PReD-Bench/PRed-Bench huggingface dataset:
Long-term efficacy and safety of mRNA therapy in two murine models of methylmalonic acidemia
Authors: Andrea Frassetto
Christine DeAntonis
Ding An
Rodrigo Laureano
Eric Jacquinet
Joseph Milano
Marianne Eybye
Jaclyn Milton
Vi Nguyen
Staci Sabnis
Lin T Guey
Christine M Lukacs
Journal: EBioMedicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: Enzyme replacement; Liver targeted therapy; Methylmalonyl-CoA mutase; Organic acidemia; Systemic mRNA therapy.
Affiliations: Moderna, Inc., 200 Technology Square, Cambridge, MA 02139, USA., Moderna, Inc., 200 Technology Square, Cambridge, MA 02139, USA. Electronic address: .

Abstract:  Background: Isolated methylmalonic acidemia/aciduria (MMA) is an ultra-rare, serious, inherited metabolic disorder with significant morbidity and mortality. Exogenously delivered mRNA encoding human methylmalonyl-CoA mutase (hMUT), the enzyme most frequently mutated in MMA, is a potential therapy to produce functional MUT enzyme in liver. Methods: Two 12-week repeat-dose studies were conducted to evaluate the efficacy and safety of intravenously-administered hMUT mRNA encapsulated in lipid nanoparticles in two murine models of MMA. Findings: In MMA hypomorphic mice, hMUT mRNA treatment resulted in dose-dependent and reproducible biomarker responses after each dose. Enzymatically-active MUT protein was produced in liver in a dose-dependent manner. hMUT mRNA was well-tolerated with no adverse effects, as indicated by the lack of clinical observations, minimal changes in clinical chemistry parameters, and histopathology examination across all tissues. In severe MMA mice, hMUT mRNA led to substantially improved survival and growth and ameliorated biochemical abnormalities, all of which are cardinal clinical manifestations in severely affected patients. Interpretation: These data demonstrate durable functional benefit of hMUT mRNA and support development of this new class of therapy for a devastating, pediatric disorder. FUND: This work was funded by Moderna, Inc. 

Retracted: No

PubPeer comments:
 This study was funded and conducted by Moderna, and *all* authors are employees of the company and have declared their competing interests. Yet we read the agrammatical, numerically incorrect and unbelievable  Funders had no role in study design, data collection, data analysis, interpretation or writing of the report. Clearly the funder had a major role in all aspects of the study, and this is fine and good. The implausible declaration of  no role should be clarified or changed with a correction to the article. ,
Exosomes secreted by palmitic acid-treated hepatocytes promote LX-2 cell activation by transferring miRNA-107
Authors: Shuting Wu
Xiaoyang Lai
Yunfeng Shen
Yunqin Han
Han Liu
Fangfang Li
Wei Wang
Journal: Cell Death Discovery (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hepatic stellate cells; Exosomes; Palmitic acid; Liver fibrogenesis; NAFLD
Affiliations: Department of Endocrinology and Metabolism, Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, The Second Affiliated Hospital of Nanchang University, 330006, Nanchang, China., Department of Endocrinology and Metabolism, Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, The Second Affiliated Hospital of Nanchang University, 330006, Nanchang, China. .

Abstract:  Activation of hepatic stellate cells (HSCs) is a key inducer of liver fibrogenesis in nonalcoholic fatty liver disease (NAFLD). Exosomes play an important role between hepatocytes and HSCs. This study aims to explore the role of exosomes derived from palmitic acid (PA)-treated hepatocytes in regulating HSCs (LX-2 cell) proliferation and activation and the underlying mechanisms. Exosomes were isolated from PA-treated human normal hepatocytes and incubated with LX-2 cells. Cell Counting Kit-8 (CCK-8) was performed to determine LX-2 cell proliferation, and the expression of fibrosis markers α-smooth muscle actin (α-SMA) and collagen type 1 α1 (CoL1A1) were examined to evaluateLX-2 cell activation. PA induced hepatocytes to release more exosomes enriched in miR-107. Mechanically, on the one hand, exosomes from PA-treated hepatocytes shuttled miR-107 to LX-2 cells, where miR-107 activated Wnt signaling by targeting DKK1 and thereby induced LX-2 cell activation; on the other hand, PA-treated hepatocytes derived exosomes also delivered miR-107 to CD4 + T lymphocytes, where miR-107 elevated IL-9 expression by targeting Foxp1, which bound to the IL-9 promoter in CD4 + T cells and suppressed Th9 cell differentiation and reduced IL-9 expression, and thus promoted LX-2 cell activation by activating Raf/MEK/ERK signaling pathway. 

