PReD-Bench/PRed-Bench huggingface dataset:
Luteolin supports osteogenic differentiation of human periodontal ligament cells
Authors: Chuanjun Wu
Xiaopeng Dai
Dan Wang
Meiyan Liu
He Quan
Journal: BMC oral health (2019)
Discipline: CLINICAL MEDICINE
Keywords: Cell differentiation; Luteolin; Osteogenesis; Periodontal ligament; Wnt signaling pathway.
Affiliations: Economic & Technological Development Area Clinic, Yantai Stomatological Hospital, No. 11 Songshan Road, Yantai, 264000, Shandong Province, China., Economic & Technological Development Area Clinic, Yantai Stomatological Hospital, No. 11 Songshan Road, Yantai, 264000, Shandong Province, China. .

Abstract:  Background: Previous research revealed that luteolin could improve the activation of alkaline phosphatase (ALP) and osteocalcin in mouse osteoblasts. We aimed to determine the effect of luteolin on osteogenic differentiation of periodontal ligament cells (PDLCs). Methods: Cultured human PDLCs (HPDLCs) were treated by luteolin at 0.01, 0.1, 1, 10, 100 μmol/L, Wnt/β-catenin pathway inhibitor (XAV939, 5 μmol/L) alone or in combination with 1 μmol/L luteolin. Immunohistochemical staining was performed to ensure cells source. Cell activity and the ability of osteogenic differentiation in HPDLCs were determined by MTT, ALP and Alizarin Red S staining. Real-time Quantitative PCR Detecting System (qPCR) and Western blot were performed to measure the expressions of osteogenic differentiation-related genes such as bone morphogenetic protein 2 (BMP2), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), Osterix (OSX) and Wnt/β-catenin pathway proteins members cyclin D1 and β-catenin. Results: Luteolin at concentrations of 0.01, 0.1, 1, 10, 100 μmol/L promoted cell viability, ALP activity and increased calcified nodules content in HPDLCs. The expressions of BMP2, OCN, OSX, RUNX2, β-catenin and cyclin D1 were increased by luteolin at concentrations of 0.01, 0.1, 1 μmol/L, noticeably, 1 μmol/L luteolin produced the strongest effects. In addition, XAV939 inhibited the expressions of calcification and osteogenic differentiation-related genes in HPDLCs, and 1 μmol/L luteolin availably decreased the inhibitory effect. Conclusion: 1 μmol/L luteolin accelerated osteogenic differentiation of HPDLCs via activating the Wnt/β-catenin pathway, which could be clinically applied to treat periodontal disease. 

Retracted: No

PubPeer comments:
 Image duplication indicated. ![file] ,
Sex differences in fear memory consolidation via Tac2 signaling in mice
Authors: L Perez-Caballero
A Gomez-Gomez
R Nadal
E R Velasco
O J Pozo
C M Soto-Faguás
A Florido
C A Saura
P Molina
R Andero
Journal: Nature Communications (2021)
Discipline: Multidisciplinary
Keywords: Memory formation; neural processes; fear-related disorders; posttraumatic stress disorder; phobias
Affiliations: Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain., Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain., Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain. .

Abstract:  Memory formation is key for brain functioning. Uncovering the memory mechanisms is helping us to better understand neural processes in health and disease. Moreover, more specific treatments for fear-related disorders such as posttraumatic stress disorder and phobias may help to decrease their negative impact on mental health. In this line, the Tachykinin 2 (Tac2) pathway in the central amygdala (CeA) has been shown to be sufficient and necessary for the modulation of fear memory consolidation. CeA-Tac2 antagonism and its pharmacogenetic temporal inhibition impair fear memory in male mice. Surprisingly, we demonstrate here the opposite effect of Tac2 blockade on enhancing fear memory consolidation in females. Furthermore, we show that CeA-testosterone in males, CeA-estradiol in females and Akt/GSK3β/β-Catenin signaling both mediate the opposite-sex differential Tac2 pathway regulation of fear memory. 

Retracted: No

PubPeer comments:
 https: thenewstatistics.com itns 2022 01 10 the-joke-of-self-correcting-science-the-andero-lab-and-nature-communications ,
Cellulose nanocrystals/ZnO as a bifunctional reinforcing nanocomposite for poly(vinyl alcohol)/chitosan blend films: fabrication, characterization and properties
Authors: Mansor B Ahmad
Farideh Namvar
Mohd Zobir Hussein
Nor Azowa Ibrahim
Susan Azizi
Journal: International Journal of Molecular Sciences (2014)
Discipline: CHEMISTRY
Keywords: cellulose nanocrystals; zinc oxide; nanocomposites; poly(vinyl alcohol); chitosan
Affiliations: Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. ., Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. ., Institute of Tropical Forestry and Forest Products, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. .

