PReD-Bench/PRed-Bench huggingface dataset:
MicroRNA-532 and microRNA-3064 inhibit cell proliferation and invasion by acting as direct regulators of human telomerase reverse transcriptase in ovarian cancer
Authors: Lin Bai
Luo-Ying Zhang
Jie Bai
Hui Wang
Ai-Hua Wang
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: hTERT; ovarian cancer; miRNA; 3'-UTR; proliferation
Affiliations: Department of Obstetrics and Gynecology, the First People's Hospital of Shangqiu, Shangqiu, China.

Abstract:  Human telomerase reverse transcriptase (hTERT) plays a crucial role in ovarian cancer (OC) progression. However, the mechanisms underlying hTERT upregulation in OC, and the specific microRNAs (miRNAs) involved in the regulation of hTERT in OC cells, remains unclear. We performed a bioinformatics search to identify potential miRNAs that bind to the 3'-untranslated region (3'-UTR) region of the hTERT mRNA. We examined the expression levels of miR-532/miR-3064 in OC tissues and normal ovarian tissues, and analyzed the correlation between miRNA expression and OC patient outcomes. The impacts of miR-532/miR-3064 on hTERT expression were evaluated by western blot analysis and hTERT 3'-UTR reporter assays. We investigated the effects of miR-532/miR-3064 on proliferation and invasion in OC cells. We found that miR-532 and miR-3064 are down-regulated in OC specimens. We observed a significant association between reduced miR-532/miR-3064 expression and poorer survival of patients with OC. We confirmed that in OC cells, these two miRNAs downregulate hTERT levels by directly targeting its 3'-UTR region, and inhibited proliferation, EMT and invasion of OC cells. In addition, the overexpression of the hTERT cDNA lacking the 3'-UTR partially restored miR-532/miR-3064-inhibited OC cell proliferation and invasion. The silencing of hTERT by siRNA oligonucleotides abolished these malignant features, and phenocopied the effects of miR-532/miR-3064 overexpression. Furthermore, overexpression of miR-532/miR-3064 inhibits the growth of OC cells in vivo. Our findings demonstrate a miR-532/miR-3064-mediated mechanism responsible for hTERT upregulation in OC cells, and reveal a possibility of targeting miR-532/miR-3064 for future treatment of OC. 

Retracted: No

PubPeer comments:
  Antimicrobial sensitivity tests for prepared silver hydroxyapatite and silver hydroxyapatite loaded gelatin-alginate-PVA cryogel scaffold against Bacillus sp. and E.coli sp. are shown in Fig. 4(a) and (b), respectively. Is there any reason why most of the plate in the Bacillus test has been masked off behind a featureless beige circle?  , 
 Fig. 2.  (a) FTIR spectra, (b) SEM image and (c) cross section SEM image of silver hydroxyapatite reinforced gelatin-alginate-PVA scaffold of definite composition [PVA] = 10 wt%, [Gelatin] = 2 wt.%, [Alginate} = 1 wt.%, [Ag-HAp] = 1.5 wt.%, No of freeze thaw cycles = 3.  2(b) previously appeared as Fig 3 of [Jain et al (2017)] ,  **SEM images of P (HEMA-co-AN) cryogel** at (a) 250 X (b) 1.00 K X magnification .  These appear to be quite different materials. The meta-data on the SEM imagery appears to have been altered to read  2017 instead of  2015 . ,
Synergistic effects of eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes on lung cancer in vitro and in vivo
Authors: Guoxing Zhong
Huashan Shi
Chuanjiang Yu
Weihan Yang
Wenjing Ou
Xiaolan Su
Yu Wang
Lingdong Li
Xiang Chen
Lijuan Chen
Wen Zhu
Jiang Ren
Sujuan Ye
Journal: Journal of Cancer Research and Clinical Oncology (2014)
Discipline: CLINICAL MEDICINE
Keywords: LKB1; FUS1; tumor suppressor genes; lung cancer; gene therapy

Abstract:  Purpose: LKB1 and FUS1 are two kinds of new tumor suppressor genes as well as early-stage genes in lung cancer. Recent studies showed that LKB1 and FUS1 play important roles in lung carcinogenesis process. We hypothesized that combined gene therapy with LKB1 and FUS1 could inhibit lung cancer growth and development synergistically. Methods: In this study, two kinds of tumor suppressor genes, LKB1 and FUS1, were constructed in an eukaryotic coexpression plasmid pVITRO(2), and then, we evaluated the synergistic effects of the two genes on anticancer activity and explored the relevant molecular mechanisms. Results: We defined coexpression of LKB1 and FUS1 could synergistically inhibited lung cancer cells growth,invasion and migration and induced the cell apoptosis and arrested cell cycle in vitro. Intratumoral administration of liposomes: pVITRO(2)‚ÄìLKB1‚ÄìFUS1 complex (LPs‚ÄìpVITRO(2)‚ÄìLKB1‚ÄìFUS1) into subcutaneous lung tumor xenograft resulted in more significant inhibition of tumor growth. Furthermore, intravenous injection of LPs‚ÄìpVITRO(2)‚ÄìLKB1‚ÄìFUS1 into mice bearing experimental A549 lung metastasis demonstrated synergistic decrease in the number of metastatic tumor nodules. Finally, combined treatment with LKB1 and FUS1 prolonged overall survival in lung tumor-bearing mice. Further study showed tha tthe synergistic anti-lung cancer effects of coexpression ofLKB1 and FUS1 might be related to upregulation of p-p53, p-AMPK and downregulation of p-mTOR, p-FAK, MMPs, NEDD9, VEGF/R and PDGF/R. Conclusions: Our results suggest that combined therapy with eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes may be a novel and efficient treatment strategy for human lung cancer. 

