PReD-Bench/PRed-Bench huggingface dataset:
EZH2 Palmitoylation Mediated by ZDHHC5 in p53-Mutant Glioma Drives Malignant Development and Progression
Authors: Haoran Yang
Zhiyou Fang
Shangrong Zhang
Zhen Wang
Xueran Chen
Huihui Ma
Journal: Cancer Research (2017)
Discipline: CLINICAL MEDICINE
Keywords: Gliomas; mutant p53; therapeutic resistance; poor outcomes; zinc finger protein ZDHHC5
Affiliations: Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.  ., Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China., Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China., Department of Radiation Oncology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China., Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.

Abstract:  Gliomas with mutant p53 occurring in 30% of glioma patients exhibit therapeutic resistance and poor outcomes. In this study, we identify a novel mechanism through which mutant p53 drives cancer cell survival and malignant growth. We documented overexpression of the zinc finger protein ZDHHC5 in glioma compared with normal brain tissue and that this event tightly correlated with p53 mutations. Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y. These events contributed to the development of glioma by promoting the self-renewal capacity and tumorigenicity of glioma stem-like cells, by altering the palmitoylation and phosphorylation status of the tumor suppressor EZH2. Taken together, our work highlighted ZDHHC5 as a candidate therapeutic target for management of p53-mutated gliomas. Cancer Res; 77(18); 4998-5010. ©2017 AACR. 

Retracted: No

PubPeer comments:
 I have concerns with Figure 6C. Could the authors please check? ![file] ,
Exploring Cognitive Concomitants of Mental Fatigue in Patients with Coronary Artery Disease
Authors: Narseta Mickuvienė
David Wellsted
Julius Neverauskas
Adomas Bunevičius
Julija Brožaitienė
Robertas Bunevičius
Julius Burkauskas
Naomi A Fineberg
Journal: Neuropsychobiology (2017)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Cognitive function; Coronary artery disease; Fatigue; Rehabilitation.
Affiliations: Laboratory of Behavioral Medicine, Neuroscience Institute, Lithuanian University of Health Sciences, Palanga, Lithuania., Highly Specialised Service for Obsessive Compulsive Disorders, Hertfordshire Partnership University NHS Foundation Trust and University of Hertfordshire, Hatfield, United Kingdom., The Centre for Health Services and Clinical Research, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom.

Abstract:  Objective: Fatigue and reduced exercise capacity are common concomitants of coronary artery disease (CAD). They are known to be associated with the deterioration in mental health, including emotional and cognitive status. However, the precise nature of the inter-relationship is poorly understood. The aim of this study was to investigate the relationship between fatigue and exercise capacity on the one hand and changes in cognitive functioning on the other, to generate new heuristics for clinical management and outcome prediction of CAD. Methods: A cross-sectional study included 827 in-patients (58 ± 9 years, 75% men) with CAD. Patients were evaluated for demographic, cardiac characteristics, and exercise capacity. The Multidimensional Fatigue Inventory-20 was used to assess fatigue, the Mini Mental State Examination for global cognitive function, the Digit Span Test, Digit Symbol Test, and Trail Making Test for executive aspects of cognitive functioning, and the Hospital Anxiety and Depression Scale for anxiety and depression symptom severity. Results: Using multiple regression analysis, after adjusting for possible confounders such as anxiety and depression, mental fatigue was associated with several executive aspects of cognitive function including short-term memory (Digit Symbol Test pairs recalled correctly [β = -0.127, p &lt; 0.005]), psychomotor performance (time to complete the Digit Symbol Test [β = 0.089, p &lt; 0.03]), and cognitive processing speed (Trail Making Test A [β = 0.081, p &lt; 0.05]). Conclusion: In rehabilitating CAD patients, certain aspects of executive functioning were independently associated with mental fatigue. These findings suggest that the subjective experience of mental fatigue, rather than reduced exercise capacity, is significantly associated with cognitive function. 