Abstract:  In this study, cellulose nanocrystals/zinc oxide (CNCs/ZnO) nanocomposites were dispersed as bifunctional nano-sized fillers into poly(vinyl alcohol) (PVA) and chitosan (Cs) blend by a solvent casting method to prepare PVA/Cs/CNCs/ZnO bio-nanocomposites films. The morphology, thermal, mechanical and UV-vis absorption properties, as well antimicrobial effects of the bio-nanocomposite films were investigated. It demonstrated that CNCs/ZnO were compatible with PVA/Cs and dispersed homogeneously in the polymer blend matrix. CNCs/ZnO improved tensile strength and modulus of PVA/Cs significantly. Tensile strength and modulus of bio-nanocomposite films increased from 55.0 to 153.2 MPa and from 395 to 932 MPa, respectively with increasing nano-sized filler amount from 0 to 5.0 wt %. The thermal stability of PVA/Cs was also enhanced at 1.0 wt % CNCs/ZnO loading. UV light can be efficiently absorbed by incorporating ZnO nanoparticles into a PVA/Cs matrix, signifying that these bio-nanocomposite films show good UV-shielding effects. Moreover, the biocomposites films showed antibacterial activity toward the bacterial species Salmonella choleraesuis and Staphylococcus aureus. The improved physical properties obtained by incorporating CNCs/ZnO can be useful in variety uses. 

Retracted: No

PubPeer comments:
 Some images in Figure 3 unexpectedly appear to have repetitive regions, some after rotation. *** ![file] , 
 Fig 3b has some explaining to do. ![file] , 
 What is with the rectangular patch in Fig 7B? (emphasised at right with higher contrast). ![file] , 
 Figure 3E, an additional occurrence of the region marked above: ![file] , 
 Thank you for your comments. The reply to comments have been given in the attached images which are the original images. The important note is that these changes did not any effects on our results; just they have been done to show a better of view. ![file] ![file] ![file] In the antibacterial image the rectangular patch was related to other sample which not related to this research and was removed. ,
NKX2-1 activation by SMAD2 signaling after definitive endoderm differentiation in human embryonic stem cell
Authors: Catherine M Verfaillie
Kristel Eggermont
Veerle Vanslembrouck
Yong Li
Journal: Stem cells and development (2013)
Discipline: CLINICAL MEDICINE
Keywords: NKX2-1; Activin-A; definitive endoderm; respiratory endoderm; human embryonic stem cell (hESC)
Affiliations: Interdepartmentaal Stamcelinstituut, Katholieke Universiteit Leuven, Leuven, Belgium.

Abstract:  Expression of NKX2-1 is required to specify definitive endoderm to respiratory endoderm. However, the transcriptional regulation of NKX2-1 is not fully understood. Here we demonstrate that aside from specifying undifferentiated human embryonic stem cell (hESC) to definitive endoderm, high concentrations of Activin-A are also necessary and sufficient to induce hESC-derived definitive endodermal progeny to a FOXA2/NKX2-1/GATA6/PAX9 positive respiratory epithelial fate. Activin-A directly mediates the induction of NKX2-1 by interacting with ALK4, leading to phosphorylation of SMAD2, which binds directly to the NKX2-1 promoter and activates its expression. Activin-A can be replaced by GDF11 but not transforming growth factor β1. Addition of Wnt3a, SHH, FGF2, or BMP4 failed to induce NKX2-1. These results suggest that direct binding of Activin-A-responsive SMAD2 to the NKX2-1 promoter plays essential role during respiratory endoderm specification. 

Retracted: No

PubPeer comments:
 ![file] ![file] ![file] , 
 ![file] ,
Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus
Authors: Tomas Racek
Julie K Stock
Jesus Gil
Gordon Peters
Goedele N Maertens
James Nicholls
Marc Rodriguez-Niedenführ
Selma El Messaoudi-Aubert
Journal: PloS one (2009)
Discipline: Multidisciplinary
Keywords: Polycomb repressive complex 1 (PRC1); cellular senescence; INK4a tumor suppressor gene; CBX7; CBX8
Affiliations: Cancer Research UK, London Research Institute, London, United Kingdom.

Abstract:  Misexpression of Polycomb repressive complex 1 (PRC1) components in human cells profoundly influences the onset of cellular senescence by modulating transcription of the INK4a tumor suppressor gene. Using tandem affinity purification, we find that CBX7 and CBX8, two Polycomb (Pc) homologs that repress INK4a, both participate in PRC1-like complexes with at least two Posterior sex combs (Psc) proteins, MEL18 and BMI1. Each complex contains a single representative of the Pc and Psc families. In primary human fibroblasts, CBX7, CBX8, MEL18 and BMI1 are present at the INK4a locus and shRNA-mediated knockdown of any one of these components results in de-repression of INK4a and proliferative arrest. Sequential chromatin immunoprecipitation (ChIP) reveals that CBX7 and CBX8 bind simultaneously to the same region of chromatin and knockdown of one of the Pc or Psc proteins results in release of the other, suggesting that the binding of PRC1 complexes is interdependent. Our findings provide the first evidence that a single gene can be regulated by several distinct PRC1 complexes and raise important questions about their configuration and relative functions. 

