PReD-Bench/PRed-Bench huggingface dataset:
Mangiferin regulates proliferation and apoptosis in glioma cells by induction of microRNA-15b and inhibition of MMP-9 expression
Authors: Cheng Xiao
Jinsong Xiao
Zian Zhong
Junjian Zhang
Li Liu
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Mangiferin; Glioma cells; Proliferation; Apoptosis; miR-15b
Affiliations: Division of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.

Abstract:  Mangiferin, a flavonoid extracted from the leaves of the Anacardiaceae plant, the mango tree, has physiological activity and pharmacological effects in many aspects. The present study aimed to clarify the effect of mangiferin on proliferation and apoptosis of glioma cells and the mechanism of these curative effects of mangiferin. In this experiment, we detected the proliferation using 3-(4,5-dimethylthylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Then, cell apoptosis of U87 glioma cells was measured with the Annexin V-FITC/propidium iodide (PI) apoptosis detection kit, DAPI staining assay and the caspase-3 and caspase-9 activity assay kit. Next, quantitative real-time PCR and gelatin zymography were used to analyze the expression of microRNA-15b (miR-15b) and matrix metalloproteinase-9 (MMP-9), respectively. MMP-9 agonist, miR-15b mimics and anti-miR-15b mimics were added to the U87 glioma cells for elucidating the mechanisms involved in the curative effects of mangiferin. In the present study, mangiferin notably restrained the proliferation and increased the apoptosis of the U87 glioma cells. Meanwhile, mangiferin specifically promoted the expression of miR-15b and suppressed the level of MMP-9 in the U87 glioma cells. miR-15b regulated the expression of MMP-9 in the U87 glioma cells. MMP-9 agonist and anti-miR‑15b reduced the curative effects of mangiferin in the U87 glioma cells. In summary, mangiferin regulates proliferation and apoptosis in glioma cells by induction of miR-15b and inhibition of MMP-9 expression. 

Retracted: No

PubPeer comments:
 *[above]*. Fig 7A.  MMP-9 agonist suppresses the effect of mangiferin on U87 glioma cells. (A and B) Representative gelatin zymography analysis of MMP-9 expression . With, *[below]*, Fig 4B from [Li et al (2015)] .  MMP-9 protein expression . Unexpected similarities. ![file] ,
Prostaglandin E2 modulates dendritic cell function via EP2 and EP4 receptor subtypes
Authors: Norbert Gualde
Hedi Harizi
Christophe Grosset
Journal: Journal of leukocyte biology (2003)
Discipline: IMMUNOLOGY
Keywords: PGE(2); dendritic cells; E prostanoid receptor; EP(2)R; EP(4)R
Affiliations: Laboratoire d'Immunologie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5540, Université de Bordeaux 2, Cedex, France. 

Abstract:  We have reported previously that PGE(2) inhibits dendritic cells (DC) functions. Because E prostanoid receptor (EPR) subtypes involved in this action are unknown, expression and functions of these receptors were examined in DC. Western blot and flow cytometry analyses showed that all EPRs were coexpressed in DC. In a dose-dependent manner, lipopolysaccharide (LPS) enhanced EP(2)R/EP(4)R but not EP(1)R/EP(3)R expressions. NS-398, a cyclooxygenase (COX)-2-selective inhibitor, suppressed LPS-enhanced EP(2)R/EP(4)R expression, suggesting that COX-2-issued prostaglandin E(2) (PGE(2)) modulates DC function through stimulation of specific EPR subtypes. Using selective agonists, we found that butaprost, an EP(2)R agonist, and PGE(1) alcohol, an EP(2)R and EP(2)R/EP(4)R agonist, inhibited major histocompatibility complex class II expression and enhanced interleukin-10 production from DC. However, no effect was observed with sulprostone and 17-phenyl-omega-trinor-PGE(2), selective agonists for EP(1)R and EP(1)R/EP(3)R, respectively. Treatment of DC with dibutyryl cyclic adenosine monophosphate (cAMP), an analog of cAMP, mimics PGE(2)-induced, inhibitory effects. Taken together, our data demonstrate that EP(2)R/EP(4)R are efficient for mediating PGE(2)-induced modulation of DC functions. 

Retracted: No

PubPeer comments:
 I realize this is an older paper, but Figure 1A and 1B include very similar image for EP1 for different treatments; a-tubulin appears to repeat too. Could the authors review and comment? Figure 1 with caption below. *** ![file] , 
 Another reader on Twitter notes that the Ep2 and 4 in the B panel are also similar. Iu2019ve identified those in yellow below. *** ![file] ,
Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina
Authors: Gabriel H Travis
Anh Miu
Jeremy Cook
Steven Nusinowitz
C Nathaniel Roybal
Anita Kim
Joanna J Kaylor
Shanta Sarfare
Paul Kim
Quan Yuan
Samer Habib
Jacob Makshanoff
Tongzhou Xu
Journal: Nature Chemical Biology (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: opsin-pigment; photoisomerization; retinaldehyde chromophore; visual cycle; alternative pathway
Affiliations: Jules Stein Eye Institute, University of California, Los Angeles School of Medicine, Los Angeles, California, USA.

