PReD-Bench/PRed-Bench huggingface dataset:
Neural epidermal growth factor-like like protein 2 (NELL2) promotes aggregation of embryonic carcinoma P19 cells by inducing N-cadherin expression
Authors: Jeong Woo Park
Dong Yeol Kim
Byung Ju Lee
Byung Sam Kim
Kwang Kon Kim
Eun Jung Choi
Han Rae Kim
Dong Hee Kim
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: NELL2; neural differentiation; neurons; rat brain; mouse embryonic carcinoma P19 cells
Affiliations: Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.

Abstract:  NELL2 was first identified as a mammalian homolog of chick NEL (Neural EGF-like) protein. It is almost exclusively expressed in neurons of the rat brain and has been suggested to play a role in neural differentiation. However, there is still no clear evidence for the detailed function of NELL2 in the differentiation of neurons. In this study, we identified NELL2 function during neural differentiation of mouse embryonic carcinoma P19 cells. Endogenous expression of NELL2 in the P19 cells increased in parallel with the neuronal differentiation induced by retinoic acid (RA). We found that the mouse NELL2 promoter contains RA response elements (RAREs) and that treatment with RA increased NELL2 promoter activity. Transfection of P19 cells with NELL2 expression vectors induced a dramatic increase in cell aggregation, resulting in the facilitation of neural differentiation. Moreover, NELL2 significantly increased N-cadherin expression in the P19 cell. These data suggest that NELL2 plays an important role in the regulation of neuronal differentiation via control of N-cadherin expression and cell aggregation. 

Retracted: No

PubPeer comments:
 Figure 4C appears to have two images that overlap. *** ![file] ,
Prevention of neointimal hyperplasia in balloon-injured rat carotid artery via small interference RNA mediated downregulation of osteopontin gene
Authors: Guinan Liu
Jian Xu
Yingxian Sun
Tairan Wang
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Osteopontin; siRNA; Carotid artery; VSMCs; Intima-injured model
Affiliations: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

Abstract:  The aim of the present study was to take osteopontin (OPN) as molecular target to study its effects on injured intima model of carotid artery in rat using perivascular transfer of OPN-small interference RNA (siRNA). OPN mRNA in cultured VSMCs was quantified by real-time RT-PCR, and OPN-siRNA-002 was determined as the most sensitive sequence and used as transfected siRNA in the subsequent animal experiments. We established rat carotid arterial intima-injured model with balloon-injured method, and then perivascularly transfected OPN-siRNA-002 to study the role of OPN-siRNA in regulating several related genes including proliferating cell nuclear antigen (PCNA), transforming growth factor β1(TGF-β1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-14 (MMP-14), as well as its role in neointimal formation. OPN mRNA and protein decreased about 50 % with corresponding decrease in intima thickness after transfecting with specific OPN-siRNA-002 compared with Pluronic control group and OPN-SCR-siRNA group on each time point (n = 6, p &lt; 0.001), and this inhibiting effects persisted up to 14 days after balloon injury. PCNA, TGF-β1, MMP-2, and MMP-14 mRNA and protein correlated directly with the respective levels of OPN, suggesting its functions via regulating these downstream factors (n = 6, p &lt; 0.001). OPN may be a potential target gene in reducing the risk for arterial restenosis after vascular intervention. 

Retracted: No

PubPeer comments:
 Same data used in two different articles with some scale adjustment without any reference to each other. ![file] ,
Exaggerated translation causes synaptic and behavioural aberrations associated with autism
Authors: Philippe Pierre
Eric Klann
Adam G Carter
Andrew F MacAskill
Emanuela Santini
Thu N Huynh
Hanoch Kaphzan
Davide Ruggero
Journal: Nature (2013)
Discipline: Multidisciplinary
Keywords: Autism spectrum disorders; translational control; EIF4E gene; eIF4E; cap-dependent translation
Affiliations: Center for Neural Science, New York University, New York, New York 10003, USA.

Abstract:  Autism spectrum disorders (ASDs) are an early onset, heterogeneous group of heritable neuropsychiatric disorders with symptoms that include deficits in social interaction skills, impaired communication abilities, and ritualistic-like repetitive behaviours. One of the hypotheses for a common molecular mechanism underlying ASDs is altered translational control resulting in exaggerated protein synthesis. Genetic variants in chromosome 4q, which contains the EIF4E locus, have been described in patients with autism. Importantly, a rare single nucleotide polymorphism has been identified in autism that is associated with increased promoter activity in the EIF4E gene. Here we show that genetically increasing the levels of eukaryotic translation initiation factor 4E (eIF4E) in mice results in exaggerated cap-dependent translation and aberrant behaviours reminiscent of autism, including repetitive and perseverative behaviours and social interaction deficits. Moreover, these autistic-like behaviours are accompanied by synaptic pathophysiology in the medial prefrontal cortex, striatum and hippocampus. The autistic-like behaviours displayed by the eIF4E-transgenic mice are corrected by intracerebroventricular infusions of the cap-dependent translation inhibitor 4EGI-1. Our findings demonstrate a causal relationship between exaggerated cap-dependent translation, synaptic dysfunction and aberrant behaviours associated with autism. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 1D and Figure 4E: The  WT bands in both panels appear to look unexpectedly similar. They both have two lighter spots around 70 kDa, and a light spot in the dark area just below the 55 kDa marker. In Figure 4E the mouse was treated with Puromycin as marked in the figure, but it is not clear if the WT mouse in Figure 1D was treated with Puromycin. Even if the lanes represent the same mouse, they are show in the context of different adjacent lanes. Could the authors please clarify? ![file] ,
Regulation of DNA end joining, resection, and immunoglobulin class switch recombination by 53BP1
Authors: Samuel F Bunting
André Nussenzweig
Elsa Callen
Hua-Tang Chen
Davide F Robbiani
Isaac A Klein
Niklas Feldhahn
Michel C Nussenzweig
Jacqueline Barlow
Michela Di Virgilio
David Bosque
Anne Bothmer
Journal: Molecular Cell (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: 53BP1; DNA damage; H2AX; genomic stability; DSBs
Affiliations: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.