Retracted: No

PubPeer comments:
 Figure 3B. ATM and GAPDH panels likely out of register by one lane. https: imgur.com 7pdD1rF , 
 Figure 3B Oncogene. 2002 Sep 12;21(41):6377-81r much more similar to figure 4B Cancer Res. 2002 Mar 15;62(6):1598-603. than expected. ![image] ,
Effect of local zoledronate on implant osseointegration in a rat model
Authors: Gerhard Schmidmaier
Lisa Rommel
Stefan H Greiner
Norbert P Haas
David A Back
Britt Wildemann
Stephan Pauly
Journal: BMC Musculoskeletal Disorders (2012)
Discipline: CLINICAL MEDICINE
Keywords: implant coating; poly(D, L-lactide); PDLLA; zoledronic acid; ZOL
Affiliations: Department of Orthopedics and Traumatology, German Armed Forces Hospital Berlin, Berlin, Germany.

Abstract:  Background: An implant coating with poly(D, L-lactide) (PDLLA) releasing incorporated zoledronic acid (ZOL) has already proven to positively effect osteoblasts, to inhibit osteoclasts and to accelerate fracture healing. Aim of this study was to investigate the release kinetics of the chosen coating and the effect of different concentrations of ZOL locally released from this coating on the osseointegration of implants. Methods: For release kinetics the release of C14-labled ZOL out of the coating was monitored over a period of six weeks in vitro. For testing the osseointegration, titanium Kirschner wires were implanted into the medullary canal of right femurs of 100 Sprague Dawley rats. The animals were divided into five groups receiving implants either uncoated or coated with PDLLA, PDLLA/ZOL low (1.2% w/w) or PDLLA/ZOL high (2% w/w). Additionally, a group with uncoated implants received ZOL intravenously (i.v.). After 56 days animals were sacrificed, femurs dissected and either strength of fixation or histological bone/implant contacts and newly formed bone around the implants were determined. Results: Release kinetics revealed an initial peak in the release of C14-ZOL with a slight further progression over the following weeks. There was no significant enhancement of osseointegration for both groups who received ZOL-coated implants or ZOL i.v. compared to the controls in biomechanical or histological analyses, except for a significant raise in strength of fixation of ZOL i.v. versus PDLLA. Conclusions: Even though the investigated local ZOL application did not enhance the osseointegration of the implant, the findings might support its application in fracture treatment, since fracture stabilization devices are often explanted after consolidation. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Chloroquine is a zinc ionophore
Authors: Jinchang Wu
Wei-Qun Ding
Bing Peng
Bethany N Hannafon
Amanda Moyer
Jing Xue
Journal: PloS one (2014)
Discipline: Multidisciplinary
Keywords: Chloroquine; Anticancer activity; Zinc ions; Zinc uptake; A2780 cells
Affiliations: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China., Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America., Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Department of Pharmacology, School of Pharmacy, Xuzhou Medical College, Xuzhou, China., Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China.

Abstract:  Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780). Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity. 

Retracted: No

PubPeer comments:
 Some people have referred to this article, arguing that zinc is important in combination with Chloroquine for treatment of covid-19. First of all, this article is studying the anti-cancer effect of chloroquine. The article is studying zinc uptake and cytotoxicity in an artificial ovarian carcinoma cell line A2780, which is not clinical relevant. The statistical significance of the increased cytotoxicity with chloroquine+zinc vs chloroquine is not clearly presented (Figure 5A). In Figure 4A some of the merged micrographs do not correspond with the single staining micrographs. Conclusion: the effect of zinc in combination with chloroquine on cell viablity is questionable, especially in vivo. More importantly: if zinc really increased the cytotoxicity, so what? It is not the cells we want to kill, but the virus. Increased cytotoxicity in the valuable lung epithelial cells would only increase the covid-19 death rate. ![file] ,
Preparation of monoclonal antibodies cross-reactive with orthopoxviruses and their application for direct immunofluorescence test
Authors: Hiroyuki Miyamoto
Noritoshi Kitamoto
Shiro Kato
Kazuyoshi Ikuta
Yoji Kato
Tomoyuki Tanaka
Takayuki Kobayashi
Nobutaka Wakamiya
Shigeharu Ueda
Journal: Microbiology and Immunology (2005)
Discipline: MICROBIOLOGY
Keywords: Variola virus; vaccinia virus; cowpox virus; ectromelia virus; monoclonal antibodies
Affiliations: School of Human Science and Environment; University of Hyogo; Himeji Hyogo 670-0092 Japan, Asahikawa Medical College; Asahikawa Hokkaido 078-8510 Japan, Research Institute for Microbial Diseases; Osaka University; Suita Osaka 565-0871 Japan, Sakai City Institute of Public Health; Sakai Osaka 590-0953 Japan, Osaka Prefecture Saiseikai-Sennan Medical Welfare Center; Sennan Osaka 590-0535 Japan

Abstract:  Variola virus (smallpox virus), vaccinia virus (VV), cowpox virus (CPV) and ectromelia virus (EV) belong to the genus Orthopoxvirus of the family Poxviridae. To establish the possible diagnosis for smallpox infection, monoclonal antibodies (MAbs) against VV and CPV were produced. The cross-reactivity of seven MAbs with cells infected with various strains of the orthopoxviruses (CPV, VV and EV) was confirmed by an immunofluorescence (IF) test and other immunological analyses. Four and three MAbs reacted with the common antigen of all poxviruses (probably NP antigen) and the antigen involved in neutralization, respectively. We developed the IF test using these MAbs. The direct IF test required only 45 min to perform. Smallpox infection is now eradicated, but it is important to prepare for the diagnosis of smallpox in an emergency. The direct IF assay using MAbs cross-reactive with orthopoxviruses is rapid, simple, specific, applicable for multiple samples, and will make it possible to screen for and detect orthopoxviruses that include variola virus with tissue impression smears from skin lesions in most laboratories or institutes. 