Abstract:  Absorption of a light particle by an opsin-pigment causes photoisomerization of its retinaldehyde chromophore. Restoration of light sensitivity to the resulting apo-opsin requires chemical re-isomerization of the photobleached chromophore. This is carried out by a multistep enzyme pathway called the visual cycle. Accumulating evidence suggests the existence of an alternative visual cycle for regenerating opsins in daylight. Here we identified dihydroceramide desaturase-1 (DES1) as a retinol isomerase and an excellent candidate for isomerase-2 in this alternative pathway. DES1 is expressed in retinal Müller cells, where it coimmunoprecipitates with cellular retinaldehyde binding protein (CRALBP). Adenoviral gene therapy with DES1 partially rescued the biochemical and physiological phenotypes in Rpe65(-/-) mice lacking isomerohydrolase (isomerase-1). Knockdown of DES1 expression by RNA interference concordantly reduced isomerase-2 activity in cultured Müller cells. Purified DES1 had very high isomerase-2 activity in the presence of appropriate cofactors, suggesting that DES1 by itself is sufficient for isomerase activity. 

Retracted: No

PubPeer comments:
 In Fig.2 the author demonstrated the isomerase activity of DES1. How do they rule out the influence of ceramide synthesis on the activity of isomerases? Could the increased synthesis of 11-cis-ROL in homogenates be **a secondary effect** of increased ceramide biosynthesis (classic DEG1 function)? ,
Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53
Authors: Kathryn L Ball
Ted R Hupp
Eleanor Ramsay
Mirjam Eckert
David Dornan
Maura Wallace
Harumi Shimizu
Journal: Molecular and Cellular Biology (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Interferon regulatory factor 1; p53; p21 gene expression; tumor formation; transcription
Affiliations: CRUK Interferon and Cell Signalling Group, Cell Signalling Unit, Cancer Research Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, United Kingdom., CRUK Interferon and Cell Signalling Group, Cell Signalling Unit, Cancer Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom, CRUK p53 Signal Transduction Group

Abstract:  Interferon regulatory factor 1 (IRF-1) and p53 control distinct sets of downstream genes; however, these two antioncogenic transcription factors converge to regulate p21 gene expression and to inhibit tumor formation. Here we investigate the mechanism by which IRF-1 and p53 synergize at the p21 promoter and show that stimulation of p21 transcription by IRF-1 does not require its DNA-binding activity but relies on the ability of IRF-1 to bind the coactivator p300 and to stimulate p53-dependent transcription by an allosteric mechanism. Deletion of the p300-binding sites in IRF-1 eliminates the ability of IRF-1 to stimulate p53 acetylation and associated p53 activity. Complementing this, small peptides derived from the IRF-1-p300 interface can bind to p300, stabilize the binding of p300 to DNA-bound p53, stimulate p53 acetylation in trans, and up-regulate p53-dependent activity from the p21 promoter. The nonacetylatable p53 mutant (p53-6KR) cannot be stimulated by IRF-1, further suggesting that p53 acetylation is the mechanism whereby IRF-1 modifies p53 activity. These data expand the core p300-p53 protein LXXLL and PXXP interface by including an IRF-1-p300 interface as an allosteric modifier of DNA-dependent acetylation of p53 at the p21 promoter. 

Retracted: No

PubPeer comments:
 Much more similar than expected. ![file] ![file] ![file] , 
 Figure 2A. Much more similar after vertical compression than expected. ![file] , 
 Figure 6. Much more similar than expected. ![file] , 
 #2 Figure 2A. Much more similar after horizontal flip than expected. ![file] , 
 #3 Figure 6B. Much more similar than expected. ![file] , 
 Figure 2A. Much more similar after vertical compression than expected. ![file] , 
 Thank you for highlighting your concerns. We have taken this seriously and have asked the University of Dundee research integrity adviser s for their opinion. We will post a response on PubPeer once an evaluation has been completed. ,
RETRACTED: Boosting fermentable sugars by integrating magnesium oxide-treated corn stover and corn stover liquor without washing and detoxification
Authors: Dan Liu
Kraig L Roozeboom
Meng Zhang
Donghai Wang
Jun Li
Journal: Bioresource Technology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Biomass slurry; Corn stover; Enzymatic hydrolysis; MgO pretreatment; Sugar yield.
Affiliations: Department of Biological and Agricultural Engineering, Kansas State University, Manhattan, KS 66506, United States., Department of Biological and Agricultural Engineering, Kansas State University, Manhattan, KS 66506, United States; College of Engineering, Heilongjiang Bayi Agricultural University, Daqing 163319, China., Department of Industrial and Manufacturing Systems Engineering, Kansas State University, Manhattan, KS 66506, United States., Department of Agronomy, Kansas State University, Manhattan, KS 66506, United States., Department of Biological and Agricultural Engineering, Kansas State University, Manhattan, KS 66506, United States. Electronic address: .

