PReD-Bench/PRed-Bench huggingface dataset:
Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials
Authors: Kholoud F Aliter
Rami A Al-Horani
Srabani Kar
Journal: International Journal of Molecular Sciences (2020)
Discipline: CHEMISTRY
Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; coronavirus
Affiliations: Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA., Department of Chemistry, School of STEM, Dillard University, New Orleans, LA 70122, USA.

Abstract:  The ongoing pandemic of coronavirus disease-2019 (COVID-19) is being caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease continues to present significant challenges to the health care systems around the world. This is primarily because of the lack of vaccines to protect against the infection and the lack of highly effective therapeutics to prevent and/or treat the illness. Nevertheless, researchers have swiftly responded to the pandemic by advancing old and new potential therapeutics into clinical trials. In this review, we summarize potential anti-COVID-19 therapeutics that block the early stage of the viral life cycle. The review presents the structures, mechanisms, and reported results of clinical trials of potential therapeutics that have been listed in clinicaltrials.gov. Given the fact that some of these therapeutics are multi-acting molecules, other relevant mechanisms will also be described. The reviewed therapeutics include small molecules and macromolecules of sulfated polysaccharides, polypeptides, and monoclonal antibodies. The potential therapeutics target viral and/or host proteins or processes that facilitate the early stage of the viral infection. Frequent targets are the viral spike protein, the host angiotensin converting enzyme 2, the host transmembrane protease serine 2, and clathrin-mediated endocytosis process. Overall, the review aims at presenting update-to-date details, so as to enhance awareness of potential therapeutics, and thus, to catalyze their appropriate use in combating the pandemic. 

Retracted: No

PubPeer comments:
 u201cPrimaquine is being tried in one interventional study (NCT04349410) with hydroxychloroquine and clindamycin for COVID-19 pneumonia as a part of the Fleming Method for Tissue and Vascular Differentiation and Metabolism (FMTVDM) protocol.u201d The authors may wish to look a bit deeper into this purported trial, including this skeptical post on Retraction Watch: https: retractionwatch.com 2020 05 29 a-convicted-felon-wants-people-to-enroll-in-a-covid-19-clinical-trial-what-could-go-wrong ![file] ,
Study on correlation between liver ultrasonic appearance of patients with chronic hepatitis B and cirrhosis and hydrothorax
Authors: Y-H Li
S Wang
H Shi
F Chen
L-L Sun
Journal: European review for medical and pharmacological sciences (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Liver ultrasonic appearance; chronic hepatitis B; cirrhosis; hydrothorax; correlation
Affiliations: Department of Medical Imaging, Qianfoshan Hospital Affiliated to Shandong University, Jinan, China.

Abstract:  The article "Study on correlation between liver ultrasonic appearance of patients with chronic hepatitis B and cirrhosis and hydrothorax" by L.-L. Sun, Y.-H. Li, F. Chen, S. Wang, H. Shi, published in Eur Rev Med Pharmacol Sci 2015; 20 (17): 3412-3605-3608 has been withdrawn. 

Retracted: No

PubPeer comments:
 Figs 3D, 4B, 5A B. ![file] Surprisingly similar Western Blots, stylised in the same manner, illustrate a corpus of [at least 150 papers] (with 50 so far retracted). Here , for example, Figs 3D, 4A, 5A from [Li et al (2018)] : ![] Figs 3D, 4B, 5A from [Lv, Zheng Huang (2018)] . ![] ,
The Transcriptional Repressor DEC2 Regulates Sleep Length in Mammals
Authors: Seiji Nishino
Ying He
Christopher R Jones
Ying-Hui Fu
Ying Xu
Bin Guo
Nobuhiro Fujiki
Jimmy L Holder Jr
Moritz J Rossner
Journal: Science (2009)
Discipline: Multidisciplinary
Keywords: Sleep deprivation; Genetic loci; Transcriptional repressor; hDEC2-P385R mutation; Short sleep phenotype

Abstract:  Sleep deprivation can impair human health and performance. Habitual total sleep time and homeostatic sleep response to sleep deprivation are quantitative traits in humans. Genetic loci for these traits have been identified in model organisms, but none of these potential animal models have a corresponding human genotype and phenotype. We have identified a mutation in a transcriptional repressor (hDEC2-P385R) that is associated with a human short sleep phenotype. Activity profiles and sleep recordings of transgenic mice carrying this mutation showed increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner. These mice represent a model of human sleep homeostasis that provides an opportunity to probe the effect of sleep on human physical and mental health. 

Retracted: No

PubPeer comments:
 Alright I found an error in the article, There is a Proline nearby but in the 384th position in the peptide. not the 385th as stated by the article. To the authors, please correct your mistake! ,
Inhibition of STAT3 by niclosamide synergizes with erlotinib against head and neck cancer
Authors: Shuo You
Gabriel L Sica
Rui Li
Dong M Shin
Zhuo G Chen
Walter J Curran
Xingming Deng
Zhongliang Hu
Fadlo R Khuri
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: EGFR; head and neck cancer; erlotinib; STAT3; Bcl2/Bcl-XL
Affiliations: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia, United States of America.

