PReD-Bench/PRed-Bench huggingface dataset:
Chemical characterisation and appraisal of antidiabetic potential of Terminalia citrina extract in streptozotocin induced hyperglycaemia in Wistar rats
Authors: Ammara Saleem
Ayesha Latif
Mohammad Saleem
Mohamed M Abdel-Daim
Malik Hassan Mehmood
Mirza Muhammad Faran Ashraf Baig
Muhammad Furqan Akhtar
Journal: Archives of Physiology and Biochemistry (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: GC-MS; Streptozotocin; Terminalia citrina; acute toxicity: oxidative stress; alpha-amylase
Affiliations: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan, Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia, Laboratory of Stem Cells Research and Biomedical Engineering for Novel Bio-functional and Pharmaceutical Nano-materials, Prince Philip Dental Hospital, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China, Department of Pharmacology, University College of Pharmacy, University of the Punjab, Lahore, Pakistan

Abstract:  The current research was aimed to evaluate the antidiabetic activity of Terminalia citrina methanolic extract (TCME) by streptozotocin-induced diabetes in male Wistar rats. TCME exhibited better in-vitro antioxidant and alpha-amylase inhibitory activity as compared to other tested extracts. TCME at 250, 500, and 750 mg/kg showed notable (p &lt; .05) antidiabetic potential by lowering fasting blood glucose level, restoring lipid level, serum amylase, HbA1c, kidney, and liver function tests as coevidenced from histological findings of the liver, pancreas, and kidney. TCME remarkably reinstated the antioxidant enzymatic activities (CAT: 0.181 ¬± 0.011 IU/mg protein, SOD: 21.45 ¬± 1.53 IU/mg protein) and reduced lipid peroxidation level (40.60 ¬± 2.41 ¬µM/mg protein) in the liver and kidney tissue of diabetic rats at 750 mg/kg dose. The acute and subacute oral toxicity study of TCME exhibited no clinical toxicity signs and mortality. Its GC-MS spectrum unveiled the existence of 10-octadecenoic acid and other compounds which might have contributed to antidiabetic potential. 

Retracted: No

PubPeer comments:
  The authors declare no competing financial interests. However, on 2012-10-05, the authors submitted a patent entitled  Methods of treating tumors having elevated mct1 expression . Inventors: Kivanc Birsoy, David M. Sabatini, Richard Possemato and Tim Wang. https: patents.google.com patent US20140142180A1 According to the Nature Research guidelines:  For patents and patent applications, disclosure of the following information is requested: patent applicant (whether author or institution), name of inventor(s), application number, status of application, specific aspect of manuscript covered in patent application. https: www.nature.com nature-research editorial-policies competing-interests  ,
Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR
Authors: Ivor J Benjamin
Teresa A Mills
Le Meng
Vladimir L Gabai
Geunwon Kim
Michael Y Sherman
Journal: Molecular and Cellular Biology (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hsf1; oncogene-induced senescence; tumor initiation; mammary hyperplasia; tumor emergence
Affiliations: Department of Biochemistry, Boston University Medical School, Boston, Massachusetts, USA. 

Abstract:  Previously we demonstrated that the heat shock transcription factor Hsf1 is indispensable for transformation of mammary epithelial cells by the Her2 oncogene. Since Hsf1 affects oncogene-induced senescence (OIS), these findings suggest that Hsf1 affects tumor initiation when OIS plays a role. Indeed, here we report that Hsf1 knockout suppressed mammary hyperplasia in Her2-expressing mice and reduced tumor emergence. On the other hand, Hsf1 expression increases with advanced breast cancer, indicating that there is an additional role of Hsf1 in tumor progression. We studied rare tumors that developed in Hsf1-knockout mice and found that these tumors grew slower than tumors in control animals and showed suppressed angiogenesis. Similarly, in the xenograft model, knockdown of Hsf1 suppressed angiogenesis, which was associated with suppression of the HIF-1 pathway. Suppression of HIF-1 was at the level of translation due to downregulation of the RNA-binding protein HuR. Importantly, besides HIF-1, HuR controls translation of other major regulators of cancer progression, many of which were suppressed in Hsf1-knockdown cells. Therefore, in addition to OIS, Hsf1 regulates the HuR-HIF-1 pathway, thus affecting both cancer initiation and progression. 

Retracted: No

PubPeer comments:
 This paper was part of a structured search into possible cases of image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long Here is my finding, reported to the journal in 2016. Figure 6A: * Red boxes: The same actin band might be visible twice  This issue was addressed with a correction in September 2017, found here: https: mcb.asm.org content 37 20 e00415-17 It reads:  *Fig. 6A: During preparation of the manuscript, the left actin panel was accidentally replicated in the right actin panel. This error does not affect any conclusions of the study. We apologize for the error.* ,
Secreted frizzled-related protein-5 is epigenetically downregulated and functions as a tumor suppressor in kidney cancer
Authors: Ken Kawamoto
Kazumori Kawakami
Hiroshi Hirata
Rajvir Dahiya
Masayuki Nakagawa
Yuichiro Tanaka
Soichiro Yamamura
Shahana Majid
Hideki Enokida
Sharanjot Saini
Koji Ueno
Journal: International Journal of Cancer (2011)
Discipline: CLINICAL MEDICINE
Keywords: sFRP-5; renal cell cancer; DNA methylation; histone modification; tumor suppressor gene
Affiliations: Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, CA 94121, USA.