Abstract:  Integration of MgO-treated corn stover and corn stover liquor for enzymatic hydrolysis was studied to improve sugar yield and concentration as well as to simplify the bioconversion process. Results showed that under the same enzymatic hydrolysis conditions (2 mL enzyme/g biomass and 10% substrate loading), MgO-treated corn stover plus corn stover liquor had a similar glucose yield (70.4 vs. 68.8%) and concentration (40.4 vs. 41.5 g/L) but a higher xylose yield (56.6 vs. 25.3%) and concentration (16.7 vs. 10.6 g/L) compared with using MgO-treated corn stover only. Corn stover slurry from MgO pretreatment was near-neutral and free of 5-hydroxymethylfurfural and furfural, eliminating the need for washing and detoxification and lightening the burden for wastewater treatment. In addition, Tween 80 significantly reduced the irreversible binding of lignin to enzyme, increasing xylose and glucose yields by 14.7 and 6.2% and sugar concentration by 7.4 g/L, respectively. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: www.sciencedirect.com science article pii S0960852420300882 This article has been retracted: please see Elsevier Policy on Article Withdrawal (http: www.elsevier.com locate withdrawalpolicy). This article has been retracted at the request of the Authors and the Editor-in-Chief. This article contains some flaws in experimental method protocol used. The major issue is that the filtration aperture (cheese cloth) used for solid and liquid separation after biomass pretreatment was not well controlled over the research period. Using used-cheese-cloths with varied aperture size unintentionally caused a large variation in mass recovery and chemical composition of treated biomass. New cheese cloth should be used each time to assure reproducibility. ,
Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis
Authors: Michael W Susman
K Christopher Garcia
Chan Young Park
Stephen J Smith
Chandrani Chakraborty
Sara B Mulinyawe
Nancy A O&#x27;Rourke
Andrew D Huberman
Deane F Mosher
Arnon Rosenthal
Ben A Barres
Nicola J Allen
Cagla Eroglu
Z David Luo
Douglas S Annis
Jack Lawler
Engin Ozkan
Ricardo Dolmetsch
Eric M Green
Journal: Cell (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Synapses; cellular adhesions; nervous system development; thrombospondin; astrocyte-secreted protein
Affiliations: Duke University Medical Center, Cell Biology Department, Durham, NC 27710, USA. 

Abstract:  Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS synapse formation as alpha2delta-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of alpha2delta-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. alpha2delta-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to alpha2delta-1 and powerfully inhibits excitatory synapse formation in vitro and in vivo. These findings identify alpha2delta-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation. 

Retracted: No

PubPeer comments:
 In Figure 7 of this paper (with details given in Fig S12). 8 mice had whisker follicle ablation, 4 of those received saline, four received a drug called gabapentin. The authors want to show that gabapentin prevents synaptogenesis. In only 2 of the 4 drug injected mice there is some abnormality in the barrel cortex, the other 2 are like the saline controls, but the Figure S12 images are very blurred. There is no quantitation of this and it only happened in half the mice. Then they test thrombospondin 1 2 knockout mice and state  A third of the TSP1 2KO mice we analyzed showed a very similar, aberrant barrel cortex plasticity phenotype . Again there is no quantitation, and 2 3 of the KO mice were normal. I am surprised that reviewers did not ask for more evidence, since the effect only occured in a some of the mice, has this been repeated anywhere? ,
Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren's syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18
Authors: S Raimondo
G Guggino
F Dieli
A Rizzo
G Sireci
Paola Cipriani
R Alessandro
F Carubbi
M Bombardieri
F Ciccia
G De Leo
G Campisi
R Giacomelli
G Triolo
A Cannizzaro
Journal: Clinical and experimental immunology (2015)
Discipline: IMMUNOLOGY
Keywords: IL-18; IL-22; IL-22BP; IL-22R1; Sjögren's syndrome
Affiliations: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Palermo, Italy., Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy., Azienda Ospedaliera Ospedali riuniti Villa Sofia-Cervello, Anatomia Patologica, Palermo, Italy., Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University London, UK., Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Sezione di Reumatologia, Università di L'Aquila, Italy., Dipartimento di discipline Chirurgiche, Università di Palermo, Italy.

Abstract:  The aim of this study was to elucidate more clearly the role of interleukin (IL)-18 in modulating the IL-22 pathway in primary Sjögren's syndrome (pSS) patients and in pSS-associated lymphomas. Minor salivary glands (MSGs) from patients with pSS and non-specific chronic sialoadenitis (nSCS), parotid glands biopsies from non-Hodgkin lymphomas (NHL) developed in pSS patients, were evaluated for IL-18, IL-22, IL-22 receptor 1 (IL-22R1), IL-22 binding protein (IL-22BP) and signal transducer and activator of transcription-3 (STAT-3) expression. MSGs IL-22R1-expressing cells were characterized by confocal microscopy and flow cytometry in pSS, nSCS and healthy controls . The effect of recombinant IL-18 and IL-22 on peripheral blood mononuclear cells (PBMCs) from pSS and nSCS was studied by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR). MSGs of pSS and NHL were characterized by an imbalance between IL-22 and IL-22BP protein expression, with IL-18 and IL-22BP being expressed in a mutually exclusive manner and IL-18 and IL-22R1 being correlated directly. Aberrant expression of IL-22R1, induced by IL-18, was observed only among tissue and circulating myeloid cells of pSS patients and macrophages of NHL tissues of pSS patients, but not nSCS. IL-22R1 expression on PBMC of pSS was functional, as its stimulation with recombinant IL-22 significantly up-regulated the expression of STAT-3, IL-17 and IL-22. An IL-18-dependent aberrant expression of IL-22R1 on cells of haematopoietic origin seems to be a specific immunological signature of patients with pSS and pSS-associated lymphomas. 