Abstract:  Epidermal growth factor receptor (EGFR) is extensively expressed in head and neck cancer. However, EGFR-targeted therapy has only modest efficacy in head and neck cancer, through mechanisms that are not fully understood. Here, we found that inhibition of EGFR by erlotinib stimulated phosphorylation and activation of STAT3 leading to increased Bcl2/Bcl-XL expression in head and neck cancer cells, which may dampen the therapeutic efficacy of erlotinib against head and neck cancer. Erlotinib-enhanced STAT3 phosphorylation results, at least in part, from suppression of its physiological phosphatase, PTPMeg2. Specific knockdown of STAT3 by RNA interference significantly sensitized head and neck cancer cells to erlotinib treatment. Pharmacological inhibition of STAT3 by niclosamide not only blocked erlotinib-stimulated STAT3 phosphorylation but also synergistically repressed head and neck cancer growth in vitro and in vivo. Combined inhibition of EGFR and STAT3 by erlotinib and niclosamide more effectively induced apoptosis in tumor tissues without toxicity for normal tissues. Based on our findings, treatment with erlotinib combined with niclosamide may offer an effective therapeutic approach to improve the prognosis of head and neck cancer. 

Retracted: No

PubPeer comments:
 The mean values in Table 1 appear to be all ending in a 0 at the second decimal (e.g. 15.20, 16.20), which is unexpected with 5 measurements. Secondly, many values, both in the means or in the SEMs, appear to duplicated, or very similar across different measurements. Could the authors please share a table with the individual measurement? ![file] , 
 The same question goes for Table 2. Some SEM values appear to be reported more times than expected (e.g. 0.22, 0.17, 0.13, 0.12, 0.11). Could the authors share their original measurements, please? ![file] , 
 Figure 7. Some bands appear to be visible multiple times within the same panel or across panels, albeit sometimes in mirror image. Arrows of the same color show similarities and orientation. Image contrast slightly adjusted to bring out details. ![file] ,
Cyclin D3 accumulation and activity integrate and rank the comitogenic pathways of thyrotropin and insulin in thyrocytes in primary culture
Authors: A Van Keymeulen
P P Roger
J E Dumont
J Bartek
Journal: Oncogene (1999)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cell cycle; growth factors; hormones; insulin; IGF-1
Affiliations: Institute of Interdisciplinary Research, Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium.

Abstract:  The proliferation of most normal cells depends on the synergistic interaction of several growth factors and hormones, but the cell cycle basis for this combined requirement remains largely uncharacterized. We have addressed the question of the requirement for insulin/IGF-1 also observed in many cell culture systems in the physiologically relevant system of primary cultures of dog thyroid epithelial cells stimulated by TSH, which exerts its mitogenic activity only via cAMP. The induction of cyclin A and cdc2, the phosphorylation of cdk2, the nuclear translocation of cdk4 and the assembly of cyclin D3-cdk4 complexes required the synergy of TSH and insulin. Cyclin D3 (the most abundant cyclin D) was necessary for the proliferation stimulated by TSH in the presence of insulin as shown by microinjection of a neutralizing antibody. Cyclin D3 accumulation and activity were differentially regulated by insulin and TSH, which points out this cyclin as an integrator that ranks these comitogenic pathways as supportive and activatory, respectively. Paradoxically TSH alone strongly repressed cyclin D3 accumulation. This inhibition was overridden by insulin, which markedly stimulated cyclin D3 mRNA and protein accumulation, but failed to assemble cyclin D3-cdk4 complexes in the absence of TSH. TSH unmasked the DCS-22 epitope of cyclin D3 and assembled cyclin D3-cdk4 in the presence of insulin. These data demonstrate that cyclin D synthesis and cyclin D-cdk assembly can be dissociated and complementarily regulated by different agents and signalling pathways. 

Retracted: No

PubPeer comments:
 Figure 4. Vertical splice Cyclin D2 panel, no vertical splice Cyclin D1 panel. ![file] ,
WITHDRAWN: Differential molecular signature alterations of RBSP3, LIMD1 and CDC25A in normal oral epithelium during oral tumorigenesis
Authors: Shreya Sarkar
Jaydip Biswas
Tyson Sharp
Chinmay Kumar Panda
Supratim Ghosh
Kabita Chatterjee
Susanta Roychoudhury
Neyaz Alam
Jayanta Chakraborty
Syam Sundar Mandal
Journal: Bioscience reports (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Accepted Manuscript; withdrawn; authors; request; June 2016
Affiliations: Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, 700026, India., Dept. of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, India., Chittaranjan National Cancer Institute, Kolkata, India., Dept. of Epidemiology and Biostatistics, Chittaranjan National Cancer Institute, Kolkata, India., Dept. of Oral and Maxillofacial Pathology, Buddha Institute of Dental Sciences and Hospital, Patna, India., North Bengal Dental College and Hospital, Dept. of Oral and Maxillofacial Pathology, India., Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Centre for Molecular Oncology, Barts Cancer Institute, London, United Kingdom., Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, 700026, India

Abstract:  The Accepted Manuscript version of this article (published on 1 June 2016) was withdrawn on 24 November 2017 at the request of the authors. 