Retracted: No

PubPeer comments:
 This paper is highly problematic for at least two reasons: The presentation of the exosome data in Figure 1 show no proof that they actually are studying exosomes. The TEM micrographs of so called exosomes can be anything. Without immunostaining for exosome markers, this data is worthless. Furthermore, the Western immunoblot of CD63 in the same figure has not the usual smearing, indicating that it is not CD63. In Figure 2 the authors are revealed for their obvious data manipulation. ![file] ,
Alterations of tumor suppressor gene p16INK4a in pancreatic ductal carcinoma
Authors: Jaidev Wig
Jyotika Attri
Radhika Srinivasan
Bishan Dass Radotra
Siddhartha Majumdar
Journal: BMC Gastroenterology (2005)
Discipline: CLINICAL MEDICINE
Keywords: p16; pancreatic ductal adenocarcinoma; gene alterations; methylation; mutations
Affiliations: Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 

Abstract:  Background: Cell cycle inhibitor and tumor suppressor gene p16/MTS-1 has been reported to be altered in a variety of human tumors. The purpose of the study was to evaluate primary pancreatic ductal adenocarcinomas for potentially inactivating p16 alterations. Methods: We investigated the status of p16 gene by polymerase chain reaction (PCR), nonradioisotopic single strand conformation polymorphism (SSCP), DNA sequencing and hypermethylation analysis in 25 primary resected ductal adenocarcinomas. In addition, we investigated p16 protein expression in these cases by immunohistochemistry (IHC) using a monoclonal antibody clone (MS-887-PO). Results: Out of the 25 samples analyzed and compared to normal pancreatic control tissues, the overall frequency of p16 alterations was 80% (20/25). Aberrant promoter methylation was the most common mechanism of gene inactivation present in 52% (13/25) cases, followed by coding sequence mutations in 16% (4/25) cases and presumably homozygous deletion in 12% (3/25) cases. These genetic alterations correlated well with p16 protein expression as complete loss of p16 protein was found in 18 of 25 tumors (72%). Conclusion: These findings confirm that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behaviour of this tumor type. 

Retracted: No

PubPeer comments:
 unclear legend, lanes more similar than expected ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Orphan nuclear receptor Errγ induces C-reactive protein gene expression through induction of ER-bound Bzip transmembrane transcription factor CREBH
Authors: Dipanjan Chanda
Sung Hoon Back
Hueng-Sik Choi
Don-Kyu Kim
Seung-Hoi Koo
Jagannath Misra
Chul-Ho Lee
Seung-Rye Cho
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: ERRγ; CREBH; ER stress; gene regulation; transcription factor
Affiliations: National Creative Research Initiatives Center for Nuclear Receptor Signals, Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea., Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea., Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea., School of Biological Sciences, University of Ulsan, Ulsan, South Korea., National Creative Research Initiatives Center for Nuclear Receptor Signals, Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea ; Research Institute of Medical Sciences, Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.

Abstract:  The orphan nuclear receptor estrogen-related receptor-γ (ERRγ) is a constitutively active transcription factor regulating genes involved in several important cellular processes, including hepatic glucose metabolism, alcohol metabolism, and the endoplasmic reticulum (ER) stress response. cAMP responsive element-binding protein H (CREBH) is an ER-bound bZIP family transcription factor that is activated upon ER stress and regulates genes encoding acute-phase proteins whose expression is increased in response to inflammation. Here, we report that ERRγ directly regulates CREBH gene expression in response to ER stress. ERRγ bound to the ERRγ response element (ERRE) in the CREBH promoter. Overexpression of ERRγ by adenovirus significantly increased expression of CREBH as well as C-reactive protein (CRP), whereas either knockdown of ERRγ or inhibition of ERRγ by ERRγ specific inverse agonist, GSK5182, substantially inhibited ER stress-mediated induction of CREBH and CRP. The transcriptional coactivator PGC1α was required for ERRγ mediated induction of the CREBH gene as demonstrated by the chromatin immunoprecipitation (ChIP) assay showing binding of both ERRγ and PGC1α on the CREBH promoter. The ChIP assay also revealed that histone H3 and H4 acetylation occurred at the ERRγ and PGC1α binding site. Moreover, chronic alcoholic hepatosteatosis, as well as the diabetic obese condition significantly increased CRP gene expression, and this increase was significantly attenuated by GSK5182 treatment. We suggest that orphan nuclear receptor ERRγ directly regulates the ER-bound transcription factor CREBH in response to ER stress and other metabolic conditions. 

Retracted: No

PubPeer comments:
 Concern about Figure 3D. Three of the eight presented qPCR panels appear to look very similar. Note the presence of several vertical stripes and the position of three white dots (indicated by green arrows). ![file] ,
WISP1 neuroprotection requires FoxO3a post-translational modulation with autoregulatory control of SIRT1
Authors: Yan Chen Shang
Kenneth Maiese
Zhao Zhong Chong
Shaohui Wang
Journal: Current Neurovascular Research (2013)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: WISP1; FoxO3a; PI 3-K; Akt1; caspase 1
Affiliations: Laboratory of Cellular and Molecular Signaling, New Jersey Health Sciences University, Newark, NJ 07101.