Retracted: No

PubPeer comments:
 There are many overlaps between various FACS panels that are supposed to each contain unique data. ![file] ,
Metformin induces apoptosis of pancreatic cancer cells
Authors: Zhao-Shen Li
Jun Gao
Guo-Ming Xu
Duo-Wu Zou
Zhen-Dong Jin
Luo-Wei Wang
Journal: World Journal of Gastroenterology (2008)
Discipline: CLINICAL MEDICINE
Keywords: Metformin; apoptosis; pancreatic cancer cells; cell proliferation; PARP cleavage
Affiliations: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

Abstract:  Aim: To assess the role and mechanism of metformin in inducing apoptosis of pancreatic cancer cells. Methods: The human pancreatic cancer cell lines ASPC-1, BxPc-3, PANC-1 and SW1990 were exposed to metformin. The inhibition of cell proliferation and colony formation via apoptosis induction and S phase arrest in pancreatic cancer cell lines of metformin was tested. Results: In each pancreatic cancer cell line tested, metformin inhibited cell proliferation in a dose dependent manner in MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays). Flow cytometric analysis showed that metformin reduced the number of cells in G1 and increased the percentage of cells in S phase as well as the apoptotic fraction. Enzymelinked immunosorbent assay (ELISA) showed that metformin induced apoptosis in all pancreatic cancer cell lines. In Western blot studies, metformin induced poly-ADP-ribose polymerase (PARP) cleavage (an indicator of caspase activation) in all pancreatic cancer cell lines. The general caspase inhibitor (VAD-fmk) completely abolished metformin-induced PARP cleavage and apoptosis in ASPC-1 BxPc-3 and PANC-1, the caspase-8 specific inhibitor (IETD-fmk) and the caspase-9 specific inhibitor (LEHD-fmk) only partially abrogated metformin-induced apoptosis and PARP cleavage in BxPc-3 and PANC-1 cells. We also observed that metformin treatment dramatically reduced epidermal growth factor receptor (EGFR) and phosphorylated mitogen activated protein kinase (P-MAPK) in both a time- and dose-dependent manner in all cell lines tested. Conclusion: Metformin significantly inhibits cell proliferation and apoptosis in all pancreatic cell lines. And the metformin-induced apoptosis is associated with PARP cleavage, activation of caspase-3, -8, and -9 in a time- and dose-dependent manner. Hence, both caspase-8 and -9-initiated apoptotic signaling pathways contribute to metformin-induced apoptosis in pancreatic cell lines. 

Retracted: No

PubPeer comments:
 Is it possible the authors can show the original data? ![file] , 
 Due to the study was published more than 10 years ago, and I had changed lab and research direction, I am so sorry I cannot find the original film. ,
Reduced Graphene Oxide/Poly(Pyrrole-co-Thiophene) Hybrid Composite Materials: Synthesis, Characterization, and Supercapacitive Properties
Authors: Gul Rahman
Humaira Seema
Sami Ullah
Salma Bilal
Anwar Ul Haq Ali Shah
Journal: Polymers (2020)
Discipline: CHEMISTRY
Keywords: energy density; poly(pyrrole-co-thiophene) (COP); power density; reduced graphene oxide (RGO); supercapacitor.
Affiliations: Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, Pakistan., National Center of Excellence in Physical Chemistry, University of Peshawar, Peshawar 25120, Pakistan., TU Braunschweig Institute of Energy and Process Systems Engineering, Franz-Liszt-Straße 35, 38106 Braunschweig, Germany.

Abstract:  Reduced graphene oxide/poly(pyrrol-co-thiophene) (RGO/COP), prepared by facile in-situ oxidative copolymerization, is reported as a new hybrid composite material with improved supercapacitance performance as compared to the respective homopolymers and their composites with RGO. The as-prepared hybrid materials were characterized with ultraviolet-visible (UV-Vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) analysis. The electrochemical behavior and energy storage properties of the materials were tested by cyclic voltammetry (CV), galvanostatic charge/discharge (GCD), and electrostatic impedance spectroscopy (EIS) techniques in 0.5 M H2SO4. The specific capacitance (Csp) for RGO/COP calculated from the CV curve was 467 F/g at a scan rate of 10 mV/s. While the Csp calculated from the GCD was 417 F/g at a current density of 0.81 A/g. The energy density calculated was 86.4 Wh/kg with a power density of 630 W/kg. The hybrid composite exhibits good cyclic stability with 65% capacitance retention after 1000 cycles at a scan rate of 100 mV/s. The present work brings a significance development of RGO/COP composites to the electrode materials for pseudocapacitive application. 