Retracted: No

PubPeer comments:
 WITHDRAWN: Differential molecular signature alterations of RBSP3, LIMD1 and CDC25A in normal oral epithelium during oral tumorigenesis Shreya Sarkar, Neyaz Alam, Jayanta Chakraborty, Jaydip Biswas, Syam Sundar Mandal, Kabita Chatterjee, Supratim Ghosh, Susanta Roychoudhury, Tyson Sharp, Chinmay Kumar Panda Bioscience Reports Nov 24, 2017, BSR20160050; DOI: 10.1042 BSR20160050 The Accepted Manuscript version of this article (published on 1 June 2016) was withdrawn on 24 November 2017 at the request of the authors. , 
 Thank you for your comment. There was a misunderstanding with the journal s policy of publication charges, and we had run out of grant money to pay for the publication charges. Therefore, we had withdrawn the manuscript and recommunicated to another international peer- reviewed journal. , 
 I second the First author of the paper. ,
Attenuation of endoplasmic reticulum stress using the chemical chaperone 4-phenylbutyric acid prevents cardiac fibrosis induced by isoproterenol
Authors: José Miguel Vicencio
Pedro Ayala
Deisy Pivet
Alan Letelier
Claudio Humeres
Pablo Aránguiz Urroz
José Montenegro
Guillermo Díaz-Araya
Miguel Copaja
Rodrigo Troncoso
Sergio Lavandero
Raúl Vivar
Journal: Experimental and molecular pathology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Endoplasmic reticulum stress; Ischemia/reperfusion; Unfolded protein response; Cardiac remodeling; Cardiac fibrosis
Affiliations: FONDAP CEMC, Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.

Abstract:  Increasing evidence indicates that endoplasmic reticulum (ER) stress is involved in various diseases. In the human heart, ischemia/reperfusion has been correlated to ER stress, and several markers of the unfolded protein response (UPR) participate during cardiac remodeling and fibrosis. Here, we used isoproterenol (ISO) injection as a model for in vivo cardiac fibrosis. ISO induced significant cardiomyocyte loss and collagen deposition in the damaged areas of the endocardium. These responses were accompanied by an increase in the protein levels of the luminal ER chaperones BIP and PDI, as well as an increase in the UPR effector CHOP. The use of the chemical chaperone 4-phenylbutyric acid (4-PBA) prevented the activation of the UPR, the increase in luminal chaperones and also, leads to decreased collagen deposition, cardiomyocyte loss into the damaged zones. Our results suggest that cardiac damage and fibrosis induced in vivo by the beta-adrenergic agonist ISO are tightly related to ER stress signaling pathways, and that increasing the ER luminal folding capacity with exogenously administrated 4-PBA is a powerful strategy for preventing the development of cardiac fibrosis. Additionally, 4-PBA might prevent the loss of cardiomyocytes. Our data suggests that the attenuation of ER stress pathways with pharmacological compounds such as the chemical chaperone 4-PBA can prevent the development of cardiac fibrosis and adverse remodeling. 

Retracted: No

PubPeer comments:
 Figure 1B and 1C u2013 more similar than expected ![file] ,
Skin rejuvenation by microneedle fractional radiofrequency treatment in Asian skin; clinical and histological analysis
Authors: Moon Soo Yoon
Hee Jung Lee
Kyu Young Seo
Dong Hyun Kim
Journal: Lasers in surgery and medicine (2012)
Discipline: CLINICAL MEDICINE
Keywords: microneedle fractional radiofrequency; skin rejuvenation; Asian skin; efficacy; safety
Affiliations: Department of Dermatology, CHA Bundang Medical Center, CHA University, Republic of Korea.

Abstract:  Background: For skin rejuvenation, microneedle fractional radiofrequency (RF) is a recently developed minimally invasive method for delivering RF energy directly into the skin using microneedle. Objective: We evaluated efficacy and safety of microneedle fractional RF for skin rejuvenation in Asian skin and also conducted immunohistochemical analysis before and after treatment. Patients and methods: Twenty-five females (mean age 54.2, Fitzpatrick skin phototypes III-IV) received three consecutive fractional RF treatment at 4-week intervals. Outcome assessments included standardized photography, physician's global assessment, patient's satisfaction scores, objective biophysical measurements, and histologic analysis including immunohistochemical staining. Results: All patients showed clinical improvement on physician's global assessment and patient's satisfaction scores. Among objective biophysical measurements, improvement in hydration and skin roughness was noticed. Histologic examination revealed marked increase in dermal thickness, dermal collagen content and dermal fibrillin content. Side effects were minimal. Limitations: The limitations are the small number of patients and lack of long-term follow-up. Conclusion: Microneedle fractional RF is a safe and effective skin rejuvenation method in Asians. 