Retracted: No

PubPeer comments:
 The table 1 reports that 558 participants had a myocardial infarction. However, in page 3, left column, first paragraph, authors said: Most patients (n=358,68%) had experienced MI and ... The number of participants in the text and table do not match up. ,
Mutant ras elevates dependence on serum lipids and creates a synthetic lethality for rapamycin
Authors: Darin Salloum
David A Foster
Aleksandra Polonetskaya
Suman Mukhopadhyay
Kaity Tung
Journal: Molecular Cancer Therapeutics (2014)
Discipline: CLINICAL MEDICINE
Keywords: cancer cells; metabolism; serum lipids; Ras-driven; proliferation
Affiliations: Corresponding Author: David A. Foster, Department of Biological Sciences, Hunter College of the City University of New York, 695 Park Avenue, New York, NY 10065. .

Abstract:  The conversion of normal cells to cancer cells involves a shift from catabolic to anabolic metabolism involving increased glucose uptake and the diversion of glycolytic intermediates into nucleotides, amino acids, and lipids needed for cell growth. An underappreciated aspect of nutrient uptake is the utilization of serum lipids. We investigated the dependence of human cancer cells on serum lipids and report here that Ras-driven human cancer cells are uniquely dependent on serum lipids for both proliferation and survival. Removal of serum lipids also sensitizes Ras-driven cancer cells to rapamycin-indicating that the enhanced need for serum lipids creates a synthetic lethal phenotype that could be exploited therapeutically. Although depriving humans of serum lipids is not practical, suppressing uptake of lipids is possible. Suppressing macropinocytosis in Ras-driven cancer cells also created sensitivity to suppression of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1). It is speculated that this property displayed by Ras-driven cancer cells represents an Achilles' heel for the large number of human cancers that are driven by activating Ras mutations. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than expected. ![file] ,
A New Clade of African Body and Head Lice Infected by Bartonella quintana and Yersinia pestis—Democratic Republic of the Congo
Authors: Georges Diatta
Bernard Davoust
Didier Raoult
Rezak Drali
Jean-Christophe Shako
Journal: American Journal of Tropical Medicine and Hygiene (2015)
Discipline: CLINICAL MEDICINE
Keywords: human body louse; vector; diseases; epidemic typhus; trench fever
Affiliations: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Centre National de la Recherche Scientifique No. 7278 (CNRS7278), Institut de Recherche pour le Développement No. 198 (IRD198), Institut National de la Santé et de la Recherche Médicale Unité No. 1095 (InsermU1095), Institut Hospitalo-Universitaire Méditerranée-Infection, Aix-Marseille Université, Marseille, France; Plague Reference Laboratory, Bunia, Democratic Republic of the Congo; Institute of Research for the Development, Dakar, Senegal., Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Centre National de la Recherche Scientifique No. 7278 (CNRS7278), Institut de Recherche pour le Développement No. 198 (IRD198), Institut National de la Santé et de la Recherche Médicale Unité No. 1095 (InsermU1095), Institut Hospitalo-Universitaire Méditerranée-Infection, Aix-Marseille Université, Marseille, France; Plague Reference Laboratory, Bunia, Democratic Republic of the Congo; Institute of Research for the Development, Dakar, Senegal .

Abstract:  The human body louse is known as a vector for the transmission of three serious diseases-specifically, epidemic typhus, trench fever, and relapsing fever caused by Rickettsia prowazekii, Bartonella quintana, and Borrelia recurrentis, respectively-that have killed millions of people. It is also suspected in the transmission of a fourth pathogen, Yersinia pestis, which is the etiologic agent of plague. To date, human lice belonging to the genus Pediculus have been classified into three mitochondrial clades: A, B, and C. Here, we describe a fourth mitochondrial clade, Clade D, comprising head and body lice. Clade D may be a vector of B. quintana and Y. pestis, which is prevalent in a highly plague-endemic area near the Rethy Health District, Orientale Province, Democratic Republic of the Congo. 

Retracted: No

PubPeer comments:
 In this paper, 37 subjects living in the Democratic Republic of the Congo were screened for the presence of body and head lice. Lice were collected and screened for the presence of microbial pathogens. I could not find any wording about approval by an ethical board or patient consent. Could the authors please clarify? The paper cites Piarroux et al., Emerg Infect Dis (2013), DOI 10.3201 eid1903.121542 (reference 10), but that paper only describes 10 patients, and does not appear to have ethical approval or consent wording either. ,
SmMYC2a and SmMYC2b played similar but irreplaceable roles in regulating the biosynthesis of tanshinones and phenolic acids in Salvia miltiorrhiza
Authors: Ying Xiao
Wansheng Chen
Wei Sun
Shilin Chen
Qing Li
Li Chen
Junfeng Chen
Qian Ji
Hexin Tan
Lei Zhang
Shouhong Gao
Yangyun Zhou
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Salvia miltiorrhiza Bunge; tanshinones; phenolic acids; methyl jasmonate; transcription factor MYC2
Affiliations: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China., Institute of Chinese Materia Medica, China Academy of Chinese Medicinal Sciences, Beijing 100700, China., Department of Pharmaceutical Botany, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.

