSCs under hypoxia. Expression analysis suggested that p53, phosphate-p53 and p21 were repressed by HIF1A overexpression and promoted by HIF1A knockdown, and B-cell CLL/lymphoma 2 (BCL2) expression had the opposite pattern (P &lt; 0.05). These results suggest that HIF1A may improve viability and suppress apoptosis of MSCs, implying the protective effect of HIF1A on MSC survival under hypoxia. The underlying mechanisms may involve the HIF1A-suppressed p53 pathway. This study helps to explain the mechanism of MSC survival under hypoxia, and facilitates the application of MSCs in cell therapy. 

Retracted: No

PubPeer comments:
 Fig 4.  These stylised figures are not enormously convincing as flow-cytometry diagrams. Compare, for instance, Fig 4D from [Liu et al 2019)] , and other products of the [ tadpole papermill ] :  ,
Circular RNA PVT1 promotes metastasis via miR-145 sponging in CRC
Authors: Zhongmiao Wang
Kai Zhao
Meng Su
Bowen Xiang
Baoli Qin
Journal: Biochemical and Biophysical Research Communications (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Colorectal cancer; Metastasis; circPVT1; miR-145.
Affiliations: Department of Internal Medicine, Cancer Hospital of China Medical University/ Liaoning Cancer Hospital & Institute, Shenyang, PR China. Electronic address: .

Abstract:  Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and are widely involved in various cancers including colorectal cancer (CRC). Circular RNA PVT1 (circPVT1) was reported in several malignancies but the role it plays in CRC remains unclear. In our current research, we focused on the expression and function of circPVT1) works in CRC. We found that circPVT1 was upregulated in CRC. Also, we illustrated that the upregulated circPVT1 was closely correlated with poor prognosis and bad clinicopathological features of patients with CRC. Through a loss of function experiment, we showed that a downregulation of circPVT1 suppressed CRC cells metastasis. Through online prediction, we found that circPVT1 had a microRNA response element (MRE) for miR-145. Additionally, we demonstrated that miR-145 was downregulated in CRC. Even further, we showed that miR-145 was involved in circPVT1 mediated facilitation of CRC metastasis. In a further mechanical study, we demonstrated that circPVT1 could target miR-145. Lastly, we revealed that the metastasis-promoting role of circPVT1 in CRC was partially achieved via miR-145 sponging. In brief, the findings of the present study illustrated that circPVT1, working as an oncogene, promotes metastasis via miR-145 sponging in CRC. CircPVT1/miR-145 axial might be a novel point in targeting treatment of CRC. 

Retracted: No

PubPeer comments:
 The images in this paper have multiple areas of overlap, with some apparent editing. Common author on this paper: https: pubpeer.com publications ED88823E95B8CDD6F51E0809D0F510 *** Closeup  ***     , 
 Reported to the Editor-in-Charge 10 months ago, no apparent action. Sent to other editors today.  BBRC -- the fastest submission-to-online journal! ,
Protective effects of isolated polyphenolic and alkaloid fractions of Ruta graveolens L. on acute and chronic models of inflammation
Authors: A Helen
M Ratheesh
G Sindhu
G L Shyni
Journal: Inflammation (2010)
Discipline: IMMUNOLOGY
Keywords: Ruta graveolens; inflammation; polyphenolic; alkaloid fraction; anti-inflammatory
Affiliations: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram 695 581, India.

Abstract:  Ruta graveolens L. (Rutaceae) are traditionally used for the treatment of rheumatism, arthritis and other inflammatory conditions in the traditional medicine of India, were evaluated for their protective effect in acute and chronic models of inflammation. Carrageenan induced rat paw edema and adjuvant induced arthritis were employed as the experimental models of acute and chronic inflammation respectively. Isolated polyphenolic and alkaloid fraction (AFR) from Ruta graveolens and evaluated its anti inflammatory activity in carrageenan induced acute model. AFR with a dose 10 mg/kg showed higher anti inflammatory effect than polyphenols and standard drug diclofenec. AFR significantly decreased the paw edema in arthritic rats. TBARS, COX-2, 5-LOX and MPO level were decreased and the levels of antioxidant enzymes and GSH level were increased on treatment with AFR. The increment in CRP level and ceruloplasmin level observed in arthritic animals were also found to be significantly restored in AFR treated rats. The results demonstrated the potential beneficiary effect of isolated polyphenolic and alkaloid fraction of Ruta graveolens L. on acute and chronic models of inflammation in rats. 