Retracted: No

PubPeer comments:
 Figures 4(A) and 4(B) also appear as Figures 4(A) and 4(B) in: Kyu Young Seo, Dong Hyun Kim, Sang Eun Lee, Moon Soo Yoon Hee Jung Lee (2013) Skin rejuvenation by microneedle fractional radiofrequency and a human stem cell conditioned medium in Asian skin: a randomized controlled investigator blinded split-face study, Journal of Cosmetic and Laser Therapy, https: doi.org 10.3109 14764172.2012.748201 ![file] *Above: Seo, 2012* *Below: Seo, 2013* ![file] One study uses stem cells, and the other does not. Could the authors explain how they obtained identical results? , 
 Further, panels C and D also appear in Seo, 2013 as figures 5(A) and 5(B) - outlined in green: ![file] , 
 And finally, the Immunohistochemical stains make a double-appearance as Figures 5(A) and 5(B) in Seo, 2012, and as Figures 6(C) and 6(D) in Seo, 2013 - as outlined in blue: ![file] *Above: Seo, 2012* *Below: Seo, 2013* ![file] ,
Up-regulation of vascular endothelial growth factor-A by active membrane-type 1 matrix metalloproteinase through activation of Src-tyrosine kinases
Authors: Agnès Noel
Nor Eddine Sounni
Jean-Michel Foidart
Christian Roghi
Francis Frankenne
Gillian Murphy
Beatriz G Galvez
Mathias Janssen
Carine Munaut
Vincent Chabottaux
Erik Maquoi
Christine Gilles
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MT1-MMP; VEGF; angiogenesis; tumor growth; proteolysis
Affiliations: Laboratory of Tumor and Development Biology University of Liège, Sart Tilman, 4000 Sart-Tilman, B-4000 Liège, Belgium.

Abstract:  Membrane-type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF) are two key molecules involved in pericellular proteolysis and cell proliferation during tumor growth and angiogenesis. Our previous data showed that MT1-MMP overexpression in human breast carcinoma MCF7 cells induced an up-regulation of VEGF expression. This effect was associated in vivo with accelerated tumor growth and angiogenesis. We now provide evidence that MT1-MMP overexpression specifically affected VEGF-A production and failed to influence that of other VEGF family members (VEGF, B, C, D, or PlGF) or their receptors. The up-regulation of VEGF-A by MT1-MMP was related to an increased transcriptional activation rather than to a modification of mRNA stability. It was blocked by synthetic MMP inhibitors, TIMP2, but not TIMP-1 and abolished by a partial deletion of the catalytic domain or the cytoplasmic tail of MT1-MMP. Analysis of the signal transduction mechanisms demonstrated that MT1-MMP acts through a signaling pathway involving Src tyrosine kinases. Thus, our results provide new insight into the mechanisms of action of MT1-MMP during angiogenesis and suggest that the full enzymatic activity of MT1-MMP is required for a specific up-regulation of VEGF-A through an activation of Src tyrosine kinase pathways. 

Retracted: No

PubPeer comments:
 Figure 2. Much more similar than you would expect. https: imgur.com yaZ0hSU , 
 Figure 6A. Much more similar than you would expect. https: imgur.com ZD9k4f9 , 
 ![file] ![file] ![file] ![file] ![file] , 
 #3 Figures 3A and 5B. Much more similar than expected. https: imgur.com 3ROpmc4 , 
 Figure 2. Much more similar than expected. ![file] ,
The RNA-binding protein HuD regulates autophagosome formation in pancreatic β cells by promoting autophagy-related gene 5 expression
Authors: Hideyuki Okano
Yun-Jeong Choe
Wook Kim
Ho-Shik Kim
Eun Kyung Lee
Chongtae Kim
Suk Woo Nam
Myriam Gorospe
Wado Akamatsu
Heejin Lee
Eunbyul Ji
Jennifer L Martindale
Journal: Journal of Biological Chemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Autophagy; RNA Metabolism; RNA Turnover; RNA-Protein Interaction; RNA-binding Protein.
Affiliations: From the Departments of Biochemistry and.

Abstract:  Tight regulation of autophagy is critical for the fate of pancreatic β cells. The autophagy protein ATG5 is essential for the formation of autophagosomes by promoting the lipidation of microtubule-associated protein LC3 (light chain 3). However, little is known about the mechanisms that regulate ATG5 expression levels. In this study, we investigated the regulation of ATG5 expression by HuD. The association of HuD with ATG5 mRNA was analyzed by ribonucleoprotein complex immunoprecipitation and biotin pulldown assays. HuD expression levels in pancreatic β cells were knocked down via siRNA, elevated by overexpression of a HuD-expressing plasmid. The expression levels of HuD, ATG5, LC3, and β-actin were determined by Western blot and quantitative RT-PCR analysis. Autophagosome formation was assessed by fluorescence microscopy in GFP-LC3-expressing cells and in pancreatic tissues from WT and HuD-null mice. We identified ATG5 mRNA as a post-transcriptional target of the mammalian RNA-binding protein HuD in pancreatic β cells. HuD associated with the 3'-UTR of the ATG5 mRNA. Modulating HuD abundance did not alter ATG5 mRNA levels, but HuD silencing decreased ATG5 mRNA translation, and, conversely, HuD overexpression enhanced ATG5 mRNA translation. Through its effect on ATG5, HuD contributed to the lipidation of LC3 and the formation of LC3-positive autophagosomes. In keeping with this regulatory paradigm, HuD-null mice displayed lower ATG5 and LC3 levels in pancreatic β cells. Our results reveal HuD to be an inducer of ATG5 expression and hence a critical regulator of autophagosome formation in pancreatic β cells. 