Abstract:  Salvia miltiorrhiza Bunge, which contains tanshinones and phenolic acids as major classes of bioactive components, is one of the most widely used herbs in traditional Chinese medicine. Production of tanshinones and phenolic acids is enhanced by methyl jasmonate (MeJA). Transcription factor MYC2 is the switch of jasmontes signaling in plants. Here, we focused on two novel JA-inducible genes in S. miltiorrhiza, designated as SmMYC2a and SmMYC2b, which were localized in the nucleus. SmMYC2a and SmMYC2b were also discovered to interact with SmJAZ1 and SmJAZ2, implying that the two MYC2s might function as direct targets of JAZ proteins. Ectopic RNA interference (RNAi)-mediated knockdown experiments suggested that SmMYC2a/b affected multiple genes in tanshinone and phenolic acid biosynthetic pathway. Besides, the accumulation of tanshinones and phenolic acids was impaired by the loss of function in SmMYC2a/b. Meanwhile, SmMYC2a could bind with an E-box motif within SmHCT6 and SmCYP98A14 promoters, while SmMYC2b bound with an E-box motif within SmCYP98A14 promoter, through which the regulation of phenolic acid biosynthetic pathway might achieve. Together, these results suggest that SmMYC2a and SmMYC2b are JAZ-interacting transcription factors that positively regulate the biosynthesis of tanshinones and Sal B with similar but irreplaceable effects. 

Retracted: No

PubPeer comments:
 Error bars are shown in Fig. 2 and Fig. 3, but neither the figure legends nor the Materials and Methods say what the error bars are (e.g. SD, SEM, CI). Could the authors please check, and make corrections to say what the error bars are, so that readers are able to interpret the data? , 
 https: retractionwatch.com 2022 02 17 science-issues-expression-of-concern-nine-months-after-its-reporter-uncovers-potential-misconduct ,
Ameliorative effect of biofabricated ZnO nanoparticles ofTrianthema portulacastrumLinn. on dermal woundsviaremoval of oxidative stress and inflammation
Authors: Ekta Yadav
Pankajkumar Yadav
Deepika Singh
Amita Verma
Journal: RSC Advances (2018)
Discipline: CHEMISTRY
Keywords: wound healing; zinc oxide nanoparticles; antioxidant; anti-inflammatory; green synthesis
Affiliations: Bioorganic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences (SHUATS), Allahabad 211007, Pharmaceutics Laboratory, Allahabad-211007

Abstract:  An impediment in the process of wound healing can be attributed to reactive oxygen species and inflammation. The curative efficacy of green synthesized Trianthema portulacastrum Linn. zinc oxide nanoparticles (ZnOTP) was investigated in the present study for evaluation of their wound healing potential in rodents. Total phenolic and flavonoid content of ZnOTP was determined, and antioxidant potential was evaluated by the DPPH method. In vitro anti-inflammatory activity of ZnOTP was evaluated by membrane stabilization and albumin denaturation, along with proteinase inhibitory assays. The synthesized ZnOTP were characterized by UV-Visible spectroscopy, Fourier transform infrared (FT-IR) studies, Field Emission Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray (EDX) studies. The wound healing potential of ZnOTP was monitored by excision and incision wound models. Analyses confirmed the formation of spherical nanoparticles of 10-20 nm size along with strong signals of zinc and oxygen atoms. Significant results (p &lt; 0.05) of wound contraction rate, epithelialization and histopathology of the healed tissues of rats confirmed the promising wound healing property of ZnOTP. In addition, inflammatory markers, biochemical estimation such as the hydroxyproline content of granulation tissue, and the profile of antioxidant enzymes also supported the wound healing potential of ZnOTP. The present study advocated the attenuation of wounds via antioxidant and anti-inflammatory activities of a green synthesized nano-ointment. 