Retracted: No

PubPeer comments:
 The mean and SEM in the experimental data of tables 2 and 3 were as same in another publication. For Table 2, only one value was found to be different. For table 3, the first two group shows exactly the same experimental data. Could the authors show their raw data obtained from the ELISA reader for the two papers separately to clarify this?   , 
 #1 These concerns are well founded given the problems in another paper by this group, [Ratheesh et al. 2017](http: pubpeer.com publications 04967355EED1938046187F153D5A39). Could the authors please comment? ,
DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions
Authors: Keith D Robertson
Beth A Sullivan
Suhasni Gopalakrishnan
Stefania Trazzi
Giuliano Della Valle
Journal: Human molecular genetics (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DNA methylation; transcriptional repression; chromatin structure; genomic stability; DNA methyltransferases
Affiliations: Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.

Abstract:  DNA methylation is an epigenetically imposed mark of transcriptional repression that is essential for maintenance of chromatin structure and genomic stability. Genome-wide methylation patterns are mediated by the combined action of three DNA methyltransferases: DNMT1, DNMT3A and DNMT3B. Compelling links exist between DNMT3B and chromosome stability as emphasized by the mitotic defects that are a hallmark of ICF syndrome, a disease arising from germline mutations in DNMT3B. Centromeric and pericentromeric regions are essential for chromosome condensation and the fidelity of segregation. Centromere regions contain distinct epigenetic marks, including dense DNA hypermethylation, yet the mechanisms by which DNA methylation is targeted to these regions remains largely unknown. In the present study, we used a yeast two-hybrid screen and identified a novel interaction between DNMT3B and constitutive centromere protein CENP-C. CENP-C is itself essential for mitosis. We confirm this interaction in mammalian cells and map the domains responsible. Using siRNA knock downs, bisulfite genomic sequencing and ChIP, we demonstrate for the first time that CENP-C recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and that CENP-C and DNMT3B regulate the histone code in these regions, including marks characteristic of centromeric chromatin. Finally, we demonstrate that loss of CENP-C or DNMT3B leads to elevated chromosome misalignment and segregation defects during mitosis and increased transcription of centromeric repeats. Taken together, our data reveal a novel mechanism by which DNA methylation is targeted to discrete regions of the genome and contributes to chromosomal stability. 

Retracted: No

PubPeer comments:
 Abrupt change of background in Fig. 3  ,
Differential temporal expression of S100Œ≤ in developing rat brain
Authors: Nisha Patro
Aijaz Naik
Ishan K Patro
Journal: Frontiers in cellular neuroscience (2015)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: GFAP; S100Œ≤; astrocyte; nestin; neural development.
Affiliations: School of Studies in Neuroscience, Jiwaji University Gwalior, India., School of Studies in Neuroscience, Jiwaji University Gwalior, India ; School of Studies in Zoology, Jiwaji University Gwalior, India.

Abstract:  Radial glial cells (RGs) originally considered to provide scaffold to the radially migrating neurons constitute a heterogeneous population of the regionally variable precursor cells that generate both neurons as well as glia depending upon the location and the timing of development. Hence specific immunohistochemical markers are required to specify their spatiotemporal location and fate in the neurogenic and gliogenic zones. We hypothesize S100Œ≤ as a potential and unified marker for both primary and secondary progenitors. To achieve this, cryocut sections from rat brains of varied embryonic and postnatal ages were immunolabeled with a combination of antibodies, i.e., S100Œ≤ + Nestin, Nestin + GFAP and S100Œ≤ + GFAP. A large population of the primary and secondary progenitors, lining the VZ and SVZ, simultaneously co-expressed S100Œ≤ and nestin establishing their progenitor nature. A downregulation of both S100Œ≤ and nestin noticed by the end of the 1st postnatal week marks their differentiation towards neuronal or glial lineage. In view of the absence of co-expression of GFAP (glial fibrillary acidic protein) either with S100Œ≤ or nestin, the suitability of accepting GFAP as an early marker of RG's was eliminated. Thus the dynamic expression of S100Œ≤ in both the neural stem cells (NSCs) and RGs during embryonic and early neonatal life is associated with its proliferative potential and migration of undifferentiated neuroblasts and astrocytes. Once they lose their potential for proliferation, the S100Œ≤ expression is repressed with its reemergence in mature astrocytes. This study provides the first clear evidence of S100Œ≤ expression throughout the period of neurogenesis and early gliogenesis, suggesting its suitability as a radial progenitor cell marker. 