Abstract:  53BP1 is a DNA damage protein that forms phosphorylated H2AX (γ-H2AX) dependent foci in a 1 Mb region surrounding DNA double-strand breaks (DSBs). In addition, 53BP1 promotes genomic stability by regulating the metabolism of DNA ends. We have compared the joining rates of paired DSBs separated by 1.2 kb to 27 Mb on chromosome 12 in the presence or absence of 53BP1. 53BP1 facilitates joining of intrachromosomal DSBs but only at distances corresponding to γ-H2AX spreading. In contrast, DNA end protection by 53BP1 is distance independent. Furthermore, analysis of 53BP1 mutants shows that chromatin association, oligomerization, and N-terminal ATM phosphorylation are all required for DNA end protection and joining as measured by immunoglobulin class switch recombination. These data elucidate the molecular events that are required for 53BP1 to maintain genomic stability and point to a model wherein 53BP1 and H2AX cooperate to repress resection of DSBs. 

Retracted: No

PubPeer comments:
 Figure 5F. Much more similar than expected. https: imgur.com 93URJCd.jpg ,
Hyaluronan Hybrid Cooperative Complexes as a Novel Frontier for Cellular Bioprocesses Re-Activation
Authors: Annalisa La Gatta
Antonietta Stellavato
Luisana Corsuto
Antonella D&#x27;Agostino
Mario De Rosa
Paola Diana
Chiara Schiraldi
Patrizia Bernini
Journal: PLoS ONE (2016)
Discipline: Multidisciplinary
Keywords: Hyaluronic Acid; Dermal Formulations; Skin Aging; Injectable HA; Profhilo®
Affiliations: Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Bioteknet, Naples, Italy., IBSA Farmaceutici Italia Srl, Lodi, Italy.

Abstract:  Hyaluronic Acid (HA)-based dermal formulations have rapidly gained a large consensus in aesthetic medicine and dermatology. HA, highly expressed in the Extracellular Matrix (ECM), acts as an activator of biological cascades, stimulating cell migration and proliferation, and operating as a regulator of the skin immune surveillance, through specific interactions with its receptors. HA may be used in topical formulations, as dermal inducer, for wound healing. Moreover, intradermal HA formulations (injectable HA) provide an attractive tool to counteract skin aging (e.g., facial wrinkles, dryness, and loss of elasticity) and restore normal dermal functions, through simple and minimally invasive procedures. Biological activity of a commercially available hyaluronic acid, Profhilo®, based on NAHYCO™ technology, was compared to H-HA or L-HA alone. The formation of hybrid cooperative complexes was confirmed by the sudden drop in η0 values in the rheological measurements. Besides, hybrid cooperative complexes proved stable to hyaluronidase (BTH) digestion. Using in vitro assays, based on keratinocytes, fibroblasts cells and on the Phenion® Full Thickness Skin Model 3D, hybrid cooperative complexes were compared to H-HA, widely used in biorevitalization procedures, and to L-HA, recently proposed as the most active fraction modulating the inflammatory response. Quantitative real-time PCR analyses were accomplished for the transcript quantification of collagens and elastin. Finally immunofluorescence staining permitted to evaluate the complete biosynthesis of all the molecules investigated. An increase in the expression levels of type I and type III collagen in fibroblasts and type IV and VII collagen in keratinocytes were found with the hybrid cooperative complexes, compared to untreated cells (CTR) and to the H-HA and L-HA treatments. The increase in elastin expression found in both cellular model and in the Phenion® Full Thickness Skin Model 3D also at longer time (up to 7 days), supports the clinically observed improvement of skin elasticity. The biomarkers analyzed suggest an increase of tissue remodeling in the presence of Profhilo®, probably due to the long lasting release and the concurrent action of the two HA components. 

Retracted: No

PubPeer comments:
 Figure 9:Apparent duplication ![file] ,
MiR-199 inhibits EMT and invasion of hepatoma cells through inhibition of Snail expression
Authors: Y-Q Luo
H-Y Zhang
C-H Li
J-J Chen
X-D Cao
X-C Wang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-199; liver cancer; Snail mRNA; epithelial-mesenchymal transition (EMT); invasion
Affiliations: Department of Hepatobiliary Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. .