Retracted: No

PubPeer comments:
 There appears to be images used across two papers. Marked with green and cyan boxes. Top paper RSC Advances (2018) - doi: 10.1039 c8ra03500h https: pubpeer.com publications 4493A07B5A84D448354A8EA417B1DC Bottom paper Biomedicine Pharmacotherapy (2018) - doi: 10.1016 j.biopha.2018.09.180 https: pubpeer.com publications 8E3E0A1302C631683DE0B5870EF614 *** ![file] , 
 #1 ![file] , 
 An additional concern in this paper. In the column of control images in Figure 3, Day 6 and 17 appear unexpectedly similar and may represent two photographs taken on the same day. *** Original ![file] *** Inverse image ![file] , 
 #1, #3 Figure 3 again, it shares a moltitude of images with Figure 5 of yet another paper by same group ([Yadav et al 2017 Biomed Pharmacother](http: pubpeer.com publications 7BA9503273EBCC3E78E60ED0FE1214)) published a year before. Treatment and topic were different. Please see below this orgy of duplications: ![file] ,
Prostate cancer is characterized by epigenetic silencing of 14-3-3sigma expression
Authors: Heiko Hermeking
Dimitri Lodygin
Joachim Diebold
Journal: Oncogene (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: tumor suppressive genes; CpG methylation; prostate carcinoma; 14-3-3sigma; epigenetic silencing
Affiliations: Molecular Oncology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried/Munich, Germany.

Abstract:  In order to identify tumor suppressive genes silenced by CpG methylation in prostate carcinoma (PCa), we determined genome-wide expression changes after pharmacological reversal of CpG methylation-mediated transcriptional repression in three PCa cell lines using microarray analysis. Thereby, epigenetic silencing of the 14-3-3sigma gene was detected in the cell line LNCaP. 14-3-3sigma encodes a p53-regulated inhibitor of cell cycle progression. Laser microdissection was used to isolate different cell types present in diseased prostatic tissue. Subsequent methylation-specific PCR analysis showed CpG methylation of 14-3-3sigma in all 41 primary PCa samples analysed, which was accompanied by a decrease or loss of 14-3-3sigma protein expression. In contrast, normal prostate epithelial and benign prostate hyperplasia cells showed high levels of 14-3-3sigma expression. PCa-precursor lesions (prostatic intraepithelial neoplasia) also displayed decreased levels of 14-3-3sigma expression in luminal cells, which are known to contain shortened telomeres. RNA interference-mediated inactivation of 14-3-3sigma compromised a DNA damage-induced G(2)/M arrest in the PCa cell line PC3. The generality of CpG methylation and downregulation of 14-3-3sigma expression in PCa suggests that it significantly contributes to the formation of PCa, potentially by allowing the escape from a DNA damage-induced arrest elicited by telomere shortening. 

Retracted: No

PubPeer comments:
null, 
null, 
 Figure 1c. Much more similar than you would expect. https: imgur.com XazqopZ ,
Preparation of PANI–CuZnO ternary nanocomposite and investigation of its effects on polyurethane coatings antibacterial, antistatic, and mechanical properties
Authors: Mirmohseni, Abdolreza
Rastgar, Mortaza
Olad, Ali
Journal: Journal of Nanostructure in Chemistry (2018)
Discipline: CHEMISTRY
Keywords: Antibacterial; Antistatic; Polyurethane coatings; PANI-CuZnO; Nanocomposite

Abstract: In this study, a facile method for the production of Antibacterial and Antistatic polyurethane coatings was investigated using copper modified ZnO nanoparticles–polyaniline nanofibers (PANI–CuZnO) ternary nanocomposite. PANI–CuZnO ternary nanocomposite was synthesized through two steps. First, copper-modified ZnO nanoparticles were produced through the hydrolysis method using acetate precursors, and then they were mixed with polyaniline nanofibers, which were synthesized by seeding method. The obtained nanocomposite was characterized by FTIR, XRD, and FESEM techniques. Results of evaluating the antibacterial action of the polyurethane coatings with the content of ternary nanocomposite showed that the obtained coatings have a proper antibacterial action against Gram-positive and Gram-negative bacteria. In addition, measuring the coatings’ surface electrical resistance revealed that addition of the ternary nanocomposite to the polyurethane coatings’ matrix causes the surface electrical resistance of the coatings significantly decreases and reaches 8\u2009×\u2009107&nbsp;Ω/sq. Thereby, they could be categorized as an antistatic coating. Moreover, the addition of PANI–CuZnO enhanced adhesion strength and scratch resistance of the final polyurethane coatings.