Retracted: No

PubPeer comments:
 Image reuse between two papers shown below;  , 
  , 
 Unfortunately, i am not able to make an account here and post the comment as author of the study, i am commenting here with my information in case anybody has more queries. I will be happy to take any questions and present the raw data on request. Aijaz A. Naik (Ist Author) Personal Email- Neuroaijaz@gmail.com Institutional email- aijaznaik@jiwaji.edu ,
Functional topography of converging visual and auditory inputs to neurons in the rat superior colliculus
Authors: Fernando R Nodal
Andrew J King
Irini Skaliora
Timothy P Doubell
Nicholas P Holmes
Journal: Journal of Neurophysiology (2004)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: infant rat midbrain; converging inputs; neurons; multisensory layers; superior colliculus
Affiliations: University Laboratory of Physiology, University of Oxford, Oxford OX1 3PT, United Kingdom

Abstract:  We have used a slice preparation of the infant rat midbrain to examine converging inputs onto neurons in the deeper multisensory layers of the superior colliculus (dSC). Electrical stimulation of the superficial visual layers (sSC) and of the auditory nucleus of the brachium of the inferior colliculus (nBIC) evoked robust monosynaptic responses in dSC cells. Furthermore, the inputs from the sSC were found to be topographically organized as early as the second postnatal week and thus before opening of the eyes and ear canals. This precocious topography was found to be sculpted by GABAA-mediated inhibition of a more widespread set of connections. Tracer injections in the nBIC, both in coronal slices as well as in hemisected brains, confirmed a robust projection originating in the nBIC with distinct terminals in the proximity of the cell bodies of dSC neurons. Combined stimulation of the sSC and nBIC sites revealed that the presumptive visual and auditory inputs are summed linearly. Finally, whereas either input on its own could manifest a significant degree of paired-pulse facilitation, temporally offset stimulation of the two sites revealed no synaptic interactions, indicating again that the two inputs function independently. Taken together, these data provide the first detailed intracellular analysis of convergent sensory inputs onto dSC neurons and form the basis for further exploration of multisensory integration and developmental plasticity. 

Retracted: No

PubPeer comments:
 This paper was criticised as part of a self-reflection posted on Twitter on 2nd-3rd April, 2021 (twitter TheHandLab status 1377760796130869248) Criticism: I contributed only one figure (#8) to this paper, but 30 neonatal rats paid the ultimate price for my crappy patch-clamping skills (only 17 cells) as an MSc student. I still feel the guilt. My point here was that this small dataset (17 cells from 30 animals) may have been biased by the patch-ability of the cells or animals. Since I am not an expert in this method or topic, I can say no more. ,
Myeloid loss of Beclin 1 promotes PD-L1hi precursor B cell lymphoma development
Authors: Motao Zhu
Changsheng Xing
Peng Tan
Xiao Yu
Leng Han
Jingrong Mao
Lian He
Lixia Diao
Yubin Zhou
Helen Y Wang
M James You
Rong-Fu Wang
Journal: Journal of Clinical Investigation (2019)
Discipline: CLINICAL MEDICINE
Keywords: B cells; Cellular immune response; Immunology; Neutrophils; Oncology.
Affiliations: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, USA., Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, Texas, USA., Xiangya Hospital, Central South University, Changsha, China., Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA., Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, New York, USA.

Abstract:  Beclin 1 (Becn1) is a key molecule in the autophagy pathway and has been implicated in cancer development. Due to the embryonic lethality of homozygous Becn1-deficient mice, the precise mechanisms and cell type-specific roles of Becn1 in regulating inflammation and cancer immunity remain elusive. Here, we report that myeloid-deficient Becn1 (Becn1ŒîM) mice developed neutrophilia, were hypersusceptible to LPS-induced septic shock, and had a high risk of developing spontaneous precursor B cell (pre-B cell) lymphoma with elevated expression of immunosuppressive molecules programmed death ligand 1 (PD-L1) and IL-10. Becn1 deficiency resulted in the stabilization of MEKK3 and aberrant p38 activation in neutrophils, and mediated neutrophil-B cell interaction through Cxcl9/Cxcr3 chemotaxis. Neutrophil-B cell interplay further led to the activation of IL-21/STAT3/IRF1 and CD40L/ERK signaling and PD-L1 expression; therefore, it suppressed CD8+ T cell function. Ablation of p38 in Becn1ŒîM mice prevented neutrophil inflammation and B cell tumorigenesis. Importantly, the low expression of Becn1 in human neutrophils was significantly correlated with the PD-L1 levels in pre-B acute lymphoblastic lymphoma (ALL) patients. Our findings have identified myeloid Becn1 as a key regulator of cancer immunity and therapeutic target for pre-B cell lymphomas. 