Abstract:  Secreted frizzled-related protein-5 (sFRP-5) has been identified as 1 of the secreted antagonists that bind Wnt protein. However, the functional significance of sFRP-5 in renal cell cancer (RCC) has not been reported. We hypothesized that sFRP-5 may be epigenetically downregulated through DNA methylation and histone modification and function as a tumor suppressor gene in RCC. Using tissue microarray and real-time RT-PCR, we found that sFRP-5 was significantly downregulated in kidney cancer tissues and cell lines, respectively. DNA bisulfite sequencing of the sFRP-5 promoter region in RCC cell lines showed it to be densely methylated, whereas there was few promoter methylation in normal kidney. The sFRP-5 expression was restored and the acetylation of H3 and H4 histones associated with the sFRP-5 promoter region were significantly increased after treatment with demethylation agent (5-Aza-dc) and histone deacetylase inhibitor (TSA). When RCC cells were transfected with the sFRP-5 gene, significant inhibition of anchorage independent colony formation and cell invasion were observed compared to controls. The sFRP-5 transfection also significantly induced apoptosis in RCC cells. In conclusion, this is the first report documenting that the sFRP-5 is downregulated by promoter methylation and histone acetylation and functions as a tumor suppressor gene by inducing apoptosis in RCC cells. 

Retracted: No

PubPeer comments:
 Figure 1a. Much more similar than expected. https: imgur.com X2emwHQ , 
 As mentioned in the  Materials and Methods section of both papers, we used the same tissue array - Biomax (KD481) tissue array. These are commercially available tissue arrays used by several scientists. Therefore, the same tissue array was used in both papers but with different antibodies. ,
Inflammasome-derived IL-1Œ≤ production induces nitric oxide‚Äìmediated resistance to Leishmania
Authors: Diego L Costa
Marcelo T Bozza
Dario S Zamboni
Vanessa Carregaro
Tiago W P Mineo
Jo√£o S Silva
Djalma S Lima-Junior
Larissa D Cunha
Richard A Flavell
Maria Bellio
Fredy R S Gutierrez
Karina R Bortoluci
Alexandre L N Silva
Journal: Nature Medicine (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Leishmania; leishmaniasis; parasites; Nlrp3 inflammasome; nitric oxide
Affiliations: Departmento de Biologia Celular, Molecular e Bioagentes Patog√™ncios, Universidade de S√£o Paulo, Ribeir√£o Preto, S√£o Paulo, Brazil.

Abstract:  Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study we show that the Nlrp3 inflammasome is activated in response to Leishmania infection and is important for the restriction of parasite replication both in macrophages and in vivo as demonstrated through the infection of inflammasome-deficient mice with Leishmania amazonensis, Leishmania braziliensis and Leishmania infantum chagasi. Inflammasome-driven interleukin-1Œ≤ (IL-1Œ≤) production facilitated host resistance to infection, as signaling through IL-1 receptor (IL-1R) and MyD88 was necessary and sufficient to trigger inducible nitric oxide synthase (NOS2)-mediated production of NO. In this manuscript we identify a major signaling platform for host resistance to Leishmania spp. infection and describe the molecular mechanisms underlying Leishmania-induced NO production. 

Retracted: No

PubPeer comments:
 According to the authors: **u201cTo validate the effectiveness of this method, we infected BMDMs with different multiplicities of infection (MOIs) of La-GFP+ for 3 h and determined the percentage of GFP+ BMDMs using flow cytometry. We observed a direct correlation between the MOI used for infection, the percentage of GFP+ BMDMs and the integrated mean fluorescence intensity (iMFI) of the infected BMDMs (Supplementary Fig. 2).u201d** I would like to understand why the signal for wild-type animals (gray) is exactly the same in Supplemental Fig. 2a-c. The WT animals were not infected?  , 
 Could it be that they used the same non-infected BMDM as reference control to supplemental Fig a-c? In addition, the figure and the figure legend do no match with other. According to the figure legend  The green-u00ad, red-u00ad, and blue-u00adfilled histograms represent the staining of infected WT, Pycardu2013 u2013, and Casp-u00ad1u2013 u2013 BMDMs, respectively. The gray-u00adfilled histograms indicate the uninfected BMDMs.  . Was Nlrp3- - BMDMs also included in the experiment? ,
Long lasting facial rejuvenation by repeated placement of calcium hydroxylapatite in elderly women
Authors: Uwe Wollina
Alberto Goldman
Journal: Dermatologic Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: calcium hydroxylapatite; elderly women; facial rejuvenation; filler injections; long-lasting efficacy.
Affiliations: Department of Dermatology and Allergology, St√§dtisches Klinikum Dresden, Dresden, Germany., Clinica Goldman, Porto Alegre/ RS, Brazil.