Abstract:  As a member of the secreted extracellular matrix associated proteins of the CCN family, Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4) is garnering increased attention not only as a potent proliferative entity, but also as a robust cytoprotective agent during toxic insults. Here we demonstrate that WISP1 prevents forkhead transcription factor FoxO3a mediated caspase 1 and caspase 3 apoptotic cell death in primary neurons during oxidant stress. Phosphoinositide 3-kinase (PI 3-K) and protein kinase B (Akt1) are necessary for WISP1 to foster posttranslational phosphorylation of FoxO3a and sequester FoxO3a in the cytoplasm of neurons with protein 14-3-3. Through an autoregulatory loop, WISP1 also minimizes deacytelation of FoxO3a, prevents caspase 1 and 3 activation, and promotes an effective neuroprotective level of SIRT1 activity through SIRT1 nuclear trafficking and prevention of SIRT1 caspase degradation. Elucidation of the critical pathways of WISP1 that determine neuronal cell survival during oxidative stress may offer novel therapeutic avenues for neurodegenerative disorders. 

Retracted: No

PubPeer comments:
 It appears that a set of three images in Figure 2D overlap with images in Figure 6B, after rotation - see green boxes. I have shown the overlap and rotation with the DAPI images, marked in yellow. *** ![file] ,
Actinomycin D induces histone gamma-H2AX foci and complex formation of gamma-H2AX with Ku70 and nuclear DNA helicase II
Authors: Frank Grosse
Suisheng Zhang
Peter Hemmerich
Hannah Elisabeth Mischo
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: gamma-H2AX foci; genotoxic stress; DNA double strand breaks; replication forks; actinomycin D
Affiliations: Departments of Biochemistry and Molecular Biology, Institute of Molecular Biotechnology, Postfach 100 813, D-07708 Jena, Germany.

Abstract:  Formation of gamma-H2AX foci is a P. O.cellular response to genotoxic stress, such as DNA double strand breaks or stalled replication forks. Here we show that gamma-H2AX foci were also formed when cells were incubated with 0.5 microg/ml DNA intercalating agent actinomycin D. In untreated cells, gamma-H2AX co-immunoprecipitated with Ku70, a subunit of DNA-dependent protein kinase, as well as with nuclear DNA helicase II (NDH II), a DEXH family helicase also known as RNA helicase A or DHX9. This association was increased manifold after actinomycin D treatment. DNA degradation diminished the amount of Ku70 associated with gamma-H2AX but not that of NDH II. In vitro binding studies with recombinant NDH II and H2AX phosphorylated by DNA-dependent protein kinase confirmed a direct physical interaction between NDH II and gamma-H2AX. Thereby, the NDH II DEXH domain alone, i.e. its catalytic core, was able to support binding to gamma-H2AX. Congruently, after actinomycin D treatment, NDH II accumulated in RNA-containing nuclear bodies that predominantly co-localized with gamma-H2AX foci. Taken together, these results suggest that histone gamma-H2AX promotes binding of NDH II to transcriptionally stalled sites on chromosomal DNA. 

Retracted: No

PubPeer comments:
 Figure 3A. Much more similar than you would expect after vertical stretch (note: no background). https: imgur.com RkaCFJ8 ,
Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies
Authors: M A Klein
B Oesch
T Rülicke
R M Zinkernagel
C Musahl
F L Heppner
I Arrighi
U Kalinke
A Aguzzi
Journal: Science (2001)
Discipline: Multidisciplinary
Keywords: Variant Creutzfeldt-Jakob disease; bovine spongiform encephalopathy; prions; vaccination; immunogenicity
Affiliations: Institute of Neuropathology, Institute of Laboratory Animal Science, Institute of Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland.

Abstract:  Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy are initiated by extracerebral exposure to prions. Although prion transmission from extracerebral sites to the brain represents a potential target for prophylaxis, attempts at vaccination have been limited by the poor immunogenicity of prion proteins. To circumvent this, we expressed an anti-prion protein (anti-PrP) mu chain in Prnp(o/o) mice. Transgenic mice developed sustained anti-PrP titers, which were not suppressed by introduction of Prnp+ alleles. Transgene expression prevented pathogenesis of prions introduced by intraperitoneal injection in the spleen and brain. Expression of endogenous PrP (PrP(C)) in the spleen and brain was unaffected, suggesting that immunity was responsible for protection. This indicates the feasibility of immunological inhibition of prion disease in vivo. 

Retracted: No

PubPeer comments:
 Sometimes it takes two decades to fully appreciate the importance of a work of science. This seminal paper has, for the first time, shown that antibodies against the prion protein can protect against prion diseases. All the efforts to combat neurodegeneration with biologicals, all the way down to the recent Aducanumab trials that are about to be considered by the FDA, stem from this research. Kudos to the Aguzzi lab for having started an entirely new and original line of research with their original discovery, with tremendous implications for future therapies. Table 1 shows, crucially, that spleen prion titers are suppressed by administration of the antiprion antibody 6H4. ![file] ,
Transforming growth factor-β1 treatment of oral cancer induces epithelial-mesenchymal transition and promotes bone invasion via enhanced activity of osteoclasts
Authors: Moustafa Elhousiny
Newell W Johnson
Jingjing Quan
Jin Gao
Journal: Clinical & experimental metastasis (2013)
Discipline: CLINICAL MEDICINE
Keywords: EMT; OSCC; TGF-β1; cell invasion; bone invasion