Retracted: No

PubPeer comments:
 Too many repetitions for me to mark all in Fig 3 a ![file] , 
 Fig 3 b not much better ![file] , 
 In every spectrum beyond 35 degree there is no peak except pixels (noice). I guess the base line is generated by combining several counts. In every measurement the same pattern is repeated to record base line unless dominant peaks appear due to nature of analyzing material ( below 35 degree) thereby overshadowing the repeating pattern of pixels. I hope this clarify the concerns.  comments from corresponding author , 
 If it is your procedure and equipment responsible for the noise repetition patterns, there must be more examples in your data and publications. Could you provide reference to other publications from your group where similar repetitions can be found? Otherwise it is easy to think that these repetitions are because of copy- paste manipulations with pieces of data. ,
Response to targeted therapy or chemotherapy following immunotherapy in patients with gastrointestinal cancers - a case series
Authors: Gloria Chan
Cheng Ean Chee
Rayan Alsuwaigh
Joycelyn Lee
Su Pin Choo
Journal: Journal for immunotherapy of cancer (2019)
Discipline: IMMUNOLOGY
Keywords: Gastrointestinal cancers; Immunotherapy; Targeted therapy.
Affiliations: Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore. ., Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore., National University Cancer Institute, Singapore, Singapore.

Abstract:  Background: In non-small cell lung cancer, response rates to chemotherapy given after immune checkpoint inhibitors has been reported to be higher compared to response rates to chemotherapy given before immune checkpoint inhibitors. However, this phenomenon has not been reported in patients with gastrointestinal cancers nor with the use of multi-targeted kinase inhibitors. Case presentation: We present a series of six patients who received multi-targeted kinase inhibitors or chemotherapy after progression on immune checkpoint inhibitors and showed unexpected response. Five of these patients had metastatic hepatocellular carcinoma and received salvage multi-targeted kinase inhibitors. Two of these five patients had no response to initial multi-targeted kinase inhibitors but had unexpected response to re-challenge with multi-targeted kinase inhibitors after immune checkpoint inhibitors exposure. The sixth patient had metastatic rectal cancer and showed response to salvage chemotherapy following immune checkpoint inhibitors. Conclusion: We postulate that the sequencing of immune checkpoint inhibitors prior to other forms of systemic therapy may potentially lead to an immunomodulatory effect in gastrointestinal cancers with potential improvement in response rates. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: jitc.bmj.com content 8 1 e0637-6ret  The authors have retracted this article because of confidentiality obligations. The article content has been removed for legal reasons. All authors agree to this retraction. ,
Individual external dose monitoring of all citizens of Date City by passive dosimeter 5 to 51 months after the Fukushima NPP accident (series): II. Prediction of lifetime additional effective dose and evaluating the effect of decontamination on individual dose
Authors: Makoto Miyazaki
Ryugo Hayano
Journal: Journal of Radiological Protection (2017)
Discipline: CLINICAL MEDICINE
Keywords: individual dose; ambient dose; Fukushima Daiichi Nuclear Power Plant accident; Date City; Fukushima Prefecture
Affiliations: Department of Radiation Health Management, Fukushima Medical University, Fukushima 960-1295, Japan.

Abstract:  In the first paper of this series, we showed that the ratio c of individual dose to ambient dose did not change with time in Date City, Fukushima Prefecture, after the Fukushima Daiichi Nuclear Power Plant accident. The purpose of the present paper, the second in a series, is to estimate the lifetime doses of the Date City residents, based on continuous glass badge monitoring data, extrapolated by means of the ambient-dose-rate reduction function obtained from the airborne monitoring data. As a result, we found that the external exposure contribution to the mean additional lifetime dose of residents living in Date City is not expected to exceed 18 mSv. In addition, effects of decontamination on the reduction of individual doses were not evident. This method of combining individual doses and the ambient doses, as developed in this study, has made it possible to predict with reasonable certainty the lifetime doses of residents who continue to live in this radiologically contaminated area. 

Retracted: Yes

PubPeer comments:
 Expression of Concern from the journal... Publisher s notice concerning Makoto Miyazaki and Ryugo Hayano 2017 J. Radiol. Prot. 37 623 We are issuing an Expression of Concern to raise awareness of a potential problem in this article: It has been brought to our attention that some of the data used in the study reported in this article potentially were without appropriate consent. We have further been advised that this is currently under investigation. If required, the publication record will be corrected as soon as possible. In addition, this Expression of Concern highlights that the article, referenced herein, contains a methodological miscalculation underpinning the reported results. The miscalculation may affect the main conclusions of the article. The publication record will be corrected as soon as possible. , 
 Appears to be retracted in 2020: https: iopscience.iop.org article 10.1088 1361-6498 ab9ff0 ,
<p>Long-Noncoding RNA PCAT6 Aggravates Osteosarcoma Tumourigenesis via the MiR-143-3p/ZEB1 Axis</p>
Authors: Jie Liu
Liang Li
Yanfei Xiong
Shihong Liu
Qing Wu
Kai Wu
Qiong Feng
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: PCAT6; ZEB1; miR-143-3p; osteosarcoma.
Affiliations: Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang 300006, People's Republic of China., Nursing School, Nanchang University, Nanchang 300006, People's Republic of China., Department of Orthopedics, Jingan Hospital, Yichun 330600, People's Republic of China., Jingan Hospital of Traditional Chinese Medicine, Yichun 330600, People's Republic of China.