Abstract:  Calcium hydroxylapatite (CaHA) is a biostimulatory filler with long lasting efficacy after a single injection. Data con the effect of repeated injections, however, are sparse. This is a single-center observational study. Forty Caucasian females of Fitzpatrick skin type I to III, aged between 50 and 95 years (mean age 63 ¬± 13.4 years), and seeking nonsurgical improvement of facial aging were included. Patients with previous face lifts, threads or other surgical treatments were excluded. Only women ‚â?0 years of age were included. Midface and lower face were treated, that is, cheeks, tear troughs, jawline, and Marionette lines. The usual time for a repetition of filler injection was 12 to 14 months. Mean follow-up was 36 ¬± 10.8 months after first injection of Radiesse. Outcome was measured using the Global Aesthetic Improvement Scale (GAIS). Mean patient's GAIS was 2.7 ¬± 0.7, while physicians GAIS was 2.6 ¬± 0.6 suggesting a remarkable improvement 12 months after the first procedure. Mean patient's GAIS at 3 and 5 years after first procedure was 2.4 ¬± 0.8, while physicians GAIS was 2.5 ¬± 0.7. Repeated injection of CaHA leads to a significant and long-lasting improvement of facial appearance. 

Retracted: No

PubPeer comments:
 In this paper, 40 women were treated with repeated injections with calcium hydroxylapatite in the face. Repeat injections were given yearly for a period of about 3 years on average. The results were measured using the Global Aesthetic Improvement Scale (GAIS). * How objective is this scale? Were photos of the women scored by an independent reviewer, who was blinded about the before or after status of the photos? If not, how objective could the authors be? Both authors claim no conflict of interest. Yet, both authors work at clinics where I assume they treat patients with these fillers, which might be a source of income. In addition, Dr. Wollina has previously declared he has received honoraria from d Merz Pharma, the manufacturer of the fillers tested in this paper. * Could the authors please comment on their possible perceived conflict of interest? The paper does not contain any statement about IRB approval of these repeated injections or patients consent to have their images used in the paper. Even though the eyes are blurred a bit, the faces are recognizable. * Did the patients know and agree with having their photos used for this paper? ,
Amplification of RNA by an RNA polymerase ribozyme
Authors: David P Horning
Gerald F Joyce
Journal: Proceedings of the National Academy of Sciences of the United States of America (2016)
Discipline: Multidisciplinary
Keywords: PCR; RNA enzyme; in vitro evolution; ribozyme; self-replication.
Affiliations: Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037., Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037 .

Abstract:  In all extant life, genetic information is stored in nucleic acids that are replicated by polymerase proteins. In the hypothesized RNA world, before the evolution of genetically encoded proteins, ancestral organisms contained RNA genes that were replicated by an RNA polymerase ribozyme. In an effort toward reconstructing RNA-based life in the laboratory, in vitro evolution was used to improve dramatically the activity and generality of an RNA polymerase ribozyme by selecting variants that can synthesize functional RNA molecules from an RNA template. The improved polymerase ribozyme is able to synthesize a variety of complex structured RNAs, including aptamers, ribozymes, and, in low yield, even tRNA. Furthermore, the polymerase can replicate nucleic acids, amplifying short RNA templates by more than 10,000-fold in an RNA-catalyzed form of the PCR. Thus, the two prerequisites of Darwinian life-the replication of genetic information and its conversion into functional molecules-can now be accomplished with RNA in the complete absence of proteins. 

Retracted: No

PubPeer comments:
 The article claims an RNA-world as historical fact in its conclusion and implies as much in the significance statement. In the abstract and introduction, on the other hand, the same concept is treated as a  hypothesis and its possible existence merely as  suggested . This latter claim among the two is consistent with the cited literature. It is unclear where the former claim comes from. If it is demonstrated here, it would be helpful to the community if the author makes the demonstration more clear and explicit. If it was demonstrated elsewhere, it would be helpful to the community if it could be made explicit where this demonstration can be found. ,
LncRNA myocardial infarction-associated transcript (MIAT) contributed to cardiac hypertrophy by regulating TLR4 via miR-93
Authors: Juan Wang
Shengnan Zhu
Yunwei Li
Lili Sun
Journal: European Journal of Pharmacology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: AngII; Cardiac hypertrophy; LncRNA; MIAT; MiR-93