Abstract:  Objective: MiR-199 expression is associated with liver cancer. Bioinformatics analysis revealed that miR-199 has a complementary binding site to the 3'-UTR region of Snail mRNA. This study investigated whether miR-199 plays a role in regulating Snail expression and affecting epithelial-mesenchymal transition (EMT) and invasion of hepatoma cells. Patients and methods: The Dual-Luciferase reporter gene assay validated the targeted regulation between miR-199 and Snail. QRT-PCR was used to detect and compare the expression of miR-199 and Snail mRNA in human normal liver HL7702 cells, low metastatic MHCC97L cells, and high metastatic MHCC97H cells. MHCC97H cells were cultured in vitro and divided into two groups: miR-NC group and the miR-199 mimic group followed by the analysis of the expression of Snail, E-cadherin, and N-cadherin, as well as cell invasion ability by transwell assay. Results: There was a targeted regulatory relationship between miR-199 and Snail mRNA. Compared with HL7702 cells, miR-199 expression was significantly decreased, and Snail expression was significantly increased in MHCC97L and MHCC97H cells, with more changes being observed in high metastatic MHCC97H cells. The transfection of miR-199 mimic significantly downregulated the expression of Snail and N-cadherin in MHCC97H cells, increased E-cadherin expression, inhibited the cell's EMT process, and invasion. Conclusions: The decrease of miR-199 expression plays a role in upregulating the expression of Snail and promoting EMT and invasion of hepatocarcinoma cells. The increase of the expression of miR-199 can inhibit the expression of Snail and inhibit the EMT process and invasion ability of hepatoma cells. 

Retracted: No

PubPeer comments:
  Figure 4. Transfection of miR-199 mimic significantly attenuated the invasion of MHCC97H cells. ![file] Unexpected overlaps with Fig 2B from [Wang et al (2018)] ,  Transwell assay detection of [OS-RC-2] invasive ability ... ![file] ... and with Fig 3C,  Transwell assay detection of cell invasion . ![file] , 
 This paper has features suggestive of [what has elsewhere been labeled as  Papermill #2 ] , characterised by stylised geometrical WBs that are reduced to black blobs on a featureless grey background, reminiscent of a Miro painting: ![file] ![file] Other examples are listed in a Google document. https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit?usp=sharing One curious feature of this papermill is the frequent mismatch between the name of the putative corresponding author, and the email address provided for correspondence. ![file] ,
MicroRNA-466 (miR-466) functions as a tumor suppressor and prognostic factor in colorectal cancer (CRC)
Authors: Feng Tong
Hongchen Li
Wei Zhao
Haihua Pan
Youhua Ying
Xiaoli Zhan
Journal: Bosnian Journal of Basic Medical Sciences (2018)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miR-466; colorectal cancer; prognosis; tumor development
Affiliations: Department of Surgery, Lanxi People's Hospital, Zhejiang, China. .

Abstract:  MicroRNAs (miRNAs) have an important role in the regulation of tumor development and metastasis. In this study, we investigated the clinical and prognostic value as well as biological function of miR-466 in colorectal cancer (CRC). Tumor and adjacent healthy tissues were obtained from 100 patients diagnosed with CRC. miR-466 expression was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). mRNA and protein levels of cyclin D1, apoptosis regulator BAX (BAX), and matrix metalloproteinase-2 (MMP-2) were analyzed by qRT-PCR and Western blot, respectively, in SW-620 CRC cells transfected with miR-466 mimics or negative control miRNA. Effects of miR-466 on SW-620 cell proliferation, cell cycle and apoptosis, and invasion were investigated using CCK-8 assay, flow cytometry and Transwell assay, respectively. miR-466 expression was significantly downregulated in tumor tissues compared to matched adjacent non-tumor tissues. Low expression of miR-466 was significantly correlated with the tumor size, Tumor Node Metastasis stage, lymph node metastasis, and distant metastasis. The overall survival of CRC patients with low miR-466 expression was significantly shorter compared to high-miR-466 expression group (log-rank test: p = 0.0103). Multivariate analysis revealed that low miR-466 expression was associated with poor prognosis in CRC patients. The ectopic expression of miR-466 suppressed cell proliferation and migration/invasion, as well as induced G0/G1 arrest and apoptosis in SW-620 cells. Moreover, the ectopic expression of miR-466 decreased the expression of cyclin D1 and MMP-2, but increased BAX expression in SW-620 cells. In conclusion, our findings demonstrated that miR-466 functions as a suppressor miRNA in CRC and may be used as a prognostic factor in these patients. 

Retracted: No

PubPeer comments:
  We enrolled 100 patients diagnosed with CRC by pathology and with complete clinicopathological data. The patients underwent complete surgical resection at the Second Affiliated Hospital of Zhejiang University School of Medicine, from **March 2015 to October 2016**. None of the patients received chemotherapy or radiotherapy before the surgery. Patients were followed up for **5 years** and the clinical assessment was performed in each patient at the end of study. This paper was  Received 2017 Aug 21; Accepted 2017 Sep 25 -- about **2-1 2 years** after the first subjects were recruited and less than a year after the final recruitment. Time machines, how do they work? ,
Genetic polymorphism of glucokinase on the risk of type 2 diabetes and impaired glucose regulation: evidence based on 298,468 subjects
Authors: Xueyu Yuan
Zhongwei Lv
Mingli Lv
Haidong Cai
Da Fu
Mingxiang Cai
Xianling Cong
Yushui Ma
Dan Li
Yinghui Huang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Glucokinase; GCK; type 2 diabetes; T2D; meta-analysis
Affiliations: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.