Retracted: No

PubPeer comments:
 Figure 1i: * Red boxes: The Col1a1 un-exo and the alpha-SMA-un-exo panel appear to look very similar  , 
 Dear Dr. Bik, I am Xiangfeng LIu, the author of the manuscript. We are very sorry about the problem. Actually, we found this error on Feb 18, 2020, once the paper has been online before you have checked it. On Feb 18, 2020, we contacted with the editor and the paper production manager to help us correct and repost the article. The editor and the manager helped us to correct it and is trying to repost it. The attachment is the email showing the proof. Thanks very much for your checking and helping us to note the error. We are also sorry for the negligence! Thanks, Lisha Chen For all authors ,
Kruppel-like factor 4 (KLF4) represses histidine decarboxylase gene expression through an upstream Sp1 site and downstream gastrin responsive elements
Authors: Wandong Ai
Michael Langlois
Ying Liu
Timothy C Wang
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Histidine decarboxylase; HDC; gastrin; Kruppel-like factor 4; KLF4
Affiliations: Division of Gastroenterology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

Abstract:  Histidine decarboxylase (HDC) is the enzyme that catalyzes the conversion of histidine to histamine, a bioamine that plays an important role in allergic responses, inflammation, neurotransmission, and gastric acid secretion. Previously, we demonstrated that gastrin activates HDC promoter activity in a gastric cancer (AGS-E) cell line through three overlapping downstream promoter elements. In the current study, we used the yeast one-hybrid strategy to identify nuclear factors that bind to these three elements. Among eight positives from the one-hybrid screen, we identified Kruppel-like factor 4 (KLF4) (previously known as gut-enriched Kruppel-like factor (GKLF)) as one factor that binds to the gastrin responsive elements in the HDC promoter. Electrophoretic mobility shift assays confirmed that KLF4 is able to bind all three gastrin responsive elements. In addition, transient cotransfection experiments showed that overexpression of KLF4 dose dependently and specifically inhibited HDC promoter activity. Regulation of HDC transcription by KLF4 was confirmed by changes in the endogenous HDC messenger RNA by KLF4 small interfering RNA and KLF4 overexpression. We further showed that KLF4 inhibits HDC promoter activity by competing with Sp1 at the upstream GC box and also independently by binding the three downstream gastrin responsive elements. Taken together, these results indicate that KLF4 can act to repress HDC gene expression by Sp1-dependent and -independent mechanisms. 

Retracted: No

PubPeer comments:
 Sharp margins around one ban. Looks like the band was copy-paste from another blot in Fig4D.  ,
Pleiotropic effects of neutrophils on myocyte apoptosis and left ventricular remodeling during early volume overload
Authors: Steven R Houser
Mikhail A Kolpakov
Joseph R Libonati
Abdelkarim Sabri
Rachid Seqqat
Khadija Rafiq
Kennneth B Margulies
Pamela Powel
Louis J Dell&#x27;italia
Hang Xi
Journal: Journal of Molecular and Cellular Cardiology (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: neutrophils; cardiac remodeling; inflammation; MMP activation; ECM degradation
Affiliations: Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, MRB 801, 3420 N. Broad Street, Philadelphia, PA 19140, USA.

Abstract:  Most of the available evidence on the role of neutrophils on pathological cardiac remodeling has been pertained after acute myocardial infarction. However, whether neutrophils directly contribute to the pathogenesis of cardiac remodeling after events other than acute myocardial infarction remains unknown. Here we show that acute eccentric hypertrophy induced by aorto-caval fistula (ACF) in the rats induced an increase in the inflammatory response characterized by activation of the STAT pathway and increased infiltration of neutrophils in the myocardium. This early inflammation was associated with a decrease in interstitial collagen accumulation and an increase in myocyte apoptosis. Neutrophil infiltration blockade attenuated MMP activation, ECM degradation, and myocyte apoptosis induced by ACF at 24 hours and attenuated the development of eccentric hypertrophy induced by ACF at 2 and 3 weeks, suggesting a causal relationship between neutrophils and the ACF-induced cardiac remodeling. In contrast, sustained neutrophil depletion over 4 weeks resulted in adverse cardiac remodeling with further increase in cardiac dilatation and macrophage infiltration, but with no change in myocyte apoptosis level. These data support a functional role for neutrophils in MMP activation, ECM degradation, and myocyte apoptosis during eccentric cardiac hypertrophy and underscore the adverse effects of chronic anti-neutrophil therapy on cardiac remodeling induced by early volume overload. 

Retracted: No

PubPeer comments:
 Figure 3B. Much more similar than expected. https: imgur.com DE9L9ke , 
 Figure 3B continued. Much more similar than expected. https: imgur.com Jl1QZAI ,
Synapse diversity and synaptome architecture in human genetic disorders
Authors: Seth G N Grant
Journal: Human Molecular Genetics (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: brain diseases; mutations; proteome; excitatory synapses; neurological disorders
Affiliations: Centre for Clinical Brain Science, Edinburgh University, Edinburgh, UK.