Abstract:  Introduction: The long-noncoding RNA PCAT6 plays an important regulatory role in the development of several cancers. However, the expression pattern and underlying mechanisms of PCAT6 in osteosarcoma (OS) are yet unknown. Methods: We used real-time PCR to measure PCAT6 expression in 106 tumor pairs and corresponding non-tumor tissues from OS patients. Statistical analyses were applied to evaluate the prognostic value and associations of PCAT6 expression with clinical parameters. Furthermore, the PCAT6 was silenced with siRNA in OS cells. Moreover, phenotype of PCAT6 silenced OS cells was measured using colony formation, CCK-8, cell migration and invasion assay. Finally, the molecular mechanism of PCAT6/miR-143-3p/ZEB1 axis in OS progression was explored. Results: The expression level of PCAT6 in OS tissues was significantly elevated as compared with that in the adjacent normal bone tissues and that high PCAT6 expression closely correlated with the malignant phenotype and poor survival among patients with OS. Multivariate analyses revealed PCAT6 overexpression as an independent prognostic factor for the poor outcome of patients with OS. Functional assay results demonstrated that the knockdown of PCAT6 expression notably suppressed the proliferation, migration, and invasion of OS cells. An elevated PCAT6 level aggravated the malignant phenotype of OS cells via ZEB1 expression upregulation. Mechanistic studies revealed that PCAT6 could sponge endogenous miR-143-3p and inhibit its activity, resulting in an increase in ZEB1 level. Finally, we demonstrated that the tumour-promoting role of PCAT6 in OS was dependent on the regulation of the miR-143-3p/ZEB1 axis. Conclusion: These findings highlight the potential role of PCAT6, which could serve as a valuable prognostic indicator for patients with OS. 

Retracted: No

PubPeer comments:
 Figure 2: Three cases of reuse of micrographs. Figure 3: All Western immunoblots appear artificial, with lack of background and identical bar style. In addtion there are a lot of errors in the article, and lack of method description. ![file] ,
Targeting of Cyclic AMP Degradation to β 2 -Adrenergic Receptors by β-Arrestins
Authors: George S Baillie
Trudy A Kohout
Alison J McLean
Ian McPhee
Kok Long Ang
Miles D Houslay
Maria M Magiera
Stephen J Perry
Marco Conti
Robert J Lefkowitz
William E Miller
Journal: Science (2002)
Discipline: Multidisciplinary
Keywords: Catecholamines; beta2-adrenergic receptor; adenosine 3',5'-monophosphate; desensitization; beta-arrestins
Affiliations: Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA., Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, G12 8QQ, UK., Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA., Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University, School of Medicine, Stanford, CA 94305, USA.

Abstract:  Catecholamines signal through the beta2-adrenergic receptor by promoting production of the second messenger adenosine 3',5'-monophosphate (cAMP). The magnitude of this signal is restricted by desensitization of the receptors through their binding to beta-arrestins and by cAMP degradation by phosphodiesterase (PDE) enzymes. We show that beta-arrestins coordinate both processes by recruiting PDEs to activated beta2-adrenergic receptors in the plasma membrane of mammalian cells. In doing so, the beta-arrestins limit activation of membrane-associated cAMP-activated protein kinase by simultaneously slowing the rate of cAMP production through receptor desensitization and increasing the rate of its degradation at the membrane. 

Retracted: No

PubPeer comments:
 Figure 4A. Vertical, straight change in signal IB: PDE4D panel, no splice obvious in beta-arrestin panel. ![file] ,
UCA1 confers paclitaxel resistance to ovarian cancer through miR-129/ABCB1 axis
Authors: Cong Ye
Junbao Liu
Junrong Wang
Yubo Hu
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ABCB1; Ovarian cancer; Paclitaxel resistance; UCA1; miR-129.
Affiliations: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, PR China., Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, PR China. Electronic address: .

Abstract:  Increasing evidence has demonstrated the involvement of dysregulated long non-coding RNAs (lncRNAs) in chemoresistance acting as potential oncogenes or tumor suppressors in various cancers. Nevertheless, the profound molecular mechanisms of lncRNAs in ovarian cancer (OC) chemoresistance is not well elucidated. The objective of this work was to investigate the role and molecular mechanisms of urothelial carcinoma associated 1 (UCA1) in paclitaxel (PTX) resistance in OC. Our results indicated that UCA1 was significantly up-regulated in PTX-resistant OC cells (SKOV3/PTX and HeyA-8/PTX) compared with their parental cells (SKOV3 and HeyA-8). Functionally, UCA1 knockdown sensitized SKOV3/PTX and HeyA-8/PTX cells to PTX through enhancing PTX-induced apoptosis. Mechanistically, UCA1 silencing induced PTX sensitivity of SKOV3/PTX and HeyA-8/PTX cells by de-repressing ABCB1 through sponging miR-129. Collectively, our study elaborated a novel UCA1/miR-129/ABCB1 regulatory axis underlying PTX resistance of OC cells, providing a potential therapeutic target for OC. 