Abstract:  This study investigates relationships between EMT and bone invasion by OSCC. Three OSCC cell lines, SCC25, HN5, and Tca8113 were artificially induced to display EMT by adding 5 ng/mL of TGF-β1 to culture media for 1-3 days. Cell morphology and phenotypic changes was examined by immunocytochemical staining of CK and VIM. EMT markers, cell-invasion factors, and osteoclast-related molecules were analysed at mRNA, gelatine and protein levels by real-time PCR, gelatine zymography and Western blotting respectively. Mature osteoclasts differentiated from Raw264.7 cells were treated by conditioned medium (CM) of OSCC cells with/without TGF-β1. Immunohistochemistry was performed to validate proteins of CK, VIM, E-cad and Snail1 in OSCC tissue samples with bone invasion. Results showed minimal staining of VIM was found in SCC25 and HN5, while Tca8113 cells stained strongly. EMT markers Twist1 and N-cad were up-regulated; Snail1 and E-cad down-regulated in all cells. Of factors associated with invasion, MMP-2 was unchanged and MMP-9 increased in SCC25 and Tca8113, while MMP-2 was increased and MMP-9 unchanged in HN5. For osteoclast-related molecules, both MT1-MMP and RANKL were up-regulated, while OPG was down-regulated in all cells. CM of OSCC cells pre-treated with TGF-β1 showed to prolong survival of osteoclasts up to 4 days. All target molecules were validated in OSCC samples of bone invasion. These findings suggest that TGF-β1 not only induces EMT to increase the capacity of OSCC for invasion, but also promotes factors which prolong osteoclast survival. TGF-β1 may enhance the ability of MMP2/9 in resorbing bone and favouring invasion of cancer cells. 

Retracted: No

PubPeer comments:
 Figure 6A includes an apparent image overlap (red boxes, approximately). *** ![file] ,
Remote Ischemic Preconditioning induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway
Authors: Harshini Mudaliar
Anthony Dona
Anisyah Ridiandries
Muntasir Billah
Levon M Khachigian
Usaid K Allahwala
Ravinay Bhindi
Stephen Hunyor
Journal: International Journal of Molecular Sciences (2020)
Discipline: CHEMISTRY
Keywords: JAK-STAT; autophagy; interleukin-6; ischemia reperfusion; preconditioning.
Affiliations: Department of Cardiology, Kolling Institute of Medical Research, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia., Sydney Medical School Northern, University of Sydney, Sydney, NSW 2006, Australia., School of Life Sciences, Independent University Bangladesh, Dhaka 1229, Bangladesh., Vascular Biology and Translational Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.

Abstract:  : Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in remote ischemic preconditioning (RIPC)-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by a 30-min transient blockade of the left coronary artery to simulate ischemia reperfusion (I/R) injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC, respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant interleukin-6 (IL-6) treatment prior to I/R increased in vitro autophagy in a dose-dependent manner, activating the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway without affecting the other kinase pathways, such as p38 mitogen-activated protein kinases (MAPK), and glycogen synthase kinase 3 Beta (GSK-3β) pathways. Prior to I/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6/JAK-STAT-dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease. 

Retracted: No

PubPeer comments:
 The histograms in Fig. 1 don t seem to correspond with the Westerns. ![file] , 
 The rat lysate western blots in Fig 1B appear unexpectedly similar to those from H9c2 cells in Supp Fig. 1, but the quantification of the levels is different, with statistically significant differences shown in one, but not the other. ![file] ,
Trimethoprim-Loaded PLGA Nanoparticles Grafted with WGA as Potential Intravesical Therapy of Urinary Tract Infections-Studies on Adhesion to SV-HUCs Under Varying Time, pH, and Drug-Loading Conditions
Authors: Patricia Haiss
Desireé Rauch
Bernhard Brauner
Michael Wirth
Patrik Schwarz
Melinda Nokaj
Johanna Semmler
Franz Gabor
Journal: ACS Omega (2020)
Discipline: CHEMISTRY
Keywords: Intravesical therapy; PLGA nanoparticles; urinary tract infections; adhesion; surface modification
Affiliations: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.

Abstract:  Intravesical therapy, already used to treat bladder cancer, is a potential treatment option for urinary tract infections. However, short dwelling time and washout proved to be challenging obstacles. To circumvent these issues, PLGA 503H and PLGA 2300 nanoparticles were prepared and surface modified with wheat germ agglutinin (WGA). Nanoparticles of both poly(d,l-lactic-co-glycolic acid) (PLGA) types exhibited high inherent adhesion to human uroepithelial cells. Although surface-bound WGA could be easily increased, adhesion did not. Loading the nanoparticles with trimethoprim did not counteract cell adhesion. Varying the medium for instillation revealed highest adhesion in sodium bicarbonate buffer (pH 5). To evaluate dwelling time, nanoparticles were incubated with the cell monolayer for increasing time intervals. A contact time of 15 min seems to be too short for adhesion to the cells as less than 50% particles remained bound after washing. However, after 30 min 70% of the particles added were bound, and afterward, no further increase was observed. WGA only slightly increased the adhesion of the PLGA nanoparticles, but this approach might not be economically viable. However, PLGA nanoparticles displayed a high inherent adhesion to cells that might substantially foster intravesical therapy. 