Abstract:  Over 130 brain diseases are caused by mutations that disrupt genes encoding the proteome of excitatory synapses. These include neurological and psychiatric disorders with early and late onset such as autism, schizophrenia and depression and many other rarer conditions. The proteome of synapses is highly complex with over 1000 conserved proteins which are differentially expressed generating a vast, potentially unlimited, number of synapse types. The diversity of synapses and their location in the brain are described by the synaptome. A recent study has mapped the synaptome across the mouse brain, revealing that synapse diversity is distributed into an anatomical architecture observed at scales from individual dendrites to the whole systems level. The synaptome architecture is built from the hierarchical expression and assembly of proteins into complexes and supercomplexes which are distributed into different synapses. Mutations in synapse proteins change the synaptome architecture leading to behavioral phenotypes. Mutations in the mechanisms regulating the hierarchical assembly of the synaptome, including transcription and proteostasis, may also change synapse diversity and synaptome architecture. The logic of synaptome hierarchical assembly provides a mechanistic framework that explains how diverse genetic disorders can converge on synapses in different brain circuits to produce behavioral phenotypes. 

Retracted: No

PubPeer comments:
 This is a very interesting overview on what  synaptomics could bring, and a followup on the authors [earlier work](:https: doi.org 10.1016 j.neuron.2018.07.007). My comments: 1. It would be a lot more honest to refer to one s own work, as  our study : * A recent study has mapped the synaptome across the mouse brain [...] * * The first whole brain scale synaptome was recently reported(31). * (Which otherwise is a truly fascinating paper). -------------------- 2. Extrapolating from 2 proteins to 1000 proteins is a bit too strong to my taste: * The study of synapse diversity arising from only two postsynaptic proteins revealed combinatorial principles that extend to any number of other synapse proteins.  * ... especially when the author makes it clear that it is likely not to be the case: * The number of synapse types arising from n different proteins is described as N_types_ = 2^n-1^, and 50 proteins ( 5% of the synapse proteome) could potentially generate more types than there are synapses in the human brain (5 x 10^14^). * ,
Hypoxia Predicts Poor Prognosis in Neuroblastoma Patients and Associates with Biological Mechanisms Involved in Telomerase Activation and Tumor Microenvironment Reprogramming
Authors: Nicol√≤ Zanardi
Martina Morini
Ulrich Pfeffer
Davide Cangelosi
Alberto Garaventa
Angela Rita Sementa
Massimo Conte
Alessandra Eva
Luigi Varesio
Maria Carla Bosco
Marco Muselli
Journal: Cancers (2020)
Discipline: CLINICAL MEDICINE
Keywords: cell immortalization; hypoxia; neuroblastoma; prognosis; therapeutic target.
Affiliations: Laboratory of Molecular Biology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Laboratory of Pathology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Institute of Electronics, Computer and Telecommunication Engineering, Italian National Research Council, 16149 Genova, Italy., Pediatric Oncology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Integrated Oncology Therapies Department, Molecular Pathology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.

Abstract:  The biological and clinical heterogeneity of neuroblastoma (NB) demands novel biomarkers and therapeutic targets in order to drive the most appropriate treatment for each patient. Hypoxia is a condition of low-oxygen tension occurring in poorly vascularized tumor tissues. In this study, we aimed to assess the role of hypoxia in the pathogenesis of NB and at developing a new clinically relevant hypoxia-based predictor of outcome. We analyzed the gene expression profiles of 1882 untreated NB primary tumors collected at diagnosis and belonging to four existing data sets. Analyses took advantage of machine learning methods. We identified NB-hop, a seven-gene hypoxia biomarker, as a predictor of NB patient prognosis, which is able to discriminate between two populations of patients with unfavorable or favorable outcome on a molecular basis. NB-hop retained its prognostic value in a multivariate model adjusted for established risk factors and was able to additionally stratify clinically relevant groups of patients. Tumors with an unfavorable NB-hop expression showed a significant association with telomerase activation and a hypoxic, immunosuppressive, poorly differentiated, and apoptosis-resistant tumor microenvironment. NB-hop defines a new population of NB patients with hypoxic tumors and unfavorable prognosis and it represents a critical factor for the stratification and treatment of NB patients. 

Retracted: No

PubPeer comments:
 Figures 4 and 5 appear to have at least two sets of overlapping images (red and green boxes). Authors are encouraged to look elsewhere, as I did not. ***  , 
 #1 Missed one (orange boxes). TAM. ***  , 
 #2 The orange overlap is complicated by a rotation, though I understand your reluctance to bother with showing it exactly.  , 
 Tumor Biology is now archived and no longer receiving submissions with this publisher. All articles published in the journal during its time with Springer will remain fully searchable through our websites. ,
Supported black phosphorus nanosheets as hydrogen-evolving photocatalyst achieving 5.4% energy conversion efficiency at 353‚ÄâK
Authors: Bining Tian
Ruinian Hua
M C Scott
Qin Lei
Yue Tian
Bin Tian
Bethany Smith
Journal: Nature Communications (2018)
Discipline: Multidisciplinary
Keywords: Solar-driven water splitting; powdered catalysts; hydrogen generation; four-electron-driven oxidation; slow kinetics
Affiliations: Key Lab of Advanced Transducers and Intelligent Control System of Ministry of Education, College of Physics and Optoelectronics, Taiyuan University of Technology, Taiyuan, 030024, China., Department of Materials Science and Engineering, University of California, Berkeley, Berkeley, CA, 94720, USA., Molecular Foundry, Lawrence Berkeley National Lab, Berkeley, CA, 94720, USA., College of Life science, Dalian Nationalities University, Dalian, 116600, China., Key Lab of Advanced Transducers and Intelligent Control System of Ministry of Education, College of Physics and Optoelectronics, Taiyuan University of Technology, Taiyuan, 030024, China. ., Molecular Foundry, Lawrence Berkeley National Lab, Berkeley, CA, 94720, USA. .