Retracted: No

PubPeer comments:
 Fig 2E, F. ![file] The spacing of points in these flow-cytometry plots is very regular, as if points are avoiding one another. Can I ask the authors how they were plotted? ,
Hepatoprotective and toxicological assessment of an ethnomedicinal plant Euphorbia fusiformis Buch.-Ham.ex D.Don
Authors: S Manian
N Anusuya
K Raju
Journal: Journal of Ethnopharmacology (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Euphorbia fusiformis; hepatoprotective potential; traditional medicine; liver disorders; toxicity
Affiliations: Department of Botany, Bharathiar University, Coimbatore, Tamil Nadu, India.

Abstract:  Aim of the study: The tubers of Euphorbia fusiformis Buch.-Ham.ex D.Don (Euphorbiaceae) are traditionally used in India by the Malayali tribes of Chitteri hills, Eastern Ghats, Tamil Nadu to treat liver disorders. The objective of the present study was to assess the hepatoprotective potential and biosafety of Euphorbia fusiformis tuber upon administration thereby justifying the traditional claims. Materials and methods: The hepatoprotective potential of the ethanol extract of Euphorbia fusiformis tuber against rifampicin induced hepatic damage was investigated in Wistar albino rats. The acute and subchronic toxicity were assessed in mice and rats, respectively. Results: The ethanol extract of tubers (250 mg/kg p.o.) showed remarkable hepatoprotective effect against rifampicin induced hepatic damage in Wistar albino rats. The degree of protection was measured using the biochemical parameters serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), gamma glutamyl transpeptidase (GGTP), alkaline phosphatase (ALP), total bilirubin and total protein. Treatment with ethanolic extract prior to the administration of rifampicin significantly (P&lt;0.05 to P&lt;0.001) restored the elevated levels of the said parameters on a par with the control group. The single dose LD(50) was found to be 10,000 mg/kg bw when administered orally in mice. Subchronic toxicity studies in rats with oral doses of 125, 250 and 500 mg/kg exhibited no significant changes in body weight gain, general behavior, hematological and biochemical parameters. The histological profile of liver and kidney also indicated the non-toxic nature of this drug. Conclusion: The ethanol extract of Euphorbia fusiformis tubers may have potential therapeutic value in the treatment of liver disorders and is safer to use even at higher doses when taken orally. 

Retracted: No

PubPeer comments:
 Concern about Figure 1. Panels a (control rat, received gum acacia) and c (rat treated with rifampicin and silymarin) appear to show many areas that look similar. One could even argue that both photos might have been based on the same sample. In the case of panel c, some areas appear to be visible multiple times within the same photo. ![file] ,
miR-1204 targets VDR to promotes epithelial-mesenchymal transition and metastasis in breast cancer
Authors: Xiaoyan Liu
Qin Wang
Mingxin Wen
Qinlian Jiao
Ce Li
Jian-Hua Mao
Yidan Ren
Guangwei Wei
Yunshan Wang
Chuanxin Wang
Lei Bi
Journal: Oncogene (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PVT1; lncRNA; miR-1204; breast cancer; oncogenic roles
Affiliations: Department of Human Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, 250012, Shandong, China., Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA., School of Preclinical Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China., Department of Anesthesiology, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, 250012, Jinan, China., International Biotechnology R&D Center, Shandong University School of Ocean, 180 Wenhua Xi Road, Weihai, 264209, Shandong, China., Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, 250033, Shandong, China., Department of Human Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, 250012, Shandong, China. ., Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. ., International Biotechnology R&D Center, Shandong University School of Ocean, 180 Wenhua Xi Road, Weihai, 264209, Shandong, China. .

Abstract:  Plasmacytoma variant translocation 1 (PVT1) is an lncRNA that plays vital roles in breast cancer (BC) pathogenesis. Increasing evidence suggests that miRNAs that reside in the PVT1 locus are the main driver of the oncogenic roles of PVT1 in cancer. However, the oncogenic role and underlying mechanism of miR-1204, located in the PVT1 locus, in human cancer is still unclear. In this study, we discovered that increased expression of miR-1204 is associated with poor prognosis in BC. Moreover, miR-1204 promotes proliferation, epithelial-mesenchymal transition and invasion of BC cells both in vitro and in vivo. Mechanistic investigations demonstrated that VDR is a novel target gene of miR-1204. Interference of VDR restored miR-1204-mediated BC cell proliferation, tumorigenesis, and metastasis. Collectively, our results demonstrated that the miR-1204-VDR pathway exerts oncogenic effects in BC with potential therapeutic applications in blocking BC development and progression. 