Abstract:  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 Editor-in-Chief after concerns were raised about the article on PubPeer (https://pubpeer.com/publications/88E67BAC524E92069B2AA3474D2BB8?utm_source=Chrome&amp;utm_medium=BrowserExtension&amp;utm_campaign=Chrome). In addition the editor found more issues in some Western Blot figures. 1. Bands of figure 1C ANF 30min , 60min, 12h, 24h are identical to those in Fig 4C ANF control, AngII, AngII+si-NC and AngII+si-MAT 2. Beta-actin bands of Fig 1C are identical to those in Fig 4C, but blots represent different experimental conditions/samples. 3. Bands in Fig 6 D AngII and AngII+mir-NC show similarities with these of AngII+mir-93 and AngII+mir93+vector (band shapes and irregularities appear identical) After several attempts to reach out to the corresponding author, no response was provided. The manipulation of images casts doubts on all the data, and accordingly also the conclusions based on that data, in this publication. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. 

Retracted: No

PubPeer comments:
 Fig 1C and 4C. Unexpected similarity of Actin loading controls for different combination of conditions.  ,
RETRACTED ARTICLE: LncRNA miR503HG interacts with miR-31-5p through multiple ways to regulate cancer cell invasion and migration in ovarian cancer
Authors: Lijing Zhao
Ding Zhu
Fang Liang
Xueshuang Huang
Journal: Journal of Ovarian Research (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ovarian cancer; Prognosis; miR-31-5p; miR503HG.
Affiliations: Department of Gynecology, Hunan Provincial People's Hospital, Changsha City, Hunan Province, 410005, People's Republic of China., Biomedical Research Center, Hunan University of Medicine, No.492 Jinxi South Road, Huaihua City, Hunan Province, 418000, People's Republic of China. .

Abstract:  The role of lncRNA miR503HG has been investigated in several types of cancer, but its functions in ovarian cancer (OC) is unclear. Analysis of TCGA dataset revealed a 50-fold lower expression level of miR503HG in OC tissues than that in non-tumor tissues, indicating the involvement of miR503HG in OC. Results in this study showed that miR503HG was downregulated in OC and predicted poor survival. Expression of miR503HG negatively correlated with the expression of miR-31-5p across OC and non-tumor tissues. RNA-RNA interaction analysis revealed that miR503HG can interact with miR-31-5p. Dual-luciferase assay showed that miR-31-5p and miR503HG may directly interact with each other. Methylation specific PCR (MSP) showed that overexpression of miR503HG led to increased methylation level of miR-31-5p gene. Transwell assay showed that overexpression of miR-31-5p resulted in increased invasion and migration rates of OC cells. Overexpression of MiR503HG played an opposite role and attenuated the effects of overexpressing miR-31-5p. Therefore, miR503HG may promote the methylation of miR-31-5p and serve as its sponge to inhibit OC cell invasion and migration. 

Retracted: Yes

PubPeer comments:
 There are many splice sites (indicated with red arrow) in Fig 2C, Fig 6B and 6C.  , 
 I these set of experiments, experimental interpretation is in comparing normoxic vs hypoxia conditions., we are NOT trying to compare one cell line to another insofar as relative immunoblot signals between cell lines. We have pulled the data off of different films, and if there is a space between blots then they came off another film. If there is no space then they came off the same film. ,
Differential Th17 response induced by the two clades of the pandemic ST258 Klebsiella pneumoniae clonal lineages producing KPC-type carbapenemase
Authors: Gian Maria Rossolini
Maria Gabriella Torcia
Michele Tanturli
Eloisa Perissi
Sara Paccosi
Marco Maria D&#x27;Andrea
Alberto Antonelli
Federico Cozzolino
Astrid Parenti
Giuseppe Castronovo
Ann Maria Clemente
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: KPC-type carbapenemases; Klebsiella pneumoniae; clonal group 258; sequence type 258; capsular polysaccharides
Affiliations: Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy., Department of Experimental and Clinical Biomedical Sciences, University of Firenze, Firenze, Italy., Department of Health Science, University of Firenze, Firenze, Italy., Clinical Microbiology and Virology Unit, Careggi University Hospital, Firenze, Italy.

Abstract:  The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1Œ≤, IL-23 and TNF-Œ±, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. Altogether, present results suggest that CG258-KP of the two clades are capable of inducing a different response of adaptive immunity in the human host. 

Retracted: No

PubPeer comments:
 Figure 3. * Red boxes: The KKBO-1 and KK207-1 panels look unexpectedly similar, although the gated numbers are different.  ,
Effects of acetaminophen on risk taking
Authors: Baldwin Way
Alexis Keaveney
Ellen Peters
Journal: Social Cognitive and Affective Neuroscience (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: NSAID; anti-inflammatory; decision-making; risk perception.
Affiliations: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA, School of Journalism and Communication, University of Oregon Eugene, OR 97403, USA

Abstract:  Acetaminophen, an analgesic and antipyretic available over-the-counter and used in over 600 medicines, is one of the most consumed drugs in the USA. Recent research has suggested that acetaminophen's effects extend to the blunting of negative as well as positive affect. Because affect is a determinant of risk perception and risk taking, we tested the hypothesis that acute acetaminophen consumption (1000 mg) could influence these important judgments and decisions. In three double-blind, placebo-controlled studies, healthy young adults completed a laboratory measure of risk taking (Balloon Analog Risk Task) and in Studies 1 and 2 completed self-report measures of risk perception. Across all studies (total n = 545), acetaminophen increased risk-taking behavior. On the more affectively stimulating risk perception measure used in Study 2, acetaminophen reduced self-reported perceived risk and this reduction statistically mediated increased risk-taking behavior. These results indicate that acetaminophen can increase risk taking, which may be due to reductions in risk perceptions, particularly those that are highly affect laden. 