Abstract:  Solar-driven water splitting using powdered catalysts is considered as the most economical means for hydrogen generation. However, four-electron-driven oxidation half-reaction showing slow kinetics, accompanying with insufficient light absorption and rapid carrier combination in photocatalysts leads to low solar-to-hydrogen energy conversion efficiency. Here, we report amorphous cobalt phosphide (Co-P)-supported black phosphorus nanosheets employed as photocatalysts can simultaneously address these issues. The nanosheets exhibit robust hydrogen evolution from pure water (pH = 6.8) without bias and hole scavengers, achieving an apparent quantum efficiency of 42.55% at 430 nm and energy conversion efficiency of over 5.4% at 353 K. This photocatalytic activity is attributed to extremely efficient utilization of solar energy (~75% of solar energy) by black phosphorus nanosheets and high-carrier separation efficiency by amorphous Co-P. The hybrid material design realizes efficient solar-to-chemical energy conversion in suspension, demonstrating the potential of black phosphorus-based materials as catalysts for solar hydrogen production. 

Retracted: No

PubPeer comments:
   The XRD and XPS patterns of the material before and after reaction shown in SI Fig. 18 and SI Fig. 20 are the same. Extremely stable material! , 
 Supplementary Figure 18, the XRD pattern after has the same noise (but scaled down) as the pattern before.  , 
 The below 4 curves are same in Figure 2e, except for scaling and shifting  , 
 The Fig. 1d are same.  ,
Bioisosteric Replacement of Amide Group with 1,2,3-Triazoles in Acetaminophen Addresses Reactive Oxygen Species-Mediated Hepatotoxic Insult in Wistar Albino Rats
Authors: Debashree Das
Adarsh Sahu
Shweta Mishra
Ayyamperumal Sakthivel
Ramkishore Agrawal
Preeti Sahu
Asmita Gajbhiye
Journal: Chemical research in toxicology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Acetaminophen; hepatotoxicity; bioisosteric replacement; 1,2,3-triazoles; pharmacological evaluation
Affiliations: Department of Pharmaceutical Sciences , Dr. Harisingh Gour Vishwavidyalaya , Sagar (MP) , India., Department of chemistry , Central University of Kerala , Kerala , India.

Abstract:  Acetaminophen (AP) is a popularly recommended over-the-counter analgesic-antipyretic in clinical use. However, the drug is handicapped by the occurrence of hepatotoxic insult following acute ingestion. Consequently, AP-induced hepatotoxicity is often implicated in accidental or suicidal overdose. In the current study, we investigated the potential of bioisosteric replacement of amide in AP with 1,2,3-triazoles in curbing AP-induced hepatotoxicity. The therapeutic utility of synthesized bioisosteres was established by careful tailoring and optimization of the synthetic methodology along with detailed toxicological testing of pharmacologically potent acetaminophen-triazole derivatives (APTDs). Along the same lines, we herein report a series of 17 novel APTDs synthesized via aromatic substitution using sodium azide, l-proline, and copper iodide followed by click reaction with substituted alkynes using copper sulfate and sodium ascorbate. Pharmacological evaluation of synthesized APTDs revealed that, out of the series of 17 compounds, 5a and 5e were found to be most efficacious in exerting anti-inflammatory, analgesic, and antipyretic activity in an animal model. Further toxicity studies documented that, in both acute and sub-acute toxicology, AP administration caused significant hepatotoxicity, which was found to be a consequence of ROS-mediated oxidative stress. Potent APTDs (5a and 5e), on the other hand, revealed no adverse event in both acute and sub-toxicological analyses. Median lethal dose (LD50) and no observed adverse effect level (NOAEL) values for 5a and 5e were found to be &gt;1000 mg/kg and 2000 mg/kg, respectively. The human equivalent dose, defining the maximum safe concentration of a compound in a human's physiology, was found to be 27.68 mg/kg for the most potent APTDs (5a and 5e). Thus, it can be concluded that triazole incorporation into AP nucleus produced conjugates devoid of hepatotoxic manifestations, having the added advantage of anti-inflammatory efficacy along with analgesic and antipyretic potency. 

Retracted: No

PubPeer comments:
 Image duplication between figures.  ,
Protein‚ÄìTyrosine Phosphatase 1B‚ÄìDeficient Myocytes Show Increased Insulin Sensitivity and Protection Against Tumor Necrosis Factor-Œ±‚ÄìInduced Insulin Resistance
Authors: Cristina de Alvaro
Iria Nieto-Vazquez
Angela M Valverde
Cristina M Rondinone
Margarita Lorenzo
Sonia Fern√°ndez-Veledo
Journal: Diabetes (2007)
Discipline: CLINICAL MEDICINE
Keywords: Protein-tyrosine phosphatase 1B; insulin signaling; skeletal muscle; insulin resistance; myocytes
Affiliations: Department of Biochemistry, Faculty of Pharmacy, Universidad Complutense, 28040-Madrid, Spain.