Retracted: No

PubPeer comments:
 The authors should know that Iniparib is not a PARP inhibitor. and it doesn t work in treatment of triple-negative breast cancer. This was known in 2012: https: clincancerres.aacrjournals.org content 18 2 510 https: clincancerres.aacrjournals.org content 18 6 1655 Furthermore, it doesn t work in treatment of triple-negative breast cancer and a phase 3 study was stopped in 2014 due to lack of efficacy: https: pubmed.ncbi.nlm.nih.gov 25349301 ,
A chrysanthemum heat shock protein confers tolerance to abiotic stress
Authors: Jiafu Jiang
Haishun Gao
Aiping Song
Fadi Chen
Sumei Chen
Xirong Zhu
Journal: International Journal of Molecular Sciences (2014)
Discipline: CHEMISTRY
Keywords: Heat shock proteins; abiotic stresses; chrysanthemum; cDNA; HSP70 family
Affiliations: College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. .

Abstract:  Heat shock proteins are associated with protection against various abiotic stresses. Here, the isolation of a chrysanthemum cDNA belonging to the HSP70 family is reported. The cDNA, designated CgHSP70, encodes a 647-residue polypeptide, of estimated molecular mass 70.90 kDa and pI 5.12. A sub-cellular localization assay indicated that the cDNA product is deposited in the cytoplasm and nucleus. The performance of Arabidopsis thaliana plants constitutively expressing CgHSP70 demonstrated that the gene enhances tolerance to heat, drought and salinity. When CgHSP70 was stably over-expressed in chrysanthemum, the plants showed an increased peroxidase (POD) activity, higher proline content and inhibited malondialdehyde (MDA) content. After heat stress, drought or salinity the transgenic plants were better able to recover, demonstrating CgHSP70 positive effect. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation
Authors: Ayako Kamida
Ted R Hupp
Lisa Y Pang
David J Argyle
Emma L Gatenby
Bruce A Whitelaw
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Osteosarcoma; cancer stem cells; metastasis; chemotherapy resistance; canine
Affiliations: Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom., Edinburgh Cancer Research UK Centre, The University of Edinburgh, Edinburgh, United Kingdom.

Abstract:  Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in &gt;80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation. 

Retracted: No

PubPeer comments:
 The Zeb1 band of Figure 1G appears to be missing the leftmost lane. Could the authors please provide the original data? *** ![file] *** Close up, false color ![file] , 
 Journal notified today after no response from the authors. ,
Monoclonal antibodies to Coxiella burnetii for antigenic detection in cell cultures and in paraffin-embedded tissues
Authors: J C Laurent
D Raoult
M Mutillod
Journal: American Journal of Clinical Pathology (1994)
Discipline: CLINICAL MEDICINE
Keywords: monoclonal antibodies; Coxiella burnetti; Q fever; early detection; shell vial cell cultures
Affiliations: Faculte de Medecine, Unite des Rickettsies, Marrseille, France.

Abstract:  The authors developed monoclonal antibodies to Coxiella burnetti, the agent of Q fever. The selected monoclonal antibody, Cox1D8, did not cross-react with other bacteria and was used for early detection of C burnetti in shell vial cell cultures and for staining C burnetii in paraffin embedded tissues. Formalin or Bouin fixation did not alter the reactivity of the antigen with the antibody. This monoclonal antibody could be useful in the pathologic diagnosis of Q fever hepatitis and endocarditis. 

Retracted: No

PubPeer comments:
 Figure 1 and Figure 2 look remarkably similar. Based on the legends, Figure 2 maybe should have shown something else. Could the authors please check? They might also want to check the spelling of the affiliated city,  *Marrseille* . ![file] ,
Adjunctive laser or antimicrobial photodynamic therapy to non‐surgical mechanical instrumentation in patients with untreated periodontitis: A systematic review and meta‐analysis
Authors: Christoph A Ramseier
Clemens Walter
Anton Sculean
Alexandra Stähli
Giovanni E Salvi
Julia C Schmidt
Journal: Journal Of Clinical Periodontology (2020)
Discipline: CLINICAL MEDICINE
Keywords: antimicrobial photodynamic therapy; laser; non-surgical periodontal treatment; periodontitis; systematic review.
Affiliations: Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland., Department of Periodontology, Endodontology and Cariology, University Center for Dental Medicine (UZB), University of Basel, Basel, Switzerland.

Abstract:  Aim: To compare the adjunctive effects of lasers or antimicrobial photodynamic therapy (aPDT) to non-surgical mechanical instrumentation alone in untreated periodontitis patients. Materials and methods: Two focused questions were addressed using the Population, Intervention, Comparison and Outcome criteria as follows: in patients with untreated periodontitis, (a) does laser application provide adjunctive effects on probing pocket depth (PPD) changes compared with non-surgical instrumentation alone? and (b) does application of aPDT provide adjunctive effects on PPD changes compared with non-surgical instrumentation alone? Both randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) were included. Results of the meta-analysis are expressed as weighted mean differences (WMD) and reported according to the PRISMA guidelines. Results: Out of 1,202 records, 10 articles for adjunctive laser and 8 for adjunctive aPDT were included. With respect to PPD changes, 1 meta-analysis including 2 articles (total n = 42; split-mouth design) failed to identify a statistically significant difference (WMD = 0.35 mm; 95%CI: -0.04/0.73; p = .08) in favour of adjunctive aPDT (wavelength range 650-700 nm). In terms of adjunctive laser application, a high variability of clinical outcomes at 6 months was noted. Two articles included patient-reported outcomes and 10 reported on the presence/absence of harms/adverse effects. Conclusions: Available evidence on adjunctive therapy with lasers and aPDT is limited by (a) the low number of controlled studies and (b) the heterogeneity of study designs. Patient-reported benefits remain to be demonstrated. 