Retracted: No

PubPeer comments:
 https: twitter.com rubenarslan status 1367471709754949634 , 
 https: rubenarslan.github.io posts 2020-09-23-hibar-effects-of-acetaminophen-on-risk-taking ,
Downregulation of CSN6 attenuates papillary thyroid carcinoma progression by reducing Wnt/Œ≤-catenin signaling and sensitizes cancer cells to FH535 therapy
Authors: Rong-Liang Shi
Tian Liao
Yu-Long Wang
Ben Ma
Wen-Jun Wei
Ning Qu
Duo Wen
Zhong-Wu Lu
Qing-Hai Ji
Journal: Cancer medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: EMT; CSN6; FH535; Wnt/Œ≤-catenin signaling pathway; papillary thyroid cancer
Affiliations: Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China., Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

Abstract:  The incidence of thyroid cancer has increased worldwide at a rate higher than that of any other cancer. CSN6 is overexpressed in many types of cancers, and such expression is linked to oncogenic activity. However, the detailed biological functions of CSN6 in papillary thyroid cancer (PTC) have not been well characterized. We investigated CSN6 expression in PTC specimens and cell lines. We used short-hairpin RNA-mediated gene silencing to explore the biological effects of CSN6 depletion in PTC cells. The combined effects of CSN6 silencing and FH535 therapy were assessed in terms of cell viability. The mechanism by which CSN6 regulated Œ≤-catenin expression was also analyzed. CSN6 levels were determined by real-time polymerase chain reaction (PCR) (mRNA), Western blotting, and immunochemistry (protein). The CCK-8 and migration assays and orthotopic xenograft transplantation were used to investigate the biological effects of CSN6. We assessed the combined effects of CSN6 silencing and FH535 on cell viability in vitro. We also analyzed the relationship between the CSN6 level and clinical pathological status. CSN6 was overexpressed in human PTCs, and loss of CSN6 attenuated tumor proliferation and migration both in vitro and in vivo. CSN6 stabilized Œ≤-catenin and facilitated the epidermal-to-mesenchymal transition (EMT) in PTC cells. CSN6 positively regulated Œ≤-catenin expression in a Œ≤-Trcp-dependent manner and triggered expression of several EMT-related genes regulated by Œ≤-catenin. CSN6 silencing sensitized PTC cells to FH535 therapy via downregulation of the Wnt/Œ≤-catenin signaling pathway. Finally, in PTC patients, the level of CSN6 was significantly (inversely) correlated with tumor size, the presence of multifocal lesions, and TNM stage. CSN6 overexpression in PTC is a strong indicator of enhanced tumor aggressiveness. CSN6 promotes PTC progression by inducing the EMT. CSN6 knockdown sensitizes PTC cells to FH535 therapy via downregulation of the Wnt/Œ≤-catenin signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 2A appears to have 2 images which overlap. Shown roughly with red boxes. ***  ,
Acute toxicity study of zerumbone-loaded nanostructured lipid carrier on BALB/c mice model
Authors: Reena Joys Andas
Nabilah Muhammad Nadzri
Heshu Sulaiman Rahman
Theebaa Anasamy
Abdullah Rasedee
Farideh Namvar
Chee Wun How
Swee Keong Yeap
Max Stanley Chartrand
Hemn Hassan Othman
Kuan Beng Ng
Nozlena Abdul Samad
Journal: BioMed Research International (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Zerumbone; nanostructure lipid carrier; antileukemia effect; toxicological effects; liver
Affiliations: Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM), 43400 Serdang, Selangor, Malaysia, DigiCare Behavioral Research, Casa Grande, AZ, USA, Institute of Tropical Forestry and Forest Products (INTROP), Universiti Putra Malaysia (UPM), 43400 Serdang, Selangor, Malaysia, Institute of Bioscience, Universiti Putra Malaysia (UPM), 43400 Serdang, Selangor, Malaysia

Abstract:  Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. 