Retracted: No

PubPeer comments:
 All animals are equal, but some mice in Figures 4 and 6 look more similar than others. Red and pink boxes are drawn around mice that look similar to each other, albeit in mirror image. ![file] ,
Riboregulator H19 induction of MDR1-associated drug resistance in human hepatocellular carcinoma cells
Authors: W P Tsang
T T Kwok
Journal: Oncogene (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: drug resistance; MDR1; P-glycoprotein; doxorubicin; H19
Affiliations: Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

Abstract:  Acquisition of drug resistance is one of the main obstacles encountered in cancer chemotherapy. Overexpression of multi-drug resistance 1 (MDR1) gene and its protein product P-glycoprotein, accompanied with a decrease in doxorubicin accumulation level, was observed in doxorubicin-resistant R-HepG2 cells, a subline derived by selection of human hepatocellular carcinoma HepG2 cells with doxorubicin. In addition, Northern-blot analysis revealed an eight fold upregulation of the imprinted H19 mRNA in R-HepG2 cells. H19 knockdown by transfection with antisense H19 oligonucleotides suppressed the MDR1/P-glycoprotein expression, increased the cellular doxorubicin accumulation level and sensitized doxorubicin toxicity in both HepG2 parent cells and R-HepG2 cells. Results from methylation-specific polymerase chain reaction analysis indicated that the MDR1 gene promoter was hypomethylated in R-HepG2 cells. Antisense H19 oligonucleotides transfection induced a marked increase in the percentage of MDR1 promoter methylation and decrease in MDR1 expression in R-HepG2 cells. Thus, the H19 gene is believed to induce P-glycoprotein expression and MDR1-associated drug resistance at least in liver cancer cells through regulation of MDR1 promoter methylation. 

Retracted: No

PubPeer comments:
 Figure 2D u2013 beta-actin bands more similar than expected when you rotate it horizontally. ![file] ,
IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition
Authors: Marcelo B Flores
Hernandes F Carvalho
Taize M Augusto
Rodrigo M Marin
Guilherme Z Rocha
Lício A Velloso
Claudio T de Souza
José R Pauli
Juliana C Moraes
Dennys E Cintra
Joseane Morari
José B C Carvalheira
Eduardo R Ropelle
Mario J A Saad
Patrícia O Prada
Dioze Guadagnini
Alexandre G Oliveira
Journal: PLoS Biology (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Overnutrition; insulin resistance; leptin resistance; IKKbeta activation; endoplasmic reticulum stress
Affiliations: Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Abstract:  Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKbeta activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKKbeta/NF-kappaB activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKbeta/NF-kappaB signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKKbeta and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
 Figure 4E It seems that the same DAPI image was used twice. Could the authors check if this was expected, please? ![file] , 
 not just the DAPI images, but also the IL-6R and IKKb. Clearly the same images, but shifted toward the left. , 
 #4 couldn t find the vendor for IL-6R antibody in the methods? , 
 Penultimate author [calling for] new research integrity office at Unicamp. , 
 Their in situ hybridization (in figures 4 and 7) has problems too: the tissue has lots of big holes, which indicate a freezing artifact (not blood vessels). moreover, one can only see background rather than distinct cell bodies. This is strange considering that the examined genes (Pomc, npy, ..) are very highly expressed in this region. ![file] ,
Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction
Authors: Deborah J Clegg
Boman G Irani
Joel K Elmquist
Yong Xu
Thekkethil P Nedungadi
Liangru Zhu
Nasim Sobhani
Sohaib A Khan
Fang Zou
Xiaorui Zhang
Lisa D Hahner
Lana M Gent
Kathryn E Davis
Carol F Elias
Journal: Cell Metabolism (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Estrogens; estrogen receptor-α; ERα; body weight; reproduction
Affiliations: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract:  Estrogens regulate body weight and reproduction primarily through actions on estrogen receptor-α (ERα). However, ERα-expressing cells mediating these effects are not identified. We demonstrate that brain-specific deletion of ERα in female mice causes abdominal obesity stemming from both hyperphagia and hypometabolism. Hypometabolism and abdominal obesity, but not hyperphagia, are recapitulated in female mice lacking ERα in hypothalamic steroidogenic factor-1 (SF1) neurons. In contrast, deletion of ERα in hypothalamic pro-opiomelanocortin (POMC) neurons leads to hyperphagia, without directly influencing energy expenditure or fat distribution. Further, simultaneous deletion of ERα from both SF1 and POMC neurons causes hypometabolism, hyperphagia, and increased visceral adiposity. Additionally, female mice lacking ERα in SF1 neurons develop anovulation and infertility, while POMC-specific deletion of ERα inhibits negative feedback regulation of estrogens and impairs fertility in females. These results indicate that estrogens act on distinct hypothalamic ERα neurons to regulate different aspects of energy homeostasis and reproduction. 

Retracted: No

PubPeer comments:
 6C and D superimposible ![file] , 
 Another issue is that the Nestin-Cre has a phenotype: see PMID: 20876718 ,