Retracted: No

PubPeer comments:
 In **Table 1**, two of the images of the bacterial plates appear to be the same (marked with red boxes). ![file] ,
Sandostatin impairs postresection intestinal adaptation in a rat model of short bowel syndrome
Authors: Arnold G Coran
Eitan Shiloni
Edmund Sabo
Kamal Khateeb
Michael M Krausz
Igor Sukhotnik
Leonardo Siplovich
Journal: Digestive Diseases and Sciences (2002)
Discipline: CLINICAL MEDICINE
Keywords: Sandostatin; short bowel syndrome; structural intestinal adaptation; cell proliferation; apoptosis
Affiliations: Rappaport Faculty of Medicine, Technion, Carmel Medical Center, Department of Surgery B, Haifa, Israel.

Abstract:  Because of its antisecretory properties, sandostatin has been advocated for the treatment of patients with short bowel syndrome (SBS). This study was conducted to determine the effect of sandostatin on structural intestinal adaptation, cell proliferation and apoptosis in a rat model of SBS. Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-sandostatin rats underwent bowel resection and were treated with sandostatin (SBS-SND). Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 14 following operation. We have demonstrated that SBS-SND animals demonstrated lower (vs SBS rats) duodenal and jejunal bowel weights, jejunal and ileal mucosal weight, jejunal and ileal mucosal DNA and protein, jejunal and ileal villus height, cell proliferation index in the ileum, and enterocyte apoptosis in jejunum and ileum. We conclude that in a rat model of SBS sandostatin decreases cell proliferation and inhibits structural intestinal adaptation. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a set of at least 3 papers that appear to share immunohistochemistry images. All papers list Igor Sukhotnik as the first author. Boxes of the same color highlight areas in microscopy panels that look similar. The images do not always represent the same experiments, in particular the region marked with an orange box. * Sukhotnik I et al., Digestive Diseases and Sciences (2002), DOI: 10.1023 a:1019641416671 * Sukhotnik I et al., Journal of Surgical Research (2002), DOI: 10.1006 jsre.2002.6556 * Sukhotnik I et al., Pediatr Surg Int (2002) 18: 615u2013619, DOI: 10.1007 s00383-002-0862-8 ![file] ,
Identification and analysis of CD133(+) melanoma stem-like cells conferring resistance to taxol: An insight into the mechanisms of their resistance and response
Authors: Christian R Gomez
Mohamed Hassan
Abdelouahid El-Khattouti
Youssef Haïkel
Denis Selimovic
Mosaad Megahed
Journal: Cancer Letters (2014)
Discipline: CLINICAL MEDICINE
Keywords: Apoptosis; CD133; Cancer stem cells; JNK; P38
Affiliations: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA., Institut National de la Santé et de la Recherche Médicale, U 977, University of Strasbourg, 67000 Strasbourg, France; Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France., Clinic of Dermatology, University Hospital of Aachen, Pauwelsstr. 30, 52074 Aachen, Germany., Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA; Institut National de la Santé et de la Recherche Médicale, U 977, University of Strasbourg, 67000 Strasbourg, France; Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France. Electronic address: .

Abstract:  The presence and the involvement of cancer stem-like cells (CSCs) in tumor initiation and progression, and chemo-resistance are documented. Herein, we functionally analyzed melanoma stem-like cells (MSC)/CD133(+) cells on their resistance and response to taxol-induced apoptosis. Besides being taxol resistant, the CD133(+) cells demonstrated a growth advantage over the CD133(-) subpopulation. Taxol induced apoptosis on CD133(-) cells, but not on CD133(+) cells. In the CD133(-) subpopulation, the exposure to taxol induced the activation of apoptosis signal-regulating kinase1 (ASK1)/c-jun-N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK) pathways and Bax expression, while in CD133(+) cells taxol was able only to enhance the activity of the ERK pathway. In CD133(+) cells, the direct gene transfer of Bax overcame the acquired resistance to taxol. Taken together, our data provide an insight into the mechanistic cascade of melanoma resistance to taxol and suggest Bax gene transfer as a complementary approach to chemotherapy. 