Retracted: No

PubPeer comments:
 The images in Figure 3C for Col4 and Laminin looks very similar, including some of the non-specific looking speckling:  Could the authors clarify if these images are from the same slide (ie both antibodies used simultaneously on one section)? , 
 #1 This was indeed a co-stain from the same section. One would expect the staining to be almost identical given that both collagen IV and laminin are key components of the basement membrane. ,
Caspase-8-mediated cleavage inhibits IRF-3 protein by facilitating its proteasome-mediated degradation
Authors: Nathaniel Sears
Saurabh Chattopadhyay
George R Stark
Ganes C Sen
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Interferon regulatory factor 3; IRF-3; caspase-8; proteasome-mediated degradation; antiviral genes
Affiliations: Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

Abstract:  Interferon regulatory factor 3 (IRF-3) plays a central role in inducing the expression of cellular antiviral genes, including the interferon-Œ≤ gene, in response to Pattern Recognition Receptors. IRF-3 is targeted for proteasome-mediated degradation, which modulates the strength and duration of the innate immune responses that depend on it. We have found that caspase-8, which is activated by cytosolic RIG-I-dependent signaling, catalyzes an essential intermediate step in the ubiquitination and proteasome-mediated degradation of IRF-3. Mutation of a consensus cleavage site within IRF-3 generates a form that is not cleaved by caspase-8 and that is protected from ubiquitination and degradation. An in vitro assay confirms the direct action of caspase-8 cleavage on IRF-3. We also show that caspase-8-mediated cleavage of IRF-3 helps to modulate dsRNA-dependent gene induction. 

Retracted: No

PubPeer comments:
 Figure 1B. Much more similar than you would expect. https: imgur.com QsSH21w , 
 Figures 1B and 3A. Much more similar than you would expect. https: imgur.com drdrrK0 , 
 Figure 4A. Much more similar than you would expect. https: imgur.com m5hVFpl , 
 Figure 6E. Much more similar and different than you would expect. https: imgur.com Gn0YjHn , 
 Figures 4B and 6E. Much more similar and different than you would expect. https: imgur.com cGRA6sA , 
  ,
Geniposide protects PC-12 cells against oxygen and glucose deprivation-induced injury by up-regulation of long-noncoding RNA H19
Authors: Zebao Zheng
Yanran Yuan
Journal: Life sciences (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Geniposide; Long-noncoding RNA H19; Oxygen and glucose deprivation; PI3K/AKT; Wnt/Œ≤-catenin.
Affiliations: Department of Children Rehabilitation, Jining No.1 People's Hospital, Jining 272011, China; Jining No.1 People's Hospital of Jining Medical University, Jining Medical University, Jining 272000, China., Department of Children Rehabilitation, Jining No.1 People's Hospital, Jining 272011, China; Jining No.1 People's Hospital of Jining Medical University, Jining Medical University, Jining 272000, China. Electronic address: .

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article ‚Äú‚Ä?the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated‚Ä? the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article. 

Retracted: Yes

PubPeer comments:
 Interesting paper! The methods refer to the CLU501 cell line as a model of NPY GFP neurons. It is a mistake? The CLU499 line is a NPY GFP model, but the CLU501 line is a POMC GFP model. ,
A dual fluorescent Plasmodium cynomolgi reporter line reveals in vitro malaria hypnozoite reactivation
Authors: Annemarie M Voorberg-van der Wel
Lars C Vermaat
Els J Klooster
Ivonne G Nieuwenhuis
Devendra Kumar Gupta
Nicole M van der Werff
Onny Klop
Clemens H M Kocken
Anne-Marie Zeeman
Laurent Dembele
Thierry T Diagana
Journal: Communications biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Malaria; Parasite biology.
Affiliations: 1Department of Parasitology, Biomedical Primate Research Centre, 2288 GJ, Rijswijk, The Netherlands., Novartis Institute for Tropical Diseases, Emeryville, CA USA., 3Present Address: Faculty of Pharmacy, Universit√© des Sciences, des Techniques et des Technologies de Bamako (USTTB), MRTC - DEAP, Bamako, Mali.

Abstract:  Plasmodium vivax malaria is characterized by repeated episodes of blood stage infection (relapses) resulting from activation of dormant stages in the liver, so-called hypnozoites. Transition of hypnozoites into developing schizonts has never been observed. A barrier for studying this has been the lack of a system in which to monitor growth of liver stages. Here, exploiting the unique strengths of the simian hypnozoite model P. cynomolgi, we have developed green-fluorescent (GFP) hypnozoites that turn on red-fluorescent (mCherry) upon activation. The transgenic parasites show full liver stage development, including merozoite release and red blood cell infection. We demonstrate that individual hypnozoites actually can activate and resume development after prolonged culture, providing the last missing evidence of the hypnozoite theory of relapse. The few events identified indicate that hypnozoite activation in vitro is infrequent. This system will further our understanding of the mechanisms of hypnozoite activation and may facilitate drug discovery approaches. 