Abstract:  Protein-tyrosine phosphatase (PTP)1B is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. In this study, we have assessed the role of PTP1B in the insulin sensitivity of skeletal muscle under physiological and insulin-resistant conditions. Immortalized myocytes have been generated from PTP1B-deficient and wild-type neonatal mice. PTP1B(-/-) myocytes showed enhanced insulin-dependent activation of insulin receptor autophosphorylation and downstream signaling (tyrosine phosphorylation of insulin receptor substrate [IRS]-1 and IRS-2, activation of phosphatidylinositol 3-kinase, and serine phosphorylation of AKT), compared with wild-type cells. Accordingly, PTP1B(-/-) myocytes displayed higher insulin-dependent stimulation of glucose uptake and GLUT4 translocation to the plasma membrane than wild-type cells. Treatment with tumor necrosis factor-alpha (TNF-alpha) induced insulin resistance on glucose uptake, impaired insulin signaling, and increased PTP1B activity in wild-type cells. Conversely, the lack of PTP1B confers protection against insulin resistance by TNF-alpha in myocyte cell lines and in adult male mice. Wild-type mice treated with TNF-alpha developed a pronounced hyperglycemia along the glucose tolerance test, accompanied by an impaired insulin signaling and increased PTP1B activity in muscle. However, mice lacking PTP1B maintained a rapid clearance of glucose and insulin sensitivity and displayed normal muscle insulin signaling regardless the presence of TNF-alpha. 

Retracted: Yes

PubPeer comments:
  , 
null, 
null, 
null, 
 2020 Statement of Retraction. https: diabetes.diabetesjournals.org content early 2020 09 04 db20-rt10b ,
Noggin regulates foregut progenitor cell programming, and misexpression leads to esophageal atresia
Authors: Evgenya Y Popova
Julia S Shelton
Scott D Boden
Katherine M Riera
Won Jae Huh
Elizabeth Manning
Sreedhara Sangadala
Matthew S Alexander
James R Goldenring
Carolina Pinzon-Guzman
Journal: Journal of Clinical Investigation (2020)
Discipline: CLINICAL MEDICINE
Keywords: Development; Embryonic development; Human stem cells; Surgery.
Affiliations: Department of Surgery, Vanderbilt University Medical Center , Nashville, Tennessee, USA., Department of Orthopedics, Emory School of Medicine, Atlanta, Georgia, USA., Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania, USA., Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., University of Iowa Hospitals and Clinics, Department of Surgery, Iowa City, Iowa, USA., University of Iowa Stead Family Children's Hospital, Iowa City, Iowa, USA.

Abstract:  Esophageal atresia (EA/TEF) is a common congenital abnormality present in 1 of 4000 births. Here we show that atretic esophagi lack Noggin (NOG) expression, resulting in immature esophagus that contains respiratory glands. Moreover, when using mouse esophageal organoid units (EOUs) or tracheal organoid units (TOUs) as a model of foregut development and differentiation in vitro, NOG determines whether foregut progenitors differentiate toward esophageal or tracheal epithelium. These results indicate that NOG is a critical regulator of cell fate decisions between esophageal and pulmonary morphogenesis, and its lack of expression results in EA/TEF. 

Retracted: No

PubPeer comments:
 Supp Fig 4 with image duplication  ,
NLK is a key regulator of proliferation and migration in gallbladder carcinoma cells
Authors: Zhujun Tan
Lin Zhang
Yingbin Liu
Jiasheng Mu
Maolan Li
Qichen Ding
Wenguang Wu
Xiangsong Wu
Journal: Molecular and Cellular Biochemistry (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Gallbladder cancer; metastasis; molecular pathways; nemo-like kinase (NLK); therapeutic target

Abstract:  Gallbladder cancer (GBC) is one of the most lethal neoplasm and is the fifth most common malignancy of gastrointestinal tract. The prognosis of gallbladder cancer is extremely terrible partially due to metastasis. Thus, understanding the molecular pathways controlling metastasis of this lethal disease may provide new targets for targeted therapeutic approach. In this study, we investigated the function of nemo-like kinase (NLK) in GBC growth and migration. Lentivirus-mediated siRNA was employed to alleviate the expression level of NLK in GBC cell lines (GBC-SD and SGC-996). Real-time PCR and western-blot analysis demonstrated that both mRNA and protein levels of NLK in GBC-SD and SGC-996 cells were decreased after infection with NLK-siRNA-expressing lentivirus (Lv-shNLK). The proliferation and in vitro tumorigenesis (colony formation) ability as well as migration of GBC-SD and SGC-996 cells with low NLK expression decreased significantly. Our results suggested that NLK is a key regulator involved in proliferation and migration of GBC, and it could be used as a potential therapeutic target for GBC. 

Retracted: No

PubPeer comments:
 This paper has an Erratum, found here: https: link.springer.com article 10.1007 s11010-012-1385-9 It reads:  The original paper was published without the acknowledgement section. To remedy this omission we publish the acknowledgements as follows: Acknowledgments This study was supported by National Natural Science Foundation of China (Nos. 30872502, 30972918, 81172029), Foundation of Shanghai Outstanding Academic Leaders (No. 11XD1403800), Outstanding Youth Group of Natural Science Foundation of Zhejiang Province (No. R2080452), National High Technology Research and Development Program (863 Program) (No. SS2012AA023706), Doctoral Research Foundation for Chinese University (No. 20110073110086), Post-doctoral Research Foundation of China (No. 2012M511107) and Post-doctoral Research Program of Shanghai (No. 12R21415300). Everything else in the paper remains correct. ,
Activation of M1 Macrophages in Response to Recombinant TB Vaccines With Enhanced Antimycobacterial Activity
Authors: Shiu-Ju Yang
Horng-Yunn Dou
Chih-Hao Hsu
Jia-Ru Chang
Chia-Wei Hsu
Yih-Yuan Chen
Chun-Yu Chang
Journal: Frontiers in Immunology (2020)
Discipline: IMMUNOLOGY
Keywords: Mycobacterium tuberculosis; innate immunity; macrophage; recombinant Bacille Calmette‚ÄìGu√©rin; vaccine.
Affiliations: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan., Department of Biochemical Science and Technology, National Chiayi University, Chia-Yi, Taiwan.