Retracted: No

PubPeer comments:
 In Figure 1D and E, in many of the flow cytometry dot plots the data points have been placed on top of the gating lines (dots are seen on the gating line). Furthermore, the layout is different for the different dot plots in the same figure; many of the dot plots have a blurry appearance and the gating lines have difference size. This indicates that the dot plots are taken from different experiments (different experimental setup?).  ,
Research on the expression of MRNA-518b in the pathogenesis of placenta accreta
Authors: D-Y Lao
Y Long
F Yang
Y Chen
G-L Mo
X-Q Fu
Z-W Chen
M-J Li
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-518b; placenta accreta; OPN; VEGF; mRNA
Affiliations: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. .

Abstract:  Objective: To investigate the expression of micro ribonucleic acid miR-518b and its regulatory role in the pathogenesis of placenta accreta. Patients and methods: A total of 50 parturient women in the Obstetric Department were collected and divided into observation group (placenta accreta, n=23) and control group (normal placenta, n=27). After the placental tissues were removed via surgery, the expressions of osteopontin (OPN) and vascular endothelial growth factor (VEGF) were detected using the immunohistochemical method. The relative expression levels of OPN and VEGF proteins were detected via Western blotting, and the relative expression levels of OPN messenger RNA (mRNA), VEGF mRNA and miR-518b were detected via quantitative polymerase chain reaction (qPCR). Moreover, the correlations of miR-518b with OPN mRNA and VEGF mRNA were studied via Pearson correlation analysis. Results: Compared with those in control group, the expressions of OPN and VEGF proteins in observation group were significantly increased, while the levels of OPN mRNA, VEGF mRNA and miR-518b in observation group were also significantly elevated (p&lt;0.05). There were positive correlations between miR-518b and levels of OPN, VEGF mRNA. Conclusions: The high expression of miR-518b may lead to the development of placenta accreta through upregulating the transcription and protein expression of downstream VEGF and OPN, providing insights for the future therapy against the pathogenesis of placenta accreta. 

Retracted: No

PubPeer comments:
 At right here: Figure 3.  Protein expression detected via Western blotting . At left: Figure 5 from [Pan et al (2019)] :  Protein expressions detected via Western blotting (stretched horizontally to 135% for convenience).  #2 Clockwise from upper left: Figure 3 from [Sun et al (2019)] .  NF-u03baB protein expression determined through Western blotting ; Fig 3 from [Long et a (2019)] ; Fig 4 from [Lou et al (2019)] ; and Figure 5 from [Pan et al (2019)] .  That is a versatile loading control. No authors in common. ,
Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats
Authors: Ke Meng
Huabo Cai
Simin Cai
Yucai Hong
Xiaoming Zhang
Journal: Frontiers in Cell and Developmental Biology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: TGF-beta1; adiponectin; bone marrow mesenchymal stem cells; diabetic cardiomyopathy; myocardial fibrosis.
Affiliations: Department of Anatomy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China., Department of Emergency Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Abstract:  Background: Accumulating evidence suggested that bone marrow mesenchymal stem cells (BMSCs) have therapeutic potential for diabetes and heart diseases. However, the effects of BMSC on reducing myocardial fibrosis need to be optimized. This study aimed to investigate the mechanism of adiponectin (APN) modified BMSCs on myocardial fibrosis in diabetic model in vivo and in vitro. Methods: The high-fat diet combined with streptozotocin (STZ) injection were used to induced diabetic rat model. H9c2 cells were cultured under a high glucose medium as in vitro model. The BMSCs were modified by APN plasmid or APN small interfering RNA (siRNA), then transplanted to the diabetic rats by a single tail-vein injection, or co-cultured with H9c2 cells. Results: We demonstrated that diabetic rats showed typical diabetic symptoms, such as decreased cardiac function, accumulation of pathological lesions and collagen expression. However, these impairments were significantly prevented by the APN modified BMSCs treatment while no effects on APN siRNA modified BMSCs treated diabetic rats. Moreover, we confirmed that APN modified BMSCs could attenuate the expression of TGF-beta1/smad to suppress the myocardial fibrosis in the diabetic rats and high glucose induced H9c2 cells. Conclusion: The present results for the first time showed that APN modified BMSCs exerted protection on cardiac fibrosis via inhibiting TGF-beta1/smad signal pathway in diabetic rats. Our findings suggested that APN modified BMSCs might be a novel and optimal therapy for the diabetic cardiomyopathy in future. 