Retracted: No

PubPeer comments:
 Figure 1B. * Red boxes: Two panels appear to look very similar if one of them is mirrored vertically. ![file] , 
 Figure 7B. * Sharp vertical discontinuities are visible in the Cl. Casp.9 and PARP panels. * In the PARP panel, the same lane appears to be visible twice, albeit mirrored so that it represents PARP in one lane and Cl. PARP in the other. Shown with yellow arrows. ![file] ,
Design and development of multitarget-directed N-Benzylpiperidine analogs as potential candidates for the treatment of Alzheimer's disease
Authors: Santosh Kumar Prajapati
Sushant Kumar Shrivastava
Avanish Tripathi
Vinod Tiwari
Ankit Seth
Piyoosh Sharma
Sairam Krishnamurthy
Manish Kumar Tripathi
Prabhash Nath Tripathi
Pavan Srivastava
Journal: European Journal of Medicinal Chemistry (2019)
Discipline: CHEMISTRY
Keywords: Acetylcholinesterase (AChE); Alzheimer's disease; Aβ aggregation; Multitarget-directed ligands; Structure-based drug design
Affiliations: Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India., Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India. Electronic address: .

Abstract:  The multitarget-directed strategy offers an effective and promising paradigm to treat the complex neurodegenerative disorder, such as Alzheimer's disease (AD). Herein, a series of N-benzylpiperidine analogs (17-31 and 32-46) were designed and synthesized as multi-functional inhibitors of acetylcholinesterase (AChE) and β-secretase-1 (BACE-1) with moderate to excellent inhibitory activities. Among the tested inhibitors, 25, 26, 40, and 41 presented the most significant and balanced inhibition against both the targets. Compounds 40 and 41 exhibited high brain permeability in the PAMPA-BBB assay, significant displacement of propidium iodide from the peripheral anionic site (PAS) of AChE, and were devoid of neurotoxicity towards SH-SY5Y neuroblastoma cell lines up to the maximum tested concentration of 80 μM. Meanwhile, both these compounds inhibited self- and AChE-induced Aβ aggregation in thioflavin T assay, which was also re-affirmed by morphological characterization of Aβ aggregates using atomic force microscopy (AFM). Moreover, 40 and 41 ameliorated the scopolamine-induced cognitive impairment in elevated plus and Y-maze experiments. Ex vivo and biochemical analysis established the brain AChE inhibitory potential and antioxidant properties of these compounds. Further, improvement in Aβ1-42-induced cognitive impairment was also observed by compound 41 in the Morris water maze experiment with significant oral absorption characteristics ascertained by the pharmacokinetic studies. 

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. ,
Novel approaches to oral immunization for hepatitis B
Authors: Shailja Tiwari
Suresh P Vyas
Journal: Current Infectious Disease Reports (2011)
Discipline: IMMUNOLOGY
Keywords: Hepatitis B; liver disease; vaccination; oral delivery; antigenic substance
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, Madhya Pradesh, 470003, India.

Abstract:  Hepatitis B is a necroinflammatory liver disease manifested with subacute to acute symptoms, liver cirrhosis, and mortality. Parenteral alum-adsorbed hepatitis B surface antigenic (HBsAg) vaccination, although available, poses serious concerns regarding inability to induce both cell-mediated and mucosal immune response. In this context, oral delivery may be a prospective solution to the issues associated with conventional vaccination. However, the strategy is detrimental to the antigenic substances, suffers various physical/chemical barriers, and impedes poor transcytosis via mucosal route. Therefore, surface-engineered novel carrier-based approaches are reportedly promising for effective HBsAg oral vaccine delivery. This review focuses on the efforts for developing oral mucosal vaccine against hepatitis B, with considerable attention on novel drug delivery systems for spatial distribution of antigenic substance to the immune effector cells and organs. 