Retracted: No

PubPeer comments:
 I wanted to make the authors aware of the findings on this website https: covid19.scienceofscience.org doi 10.1101 2020.03.16.993386 ![file] Disclaimer: THE SITE DO NOT SHOW OR IMPLY ANY TYPE OF RESEARCH MISCONDUCT, INCLUDING PLAGIARISM, FABRICATION, OR FALSIFICATION, EITHER DIRECTLY OR INDIRECTLY. THE SITE DOES NOT WARRANT THAT ANY RESULTS OR ANALYSES ARE COMPLETE OR ACCURATE. The site and all information available through the site are provided  as is , with all faults, and  as available . ,
Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure
Authors: Leen H Kawas
Phillip M Uribe
Allison B Coffin
Joseph W Harding
Journal: Frontiers in Cellular Neuroscience (2015)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: aminoglycosides; hair cell protection; hearing loss; hepatocyte growth factor; lateral line
Affiliations: Department of Integrative Physiology and Neuroscience, Washington State University Pullman, WA, USA., Department of Integrative Physiology and Neuroscience, Washington State University Pullman, WA, USA ; M3 Biotechnology, Inc. Seattle, WA, USA., Department of Integrative Physiology and Neuroscience, Washington State University Pullman, WA, USA ; College of Arts and Sciences, Washington State University Vancouver, WA, USA.

Abstract:  Loss of sensory hair cells from exposure to certain licit drugs (e.g., aminoglycoside antibiotics, platinum-based chemotherapy agents) can result in permanent hearing loss. Here we ask if allosteric activation of the hepatocyte growth factor (HGF) cascade via Dihexa, a small molecule drug candidate, can protect hair cells from aminoglycoside toxicity. Unlike native HGF, Dihexa is chemically stable and blood-brain barrier permeable. As a synthetic HGF mimetic, it forms a functional ligand by dimerizing with endogenous HGF to activate the HGF receptor and downstream signaling cascades. To evaluate Dihexa as a potential hair cell protectant, we used the larval zebrafish lateral line, which possesses hair cells that are homologous to mammalian inner ear hair cells and show similar responses to toxins. A dose-response relationship for Dihexa protection was established using two ototoxins, neomycin and gentamicin. We found that a Dihexa concentration of 1 μM confers optimal protection from acute treatment with either ototoxin. Pretreatment with Dihexa does not affect the amount of fluorescently tagged gentamicin that enters hair cells, indicating that Dihexa's protection is likely mediated by intracellular events and not by inhibiting aminoglycoside entry. Dihexa-mediated protection is attenuated by co-treatment with the HGF antagonist 6-AH, further evidence that HGF activation is a component of the observed protection. Additionally, Dihexa's robust protection is partially attenuated by co-treatment with inhibitors of the downstream HGF targets Akt, TOR and MEK. Addition of an amino group to the N-terminal of Dihexa also attenuates the protective response, suggesting that even small substitutions greatly alter the specificity of Dihexa for its target. Our data suggest that Dihexa confers protection of hair cells through an HGF-mediated mechanism and that Dihexa holds clinical potential for mitigating chemical ototoxicity. 

Retracted: No

PubPeer comments:
 Fig 2C.  Effect of ADAMTS9u2010AS2 on cell cycle arrest in A549 and SPCu2010A1 cells was detected by flow cytometry. ![file] NC and ADAMTS9-AS2 histograms are surprisingly similar after vertically compressing the former by 50%. ,
Guggulsterone inhibits human cholangiocarcinoma Sk-ChA-1 and Mz-ChA-1 cell growth by inducing caspase-dependent apoptosis and downregulation of survivin and Bcl-2 expression
Authors: Liu-Liu Chen
Fei Zhong
Lu-Lu Fan
Jun Li
Jing Yang
Fang Wang
Xia-Li Zha
Zhu-Ting Tong
Journal: Oncology Letters (2015)
Discipline: CLINICAL MEDICINE
Keywords: B-cell lymphoma 2; Survivin; apoptosis; caspase; cholangiocarcinoma
Affiliations: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China., Department of Neurology, Anhui Provincial Hospital, Hefei, Anhui 230001, P.R. China., Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