Abstract:  Pulmonary tuberculosis (TB) is a difficult-to-eliminate disease. Although the Bacille Calmette-Gu√©rin (BCG) vaccine against Mycobacterium tuberculosis (MTB) has been available for decades, its efficacy is variable and has lessened over time. Furthermore, the BCG vaccine no longer protects against newly emerged Beijing strains which are responsible for many current infections in adults. Development of a novel vaccine is urgently needed. In this study, we first tested the efficacy of our recombinant BCG vaccines rBCG1 and rBCG2, compared to parental BCG, against MTB strain H37Ra in mice. Both the bacterial load and the level of lymphocyte infiltration decreased dramatically in the three groups treated with vaccine, especially rBCG1 and rBCG2. Furthermore, the Th1 and Th17 responses increased and macrophage numbers rose in the vaccination groups. Th1-mediated production of cytokines TNF-Œ±, IFN-Œ≥, and MCP-1 as well as M1-polarized cells all increased in lung tissue of the rBCG1 and rBCG2 groups. Clodronate-induced depletion of macrophages reduced the level of protection. Based on these results, we conclude that rBCG vaccines induce a significant increase in the number of M1 macrophages, which augments their potential as TB vaccine candidates. 

Retracted: No

PubPeer comments:
 Figure 4G contains a duplicated FACS plot  , 
 We apologize for the error of duplicate figure, the real one will be corrected and send it to the publisher-Frontiers in Immunology. Thank you for your comment. Horng-Yunn Dou Associate Investigator National Institute of Infectious Diseases and Vaccinology National Health Research Institutes 8F,R1-8032, No,35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, R.O.C. ,
The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites
Authors: Alin Vonica
Markus Decker
Edi Brogi
Goutam Chakraborty
Hua Gao
Ronglai Shen
Qianxing Mo
Ai Ping Lee-Lim
Ali H Brivanlou
Filippo G Giancotti
Journal: Cell (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: metastatic dormancy; reactivation; Coco; TGF-Œ≤ ligands; breast cancer cells
Affiliations: Cell Biology Program, Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. 

Abstract:  The mechanistic underpinnings of metastatic dormancy and reactivation are poorly understood. A gain-of-function cDNA screen reveals that Coco, a secreted antagonist of TGF-Œ≤ ligands, induces dormant breast cancer cells to undergo reactivation in the lung. Mechanistic studies indicate that Coco exerts this effect by blocking lung-derived BMP ligands. Whereas Coco enhances the manifestation of traits associated with cancer stem cells, BMP signaling suppresses it. Coco induces a discrete gene expression signature, which is strongly associated with metastatic relapse to the lung, but not to the bone or brain in patients. Experiments in mouse models suggest that these latter organs contain niches devoid of bioactive BMP. These findings reveal that metastasis-initiating cells need to overcome organ-specific antimetastatic signals in order to undergo reactivation. 

Retracted: No

PubPeer comments:
 Figure 1H. Much more similar than expected.  , 
 #1 In addition to the same mouse with different bioluminescent overlap above, Figure 1F and 3H graphs appear to plot the same data. Identified by another reader. ***  , 
 Identified by another reader. ***  , 
 #1 Dear Colleague, Thank you for pointing out this error. It has been corrected 8 years ago. https: www.cell.com cell fulltext S0092-8674(12)01421-3 #2 Dear Colleague, Thank you for pointing this out . The duplication was intentional as we meant to show a single cell dosage in Fig.1 and the full titration experiment in Fig.3. The robustness and statistical significance of the experiment is clear from the size of the cohorts and P values. In addition, this is a negative control meant to show that Coco does not affect primary tumor growth at non-limiting cell dosage. It would have been wasteful of federal funding to repeat the experiment just for inclusion of a second version of it in the paper. This said, we do regret that mention of the duplication was accidentally removed from the legend to Fig. 1 during size reduction and final editing of the paper. #3 Dear Colleague, Thank you for pointing out this error. It has been corrected 8 years ago. https: www.cell.com cell fulltext S0092-8674(12)01421-3 ,
<p>Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2</p>
Authors: Zhiqiang Gao
Jiang Zhang
Yunxia Wu
Journal: Neuropsychiatric Disease and Treatment (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: E2F1; MAPK pathway; SPRY2; ischemic stroke; IS
Affiliations: Department of Neurology, Linyi Central Hospital, Linyi, Shandong 276400, People's Republic of China.

Abstract:  Background: It has been documented that microRNAs (miRs) assume a pivotal role in the development of ischemic stroke (IS). However, it remains poorly identified about the role of miR-122 in IS. Herein, this study was intended to explore the mechanism of E2F1-orchestrated miR-122 in IS. Patients and methods: E2F1, miR-122, and SPRY2 expression in serum from patients with IS and oxygen-glucose deprivation (OGD)-treated N2a cells was detected by RT-qPCR. After gain- and loss-of-function approaches in OGD-induced N2a cells, GAFP staining, flow cytometry, and Western blot analysis were adopted to assess neuronal viability, cell cycle and apoptosis, and expression of apoptosis- and autophagy-related proteins, respectively. Meanwhile, mice with IS were induced, in which E2F1, miR-122, and SPRY2 were overexpressed, followed by evaluation of neurological deficit and cerebral infarction area. The MAPK pathway activity in tissues of mice and cells was determined. Results: miR-122 was down-regulated, and E2F1 and SPRY2 were up-regulated in IS patients and OGD-induced N2a cells. E2F1 inhibited miR-122 transcription, while miR-122 targeted SPRY2. Overexpression (OE) of miR-122 or down-regulation of E2F1 or SPRY2 increased viability, but decreased apoptosis, cell cycle arrest, and autophagy in OGD-induced N2a cells. In IS mice, the neurological deficit score and cerebral infarction area were elevated, which was aggravated by up-regulating E2F1 or SPRY2 but attenuated by overexpressing miR-122. E2F1/miR-122/SPRY2 axis mediated the MAPK pathway in vivo and in vitro. Conclusion: Collectively, E2F1 reduced miR-122 transcription to up-regulate SPRY2, which inactivated MAPK pathway and promoted neurological deficit in IS. 