Retracted: No

PubPeer comments:
  The GIWAXS images cannot match the 1D cross-sectional curves. The coordinates of the GIWAXS images are definitely incorrect. The authors should carefully recheck this problem and give a correction. ,
EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice
Authors: Huang Yan Lin
Diao Yi
Tian Xin Hua
Journal: Cancer Investigation (2011)
Discipline: CLINICAL MEDICINE
Keywords: Orthotopic xenograft; animal model; human glioblastoma multiforme; invasive growth; epidermal growth factor receptor
Affiliations: Neurosurgical Department of Affiliated Zhongshan Hospital, Xiamen University, Xiamen, China.

Abstract:  Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM. 

Retracted: No

PubPeer comments:
 image duplication  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. , 
 Multiple images in this paper appear to overlap. ***      , 
 Some additional findings - already reported by me to the journal in October 2015, and a reminder in September 2017. * Figure 1:  * Figure 2:  * Figure 3 (I missed the little overlap in the bottom row):  * Figure 5:  ,
Okadaic acid promotes epithelial‚Äêmesenchymal transition of hepatocellular carcinoma cells by inhibiting protein phosphatase 2A
Authors: Bo Qian
Juan Kong
Yuanyuan Fu
Xiaonian Zhu
Di Li
Chunhua Bei
Shidong Zhang
Shengkui Tan
Huixia Zhang
Journal: Journal of Cellular Biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EMT; HCC; OA; PP2A; metastasis.
Affiliations: Department of Epidemiology and Statistics, School of Public Health, Guilin Medical University, Guilin, Guangxi, China.

Abstract:  As a specific inhibitor of serine/threonine protein phosphatases, okadaic acid (OA) has been found to be a tumor promoter. However, whether OA plays a role in metastasis of hepatocellular carcinoma (HCC) has not been well elucidated. In this study, Hep3B and HepG2 cells were treated with different doses of OA and the cell viability was determined by CCK8 test. As a result, Hep3B and HepG2 cells showed no obvious cytotoxicity after OA treatment below 20 or 25 nM for 12 or 24 hours. However, wound healing, invasion, and migration abilities of HCC cells were significantly enhanced in the OA-treated groups than those of the control group (P &lt; .05), measured by cell scratching and BD transwell assays. Moreover, we found that the expression of epithelial-mesenchymal transition (EMT)-related key factors was changed upon OA treatment in a dose-dependent manner. In addition, the activity of protein phosphatase 2A (PP2A) in OA-treated cells was also decreased significantly compared with the control cells (P &lt; .05). Interfering of PP2A subunit A or C caused a similar expression change of EMT-related key factors as the OA treatment in HCC cells. Our results suggest that OA promotes the EMT process of HCC cells by inhibiting the activity of PP2A. 

Retracted: No

PubPeer comments:
 Two duplications spotted after a quick look at this publication: Figure 2C: A micrograph has been duplicated and presented as something else (HepG2 72h; 12.5 vs 25 OA). Figure 3C: Same problem as in 2C (Invasion; 0 vs 6.25 OA). After so many years with ongoing discussions about manipulations and data duplications, we still are here? Publishers do not seem to care about true science.  , 
 Some additional findings in Figure 3A and 3C. Indigofera s highlighted similarities are shown in yellow, as above, and I added two areas of possible overlap in blue and orange.  , 
 Comment cancelled. ,
Chronic subclinical prion disease induced by low-dose inoculum
Authors: Alana M Thackray
Adriano Aguzzi
Michael A Klein
Raymond Bujdoso
Journal: Journal of virology (2002)
Discipline: MICROBIOLOGY
Keywords: transmission characteristics; mouse-adapted scrapie isolates; tga20 mice; PrP protein; disease incubation period
Affiliations: Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, United Kingdom CB3 OES., University Hospital Basel, Institute of Pathology, CH-4003 Basel, Institute of Neuropathology, University Hospital of ZuÃàrich, CH-8091 ZuÃàrich, Switzerland, Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom

Abstract:  We have compared the transmission characteristics of the two mouse-adapted scrapie isolates, ME7 and Rocky Mountain Laboratory (RML), in tga20 mice. These mice express elevated levels of PrP protein compared to wild-type mice and display a relatively short disease incubation period following intracerebral prion inoculation. Terminal prion disease in tga20 mice induced by ME7 or RML was characterized by a distinct pattern of clinical signs and different incubation times. High-dose RML inoculated intracerebrally into tga20 mice induced the most rapid onset of clinical signs, with mice succumbing to terminal disease after only 58 +/- 3 days. In contrast, high-dose ME7 gave a mean time to terminal disease of 74 +/- 0 days. Histological examination of brain sections from prion-inoculated tga20 mice at terminal disease showed that ME7 gave rise to a more general and extensive pattern of vacuolation than RML. Low-dose inoculum failed to induce terminal disease but did cause preclinical symptoms, including the appearance of reversible clinical signs. Some mice oscillated between showing no clinical signs and early clinical signs for many months but never progressed to terminal disease. Brain tissue from these mice with chronic subclinical prion disease, sacrificed at &gt;200 days postinoculation, contained high levels of infectivity and showed the presence of PrP(Sc). Parallel analysis of brain tissue from mice with terminal disease showed similar levels of infectivity and detectable PrP(Sc). These results show that high levels of infectivity and the presence of the abnormal isomer of PrP can be detected in mice with subclinical disease following low-dose prion inoculation. 