Retracted: No

PubPeer comments:
 Figure 9D shows ROS levels of HT-29 cells treated with 3 mM Cis-b sito-HPPS for different timepoints. However, in the bottom row, the same group of cells appears to be visible in three of the timepoint. Shown with red boxes; image made lighter to bring out more details. Could the authors please clarify? ![file] , 
 Figure 8. *Green boxes: Two panels representing different experiments appear to be showing an error of overlap. * Red circles: The same constellation of five nanoparticles appears to be visible multiple times within the same photo, and in different photos. I look forward to the authors explanation. ![file] , 
 #2 I have marked a few more pawprints to show that I was paying attention. ![file] , 
 One of the figures in another paper (doi: 10.1002 term.2964) seems to be overlap several times with several different papers, showing several different experimental groups and time-points. ![file] ,
p73 induction after DNA damage is regulated by checkpoint kinases Chk1 and Chk2
Authors: Marshall Urist
Tomoaki Tanaka
Masha V. Poyurovsky
Carol Prives
Journal: Genes & Development (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Checkpoint kinases; Chk1; Chk2; cell cycle arrest; DNA repair

Abstract: The checkpoint kinases Chk1 and Chk2 are central to the induction of cell cycle arrest, DNA repair, and apoptosis as elements in the DNA-damage checkpoint. We report here that in several human tumor cell lines, Chk1 and Chk2 control the induction of the p53 related transcription factor p73 in response to DNA damage. Multiple experimental systems were used to show that interference with or augmentation of Chk1 or Chk2 signaling strongly impacts p73 accumulation. Furthermore, Chk1 and Chk2 control p73 mRNA accumulation after DNA damage. We demonstrate as well that E2F1 directs p73 expression in the presence and absence of DNA damage. Chk1 and Chk2, in turn, are vital to E2F1 stabilization and activity after genotoxic stress. Thus, Chk1, Chk2, E2F1, and p73 function in a pathway mediating p53-independent cell death produced by cytotoxic drugs. Since p53 is often obviated through mutation as a cellular port for anticancer intervention, this pathway controlling p53 autonomous pro-apoptotic signaling is of potential therapeutic importance. 

Retracted: No

PubPeer comments:
 Figure 2D. Much more similar than you would expect. ![file] ,
Effects of PKA modulation on the expression of neuropeptide Y in rat amygdaloid structures during ethanol withdrawal
Authors: Subhash C Pandey
Huaibo Zhang
Journal: Peptides (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: neuropeptide Y; cAMP responsive element binding; CREB phosphorylation; protein kinase A activator; ethanol withdrawal
Affiliations: Department of Psychiatry, The Psychiatric Institute, University of Illinois, Chicago, IL 60612, USA.

Abstract:  We recently reported that neuropeptide Y (NPY) protein levels and cAMP responsive element binding (CREB) protein phosphorylation are lower in amygdaloid structures during ethanol withdrawal after chronic exposure. Furthermore, we reported that normalization of CREB phosphorylation by infusing protein kinase A (PKA) activator into the central amygdala prevents anxiety-like effects in rats during ethanol withdrawal. Here we investigated whether normalization of CREB phosphorylation by infusing PKA activator (Sp-cAMP) into the central amygdala also normalizes the expression of NPY during ethanol withdrawal. Sprague-Dawley male rats were cannulated targeting the central amygdala and then treated either with Lieber-DeCarli ethanol diet or control diet for 15 days. Subsequently ethanol-fed rats were withdrawn for 0 and 24h. The control-diet fed and ethanol-withdrawn rats were infused twice with PKA activator or inhibitor (Rp-cAMP). The protein and mRNA levels of NPY were determined in amygdaloid structures using gold-immunolabeling and the in situ RT-PCR procedure. It was found that chronic ethanol treatment has no effect on mRNA and protein levels of NPY in the central, medial, or basolateral amygdala. On the other hand, ethanol withdrawal produced significant reductions in mRNA and protein levels of NPY in the central and medial but not in the basolateral amygdala. The reductions in mRNA and protein levels of NPY were normalized in the central amygdala by infusion with PKA activator in ethanol-withdrawn rats. On the other hand, PKA-inhibitor infusion does not have any effect on mRNA and protein levels of NPY in the central amygdala of ethanol-withdrawn rats, but significantly decreased the expression of NPY in the central amygdala of control-diet fed rats. These results suggest that the decreased cellular expression of NPY in the central amygdala may play an important role in the CREB-mediated regulation of anxiety-like behaviors during ethanol withdrawal. 