Retracted: No

PubPeer comments:
 Fig. 1  Mechanism of generation of immunity following oral administration of nanoparticle-based formulation. a Confocal photograph showing uptake of nanoparticle via mucosal surface . ![file] More information appeared in Fig 6 of [Mishra et al (2011)] .  Confocal laser scanning microscopy images showing targeting of the nanoparticles to the M cells of the Peyeru2019s patches in mice by dual staining. M cells were primarily stained with TRITC-WGA (red). FITCu2013LTA coupled PLGA nanoparticles stain green. ... Lectinized nanoparticles (shown by arrow) were associated predominantly with M cells (B). ![] With a different description in Figure 7 from [Mishra et al (2014)] .  Confocal laser scanning microscopy images showing targeting of the nanoparticles to the M cells of the Peyeru2019s patches in mice by dual staining. M cells were primarily stained with TRITC-WGA (red). FITC-LTA coupled Chitosan nanoparticles stain green. ... Lectinized chitosan nanoparticles (shown by arrow) were associated predominantly with M cells (B). ![] ,
Circular RNA circ_0001649 acts as a prognostic biomarker and inhibits NSCLC progression via sponging miR-331-3p and miR-338-5p
Authors: Yanling Gai
Tongmiao Liu
Zhuo Song
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Circular RNA; Non-small cell lung cancer; circ_0001649; miR-331-3p; miR-338-5p.
Affiliations: Department of Respiratory Medicine, The Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China. Electronic address: ., Department of Respiratory Medicine, The Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China.

Abstract:  Accumulating evidence documented the key functions of circular RNAs (circRNAs) in various malignancies. However, the study regarding the involvement of circRNAs in non-small cell lung cancer (NSCLC) has just begun. In the present study, qRT-PCR was used to determine the expression of circ_0001649 in NSCLC tissues and cells. Its clinical significance was further assessed by Fisher's exact test, Kaplan-Meier analysis and Cox regression model. Additionally, loss-of-function and gain-of-function experiments were carried out to detect the functional role of circ_0001649 in cell proliferation, migration and invasion. Furthermore, animal study was performed to confirm the in vitro results. Importantly, luciferase reporter assay was induced to reveal the underlying mechanism of circ_0001649. As a result, circ_0001649 was decreased in NSCLC tissues and cells and this downregulation is correlated with advanced TNM stage, positive lymph node metastasis and unfavorable prognosis. Additionally, circ_0001649 inhibited cell growth and metastasis both in vitro and in vivo. In mechanism, circ_0001649 was identified as the sponge of miR-331-3p and miR-338-5p. Moreover, the biological functions of circ_0001649 is partly dependent on its regulation on miR-331-3p and miR-338-5p. Collectively, this study suggested that circ_0001649/miR-331-3p/miR-338-5p regulatory signaling might be a potential target for NSCLC therapy. 

Retracted: No

PubPeer comments:
 Figure 2D: * The metal ruler shown with the tumors looks remarkably similar to the ruler in Figure 2F of Liandi Li et al., Biomedicine Pharmacotherapy (2019), DOI: 10.1016 j.biopha.2018.10.072 - see: https: pubpeer.com publications 741D7CD87FEFB824AD2DECE9A1D847 . Note the stains under the  1 . * The tumors appear to float on the background. Could the authors please provide an explanation? Both research groups are located in different hospitals in different cities (albeit in the same province). ![file] ,
Age-Related Differences in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to Moderate Coronavirus Disease 2019 (COVID-19)
Authors: Ami B Patel
Larry K Kociolek
Jason Rippe
Taylor Heald-Sargent
William J Muller
Xiaotian Zheng
Journal: JAMA Pediatrics (2020)
Discipline: CLINICAL MEDICINE
Keywords: cohort study; age-related differences; nasopharyngeal; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); mild to moderate
Affiliations: Division of Infectious Diseases, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois., Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Abstract:  This cohort study investigates age-related differences in nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in patients with mild to moderate coronavirus disease 2019 (COVID-19). 