Abstract:  Background: Glucokinase (GCK) is the key glucose phosphorylation enzyme which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) based on its enzyme function as the first rate-limiting step in the glycolysis pathway and regulates glucose-stimulated insulin secretion. In the past decade, the relationship between GCK and T2D has been reported in various ethnic groups. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis. Methods: Databases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results: A total of 24 articles involving 88,229 cases and 210,239 controls were included. An overall random-effects per-allele OR of 1.06 (95% CI: 1.03-1.09; P&lt;10(-4)) was found for the GCK -30G&gt;A polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians; whereas no significant associations were found among Asians. In addition, we found that the -30G&gt;A polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. Besides, -30G&gt;A homozygous was found to be significantly associated with increased fasting plasma glucose level with weighted mean difference (WMD) of 0.15 (95%: 0.05-0.24, P = 0.001) compared with G/G genotype. Conclusions: This meta-analysis demonstrated that the -30G&gt;A polymorphism of GCK is a risk factor associated with increased T2D susceptibility, but these associations vary in different ethnic populations. 

Retracted: Yes

PubPeer comments:
null, 
 Here s the erratum: Reports: u201cEmpathy and pro-social behavior in ratsu201d by I. B.-A. Bartal et al. (9 December 2011, p. 1427). On p. 1428, the last full paragraph of column 1 was incorrect. The paragraph should be replaced by this corrected text: u201cAll female rats (6 6) and most male rats (17 24) in the trapped condition became door-openers. Female rats in the trapped condition opened the restrainer door at a shorter latency than males on days 7 to 12 (P 0.01, MMA, Fig. 3A), consistent with suggestions that females are more empathic than males (7, 12, 13). Furthermore, female rats were also more active than males in the trapped condition (P 0.001, ANOVA) but not in the empty condition (Fig. 3B). ,
Promoting hepatogenic differentiation of human mesenchymal stem cells using a novel laminin-containing gelatin cryogel scaffold
Authors: Hossein Tavana
Abbas Sahebghadam Lotfi
Maryam Kabir-Salmani
Sareh Arjmand
Alemeh Mohammadpour
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cryogels; Gelatin; Hepatocyte; Laminin; Mesenchymal stem cells.
Affiliations: Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran., Protein Research Center, Shahid Beheshti University, G. C, Tehran, Iran. Electronic address: ., Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: ., Department of Biomedical Engineering, The University of Akron, Akron, OH, 44325, USA.

Abstract:  Liver transplantation is the only definitive treatment currently available for acute and chronic liver failure. However, this approach has been restricted by complications including rejection and infection. Tissue engineering approaches using stem cell-derived functional hepatic cells offer a potential alternative. Using biologically compatible scaffolds is an important complementary key to achieve optimal construct for hepatic replacement. In the present study, to optimize the differentiation of human adipose-derived mesenchymal stem cells (ADMSCs) toward hepatocyte-like cells, a previously described gelatin cryogel was optimized and improved by laminin, the major component of basal lamina. The ADMSCs seeded on the scaffold displayed increased attachment in the presence of laminin and the MTT assay showed good compatibility for cell proliferation. The differentiation of stem cells were evaluated using glycogen staining, urea secretion measurement, hepatocyte specific cell surface analysis and gene expression analysis. The results of tests indicated that laminin protein and gelatin cryogel 3D scaffold, each on its own, enhanced hepatogenic differentiation of ADMSCs. However, when laminin immobilized on the gelatin cryogel surface, the differentiation was promoted significantly and the resulting cells showed striking similarity to HepG2 in terms of expressing studied hepatocyte markers. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have 2 images which overlap, although they appear to be intended to reference different groups. *** ![file] ,
A novel circular RNA circFN1 enhances cisplatin resistance in gastric cancer via sponging miR‐182‐5p
Authors: Ai-Liang Zeng
Ya-Bin Xia
Yan Jin
Qiang Zhang
Hao Hu
Xiao-Xu Huang
Li Xu
Journal: Journal of Cellular Biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: circFN1; circular RNA; cisplatin resistance; gastric cancer; miR-182-5p.
Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China., Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Department of Gastrointestinal Surgery, The Second People's Hospital of Lianyungang, Lianyungang, Jiangsu, China., Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Abstract:  Cisplatin (CDDP) is commonly used for gastric cancer (GC) chemotherapy. However, after several CDDP-based treatment cycles, patients always acquire chemotherapy resistance, which limits the overall clinical efficacy of the treatment. Clarification of the mechanisms responsible for CDDP resistance is required to improve therapeutic outcomes for patients. Circular RNAs (circRNAs) are noncoding RNAs involved in the pathogenesis of cancer, although their role in the mechanism underlying CDDP resistance in GC remains unknown. In the present study, we explored the underlying roles of circRNAs in the modulation of CDDP resistance in CDDP-sensitive and CDDP-resistant human GC cells. Using RNA sequencing and quantitative reverse transcription polymerase chain reaction, expression of circFN1 (originating from exons 10, 11, and 12 of the FN1 gene hsa_circ_0058147) was higher in CDDP-resistant GC cells and tissues. CircFN1 upregulation in GC patients treated by CDDP was significantly correlated with aggressive biological behavior. CircFN1 promoted viability and inhibited apoptosis of GC cells exposed to CDDP in vivo and in vitro. Furthermore, circFN1 suppressed GC cell apoptosis by "sponging" miR-182-5p. These findings demonstrate the involvement of circFN1 in CDDP resistance of GC and implicate circFN1 as a therapeutic target for GC patients treated with CDDP. It provides novel evidence of the function of circRNAs as microRNA sponges and highlight a potential therapeutic target for extinguishing CDDP resistance in patients with GC. 