Retracted: No

PubPeer comments:
 Some images in Figure 5A and 5B appear to overlap. This type of issue is sometimes seen in papers that have been outsourced to a third party. ***  *** This work was supported by the Zhejiang Provincial Natural Science Foundation of China (Grant No. LY18H170002) and the National Natural Science Foundation of China (Grant No. 81472149). , 
 Two images in Figure 6A also appear to overlap. ***  , 
 Two images in Figure 4A also appear to overlap. ***  ,
Circ_0078767 suppresses non-small-cell lung cancer by protecting RASSF1A expression via sponging miR-330-3p
Authors: Ting Chen
Zuozhang Yang
Chao Liu
Li Wang
Wenhui Li
Jun Yang
Long Chen
Journal: Cell Proliferation (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RASSF1A; circ_0078767; miR-330-3p; non-small-cell lung cancer; qRT-PCR.
Affiliations: Department of Nuclear Medicine, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, China., Department of Orthopedics, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, China., Department of Radiotherapy, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, China., Department of Radiology, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, China., Department of PETCT, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, China.

Abstract:  Objectives: This study was designed to investigate the role of circ_0078767/miR-330-3p/RASSF1A in non-small-cell lung cancer (NSCLC). Bioinformatic analysis was performed to screen for the differentially expressed genes in NSCLC tissues from adjacent lung tissues. Materials and methods: qRT-PCR was used to detect the RNA expression of genes in cells and tissues, and Western blot was conducted to determine the protein levels of RASSF1A in tissues and cells. A miRanda algorithm was used to predict the targeted relationship among RNAs. A dual-luciferase reporter gene assay was conducted to verify the targeted relationship. Flow cytometry was performed to investigate the effects of circ_0078767/miR-330-3p/RASSF1A on cell cycle progression and apoptosis. A CCK-8 assay was conducted to explore the effects of circ_0078767/miR-330-3p/RASSF1A on cell proliferation. A transwell invasion assay was completed to study the effects of circ_0078767/miR-330-3p/RASSF1A on cell invasion. Lastly, an in vivo assay was conducted to investigate the effects of circ_0078767/miR-330-3p/RASSF1A on tumour development. Results: Circ_0078767 and RASSF1A were downregulated, while miR-330-3p was upregulated in NSCLC tissues than that in adjacent tissues. miR-330-3p had a binding relationship with circ_0078767 and RASSF1A. The overexpression of circ_0078767 and RASSF1A or the underexpression of miR-330-3p significantly suppressed NSCLC cell viability, cell cycle progression and invasion while also significantly promoting cell apoptosis. Additionally, these modulations significantly suppressed in vivo tumour growth. Conclusions: Circ_0078767 could suppress NSCLC progression by inhibiting miR-330-3p, which thereby increased RASSF1 levels. 

Retracted: No

PubPeer comments:
 This article appears to be computer-generated with [SCIgen] .  --- This comment was written by Guillaume Cabanac and Cyril Labbu00e9. Contact: [SeekAndBlastn-Operators@univ-grenoble-alpes.fr](mailto:SeekAndBlastn-Operators@univ-grenoble-alpes.fr). ,
Sodium butyrate induces retinoblastoma protein dephosphorylation, p16 expression and growth arrest of colon cancer cells
Authors: C Avivi-Green
B Schwartz
S Polak-Charcon
Journal: Molecular and Cellular Biochemistry (1998)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Sodium butyrate; colon cancer; cell cycle; differentiation; pRb protein
Affiliations: Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Israel.