Retracted: No

PubPeer comments:
 Figure 1A is claimed to be an SEM image, but it is not. ![file] , 
 Thank you for pointing out this writing error in the text. Fig. 1A is u201cTEMu201d image instead of u201cSEMu201d. The data in this figure is true, and the writing error in text does not affect any results and conclusion of the work. Author Correction has now been published. Thanks again for your attention. , 
 #1 Author Correction has now been published. Thanks again for your attention. ,
Altered lipid and salt taste responsivity in ghrelin and GOAT null mice
Authors: Jean Sévigny
Bronwen Martin
Huan Cai
Wei-Na Cong
Matthias H Tschöp
Stuart Maudsley
Caitlin M Daimon
Rui Wang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Taste perception; Ghrelin; GOAT; Food intake; Energy metabolism
Affiliations: Metabolism Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.

Abstract:  Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT) is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both widely expressed in many organs including the gustatory system. In the current study, overall metabolic profiles were assessed in wild-type (WT), ghrelin knockout (ghrelin(-/-)), and GOAT knockout (GOAT(-/-)) mice. Ghrelin(-/-) mice exhibited decreased food intake, increased plasma triglycerides and increased ketone bodies compared to WT mice while demonstrating WT-like body weight, fat composition and glucose control. In contrast GOAT(-/-) mice exhibited reduced body weight, adiposity, resting glucose and insulin levels compared to WT mice. Brief access taste behavioral tests were performed to determine taste responsivity in WT, ghrelin(-/-) and GOAT(-/-) mice. Ghrelin and GOAT null mice possessed reduced lipid taste responsivity. Furthermore, we found that salty taste responsivity was attenuated in ghrelin(-/-) mice, yet potentiated in GOAT(-/-) mice compared to WT mice. Expression of the potential lipid taste regulators Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice, while the salt-sensitive ENaC subunit was increased in GOAT(-/-) mice compared with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible for the altered lipid and salt taste perception in ghrelin(-/-) and GOAT(-/-) mice. The data presented in the current study potentially implicates ghrelin signaling activity in the modulation of both lipid and salt taste modalities. 

Retracted: No

PubPeer comments:
 Overlapping area between WT (figure 6) and ghrelin - - (figure 7). ![file] ,
Elevated IL-13Ralpha2 in intestinal epithelial cells from ulcerative colitis or colorectal cancer initiates MAPK pathway
Authors: Debasmita Mandal
Alan D Levine
Journal: Inflammatory Bowel Diseases (2010)
Discipline: CLINICAL MEDICINE
Keywords: Chronic inflammation; Ulcerative colitis; Colorectal cancer; Interleukin-13; IL-13 receptor
Affiliations: Department of Pathology, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4952, USA.

Abstract:  Background: Chronic inflammation in ulcerative colitis (UC) is a sizeable risk factor for colorectal cancer (CRC). Interleukin-13 (IL-13) is elevated in the UC mucosa and may induce dysregulated signaling in neighboring intestinal epithelial cells (IECs) and thus function as a tumorogenic cytokine. Methods: Expression of IL-13 receptor chains on IECs obtained from control or chronically inflamed mucosa and colonic tumors was quantified by flow cytometry and immunoblot. IL-13Ralpha1 and IL-13Ralpha2 expression was significantly increased on IEC from UC and CRC patients compared to control and Crohn's disease (CD) subjects. Purified IEC from these subjects and cell lines expressing varying ratios of IL-13Ralpha1 and IL-13Ralpha2 chains were stimulated with IL-13 in vitro to investigate by immunoblot the activation of the signal transducer and activator of transcription 6 (STAT6) and mitogen activated protein kinase (MAPK) signaling pathways. Results: Despite similarly elevated receptor expression in UC and CRC, IL-13 does not activate the STAT6 or MAPK pathways in UC, while in colonic tumors only the STAT6 pathway is activated. Using neutralizing antibodies and cell lines expressing a range of surface densities for IL-13Ralpha1 and IL-3Ralpha2, we demonstrate that IL-13Ralpha2 serves a dual role, initiating MAPK signaling at low concentrations and as an inhibitory, decoy receptor at high IL-13Ralpha2 to IL-13Ralpha1 ratios. Conclusions: IL-13Ralpha2 is both a decoy receptor and induces MAPK signal transduction, depending on its relative expression and the local concentration of IL-13, which together modulate the balance and intensity of the signaling pathways initiated in UC and CRC. 