Retracted: No

PubPeer comments:
 Microscopy images have been duplicated and presented as something else between Figure 2E and Figure 2I. ![file] ,
STEEP mediates STING ER exit and activation of signaling
Authors: Zong-Liang Gao
Chiranjeevi Bodda
Yan Zhang
Sonia Assil
Ryo Narita
Ramya Nandakumar
Cheng-Long Sun
Jan J Enghild
Rune Hartmann
Thaneas Prabakaran
Zhijian J Chen
Line S Reinert
Yujia Cai
Søren R Paludan
Carsten Scavenius
Samuel J Windross
Takeshi Noda
Christine M Doucet
Anders Laustsen
Rasmus O Bak
Jinrong Huang
Harald Stenmark
Martin K Thomsen
Bao-Cun Zhang
Cong-Gang Zhang
Søren Beck Jensen
Martin F Berthelsen
David Olagnier
Zheng Guo
Raphaela Goldbach-Mansky
Anne Troldborg
Journal: Nature Immunology (2020)
Discipline: IMMUNOLOGY
Keywords: STING; STEEP; ER exit; signaling; trafficking
Affiliations: Department of Biomedicine, Aarhus University, Aarhus, Denmark., Department of Biology, University of Copenhagen , Copenhagen, Denmark., Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark., Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark., Department of Engineering, Aarhus University, Aarhus, Denmark., Department of Molecular Biology, Center for Inflammation Research, University of Texas Southwestern Medical Center, Dallas, TX, USA., Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Centre de Biochimie Structurale (CBS), INSERM, CNRS, Université de Montpellier, Montpellier, France., Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan., Translational Autoinflammatory Diseases Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA., Aarhus Institute of Advanced Studies (AIAS), Aarhus University, Aarhus, Denmark., Department of Biomedicine, Aarhus University, Aarhus, Denmark. .

Abstract:  STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signaling, the mechanism that drives this process is not understood. Here we identify STEEP as a positive regulator of STING signaling. STEEP was associated with STING and promoted trafficking from the ER. This was mediated through stimulation of phosphatidylinositol-3-phosphate (PtdIns(3)P) production and ER membrane curvature formation, thus inducing COPII-mediated ER-to-Golgi trafficking of STING. Depletion of STEEP impaired STING-driven gene expression in response to virus infection in brain tissue and in cells from patients with STING-associated diseases. Interestingly, STING gain-of-function mutants from patients interacted strongly with STEEP, leading to increased ER PtdIns(3)P levels and membrane curvature. Thus, STEEP enables STING signaling by promoting ER exit. 

Retracted: No

PubPeer comments:
 Identical image ![file] , 
 ![file] , 
 #1 Posts should specify the **Figure numbers**. ,
PLK1 promotes proliferation and suppresses apoptosis of renal cell carcinoma cells by phosphorylating MCM3
Authors: Xiaojun Man
Chuize Kong
Xiankui Liu
Zhe Zhang
Jianbin Bi
Jun Li
Zeliang Li
Zhipeng Gao
Zhenhua Li
Journal: Cancer Gene Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: Minichromosome maintenance 3 (MCM3); polo-like kinase 1 (PLK1); renal cell carcinoma (RCC); phosphorylation; proliferation
Affiliations: Department of Urology, First Hospital of China Medical University, 155 North Nanjing Street, Heping, 110001, Shenyang, Liaoning, China., Department of Urology, First Hospital of China Medical University, 155 North Nanjing Street, Heping, 110001, Shenyang, Liaoning, China. .

Abstract:  Minichromosome maintenance 3 (MCM3) protein has been widely studied due to its essential role in DNA replication. In addition, it is overexpressed in several human tumor types. However, the role of this protein in renal cell carcinoma (RCC) is not widely known. In this study, we demonstrated that polo-like kinase 1 (PLK1)-mediated MCM3 phosphorylation regulates proliferation and apoptosis in RCC. Our results confirm that PLK1 and phospho-MCM3 (p-MCM3) are highly expressed in renal cell carcinoma. The expression of PLK1 is closely related to the clinical characteristics of renal cell carcinoma. They play important roles in the proliferation and apoptosis of RCC. In vitro, after overexpression of PLK1 or MCM3, the proliferation of RCC cells was significantly enhanced and cell apoptosis was inhibited, while after knockout, the proliferation of RCC cells was weakened and cell apoptosis was promoted. In addition, Mn2+-Phos-tag SDS-PAGE, western blotting, and immunofluorescence were utilized to determine that MCM3 is a physiological substrate of PLK1, which is phosphorylated on serine 112 (Ser112) in a PLK1-dependent manner. PLK1-mediated MCM3 phosphorylation promotes RCC cell cycle proliferation and suppresses apoptosis in vitro. Moreover, we found that PLK1-mediated MCM3 phosphorylation induced cellular proliferation and decreased apoptosis, as well as tumor growth in mice. Overall, we conclude that PLK1-mediated MCM3 phosphorylation is a novel mechanism to regulate RCC proliferation and apoptosis. 