Retracted: No

PubPeer comments:
 This paper has a 2011 correction, which reads:  In the above article, errors were occurred in the Fig. 1A for NPY mRNA CeA panel during manuscript preparation and some images were identical. The correct CeA NPY mRNA panel for Fig. 1A is printed below. The authors regret this error. Here is the original Figure 1A with two possible duplications highlighted in red and blue boxes. ![file] ,
Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice
Authors: Adam M Hamilton
Bryan B Yoo
Laura A Volpicelli-Daley
Collin Challis
Rosemary C Challis
Timothy R Sampson
Viviana Gradinaru
Acacia Hori
Sarkis K Mazmanian
Journal: Nature Neuroscience (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Parkinson's disease; synucleinopathy; motor dysfunction; midbrain dopaminergic neurons; α-synuclein aggregates
Affiliations: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA., Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA., Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. .

Abstract:  Parkinson's disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson's disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology. 

Retracted: No

PubPeer comments:
 Two images in the extended data appear unexpectedly similar and different. Could the authors compare Extended Data Figure 7d (merge) with Extended Data 9b? Rectangular areas seem similar, elliptical areas seem different. Apologies if I am misunderstanding something. *** ![file] *** Original ![file] , 
 Thank you for your comment and careful read. While the 2 images are different coronal slices the areas you point out require us to review the images selected. We are reviewing the files and will update here, please allow us a few weeks for response. ,
Race and Genetics vs. ‘Race’ in Genetics: A Systematic Review of the Use of African Ancestry in Genetic Studies
Authors: Annika Weller
Theresa M Duello
Shawna Rivedal
Colton Wickland
Journal: Evolution Medicine and Public Health (2021)
Discipline: CLINICAL MEDICINE
Keywords: African American; African ancestry; black; clinical trials; evolutionary biology
Affiliations: Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53, US

Abstract:  Social scientists have long understood race to be a social category invented to justify slavery and evolutionary biologists know the socially constructed racial categories do not align with our biological understanding of genetic variation. The completion of the Human Genome Project in 2003 confirmed humans are 99.9% identical at the DNA level and there is no genetic basis for race. A systematic review of the PubMed medical literature published since 2003 was conducted to assess the use of African ancestry to denote study populations in genetic studies categorized as clinical trials, to examine the stated rationale for its use and to assess the use of evolutionary principles to explain human genetic diversity. We searched for papers that included the terms 'African', 'African American' or 'Black' in studies of behavior (20 papers), physiological responses, the pharmacokinetics of drugs and/or disease associations (62 papers), and as a genetic category in studies, including the examination of genotypes associated with life stress, pain, stuttering and drug clearance (126 papers). Of these, we identified 74 studies in which self-reported race alone or in combination with admixture mapping was used to define the study population. However, none of these studies provided a genetic explanation for the use of the self-identified race as a genetic category and only seven proffered evolutionary explanations of their data. The concept of continuous genetic variation was not clearly articulated in any of these papers, presumably due to the paucity of evolutionary science in the college and medical school curricula. 

Retracted: No

PubPeer comments:
 I am concerned about possible duplications in Fig3 (B) of this paper. The two figures of fluorescence microscopy for  200a-3p-in and  siMAPK14 were quite different, but the two figures of flow cytometry were more similar than expected. ![file] , 
 The author stated at Page 1550 : We found that miR-200a-3p inhibited levels of the phosphorylated form of p38u03b1 and led to the subsequent decreased phosphorylation of MAPK-activated protein kinase 2 (MAPKAPK2) and heat shock protein 27 (HSP27), 2 major downstream effectors of p38a (Fig. 1C). The phosphorylation of a protein should be indicated as phosphorylated protein total protein, but not phosphorylated protein a housekeeping protein. However, the WBs for the total protein of p38u03b1, MAPKAPK2 and HSP27 were not analyzed. The authors normalized the expression level of p-p38a, p-Akt, p-p53 by GAPDH throughout the manuscript (Figure 1 C and F), the conclusion would be untenable. ![file] , 
 ![file] ,
Tumor Necrosis Factor Alpha-Mediated Inflammation and Remodeling of the Extracellular Matrix Underlies Aortic Stiffening Induced by the Common Chemotherapeutic Agent Doxorubicin
Authors: Abigail G Casso
Judith Campisi
Douglas R Seals
David A Hutton
Zachary S Clayton
Brian P Ziemba
Simon Melov
Vienna E Brunt
Journal: Hypertension (2021)
Discipline: CLINICAL MEDICINE
Keywords: anthracyclines; cardiovascular diseases; doxorubicin; elastic modulus; fibrosis.
Affiliations: Department of Integrative Physiology, University of Colorado Boulder, Colorado (Z.S.C., V.E.B., D.A.H., A.G.C., B.P.Z., D.R.S.)., Buck Institute for Research on Aging, Novato, CA (S.M., J.C.)., Lawrence Berkeley National Laboratory, CA (J.C.).