Retracted: Yes

PubPeer comments:
null, 
null, 
null, 
 Although this paper has long ago been retracted, it might still be worth updating this post with the correct version of the second part of my comment under #1. The image there got eaten by a PubPeer upgrade. Here is the correct comment and correct illustration. * Red boxes: Figure 3A: the first 4 lanes of the pERK time series appear to be the same as the pERK panel of Figure 2B in Mandal D et al. Cellular Signalling 22 (2010) 1485-1494 * Blue boxes: Figure 3D (CA, time series): the STAT6 gel appears to be the same as the STAT6 panel of Figure 6 in this paper (but flipped), and part of it appears to be the same as the STAT6 panel in Figure 2B in Mandal D et al. Cellular Signalling 22 (2010) 1485-1494. ![file] ,
Mentha piperita as a pivotal neuro-protective agent against gamma irradiation induced DNA fragmentation and apoptosis
Authors: Hanaa A Hassan
Hani S Hafez
Mona S Goda
Journal: Cytotechnology (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ionizing radiation; carcinogen; oxidative stress; apoptotic cell death; CNS

Abstract:  Ionizing radiation is classified as a potent carcinogen, and its injury to living cells, in particular to DNA, is due to oxidative stress enhancing apoptotic cell death. Our present study aimed to characterize and semi-quantify the radiation-induced apoptosis in CNS and the activity of Mentha extracts as neuron-protective agent. Our results through flow cytometry exhibited the significant disturbance and arrest in cell cycle in % of M1: SubG1 phase, M2: G0/1 phase of diploid cycle, M3: S phase and M4: G2/M phase of cell cycle in brain tissue (p &lt; 0.05). Significant increase in % of apoptosis and P53 protein expression as apoptotic biomarkers were coincided with significant decrease in Bcl(2) as an anti-apoptotic marker. The biochemical analysis recorded a significant decrease in the levels of reduced glutathione, superoxide dismutase, deoxyribonucleic acid (DNA) and ribonucleic acid contents. Moreover, numerous histopathological alterations were detected in brain tissues of gamma irradiated mice such as signs of chromatolysis in pyramidal cells of cortex, nuclear vacuolation, numerous apoptotic cell, and neural degeneration. On the other hand, gamma irradiated mice pretreated with Mentha extract showed largely an improvement in all the above tested parameters through a homeostatic state for the content of brain apoptosis and stabilization of DNA cycle with a distinct improvement in cell cycle analysis and antioxidant defense system. Furthermore, the aforementioned effects of Mentha extracts through down-regulation of P53 expression and up-regulation of Bcl(2) domain protected brain structure from extensive damage. Therefore, Mentha extract seems to have a significant role to ameliorate the neuronal injury induced by gamma irradiation. 

Retracted: No

PubPeer comments:
 Figures 5A and 5F appear to overlap although horizontal dimensions differ. *** ![file] , 
 At least two images in this paper seem to have been previously published in Journal of Medicinal Plant Research, May 2012 DOI: 10.5897 JMPR11.1389 (below left). While the earlier paper appears in the references here, I did not see the image itself referenced. *** ![file] ,
ZNRF2 is released from membranes by growth factors and, together with ZNRF1, regulates the Na+/K+ATPase
Authors: Alan R Prescott
Ayaz Najafov
Rachel Toth
Carol MacKintosh
David G Campbell
Gerta Hoxhaj
Journal: Journal of Cell Science (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: phosphorylation; myristoyl switch; ZNRF2; ZNRF1; E3 ubiquitin ligase
Affiliations: MRC Protein Phosphorylation Unit, James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. 

Abstract:  Here, we describe a phosphorylation-based reverse myristoyl switch for mammalian ZNRF2, and show that this E3 ubiquitin ligase and its sister protein ZNRF1 regulate the Na(+)/K(+) pump (Na(+)/K(+)ATPase). N-myristoylation localizes ZNRF1 and ZNRF2 to intracellular membranes and enhances their activity. However, when ZNRF2 is phosphorylated in response to agonists including insulin and growth factors, it binds to 14-3-3 and is released into the cytosol. On membranes, ZNRF1 and ZNRF2 interact with the Na(+)/K(+)ATPase α1 subunit via their UBZ domains, while their RING domains interact with E2 proteins, predominantly Ubc13 that, together with Uev1a, mediates formation of Lys63-ubiquitin linkages. ZNRF1 and ZNRF2 can ubiquitylate the cytoplasmic loop encompassing the nucleotide-binding and phosphorylation regions of the Na(+)/K(+)ATPase α1 subunit. Ouabain, a Na(+)/K(+)ATPase inhibitor and therapeutic cardiac glycoside, decreases ZNRF1 protein levels, whereas knockdown of ZNRF2 inhibits the ouabain-induced decrease of cell surface and total Na(+)/K(+)ATPase α1 levels. Thus, ZNRF1 and ZNRF2 are new players in regulation of the ubiquitous Na(+)/K(+)ATPase that is tuned to changing demands in many physiological contexts. 