Retracted: No

PubPeer comments:
 In Figure 1E, a micrograph has been duplicated and presented as something else. ![file] ,
M2‐polarized tumor‐associated macrophages promote epithelial‐mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma
Authors: Pingping Dong
Jing Chen
Dalong Sun
Si Zhang
Harry L A Janssen
Ling Dong
Ningping Zhang
Shuncai Zhang
Tiancheng Luo
Journal: Journal of Cellular Biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AKT3; cytokines; epithelial-mesenchymal transition; intrahepatic cholangiocarcinoma; tumor microenvironment
Affiliations: Department of Gastroenterology and Hepatology, Zhongshan HospitalFudan University Shanghai China, Shanghai Institute of Liver Disease Shanghai China, Department of Gastroenterology and Hepatology, Xiamen Branch, Zhongshan HospitalFudan University Xiamen China, Department of Surgery, Faculty of MedicineThe University of Hong Kong Hong Kong China, Department of Neurology, Zhongshan HospitalFudan University Shanghai China, Toronto Center for Liver Disease, Toronto General Hospital, University Health NetworkUniversity of Toronto Toronto Canada, NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, Shanghai Medical CollegeFudan University Shanghai China

Abstract:  Tumor-associated macrophages (TAMs) have been considered as a major component of the tumor microenvironment. However, the crosstalk between M2-polarized tumor-associated macrophages (M2-TAMs) and intrahepatic cholangiocarcinoma (ICC) remains undetermined. In the present study, we aimed to clarify the role of M2-TAMs in ICC and the underlying mechanism. The in vitro assay demonstrated M2-TAMs promoted epithelial-mesenchymal transition (EMT) of ICC cells, resulting in enhanced cell invasion and metastasis ability. Moreover, M2-TAMs modulated the microenvironment of ICC by increasing the secretion of cytokines (GM-CSF, tumor necrosis factor-α [TNF-α], ICAM-1, interleukin-6 [IL-6], etc) and chemokines (CCL1, CCL3, etc). In addition, p-AKT (Ser473) and p-PRAS40 (Thr246) were upregulated in ICC cells when cocultured with M2-TAMs or treated with M2-TAMs secreted core cytokines (GM-CSF, TNF-α, ICAM-1, and IL-6). Consistently, AKT3 silencing (but not AKT1 silencing and AKT2 silencing) markedly inhibited phosphorylation of AKT and PRAS40 of ICC cells and inhibited the EMT process when cocultured with M2-TAMs. Taken together, the current data indicated that M2-TAMs promoted ICC cells EMT, partially through increasing secretion of cytokines and chemokines, thus modulating the microenvironment and activating the AKT3/PRAS40 signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 5 appears to have three problems. Could the authors please check? * Red boxes: The Ctrl and Akt inhibitor Invasion panels appear to look very similar to each other * Blue boxes: The Ctrl Invasion and Migration panels appear to show a (rotated) overlap * Yellow boxes: The Akt inhibitor Invasion and Migration panels appear to show an overlap. ![file] ,
miR-21 regulates the proliferation and apoptosis of ovarian cancer cells through PTEN/PI3K/AKT
Authors: H-Y Zhang
F-Z Feng
B-L Zhu
B Zhou
H Yan
H-Y Liu
Y-Y Zhang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: PTEN; miR-21; PI3K; AKT; ovarian cancer
Affiliations: Department of Obstetrics and Gynecology, Department of Infectious Disease, Department of Oncology, Department of Rehabilitation; Linyi Central Hospital, Linyi, Shandong, China. .

Abstract:  Objective: Phosphatase and tensin homologue deleted on chromosome ten (PTEN) regulates cell proliferation and apoptosis by inhibiting phosphatidylinositol-3 kinase (PI3K) and protein kinase (AKT) signaling. High expression of miR-21 was associated with ovarian cancer. This study aims to investigate whether miR-21 regulates PTEN/PI3K/AKT signaling as well as its role in the proliferation and apoptosis of ovarian cancer cells. Materials and methods: Bioinformatics analysis was used to identify the binding site between miR-21 and the 3'-UTR of PTEN mRNA. A dual-luciferase reporter gene assay was performed to confirm the relationship between miR-21 and PTEN. The expression of miR-21, PTEN, and p-AKT was measured in normal ovarian cell IOSE80, ovarian cancer cell lines A2780, and SKOV3. miR-NC or miR-21 inhibitor was transfected into A2780 or SKOV3 cells followed by the analysis of the expression of miR-21, PTEN, p-AKT, cell apoptosis by flow cytometry, and proliferation by EdU assay. Results: There was a targeted relationship between miR-21 and PTEN. Compared with IOSE80 cell, levels of miR-21 and p-AKT were significantly elevated in A2780 and SKOV3 cells, with the statistical reduction of PTEN expression (p&lt;0.05). The inhibition of miR-21 significantly reduced the expressions of miR-21 and p-AKT and induced PTEN level in A2780 and SKOV3 cells, which also restricted cell proliferation and promoted cell apoptosis. Conclusions: The miR-21 expression is found elevated in ovarian cancer cells. The suppression of miR-21 increases PTEN expression, inhibits PI3K/AKT activity, promotes cell apoptosis, and reduces cell proliferation. This finding provides new leads to the future treatment of ovarian cancer. 