Abstract:  Sodium butyrate causes alteration of colon cancer cell morphology and biology towards that of a more differentiated phenotype. The retinoblastoma gene encodes a nuclear phosphoprotein (pRb) present in a wide range of human cancer cell lines including colon cancer cell lines. pRB is synthesized throughout the cell cycle and phosphorylated in a phase specific manner: the predominant proteins in G0/G1 are the unphosphorylated species (110 kD) whereas phosphorylated pRb (112-114 kD) are in S and G2. 110 kD pRb binds transcription factors and prevents transcription of responsive genes such as the gene for thymidine kinase, which are expressed in late G1. The precise mechanisms controlling cell arrest are unknown, but recent data suggest that cyclin-dependent kinase inhibitors such as p16 may play a role. The aim of the present study was to assess the effect of sodium butyrate on cell cycle staging, thymidine kinase activity, phosphorylation of the pRb protein and expression of p16. We show that sodium butyrate treatment induces differentiation of LS174T colon cancer cells, inhibits thymidine kinase activity concomitantly with induction of pRb dephosphorylation, p16 transcription and cell cycle arrest at G0/G1. Initial dephosphorylation was observed 24 h after treatment of LS174T cells with sodium butyrate, whereas complete shift to the dephosphorylated form was observed 3 days after treatment. Induction of pRb dephosphorylation by sodium butyrate preceded inhibition of growth and the specific cell cycle arrest. RNase protection assay with a p16 specific riboprobe showed undetectable levels in proliferating cells to several fold increase in differentiated colonocytes. In conclusion, the results provide evidence for a specific cellular mechanism of butyrate induced growth arrest and differentiation of a colon cancer cell line. 

Retracted: No

PubPeer comments:
 Figure 5. * Red boxes: Lanes 1 and 2 look more similar to lanes 3 and 4 than expected. Reported to the journal in October 2015, with a friendly reminder in April 2017, but nothing has happened since then. The journal never replied or acted upon any of the 60+ papers that I reported to the editors in the past 5 years.  ,
The combined administration of parthenolide and ginsenoside CK in long circulation liposomes with targeted tLyp-1 ligand induce mitochondria-mediated lung cancer apoptosis
Authors: Zhenhai Zhang
Jianping Zhou
Huixia Lv
Xin Jin
Journal: Artificial Cells Nanomedicine and Biotechnology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Combined administration; ginsenoside CK; lung cancer; natural products; parthenolide
Affiliations: a Department of Hospital Pharmacy , Suqian Branch Jiangsu Province Hospital , Suqian , China., b Department of Pharmaceutics, State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , China., c Jiangsu Province Hospital on Integration of Chinese and Western Medicine , Nanjing University of Chinese Medicine , Nanjing , China.

Abstract:  Background: Combinations of natural products with low toxicities using tumor-targeting carriers may improve cancer treatment. The combined parthenolide and ginsenoside compound K (CK) within tLyp-1 liposomes, with the aim of improving the efficacy of lung cancer treatment. Results: In vitro studies in A549 human pulmonary adenocarcinoma cells demonstrated that parthenolide/CK tLyp-1 liposomes increased reactive oxygen species levels and induced mitochondrial apoptosis. It enters into cells via receptor-mediated uptake and micropinocytosis, followed by endosomal/lysosomal escape. In vivo studies illustrated that it produced a greater antitumor effect than combined administration of these compounds, with minimal toxicity. Conclusion: The findings of this study indicated that combined application of natural products in nanocarriers could offer attractive therapeutic options. 

Retracted: No

PubPeer comments:
 Figure 6D: some panels representing differently treated mice appear to show areas of overlap. In case of the bright green one, the similarities are not perfect but similar to e.g. as found in adjacent tissue slices.  , 
 Dear Elisabeth M Bik: Thank you for discovering this problem. As shown in Fig. 6, in the section describing in vivo anti-tumor evaluation, we have provided photos of all experimental animals. However, as the authors are specialized in pharmaceutics, we do not have the necessary knowledge and skills to perform HE staining. Therefore, the HE staining experiment was entrusted to professionals; if necessary, we can provide the relevant contract, certificate, and photos of tissue sections. After communication and examination, it was found that there was confusion in the pictures they provided. Because of our negligence, we did not identify this problem. We have now contacted the journal to correct the error. We deeply apologize for causing this situation. , 
 Dear Dr. Jin, Thank you for your answer. Yes, I d like to see the contract and photos of tissue sections - could you please post these here? And were there any other part of the paper, any other figures, that have not been performed within your own laboratory? ,
CUDC-101 overcomes arsenic trioxide resistance via caspase-dependent promyelocytic leukemia-retinoic acid receptor alpha degradation in acute promyelocytic leukemia
Authors: Jishi Wang
Kunlin Yu
Qin Fang
Tianzhuo Zhang
Zhaoyuan Zhang
Weili Wang
Danna Wei
Tingting Lu
Dan Ma
Journal: Anti-Cancer Drugs (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: arsenic trioxide; acute promyelocytic leukemia; APL; CUDC-101; resistance
Affiliations: Department of Clinical Medical School, Guizhou Medical University., Department of Hematology, Affiliated Hospital of Guizhou Medical University., Department of Guizhou Province Hematopoietic Stem Cell Transplantation Center and Key Laboratory of Hematological Disease Diagnostic and Treatment Centre., Department of Hematology and Oncology, Guiyang Maternal and Child Health Hospital., Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, PR China.