Retracted: No

PubPeer comments:
 Figure 2: More similar than expected. Could authors check please? ![file] , 
 Dear Pubpeer, I m off work just now and the first author is on holiday till 29th August. We ll do our checking then. Best wishes, Carol , 
 We apologise for our error, athough it does not affect the results or the conclusions of this work, as explained in the following publisher s note: Publisher s Note: ZNRF2 is released from membranes by growth factors and, together with ZNRF1, regulates the Na+ K+ATPase Gerta Hoxhaj, Ayaz Najafov, Rachel Toth, David G Campbell, Alan R Prescott, Carol MacKintosh, 2022, vol. 135, issue 6, 2022. Journal of cell science. ,
Gentamicin Induced Microbiome Adaptations Associate With Increased BCAA Levels and Enhance Severity of Influenza Infection
Authors: Zhili He
Shunzong Yuan
Tao Li
Fanghong Chen
Nianzhi Ning
Zhan Li
Saisai Gong
Jianxin Wang
Liangyan Zhang
Li Xing
Deyan Luo
Jiajia Li
Yakun Sun
Hui Wang
Journal: Frontiers in Immunology (2021)
Discipline: IMMUNOLOGY
Keywords: T cells; branched-chain amino acids; gut microbiota; influenza; myeloid-derived suppressor cell.
Affiliations: Anhui Medical University, Hefei, China., State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

Abstract:  Involvement of gut microbiota in pulmonary disease by the gut-lung axis has been widely observed. However, the cross-talk messengers between respiratory mucosal immunity and gut microbiota are largely unknown. Using selective pharmacologic destruction of gut microenvironment mouse models, we found gut microbiota displayed significantly lower alpha diversity and relative abundance of bacteria in Gentamicin treated mice. Metagenomic studies revealed functional differences in gut bacteria in altering metabolic profiles in mice blood. Branched-chain amino acids (BCAAs) are the essential factors linked between gut and lung. During this process, selective destruction of gut microbiota by Gentamicin induced high levels of BCAAs, and the high levels of BCAAs impacted the lung immunity against influenza virus. In vivo, Gentamicin-treated mice or mice fed with high BCAAs diets displayed reduced survival. At the sites of infection, the number of CD11b+Ly6G+ cells decreased, and CD8+ T cells increased accompanied by exuberant expression of pro-inflammatory cytokines could result in tissue damage. CD11b+Ly6G+ cells transplantation conferred remarkable protection from influenza virus infections. In vitro, BCAAs promoted bone marrow-derived cells differentiation to dendritic cells. Taken together, these findings demonstrate that Gentamicin induced disruption of the gut microbiota leads to increased BCAA levels that suppress CD11b+Ly6c+ cell development in association with overactive CD8+ T responses which may contribute to enhanced severity of the viral infection. 

Retracted: No

PubPeer comments:
 Fig 3B,  protein expression in cells determined by Western blot assay . ![file] The loading control band is versatile. It also appears in *[left]* Fig 9C from [Han, Ju Geng (2018)] *[RETRACTED]*, *[right]* 6A from [Wen et al (2018a)] and *[below]* Fig 3E from [Wen et al (2018b)] . ![] , 
 Figs 2B, 4A: ![file] Here is a montage I prepared earlier, to illustrate [the products of a papermill] . The present WB bands appear to come from the same limited gamut. Note the loading controls in particular. ![] ,
Galectins Control mTOR in Response to Endomembrane Damage
Authors: Ryan Peters
Michal H Mudd
Lee Allers
Terje Johansen
Jingyue Jia
Vojo Deretic
Seong Won Choi
Brett Phinney
Suresh Kumar
Aurore Claude-Taupin
Yakubu Princely Abudu
Yuexi Gu
Michelle Salemi
Journal: Molecular cell (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AMPK; APEX2; LC3; TAK1; TFEB
Affiliations: Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA., Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway., Proteomics Core Facility, UC Davis Genome Center, University of California, Davis, CA 95616, USA., Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA. Electronic address: .

Abstract:  The Ser/Thr protein kinase mTOR controls metabolic pathways, including the catabolic process of autophagy. Autophagy plays additional, catabolism-independent roles in homeostasis of cytoplasmic endomembranes and whole organelles. How signals from endomembrane damage are transmitted to mTOR to orchestrate autophagic responses is not known. Here we show that mTOR is inhibited by lysosomal damage. Lysosomal damage, recognized by galectins, leads to association of galectin-8 (Gal8) with the mTOR apparatus on the lysosome. Gal8 inhibits mTOR activity through its Ragulator-Rag signaling machinery, whereas galectin-9 activates AMPK in response to lysosomal injury. Both systems converge upon downstream effectors including autophagy and defense against Mycobacterium tuberculosis. Thus, a novel galectin-based signal-transduction system, termed here GALTOR, intersects with the known regulators of mTOR on the lysosome and controls them in response to lysosomal damage. VIDEO ABSTRACT. 

Retracted: No

PubPeer comments:
 Supplemental Fig. S4G (i)(ii) u2013 more similar than expected ![file] , 
 FigS4G(i) and (ii) are part of the same experiment, with the same GST control; testing Gal8 and CRD1 and CRD2 constructs against GST fusions of RagA,B,C and D. It might have been better to avoid any confusion if we had shown (i) and (ii) in the same figure panel. Thanks for the comment. ,