Abstract:  [Figure: see text]. 

Retracted: No

PubPeer comments:
 ![file] Figure 4- some of the strangest WB I have ever seen. Clearly, despite n=10, they are derived from the same samples given the apparent identity of the GAPDH blots. Massively over-exposed, slot gel without seeing other parts of the blot, no markers. Where is the QC at the journal. , 
 #1 These were obtained with a Simple Western, not a traditional blot. The images are representative, they do not contain all 10 samples. Agreed re overexposure, however, that is just the choice of the author and does not affect quant when doing Simple Western, where there is peak integration and not densitometry. ,
miR-190 suppresses breast cancer metastasis by regulation of TGF-β-induced epithelial-mesenchymal transition
Authors: Yu Ding
Jie Ge
Jiang-Rui Chi
Xu-Chen Cao
Xin Wang
Zheng-Jun Yang
Yue Yu
Wei Luo
Yun-Rui Li
Journal: Molecular cancer (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Breast cancer; Epithelial to mesenchymal transition; SMAD2; Transforming growth factor-β; ZEB1
Affiliations: The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin, 300060, China., Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China., Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China., Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, 300060, China., The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin, 300060, China. ., Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China. ., Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China. ., Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, 300060, China. .

Abstract:  Background: Breast cancer is the most common cancer among women worldwide and metastasis is the leading cause of death among patients with breast cancer. The transforming growth factor-β (TGF-β) pathway plays critical roles during breast cancer epithelial-mesenchymal transition (EMT) and metastasis. SMAD2, a positive regulator of TGF-β signaling, promotes breast cancer metastasis through induction of EMT. Methods: The expression of miR-190 and SMAD2 in breast cancer tissues, adjacent normal breast tissues and cell lines were determined by RT-qPCR. The protein expression levels and localization were analyzed by western blotting and immunofluorescence. ChIP and dual-luciferase report assays were used to validate the regulation of ZEB1-miR-190-SMAD2 axis. The effect of miR-190 on breast cancer progression was investigated both in vitro and in vivo. Results: miR-190 down-regulation is required for TGF-β-induced EMT. miR-190 suppresses breast cancer metastasis both in vitro and in vivo by targeting SMAD2. miR-190 expression is down-regulated and inversely correlates with SMAD2 in breast cancer samples, and its expression level was associated with outcome in patients with breast cancer. Furthermore, miR-190 is transcriptionally regulated by ZEB1. Conclusions: Our data uncover the ZEB1-miR-190-SMAD2 axis and provide a mechanism to explain the TGF-β network in breast cancer metastasis. 

Retracted: No

PubPeer comments:
 In Figure 6C microscopy data has been duplicated and presented as something else (PBS; control vs TGFbeta; Mir-190). ![file] ,
Characterization of an AGAMOUS-like MADS box protein, a probable constituent of flowering and fruit ripening regulatory system in banana
Authors: Dibyendu N Sengupta
Anish Nag
Swarup Roy Choudhury
Sujit Roy
Sanjay Kumar Singh
Journal: PloS one (2012)
Discipline: Multidisciplinary
Keywords: MADS-box family; AGAMOUS like; banana cultivar; Giant governor; Musa sp
Affiliations: Division of Plant Biology, Bose Institute, Kolkata, West Bengal, India. 

Abstract:  The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ~95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development. 

Retracted: No

PubPeer comments:
 Images in figures 6f and 6g appear to overlap although they are described as coming from two different zones. Could the authors please check? Area of overlap indicated with cyan box; this appears true for all four images in each row. *** ![file] ,
MiR-30e-5p inhibits proliferation and metastasis of nasopharyngeal carcinoma cells by target-ing USP22
Authors: X-H Li
Y-H Liu
H Zhang
Y-X Ma
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-30e-5p; nasopharyngeal carcinoma; proliferation; invasion; migration
Affiliations: Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China. .