Abstract:  Although arsenic trioxide (ATO) treatment has transformed acute promyelocytic leukemia (APL) from the most fatal to the most curable hematological cancer, many high-risk APL patients who fail to achieve a complete molecular remission or relapse become resistant to ATO. Herein, we report that 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) exhibits specific anticancer effects on APL and ATO-resistant APL in vitro and in vivo, while showing negligible cytotoxic effect on the noncancerous cells including normal CD34 cells and bone marrow mesenchymal stem cells from APL patients. Further mechanistic studies show that CUDC-101 triggers caspase-dependent degradation of the promyelocytic leukemia-retinoic acid receptor alpha fusion protein. As a result, APL and ATO-resistant APL cells undergo apoptosis upon CUDC-101 treatment and this apoptosis-inducing effect is even stronger than that of ATO. Finally, using a xenograft mouse model, we demonstrated that CUDC-101 significantly represses leukemia development in vivo. In conclusion, these results suggested that CUDC-101 can serve as a potential candidate drug for APL, particularly for ATO-resistant APL. 

Retracted: No

PubPeer comments:
 The two control images in figure 4 appear to be duplicates. The contrast brightness is different but the similarities are clear.  ,
MiR-4429 suppresses the malignant development of ovarian cancer by targeting YOD1
Authors: P Chen
Y-M Zhu
L Shi
X Chen
T Zhu
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-4429; ovarian cancer; prognosis; migratory potential; metastasis
Affiliations: Department of Gynecological Oncology, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China. .

Abstract:  Objective: The purpose of this study was to assess the clinical significance of microRNA-4429 (miR-4429) in the development and prognosis of ovarian cancer, and to explore the regulatory role of miR-4429 in migratory potential of ovarian cancer cells. Patients and methods: MiR-4429 levels in paired ovarian cancer species and paracancerous ones were examined. Then, the relationship between miR-4429 level and clinical features of ovarian cancer patients was analyzed. Potential influences of miR-4429 on migratory potentials in CAOV3 and SKOV3 cells were explored by transwell assay. After that, the interaction between miR-4429 and its downstream gene YOD1, and their involvement in the malignant development of ovarian cancer were finally demonstrated through Luciferase assay and rescue experiments. Results: The results revealed that miR-4429 was downregulated in ovarian cancer tissues and cell lines. Its level was significantly correlated with rates of lymphatic metastasis (p=0.018) and distant metastasis (p=0.012) but not with age, tumor size, and tumor stage in ovarian cancer patients. Survival analysis uncovered that a low level of miR-4429 was unfavorable to PFS and OS in ovarian cancer patients. Besides, the overexpression of miR-4429 inhibited migratory potential in CAOV3 cells, and conversely, the knockdown of miR-4429 in SKOV3 cells obtained the opposite result. Moreover, YOD1 was proved to be the downstream gene binding to miR-4429. It was highly expressed in ovarian cancer tissues and negatively regulated by miR-4429. Rescue experiments finally identified that YOD1 was responsible for migratory potential changes in ovarian cancer cells regulated by miR-4429. Conclusions: MiR-4429 is downregulated in ovarian cancer tissues, and its level is closely linked to metastasis and prognosis in ovarian cancer patients. By negatively regulating YOD1 level, miR-4429 suppresses the malignant development of ovarian cancer. 