Abstract:  Guggulsterone has recently been reported to demonstrate anti-tumor effects in a variety of cancers. The present study aims to investigate the biological roles and underlying mechanism of the action of guggulsterone in cholangiocarcinoma. The immortalized human cholangiocarcinoma Sk-ChA-1 and Mz-ChA-1 cell lines were treated with various concentrations of the trans isomer of guggulsterone, Z-guggulsterone. Cellular proliferation was determined using the XTT assay. The apoptotic status of cholangiocarcinoma cells was assessed by Hoechst 33258 staining, DNA fragmentation assay and ﬂow cytometry. Specific caspase inhibitor was used to explore the role of caspase in guggulsterone-induced apoptosis. A colorimetric assay was performed to measure the alterations of the activities of caspase-3, -8 and -9. Western blot analysis was used to detect the protein expression of survivin, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein and cleaved poly (adenosine diphosphate-ribose) polymerase (PARP). As revealed by the present data, guggulsterone significantly inhibited the growth of the two human cholangiocarcinoma cell lines by inducing cellular apoptosis. In addition, guggulsterone-induced apoptosis of cholangiocarcinoma cells was demonstrated to be partially inhibited by the caspase inhibitors z-VAD-fmk, z-LEHD-fmk and z-IETD-fmk, accompanied by the activation of caspases-3, -8 and -9, accumulation of cleaved PARP and decreased expression of survivin and Bcl-2. In conclusion, the present study demonstrated that guggulsterone was able to suppress the proliferation of cholangiocarcinoma by inducing caspase-dependent apoptosis and downregulating survivin and Bcl-2. 

Retracted: No

PubPeer comments:
 The html version of this preprint indicates 4 authors (SAMIT GHOSAL, Binayak Sinha, Sumit Sengupta, Milan Majumder) [1]. The PDF version of this preprint indicates 3 authors (Binayak Sinha, Sumit Sengupta, Samit Ghosal) [2]. Could the authors kindly clarify what is the veritable author list and correct order of authors. [1] https: www.medrxiv.org content 10.1101 2020.04.01.20047373v1 [2] https: www.medrxiv.org content 10.1101 2020.04.01.20047373v1.full.pdf ,
MED13L integrates Mediator-regulated epigenetic control into lung cancer radiosensitivity
Authors: Ming Yang
Jinming Yu
Liqing Zhou
Yue Shen
Yeyang Xu
Nasha Zhang
Yemei Song
Jiandong Liu
Journal: Theranostics (2020)
Discipline: CLINICAL MEDICINE
Keywords: H3K27ac; MED13L; Mediator; PRKCA; lung cancer radiotherapy
Affiliations: Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250117, China., Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250117, China., Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, 223002, China.

Abstract:  To date, efforts to improve non-small-cell lung cancer (NSCLC) outcomes with increased radiation dose have not been successful. Identification of novel druggable targets that are capable to modulate NSCLC radiosensitivity may provide a way forward. Mediator complex is implicated in gene expression control, but it remains unclear how Mediator dysfunction is involved in cancer radiotherapy. Methods: The biologic functions of miR-4497, MED13L and PRKCA in NSCLC radiosensitivity were examined through biochemical assays including gene expression profilling, cell proliferation assay, colony formation assay, wound healing assay, transwell assay, dual luciferase reporter assay, xenograft models, immunoprecipitation, and chromatin immunoprecipitation sequencing. Clinical implications of miR-4497, MED13L and PRKCA in radiosensitivity were evaluated in NSCLC patients treated with concurrent chemoradiotherapy or radiotherapy alone. Results: We found that radiation can trigger disassemble of Mediator complex via silencing of MED13L by miR-4497 in NSCLC. Although not interrupting structure integrity of the core Mediator or the CDK8 kinase module, suppression of MED13L attenuated their physical interactions and reduced recruitment of acetyltransferase P300 to chromatin via Mediator. Silencing of MED13L therefore diminishes global H3K27ac signals written by P300, activities of enhancer and/or promoters and expression of multiple oncogenes, especially PRKCA. Inhibition of PRKCA expression potentiates the killing effect of radiotherapy in vitro and in vivo. Remarkably, high PRKCA expression in NSCLC tissues is correlated with poor prognosis of patients received radiotherapy. Conclusions: Our study linking PRKCA to radiosensitivity through a novel mechanism may enable the rational targeting of PRKCA to unlock therapeutic potentials of NSCLC. 

Retracted: No

PubPeer comments:
 In Fig3 F and Fig6 C of mice xenograft tumors, the largest diameters of some seem larger than 20mm. ![file] Is it complied with animal ethics ? ,
Wnt/β-catenin signaling cascade down-regulation following massive small bowel resection in a rat
Authors: Arnold G Coran
Ibrahim Matter
Alex Roitburt
Jorge G Mogilner
Igor Sukhotnik
Jacob Bejar
Yulia Pollak
Tatiana Dorfman
Journal: Pediatric Surgery International (2014)
Discipline: CLINICAL MEDICINE
Keywords: Wnt/β-catenin signaling; intestinal adaptation; cell proliferation; cell differentiation; gastrointestinal epithelium
Affiliations: Laboratory of Intestinal Adaptation and Recovery, Department of Pediatric Surgery and Pathology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel, .