Abstract:  Objective: To investigate the effects of miR-30e-5p on the proliferation, invasion and migration of nasopharyngeal carcinoma (NPC) cells, as well as its underlying mechanism. Patients and methods: We detected the expressions of miR-30e-5p in NPC tissues, adjacent normal tissues, NPC cells (5-8F cells) and control cells (293T cells) by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The target gene of miR-30e-5p was predicted by online software and ubiquitin-specific peptidase 22 (USP22) was screened out. Luciferase reporter gene assay was performed after NPC cells were co-transfected miR-30e-5p mimics or miR-30e-5p inhibitor and mutant-type or wild-type USP22, respectively. Expressions of miR-30e-5p and USP22 in 5-8F cells were detected by qRT-PCR and Western blotting. The proliferation of 5-8F cells was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, and the invasion and migration abilities were detected by transwell assay. The activation of the epithelial-mesenchymal transition (EMT) was analyzed by detecting expressions of EMT-associated proteins (E-cadherin and Vimentin) in NPC cells. Results: Expression level of miR-30e-5p was remarkably reduced, while USP22 expression was elevated in NPC tissues and cells compared with the controls. Molecular mechanism analysis con-firmed that miR-30e-5p could negatively regulate mRNA and protein levels of USP22 by binding to its specific sequence of 3'UTR. Subsequent experiments showed that USP22 knockdown resulting from up-regulation of miR-30e-5p could inhibit proliferation, invasion, migration, and EMT in 5-8F cells. Conclusions: MiR-30e-5p was lowly expressed in NPC by targeting USP22, suggesting that miR-30e-5p could be used as a potential therapeutic target for NPC. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: Two panels appear to show an overlap. ![file] ,
Merkel cell polyomavirus activates LSD1-mediated blockade of non-canonical BAF to regulate transformation and tumorigenesis
Authors: Laurence Florens
Matthew Y Lim
Jingwei Cheng
Donglim Esther Park
Michelle L Tillgren
Prafulla C Gokhale
Patrick Trojer
Selene K Swanson
Camille Cushman
Michael P Washburn
John P McGrath
James A DeCaprio
Joao A Paulo
Journal: Nature cell biology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Merkel cell carcinoma; neuroendocrine cancer; skin; Merkel cell polyomavirus; large T antigen
Affiliations: Program in Virology, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Constellation Pharmaceuticals, Cambridge, MA, USA., Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Stowers Institute for Medical Research, Kansas City, MO, USA., Experimental Therapeutics Core, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA., Program in Virology, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, USA. ., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. ., Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. .

Abstract:  Merkel cell carcinoma (MCC)-a neuroendocrine cancer of the skin-is caused by the integration of Merkel cell polyomavirus and persistent expression of large T antigen and small T antigen. We report that small T antigen in complex with MYCL and the EP400 complex activates the expression of LSD1 (KDM1A), RCOR2 and INSM1 to repress gene expression by the lineage transcription factor ATOH1. LSD1 inhibition reduces the growth of MCC in vitro and in vivo. Through a forward-genetics CRISPR-Cas9 screen, we identified an antagonistic relationship between LSD1 and the non-canonical BAF (ncBAF) chromatin remodelling complex. Changes in gene expression and chromatin accessibility caused by LSD1 inhibition were partially rescued by BRD9 inhibition, revealing that LSD1 and ncBAF antagonistically regulate an overlapping set of genes. Our work provides mechanistic insight into the dependence of MCC on LSD1 and a tumour suppressor role for ncBAF in cancer. 

Retracted: No

PubPeer comments:
 The blots for LSD1 and VINC in Fig. 3g are same. Source blots in supplement show different blots though. ,
Potential role of a novel transcriptional coactivator PELP1 in histone H1 displacement in cancer cells
Authors: Sujit S Nair
Sandip K Mishra
Zhibo Yang
Rakesh Kumar
Seetharaman Balasenthil
Ratna K Vadlamudi
Journal: Cancer Research (2004)
Discipline: CLINICAL MEDICINE
Keywords: Estrogen receptor; PELP1; chromatin remodeling; histone 1; transcription regulation
Affiliations: Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.

Abstract:  The estrogen receptor plays an important role in breast cancer progression. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), also called modulator of nongenomic activity of estrogen receptor (MNAR), a novel coactivator of estrogen receptor, modulates estrogen receptor transactivation functions. The mechanisms by which PELP1 modulates estrogen receptor genomic functions is not known. Here, using biochemical and scanning confocal microscopic analysis, we have demonstrated nuclear localization and functional implications of PELP1. Subnuclear fractionation showed PELP1 association with chromatin and nuclear matrix fractions. Ligand stimulation promoted recruitment of PELP1 to 17beta-estradiol responsive promoters, its colocalization with acetylated H3, and increased PELP1-associated histone acetyltransferase enzymatic activity. Far Western analysis revealed that PELP1 interacts with histone 1 and 3, with more preference toward histone 1. Using deletion analysis, we have identified the PELP1 COOH-terminal region as the histone 1 binding site. The PELP1 mutant lacking histone 1-binding domain acts as a dominant-negative and blocks estrogen receptor alpha-mediated transcription. Chromatin immunoprecipitation analysis showed a cyclic association and dissociation of PELP1 with the promoter, with recruitment of histone 1 and PELP1 occurring in opposite phases. PELP1 overexpression increased the micrococcal nuclease sensitivity of estrogen response element-containing nucleosomes. Our results provide novel insights about the transcription regulation of PELP1 and suggest that PELP1 participates in chromatin remodeling activity via displacement of histone 1 in cancer cells. 

Retracted: No

PubPeer comments:
 Figure 3B. Much more similar than expected. https: imgur.com 4NfYUtT , 
 https: retractionwatch.com 2017 03 20 scientist-sued-university-earns-two-retractions-bringing-total-five ,