Retracted: No

PubPeer comments:
 Figs 3C and 5D.  Cell cycle distribution of N2a cells evaluated by flow cytometry ;  Cell cycle distribution of N2a cells evaluated by flow cytometry .  Inquiring minds are wondering how these histograms were plotted. ,
Cell-based RNAi screening and high-content analysis in primary calvarian osteoblasts applied to identification of osteoblast differentiation regulators
Authors: Alexander Rauch
Torsten Kroll
Jeanette Jakob
Mubashir Ahmad
Jan Tuckermann
Aspasia Ploubidou
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: Osteoblasts; bone homeostasis; differentiation; regulators; therapeutic intervention
Affiliations: Institute of Comparative Molecular Endocrinology (CME), Ulm University, Helmholtzstrasse 8/1, 89081, Ulm, Germany., Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, D-07745, Jena, Germany., Institute of Comparative Molecular Endocrinology (CME), Ulm University, Helmholtzstrasse 8/1, 89081, Ulm, Germany. ., Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, D-07745, Jena, Germany. .

Abstract:  Osteoblasts are responsible for the maintenance of bone homeostasis. Deregulation of their differentiation is etiologically linked to several bone disorders, making this process an important target for therapeutic intervention. Systemic identification of osteoblast regulators has been hampered by the unavailability of physiologically relevant in vitro systems suitable for efficient RNAi and for differentiation read-outs compatible with fluorescent microscopy-based high-content analysis (HCA). Here, we report a new method for identification of osteoblast differentiation regulators by combining siRNA transfection in physiologically relevant cells with high-throughput screening (HTS). Primary mouse calvarial osteoblasts were seeded in 384-well format and reverse transfected with siRNAs and their cell number and differentiation was assayed by HCA. Automated image acquisition allowed high-throughput analyses and classification of single cell features. The physiological relevance, reproducibility, and sensitivity of the method were validated using known regulators of osteoblast differentiation. The application of HCA to siRNAs against expression of 320 genes led to the identification of five potential suppressors and 60 activators of early osteoblast differentiation. The described method and the associated analysis pipeline are not restricted to RNAi-based screening, but can be adapted to large-scale drug HTS or to small-scale targeted experiments, to identify new critical factors important for early osteoblastogenesis. 

Retracted: No

PubPeer comments:
 There seems to be an error in figure 3. There is one control (right graph) that had drop in SMI of over 6 kg m2. This is impossible. One average subjects have a SMI of 6 u00b1 1 kg m2 - this partical control would thus have no more skeletal muscle left at all. Could the authors comments on this?  , 
 Thank you for pointing out the error. I rechecked original data and noticed the mistake. Although I assessed relationship between change of SMI and length of hospital-stay using true data, the correlation was not detected in control group. (r=0.32, P=0.31)  , 
 I noticed that the graph has also been corrected on the journal website ud83dudc4dud83cudffc , 
 Thank you for reading the article again. ,
HNF6 promotes tumor growth in colorectal cancer and enhances liver metastasis in mouse model
Authors: Yue Liu
Kefeng Ding
Xiangfeng Shen
Haiyan Chen
Dongliang Fu
Lifeng Sun
Haitao Geng
Yurong Jiao
Kai Jiang
Liubo Chen
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HNF6; anoikis; colorectal cancer; liver metastasis; tumor growth.
Affiliations: Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Department of Oncology, Binzhou Medical University Hospital, Binzhou, China., Department of Mastopathy, Zhejiang Provincial Hospital of TCM, Hangzhou, China.

Abstract:  Hepatocyte nuclear factor 6 (HNF6), as a transcription factor, has been reported to be involved in cell proliferation, carcinogenesis, and tumor metastasis. Here, we demonstrated the role of HNF6 in tumor growth and liver metastasis in colorectal cancer (CRC). Through bioinformatics and clinical samples analysis, we found HNF6 messenger RNA was upregulated both in CRC primary sites and liver metastases, and its high expression indicated poor survival in CRC patients. In vitro studies confirmed that HNF6 promoted cell proliferation and colony formation. What is more, in mouse models, the xenografts grew significantly faster and liver metastasis rate was nearly 45% higher in mice injected with HNF6-overexpressing cells. Further mechanism exploration showed that HNF6 expression affected cell adhesion and conferred resistance to anoikis in CRC cells. Taken together, HNF6 expression was upregulated in CRC and closely correlated with poor survival. HNF6 promoted CRC cell proliferation and tumor growth, and may contribute to liver metastasis via conferring cell resistance to anoikis. 

Retracted: No

PubPeer comments:
  It is hard to confirm that HNF6 was expressed significantly higher in tumor samples than in normal colonic mucosa according to this data. The median value of HNF6 in cancer is lower than normal, and its larger variable coefficient confused its result. ,
Cross Talk between Receptor Guanylyl Cyclase C and c-src Tyrosine Kinase Regulates Colon Cancer Cell Cytostasis
Authors: Rashna Bhandari
Vivek T Natarajan
Nirmalya Basu
Sandhya S Visweswariah
Journal: Molecular and Cellular Biology (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: c-src; Guanylyl cyclase C (GC-C); colorectal cancer; downstream effectors; therapy
Affiliations: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.