Retracted: No

PubPeer comments:
 Fig 1.  C, Progression-free survival in ovarian cancer patients with high or low expression of miR-4429. D, Overall survival in ovarian cancer patients with a high or low expression of miR-4429. I am not an expert but I am happy to speculate that the  Progression-free survival rate should not be higher than  Overall survival .  Compare figs 1C,D from [Liu et al (2020)] .  ,
FoxO3 regulates neural stem cell homeostasis
Authors: Dervis A M Salih
Saul A Villeda
Ashley E Webb
Atul J Butte
Victoria A Rafalski
Val√©rie M Renault
Theo D Palmer
Alex A Morgan
Camille Guillerey
Pramod U Thekkat
Jamie O Brett
Anne Brunet
Nicholas C Denko
Journal: Cell stem cell (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: neural stem cells; FoxO3; gene expression profile; NSC pool; self-renewal
Affiliations: Department of Genetics, Stanford University, CA 94305, USA.

Abstract:  In the nervous system, neural stem cells (NSCs) are necessary for the generation of new neurons and for cognitive function. Here we show that FoxO3, a member of a transcription factor family known to extend lifespan in invertebrates, regulates the NSC pool. We find that adult FoxO3(-/-) mice have fewer NSCs in vivo than wild-type counterparts. NSCs isolated from adult FoxO3(-/-) mice have decreased self-renewal and an impaired ability to generate different neural lineages. Identification of the FoxO3-dependent gene expression profile in NSCs suggests that FoxO3 regulates the NSC pool by inducing a program of genes that preserves quiescence, prevents premature differentiation, and controls oxygen metabolism. The ability of FoxO3 to prevent the premature depletion of NSCs might have important implications for counteracting brain aging in long-lived species. 

Retracted: No

PubPeer comments:
 Table 1 looks like it has some errors. Specifically, the counts and percentages for the black race groups don t seem to add up. It says there are 118 of 500 nulliparous women and that this represents 20.8% of the sample. However, 118 500*100=23.6%. The remainder of the percentages for black race seem to also be off as do some of the other values in the table. Am I misunderstanding what is intended in this table or is it wrong? ,
Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P-gp-overexpressing MCF-7 cells
Authors: Bahman Yousefi
Nosratollah Zarghami
Roya Salehi
Kobra Velaei
Nasser Samadi
Vahid Shafiei-Irannejad
Journal: Chemical Biology & Drug Design (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: breast cancer; doxorubicin resistance; metformin.
Affiliations: Stem Cell Research Center; Tabriz University of Medical Sciences; Tabriz Iran, Department of Clinical Biochemistry and Laboratory Medicine; Faculty of Medicine; Tabriz University of Medical Sciences; Tabriz Iran, Department of Medical Nanotechnology; Faculty of Advanced Medical Sciences; Tabriz University of Medical Sciences; Tabriz Iran, Department of Medical Biotechnology; Faculty of Advanced Medical Sciences; Tabriz University of Medical Sciences; Tabriz Iran

Abstract:  Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side-effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX)-resistant breast cancer (MCF-7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P-gp mRNA/protein expression levels following treatment with metformin were determined using real-time polymerase chain reaction and Western blot analysis, respectively. Intracellular rhodamine 123 accumulation assay was performed to evaluate the P-gp function. Cellular ATP content was determined using ATP assay kit. The effect of metformin on DOX-induced apoptosis was evaluated by annexin V/FITC assay. Exposure to metformin considerably enhanced the cytotoxicity of DOX. Metformin had no substantial effect on P-gp expression, while the activity of P-gp and intracellular ATP content decreased with metformin treatment in a dose-dependent manner. Furthermore, metformin significantly increased the DOX-induced apoptosis. These results indicate that metformin could reverse MDR in breast cancer cells by reducing P-gp activity. Therefore, metformin can be suggested as a potent adjuvant in breast cancer chemotherapy. 

Retracted: No

PubPeer comments:
 Figure 6: This paper reviewers must not be aware of the flow cytometry principles. PI and doxorubicin both belong to the same channel (FL2 red). I wonder how the cells are not positive for the doxorubicin in the second panel (even resistant cells have some degree of drug update). The third-panel shows a high number of PI-positive cells. Is this because of cell death or an increase in doxorubicin uptake (although both can be explained as PI Doxorubicin are in the same channel for flow cytometry)? , 
 These two recent articles show opposite results. The metformin effect on cancer therapy must be evaluated. The biased studies are misleading the clinical trials. https: www.researchsquare.com article rs-104610 v1 https: www.sciencedirect.com science article pii S0925443920303598 ,