Abstract:  Background: Growing evidence suggests that the Wnt/β-catenin signaling cascade is implicated in the control of stem cell activity, cell proliferation, lineage commitment, and cell survival during normal development and tissue regeneration of the gastrointestinal epithelium. The roles of this signaling cascade in stimulation of cell proliferation after massive small bowel resection are unknown. The purpose of this study was to evaluate the role of Wnt/β-catenin signaling during late stages of intestinal adaptation in a rat model of short bowel syndrome (SBS). Methods: Male rats were divided into two groups: sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined 2 weeks after operation. Illumina's digital gene expression analysis was used to determine Wnt/β-catenin signaling gene expression profiling. Twelve Wnt/β-catenin-related genes and β-catenin protein expression were determined using real-time PCR, western blotting and immunohistochemistry. Results: From the total number of 20,000 probes, 20 genes related to Wnt/β-catenin signaling were investigated. From these genes, seven genes were found to be up-regulated and eight genes to be down-regulated in SBS vs. sham animals with a relative change in gene expression level of 20 % or more. From 12 genes determined by real-time PCR, nine genes were down-regulated in SBS rats compared to control animals including target gene c-Myc. SBS rats also showed a significant decrease in β-catenin protein compared to control animals. Conclusion: Two weeks following massive bowel resection in rats, Wnt/β-catenin signaling pathway is inhibited. In addition, it appears that cell differentiation rather than proliferation is most important in the late stages of intestinal adaptation. 

Retracted: No

PubPeer comments:
 Figure 2. * Blue and green boxes: the panels here (representing rats tissues) look very similar to panels in another paper by the same first author, where they represent mouse tissues. That paper is: Sukhotnik et al., Journal of Pediatric Surgery (2011), DOI: 10.1016 j.jpedsurg.2011.04.007, https: pubpeer.com publications 79750310865EAC0B75CE09E0EC1AF7 ![file] ,
Biocompatible conducting chitosan/polypyrrole–alginate composite scaffold for bone tissue engineering
Authors: K P Chennazhi
K M Sajesh
R Jayakumar
Shantikumar V Nair
Journal: International Journal of Biological Macromolecules (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bone tissue engineering; Conducting scaffold; Polypyrrole–alginate–chitosan.
Affiliations: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682 041, India.

Abstract:  A polypyrrole based conducting scaffold was developed by incorporating polypyrrole-alginate (PPy-Alg) blend with chitosan using lyophilization technique and employed this composite as a substrate for bone tissue engineering. PPy-Alg blend was developed by oxidative chemical synthesis of polypyrrole using FeCl3 as oxidizing agent and characterized. The physiochemical characterization of the scaffold was done using SEM, FT-IR along with porosity measurement, swelling and in vitro degradation studies. Surface conductivity of the scaffolds was analyzed using Scanning Electrochemical microscopy (SECM). Results from cell viability and cell proliferation with MG-63 cells using Alamar blue assay confirmed the cytocompatible nature of the developed scaffold. In vitro biomineralization ability of the scaffold was assessed and thus the effectiveness of PPy-Alg/chitosan scaffold in the field of tissue engineering was evaluated. 

Retracted: No

PubPeer comments:
 Figure 2A: Expression of broccoli cysteine protease (BoCP5), RNA was extracted from floret tissues of branchlets that had been held dry or in water or in sucrose, RNA loadings were visualized by hybridisation with pTIP6 (asparagus 25 26S rRNA). Much more similar than expected (red boxes). Could the authors please check? ![file] ,
Circular RNA_LARP4 inhibits cell migration and invasion of prostate cancer by targeting FOXO3A
Authors: X-D Weng
C-L Liu
T Yan
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Circular RNA_LARP4; prostate cancer; tumor suppressor; PCa development; RT-qPCR
Affiliations: Department of Urology Surgery, Yinzhou People's Hospital, Yinzhou, China. .

Abstract:  Objective: The importance of circular RNAs in malignant tumors causes more attention in researchers. Circular RNA_LARP4 is identified as a tumor suppressor in gastric cancer, but the role of circular RNA_LARP4 in prostate cancer (PCa) remains unclear. Our work aims to uncover whether and how circular RNA_LARP4 functions in the PCa development. Patients and methods: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to determine the level of circular RNA_LARP4 in PCa tissues and cell lines. The patients' prognosis was analyzed. Circular RNA_LARP4 lentivirus was constructed for transfection of PCa cells. Cell migrated and invaded ability was detected through wound healing assay and transwell assay. Western blot assay was performed to analyze the protein level of FOXO3A. Results: The low circular RNA_LARP4 expression was associated with poor prognosis of PCa patients. The circular RNA_LARP4 was lowly expressed in PCa tissues compared with adjacent samples. The expression of circular RNA_LARP4 was downregulated in PCa cell lines. The cell migrated and invaded ability of PCa cells was inhibited after circular RNA_LARP4 was overexpressed. Furthermore, FOXO3A expression was increased via the overexpression of circular RNA_LARP4. Conclusions: Circular RNA_LARP4 could suppress cell migration and invasion of PCa by upregulating FOXO3A. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. ,
MiR-22 inhibits lung cancer cell EMT and invasion through targeting Snail
Authors: Y-H Zhao
Z-M Wang
X-Y Li
K Zhang
Z-F Han
Journal: European Review for Medical and Pharmacological Sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Snail; MiR-22; lung cancer; invasion; metastasis
Affiliations: Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, Jilin, China. .