Abstract:  Increased activation of c-src seen in colorectal cancer is an indicator of a poor clinical prognosis, suggesting that identification of downstream effectors of c-src may lead to new avenues of therapy. Guanylyl cyclase C (GC-C) is a receptor for the gastrointestinal hormones guanylin and uroguanylin and the bacterial heat-stable enterotoxin. Though activation of GC-C by its ligands elevates intracellular cyclic GMP (cGMP) levels and inhibits cell proliferation, its persistent expression in colorectal carcinomas and occult metastases makes it a marker for malignancy. We show here that GC-C is a substrate for inhibitory phosphorylation by c-src, resulting in reduced ligand-mediated cGMP production. Consequently, active c-src in colonic cells can overcome GC-C-mediated control of the cell cycle. Furthermore, docking of the c-src SH2 domain to phosphorylated GC-C results in colocalization and further activation of c-src. We therefore propose a novel feed-forward mechanism of activation of c-src that is induced by cross talk between a receptor GC and a tyrosine kinase. Our findings have important implications in understanding the molecular mechanisms involved in the progression and treatment of colorectal cancer. 

Retracted: No

PubPeer comments:
  ,
Key residues in Mycobacterium tuberculosis protein kinase G play a role in regulating kinase activity and survival in the host
Authors: Balaji Prakash
Divya Tiwari
Rajnish Kumar Singh
Vinay Kumar Nandicoori
Sunil Kumar Verma
Kasturi Goswami
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Protein kinase G; Mycobacterium tuberculosis; phagosome-lysosome fusion; Trx domain; kinase domain
Affiliations: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Abstract:  Protein kinase G (PknG) in Mycobacterium tuberculosis has been shown to modulate phagosome-lysosome fusion. The protein has three distinct domains, an N-terminal Trx domain, a kinase domain, and a C-terminal TPR domain. The present study extensively analyzes the roles of these domains in regulating PknG kinase activity and function. We find that the kinase domain of PknG by itself is inactive, signifying the importance of the flanking domains. Although the deletion of the Trx domain severely impacts the activity of the protein, the C-terminal region also contributes significantly in regulating the activity of the kinase. Apart from this, PknG kinase activity is dependent on the presence of threonine 309 in the p + 1 loop of the activation segment. Mutating the conserved cysteine residues in the Trx motifs makes PknG refractory to changes in the redox environment. In vitro experiments identify threonine 63 as the major phosphorylation site of the protein. Importantly, we find that this is the only site in the protein that is phosphorylated in vivo. Macrophage infection studies reveal that the first 73 residues, the Trx motifs, and the threonine 63 residue are independently essential for modulating PknG-mediated survival of mycobacteria in its host. We have extended these studies to investigate the role of PknG and PknG mutants in the pathogenesis of mycobacteria in mice. Our results reinforce the findings from the macrophage infection experiments, and for the first time demonstrate that the expression of PknG in non-pathogenic mycobacteria allows the continued existence of these bacteria in host tissues. 

Retracted: No

PubPeer comments:
  , 
 Thank you for your observation. We are working on doing the needful. , 
 We have contacted the journal. Appropriate corrections have been made. Correction notice would be coming out very soon. , 
 Correction notice https: www.ncbi.nlm.nih.gov pubmed 32060126 , 
 #4 Thank you for the follow-up. ,
Dengue virus serotype infection specifies the activation of the unfolded protein response
Authors: Olivier Pluquet
Qing Yin Wang
Indira Umareddy
Subhash G Vasudevan
Feng Gu
Eric Chevet
Journal: Virology Journal (2007)
Discipline: MICROBIOLOGY
Keywords: Dengue; Dengue hemorrhagic fever; pathogenesis; Unfolded Protein Response (UPR); virus-induced apoptosis
Affiliations: Novartis Institute for Tropical Diseases, 10-Biopolis Road, #05-01 Chromos, 138670, Singapore. 

Abstract:  Background: Dengue and Dengue hemorrhagic fever have emerged as some of the most important mosquito-borne viral diseases in the tropics. The mechanisms of pathogenesis of Dengue remain elusive. Recently, virus-induced apoptosis mediated by the Unfolded Protein Response (UPR) has been hypothesised to represent a crucial pathogenic event in viral infection. In an attempt to evaluate the contribution of the UPR to virus replication, we have characterized each component of this signalling pathway following Dengue virus infection. Results: We find that upon Dengue virus infection, A549 cells elicit an UPR which is observed at the level of translation attenuation (as visualized by the phosphorylation of eIF2alpha) and activation of specific pathways such as nuclear translocation of ATF-6 and splicing of XBP-1. Interestingly, we find that specific serotype of virus modulate the UPR with different selectivity. In addition, we demonstrate that perturbation of the UPR by preventing the dephosphorylation of the translation initiation factor eIF2alpha using Salubrinal considerably alters virus infectivity. Conclusion: This report provides evidence that Dengue infection induces and regulates the three branches of the UPR signaling cascades. This is a basis for our understanding of the viral regulation and conditions beneficial to the viral infection. Furthermore, modulators of UPR such as Salubrinal that inhibit Dengue replication may open up an avenue toward cell-protective agents that target the endoplasmic reticulum for anti-viral therapy. 

Retracted: No

PubPeer comments:
 Figure 5. https: imgur.com rbUdsXB ,