Retracted: No

PubPeer comments:
 Fig 2: ![file] Fig 4: ![file] This is an example of what has elsewhere been labeled as  Papermill #2 , characterised by stylised WBs reminiscent of the blobs in a Miro painting, ![] ...and by a small repertoire of recurring FACS plots, slightly modified by artisanal stippling on each of their occurrences. ![] https: forbetterscience.com 2020 02 27 dark-satanic-papermills https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit#gid=0 ,
PHOX2B regulates its own expression by a transcriptional auto-regulatory mechanism
Authors: Francesca Cargnin
Elena Battaglioli
Simona Di Lascio
Renato Longhi
Adriano Flora
Francesco Clementi
Diego Fornasari
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Neuronal identity; Extrinsic factors; Intrinsic factors; Transcription factors; Phox2b
Affiliations: Department of Pharmacology, School of Medicine, University of Milan, Italy.

Abstract:  The specification of neuronal identity is a result of interactions between the following two distinct classes of determinants: extrinsic factors that include secreted or cell membrane-associated signals in the local environment, and intrinsic factors that generally consist of ordered cascades of transcription factors. Little is known about the molecular mechanisms underlying the interplay between these extrinsic and intrinsic factors and the transcriptional processes that establish and maintain a given neuronal phenotype. Phox2b is a vertebrate homeodomain transcription factor and a well established intrinsic factor in developing autonomic ganglia, where its expression is triggered by the bone morphogenic proteins secreted by the dorsal aorta. In this study we characterized its proximal 5'-regulatory region and found that it contained five putative DNA sites that potentially bind homeodomain proteins, including PHOX2B itself. Chromatin immunoprecipitation assays showed that PHOX2B could bind its own promoter in vivo, and electromobility gel shift assays confirmed that four of the five sites could be involved in PHOX2B binding. Functional experiments demonstrated that 65% of the transcriptional activity of the PHOX2B promoter in neuroblastoma cells depends on this auto-regulatory mechanism and that all four sites were required for full self-transactivation. Our data provide a possible molecular explanation for the maintenance of PHOX2B expression in developing ganglia, in which initially its expression is triggered by bone morphogenic proteins, but may become independent of external stimuli when it reaches a certain nuclear concentration and sustains its own transcription. 

Retracted: No

PubPeer comments:
null, 
null, 
 Figure 3. Refinement. https: imgur.com 8KhUz79 ,
miR-330-5p suppresses glioblastoma cell proliferation and invasiveness through targeting ITGA5
Authors: Haiming Ji
Jianhua Ma
Yichun Liu
Weixing Hu
Linsen Feng
Journal: Bioscience Reports (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ITGA5; glioblastoma (GBM); invasiveness; miR-330-5p; proliferation.
Affiliations: Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China., Department of Neurosurgery, Taixing People's Hospital, Taixing, Jiangsu 225400, China., Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China .

Abstract:  The present study intended to investigate the biological effects of miR-330-5p on glioblastoma (GBM) cell proliferation and invasiveness by targeting integrin α5 (ITGA5). The expressions of miR-330-5p and ITGA5 mRNA in GBM cell lines (U87, U251, and U373) and normal brain glial cell line (HEB) were detected using RT-qPCR. Protein expression of ITGA5 was examined using Western blot. The present study used MTT assay, colony formation assay, Transwell assay, wound healing assay, and flow cytometry analysis in order to determine the biological functions of GBM cells (including cell proliferation, invasion, migration, apoptosis, and cell cycle). The present study applied dual-luciferase reporter gene assay to identify the target relationship between miR-330-5p and ITGA5. miR-330-5p was low-expressed in GBM cell lines while ITGA5 was high-expressed compared with HEB. miR-330-5p could directly target ITGA5 as well as suppress its expression in GBM cells. Up-regulation of miR-330-5p and down-regulation of ITGA5 both have an inhibitory effect on cell proliferation, invasion, and migration. Meanwhile, they could also promote GBM cell apoptosis. miR-330-5p could suppress proliferation and invasion of GBM cells through targeting ITGA5. 