Abstract:  Objective: Snail is an important factor in regulating epithelial mesenchymal transition (EMT). Its elevation is related to the enhancement of lung cancer invasion. MicroRNA-22 (MiR-22) plays a role in regulating lung cancer cell invasion. Bioinformatics analysis showed the complementary binding site between miR-22 and Snail. This study aimed to investigate the role of miR-22 in regulating Snail and affecting lung cancer cell invasion and metastasis. Materials and methods: Dual luciferase assay confirmed the targeted relationship between miR-22 and Snail. MiR-22 and Snail expressions were compared in MRC-5, Anip973, and AGZY83-a cells. Cell colony formation and invasion were tested in Anip973 and AGYZ83-a cells. Anip973 and AGYZ83-a cells were treated by 5 ng/ml transforming growth factor β1 (TGF-β1) to detect miR-22, Snail, E-cadherin, and N-cadherin expressions. Anip973 cells were cultured in vitro and divided into five groups, including miR-Normal control (miR-NC), miR-22 mimic, small interfering RNA-Normal control (si-NC), si-Snail, and miR-22 mimic + si-Snail groups. Results: MiR-22 targeted inhibited Snail expression. MiR-22 significantly down-regulated, while Snail obviously elevated in Anip973 and AGYZ83-a cells compared with that in MRC-5 cells. Anip973 exhibited markedly stronger invasive and colony formation abilities than AGYZ83-a. TGFβ1 apparently reduced miR-22 and E-cadherin, whereas increased Snail and N-cadherin stronger in Anip973 than that in AGYZ83-a. MiR-22 mimic and/or si-Snail transfection significantly reduced Snail and N-cadherin levels, up-regulated E-cadherin expression, and attenuated cell colony formation and invasion. Conclusions: Down-regulation of miR-22 plays a role in facilitating lung cancer cell EMT and invasion by elevating Snail. MiR-22 over-expression attenuated lung cancer cell EMT and invasion via targeted inhibiting Snail. 

Retracted: No

PubPeer comments:
 ![file] The Western Blots in this paper are sharp-edged black oval blobs on a featureless grey background. These are among the characteristics of [a papermill discussed here] , with examples listed in a Google document. https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit#gid=0 ,
Interaction between LncRNA-ROR and miR-145 contributes to epithelial-mesenchymal transition of ovarian cancer cells
Authors: Jie Li
Lei Wu
Meili Pei
Songlin Zhang
Journal: General physiology and biophysics (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: LncRNA; ROR; ovarian cancer; cell reprogramming; chemoresistance
Affiliations: Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract:  Emerging evidence has indicated that long noncoding RNAs (LncRNAs) play critical roles in tumor development. LncRNA-regulator of reprogramming (ROR) could enhance the malignance of numerous tumors through promoting cell reprogramming and the chemoresistance of several cancers. Nevertheless, the detailed molecular mechanisms of LncRNA-ROR in ovarian cancer are not well elucidated. In our study, we demonstrated that LncRNA-ROR was high expression in ovarian cancer tissues than in normal ovarian tissues, and LncRNA-ROR level was positively associated with clinical stages and the differentiation grades of malignant cells. Functionally, LncRNA-ROR could induce epithelial-mesenchymal transition (EMT), and regulated ovarian cancer cell migration and invasion by decreasing the expression of tumor suppressive miR-145 and its target gene FLNB. Moreover, the binding site for miR-145 within LncRNA-ROR contributed to the reciprocal negative regulation of LncRNA-ROR and miR-145. Taken together, LncRNA-ROR promoted EMT by the miR-145/FLNB regulatory axis in ovarian cancer, providing a potential therapeutic target for ovarian cancer. 