Retracted: No

PubPeer comments:
 Figure 3: Much more similar than expected (in red). Could authors check it please?  , 
 #1  ,
<p>CLDN8 promotes colorectal cancer cell proliferation, migration, and invasion by activating MAPK/ERK signaling</p>
Authors: Wenlu Li
Quanbo Zhou
Aimei Rong
Bo Cheng
Journal: Cancer Management and Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: CLDN8; MAPK/ERK signaling; colorectal cancer.
Affiliations: Department of Emergency Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China., Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450000, China., Department of Anus and Intestine Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China., Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China, .

Abstract:  Background: Claudin 8 (CLDN8), an integral membrane protein that constitutes tight junctions in cell membranes, was recently implicated in tumor progression. However, its roles in colorectal cancer (CRC) progression and metastasis remain unknown. Methods: In this study, we examined the effect of CLDN8 on the progression of CRC, including cell proliferation, migration, and invasion, and determines its underlying molecular mechanism using in vitro CRC cell lines and in vivo mouse xenograft models. Results: We found that CLDN8 expression in human CRC tissues was significantly higher than that in adjacent normal tissues. The knockdown of CLDN8 markedly suppressed the proliferation, migration, and invasion of SW480 and HT-29 CRC cells, whereas the overexpression of CLDN8 notably promoted tumor progression in SW480 and HT-29 CRC cells. Mechanistic studies revealed that CLDN8 upregulated p-ERK (p-PKB/AKT) and MMP9 in CRC cells. Notably, the MAPK/ERK inhibitor PD98095 dramatically attenuated the effects of CLDN8 on p-ERK and MMP9. Moreover, PD98095 remarkably blocked the tumor-promoting activity of CLDN8. The knockdown of CLDN8 also inhibited the in vivo tumor growth in a nude mouse xenograft model. Collectively, CLDN8 promoted CRC cell proliferation, migration, and invasion, at least in part, by activating the MAPK/ERK signaling pathway. Conclusion: These findings suggest that CLDN8 exhibits an oncogenic effect in human CRC progression. 

Retracted: No

PubPeer comments:
 In Figure 2D, a micrograph has been duplicated and presented as something else.  ,
Integrin-associated Lyn kinase promotes cell survival by suppressing acid sphingomyelinase activity
Authors: Tatyana I Gudz
Yusuf A Hannun
Brian W Wheeler
Daria A Chudakova
Sergei A Novgorodov
Mark S Kindy
Jin Yu
Youssef H Zeidan
Journal: Journal of Biological Chemistry (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Integrins; Oligodendrocytes; Apoptosis; Fibronectin; Laminin
Affiliations: Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

Abstract:  Integrins govern cellular adhesion and transmit signals leading to activation of intracellular signaling pathways aimed to prevent apoptosis. Herein we report that attachment of oligodendrocytes (OLs) to fibronectin via alpha(v)beta(3) integrin receptors rendered the cells more resistant to apoptosis than the cells attached to laminin via alpha(6)beta(1) integrins. Investigation of molecular mechanisms involved in alpha(v)beta(3) integrin-mediated cell survival revealed that ligation of the integrin with fibronectin results in higher expression of activated Lyn kinase. Both in OLs and in the mouse brain, Lyn selectively associates with alpha(v)beta(3) integrin, not with alpha(v)beta(5) integrin, leading to suppression of acid sphingomyelinase activity and preventing ceramide-mediated apoptosis. In OLs, knockdown of Lyn with small interfering RNA resulted in OL apoptosis with concomitant accumulation of C(16)-ceramide due to activation of acid sphingomyelinase (ASMase) and sphingomyelin hydrolysis. Knocking down ASMase partially protected OLs from apoptosis. In the brain, ischemia/reperfusion (IR) triggered rearrangements in the alpha(v)beta(3) integrin-Lyn kinase complex leading to disruption of Lyn kinase-mediated suppression of ASMase activity. Thus, co-immunoprecipitation studies revealed an increased association of alpha(v)beta(3) integrin-Lyn kinase complex with ionotropic glutamate receptor subunits, GluR2 and GluR4, after cerebral IR. Sphingolipid analysis of the brain demonstrated significant accumulation of ceramide and sphingomyelin hydrolysis. The data suggest a novel mechanism for regulation of ASMase activity during cell adhesion in which Lyn acts as a key upstream kinase that may play a critical role in cerebral IR injury. 

Retracted: No

PubPeer comments:
 The four Fyn lanes (indicated with boxes) in Fig.5A share unexpected similarity.  ,