Retracted: Yes

PubPeer comments:
 Fig 4A, the percentage of G0 G1, S, and G2 phase is the same ![file] Fig 3E, two same images ![file] , 
 Retracted, [22 September 2021] . ------------------------------- This article is being retracted from *Bioscience Reports* at the request of the Editor-in-Chief and the Editorial Board following receipt of a notification from a reader, alerting the Editorial Board to incorrect data in Figure 4A, as well as a duplicated panel in Figure 3E. Post publication review by the Editorial Office also identified signs of image manipulation in the original versions of Figures 3B, 3C and 3E which were replaced by the authors during the revision process. The authors have been contacted in regards to the Retraction, and have not responded to the Journal s queries and the concerns raised. Given the extent of the issues raised, the Editorial Board stand by the decision to retract the article. ,
Isolation of stem-like cells from human MG-63 osteosarcoma cells using limiting dilution in combination with vincristine selection
Authors: Dahui Sun
Jianwu Zhao
Yang Wang
Zhongli Gao
Nan Lou
Yan Wang
Journal: Indian journal of biochemistry & biophysics (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: stem-like cells; MG-63 osteosarcoma; subpopulations; clonogenicity; proliferation assay
Affiliations: Department of Orthopaedic Trauma, First Hospital of Jilin University, Changchun 130021, China.

Abstract:  To isolate stem-like cells from the human MG-63 osteosarcoma cell line, different subpopulations of MG-63 cells were cloned by limiting dilution and passaged to obtain different sublines. The subline with highest clonogenicity was identified using a proliferation assay, cell-cycle analysis, and soft-agar colony-forming assay. The sublines were further selected in serum-free medium containing 20 ng/ml vincristine to identify cells that could form suspended sarcospheres. Identified cells were then characterized based on morphology, cell surface markers, adipogenic and osteogenic differentiation, and tumorigenicity in nude mice. A total of 19 holoclones that could be stably passaged were obtained. Sublines A1, A3, and D1 were markedly different from other sublines and the parental cell line. Subline D1 not only had a higher colony-forming efficiency and formed larger colonies, but also possessed a shorter latency of tumorigenesis in vivo. After subline D1 was cultured in suspension in medium containing vincristine, a highly enriched subpopulation of cells that could form sarcospheres and be stably passaged were obtained. These cells, designated as MG-63-M expressed multiple markers of multipotent or embryonic stem cells and possessed the capacity for self-renewal, multilineage differentiation, and significant multi-drug resistance. Thus, our results suggest that a subpopulation of stem-like cells can be isolated from human MG-63 osteosarcoma cell line. 

Retracted: No

PubPeer comments:
 ![file] internal controls are same ,
Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats
Authors: Ji-Ye Yin
Xiao-Yuan Mao
Xi Li
Hong-Hao Zhou
Zhi-Bin Wang
Chen-Xue Mao
Ying Zhang
Zhao-Qian Liu
Dan-Feng Cao
Journal: International Journal of Molecular Sciences (2014)
Discipline: CHEMISTRY
Keywords: Huperzine A; diabetes-associated cognitive decline; streptozotocin; rat model; memory functions
Affiliations: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. ., Department of Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China. ., School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China. .

Abstract:  The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have a repeated image. *** ![file] , 
 #1 Dear Prof. Actinopolyspora Biskrensis, Thank you very much for your very helpful comments. I deeply apologize for this careless mistake. Fortunately, however, this mistake does not affect the correctness of the results and conclusions in our article. Now, I have contacted with the editorial department aimed to publish the a corrigendum for our paper. Thanks again for you comment! Kind regardsuff01 Xiao-Yuan Mao ,
Oxidation of Benzyl Alcohol Compounds in the Presence of Carbon Hybrid Supported Platinum Nanoparticles (Pt@CHs) in Oxygen Atmosphere
Authors: Hakan Burhan
Sibel Demiroğlu Mustafov
Fatih Şen
Haydar Göksu
Journal: Scientific Reports (2020)
Discipline: Multidisciplinary
Keywords: catalyst; platinum nanoparticles; oxidation; benzyl alcohol derivatives; benzaldehyde compounds
Affiliations: Kaynasli Vocational College, Düzce University, Düzce, 81900, Turkey. ., Sen Research Group, Department of Biochemistry, Dumlupınar University, 43100, Kütahya, Turkey., Sen Research Group, Department of Biochemistry, Dumlupınar University, 43100, Kütahya, Turkey. .

Abstract:  A novel catalyst which carbon hybrid supported platinum nanoparticles were synthesized by our group for the oxidation of benzyl alcohol derivatives. In this study, this catalyst was utilized for the oxidation of benzyl alcohol derivatives to benzaldehyde compounds in aqueous toluene at 80 °C. The benzaldehyde derivatives were synthesized in high yields and mild conditions in the presence of the catalyst by the developed method. Additionally, the prepared nanoparticles have been characterized by Transmission Electron Microscopy (TEM), the high-resolution electron micrograph (HR-TEM), X-ray Photoelectron Spectroscopy (XPS), and X-ray Diffraction (XRD). The mean particle size of the nanoparticles determined by the XRD technique was found to be 2.83 nm in parallel with TEM analysis. TEM analysis also indicated that the Pt nanoparticles were evenly dispersed on the support material. Finally, the Pt@CHs catalyst was shown also stable and reusable for the oxidation reaction, providing ≤95% conversion after its 3rd consecutive use in the oxidation reaction of various compounds. 

Retracted: No

PubPeer comments:
 It seems that the authors of this paper used the conventional AHP method to determine the weights of the criteria (or factors). The conventional AHP method usually performs a consistency check and requires the inconsistency index **below $0.1$**. However, the two plots on page 60 are identical and **the inconsistency displayed is** $$0.13040$$ This means that the pairwise comparison **does not pass the consistency check.** Could the authors address this issue? ![file] ![file] ,