Retracted: No

PubPeer comments:
 Figures 1 and 3 appear to have image overlaps ![file] ![file] ![file] , 
 #1 Thanks so much for pointing out these errors for us. After checking the data, we are so sorry not to notice the duplicated images. Because these experiments were done at the same time, there is a confusion of naming when saving picture, and the images were continuously taken, so there was some overlapamong the images, and it was easy to make a mistake. we will contact the editor as soon as possible to replace these images. Thanks again for your comments. We apologize for these mistakes to the journal editors, reviewers and readers for any inconvenience, and will pay attention to this and not make the same mistakes in the future. Best Wishes. , 
 Figure 4 has images seen in[ another paper](http: pubpeer.com publications CF00BD2AB8154F0BCDDB17888BC19C): ![file] ![file] To help people keep track, there is a total of 5 papers that share images all by Jie Li. https: pubpeer.com publications AEA8F680DF2B92BA9380932C779BE0 https: pubpeer.com publications B00AC97C35BDA0267A1D0C7E61AF6F https: pubpeer.com publications 470F62FC5EADC48D9D3134BD2F7D9B https: pubpeer.com publications CF00BD2AB8154F0BCDDB17888BC19C ,
In vitro differentiation of rat mesenchymal stem cells to hepatocyte lineage
Authors: Mohammad Taghi Joghataei
Nima Sanadgol
Kazem Parivar
Samaneh Solati Sarvandi
Arash Sarveazad
Maryam Khosravi
Journal: Iranian journal of basic medical sciences (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Hepatocyte; Liver extract; Mesenchymal stem cells; Omentum tissue.
Affiliations: Department of Biology, Faculty of Biological Sciences, North Branch of Islamic Azad University, Tehran, Iran., Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran., Department of Biology, Faculty of Basic Science, Sciences and Researches branch of Islamic Azad University, Tehran, Iran., Department of Anatomy, School of medicine, Iran University of Medical Sciences, Tehran, Iran., Department of Biology, Faculty of Science, University of Zabol, Zabol, Iran. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Abstract:  Objectives: Mesenchyme is a type of undifferentiated loose connective tissue that is derived mostly from mesoderm. Recently, mesenchymal stem cells (MSCs), as adult stem cells (ASCs) able to divide into a variety of different cells, are of utmost importance for stem cell research. In this research, ability of the liver extract to induce differentiation of rat derived omentum tissue mesenchymal stem cells (rOT-MSCs) into hepatocyte cells (HCs) was investigated. Materials and methods: After isolation and confirmation of rOT-MSCs they were co-cultured with liver extract and hepatogenic differentiation was monitored. Expressions of mesenchymal stem cell markers were also analyzed via flow cytometry. Moreover, expressions of octamer-binding transcription factor-4 (Oct-4), Wilm's tumor suppressor gene-1 (WT-1), albumin (ALB), alpha fetoprotein (AFP), cytokeratin-18 (CK-18), and mRNAs were analyzed using RT-PCR on days 16, 18 and 21. ALB production was analyzed by immunocytochemistry and western blot. Furthermore, glycogen and urea production were determined via periodic acid-Schiff (PAS) staining and colorimetric assays respectively. Results: The phenotypic characterization revealed the positive expressions of CD90, CD44 and negative expression of CD45 in rOT-MSCs. These cells also expressed mRNA of Oct-4 and WT-1 as markers of omentum tissue. Differentiated rOT-MSCs in presence of 6 µg/ml liver extract expressed ALB, AFP, CK-18, glycogen and urea as specific markers of HCs. Conclusion: These observations suggest that liver extract is potentially able to induce differentiation of MSCs into hepatocyte lineage and can be considered an available source for imposing tissue healing on the damaged liver. 

Retracted: No

PubPeer comments:
 Figure 5 seems very confused. *** ![file] *** Closeup ![file] ,
Long noncoding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression
Authors: Tong-peng Xu
Min Xie
Feng-qi Nie
Yong-qian Shu
Kai-hua Lu
Er-bao Zhang
Ming Sun
Rui Xia
Xiang-hua Liu
Jin-song Yang
Yan-wen Liu
Journal: Molecular Cancer Therapeutics (2015)
Discipline: CLINICAL MEDICINE
Keywords: lncRNA; cancer biology; NSCLC; tumorigenesis; ANRIL
Affiliations: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China., Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China., Department of Oncology, Nanjing First Hospital, Nanjing Medical University, People's Republic of China., Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.  .

Abstract:  Recent evidence highlights long noncoding RNAs (lncRNA) as crucial regulators of cancer biology that contribute to essential cancer cell functions such as cell proliferation, apoptosis, and metastasis. In non-small cell lung cancer (NSCLC), several lncRNAs' expressions are misregulated and have been nominated as critical actors in NSCLC tumorigenesis. LncRNA ANRIL was first found to be required for the PRC2 recruitment to and silencing of p15(INK4B), the expression of which is induced by the ATM-E2F1 signaling pathway. Our previous study showed that ANRIL was significantly upregulated in gastric cancer, and it could promote cell proliferation and inhibit cell apoptosis by silencing of miR99a and miR449a transcription. However, its clinical significance and potential role in NSCLC is still not documented. In this study, we reported that ANRIL expression was increased in NSCLC tissues, and its expression level was significantly correlated with tumor-node-metastasis stages and tumor size. Moreover, patients with high levels of ANRIL expression had a relatively poor prognosis. In addition, taking advantage of loss-of-function experiments in NSCLC cells, we found that knockdown of ANRIL expression could impair cell proliferation and induce cell apoptosis both in vitro and vivo. Furthermore, we uncover that ANRIL could not repress p15 expression in PC9 cells, but through silencing of KLF2 and P21 transcription. Thus, we conclusively demonstrate that lncRNA ANRIL plays a key role in NSCLC development by associating its expression with survival in patients with NSCLC, providing novel insights on the function of lncRNA-driven tumorigenesis. 

Retracted: No

PubPeer comments:
 Fig 7A.  Flow cytometry revealed that miR-494 overexpression promotes cell apoptosis by inhibiting SDC1. (A) Flow cytometry was used to measure apoptosis . ![file] The Blank panel is surprisingly similar in the upper left quadrant (green box) to the NC panel of Fig 6A of [Zhu et al (20178)](hhttps: pubpeer.com publications F889F09553D18531E5A3F480ED3975). Yellow boxes show another parallelism. Other manifestations are linked in that other thread. ![] ,