Retracted: No

PubPeer comments:
 Inadequate qPCR data: - Cq = not a quantitative measure. As you took calibrators with know copy numbers, calculations should have been performed. - A validation of using the Abbot qPCR in a quantitative way should have been included. What are the upper and lower limits? This qPCR waq only validated for qualitative detection of COVID. - Was there any normalisation performed for volume or IC human control? This is necessary to assess for loss during extraction purification RT and preferably also for swabbing efficiency. - The reported Cqs are super low. Was this even quantifiable? This looks like overshooting. To get accurate Cq-values (and calculations therefrom), dilutions should have been taken into account. Correct baseline subtraction becomes hard at these low values. Can the authors show their standard curve and validation? And their amplification plots? The abbot test is only EUA for qualitative detection. - This is a multiplex assay. Was is validated for quantification? In multiplex PCRs quantification requires more validation. There is a high chance that the different Cqs have are influencing each other... , 
 #1 As this publication is getting quite some media attention, I would really like to express my concerns. I would like to ask the authors to publish their validation of the qPCR and their amplification curves (as their Cq values just seem quite unlikely). This was clearly a quick and dirty paper and should never have passed peer review. Papers that rely heavily on qPCR-data should be checked by people that have expertise in qPCR. This did clearly not happen here. In general, it is very worrisome that that many papers reporting Cq-values get published as such. These data can be part of supplementary information, but the final data should be data like copy number, fold change, .... Quantitative validation, correct standard curves and normalization (for swapping, volume, RT-activity, run-to-run variability, ...) are just essential. This is even more important when the (extra-ordinary) claims solely rely on those qPCR-data. ,
Let-7 expression defines two differentiation stages of cancer
Authors: Emily O Kistner
David A Jewell
Scott Shell
Sun-Mi Park
Robert Schickel
Christine Feig
Amir Reza Radjabi
Marcus E Peter
Ernst Lengyel
Journal: Proceedings of the National Academy of Sciences of the United States of America (2007)
Discipline: Multidisciplinary
Keywords: carcinogenesis; embryonic development; mesenchymal genes; NCI60 panel; human tumor cell lines
Affiliations: Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.

Abstract:  The early phases of carcinogenesis resemble embryonic development, often involving the reexpression of embryonic mesenchymal genes. The NCI60 panel of human tumor cell lines can genetically be subdivided into two superclusters (SCs) that correspond to CD95 Type I and II cells. SC1 cells are characterized by a mesenchymal and SC2 cells by an epithelial gene signature, suggesting that SC1 cells represent less differentiated, advanced stages of cancer. miRNAs are small 20- to 22-nucleotide-long noncoding RNAs that inhibit gene expression at the posttranscriptional level. By performing miRNA expression analysis on 10 Type I and 10 Type II cells, we have determined that SC1 cells express low and SC2 cells high levels of the miRNA let-7, respectively, suggesting that let-7 is a marker for less advanced cancers. Expression of the let-7 target high-mobility group A2 (HMGA2), an early embryonic gene, but not of classical epithelial or mesenchymal markers such as E-cadherin or vimentin, inversely correlated with let-7 expression in SC1 and SC2 cells. Using ovarian cancer as a model, we demonstrate that expression of let-7 and HMGA2 is a better predictor of prognosis than classical markers such as E-cadherin, vimentin, and Snail. These data identify loss of let-7 expression as a marker for less differentiated cancer. 

Retracted: No

PubPeer comments:
 ![file] , 
 ![file] The comment is correct. This was based on an error when assembling the Western blot. In the attached raw blots the regions shown in this figure are boxed in red. On the left is the data on using the let-7 inhibitor cocktail (labeled in the figure as 7a c g). On the right side are the data with only the Let-7g inhibitor. This inhibitor was used at three different concentrations, 60, 90 and 120 uM. The 60uM condition is shown in the figure. Unfortunately, the actin band that corresponds to that lane was not shown. The correct and matching actin band that should have appeared in the figure is boxed in green. We regret the error but the raw blots document that the findings shown are correct. In addition, it is obvious that we also merged the data on the right closer to the data on the left in the final figure. This kind of splicing was allowed and quite common back in 2007. Not done anymore these days. Most journals adopted new image manipulation rules about ten years ago. ,
Autoantibodies in SLE but not in scleroderma react with protein-stripped nucleosomes
Authors: Cornelia Dähnrich
Waltraud Suer
Wolfgang Schlumberger
Winfried Stöcker
Journal: Journal of Autoimmunity (2004)
Discipline: IMMUNOLOGY
Keywords: Autoantibodies; Nucleosomes; Systemic lupus erythematosus; Progressive systemic sclerosis; ELISA
Affiliations: EUROIMMUN AG, Seekamp 31, D-23560 Lübeck, Germany. 

Abstract:  Autoantibodies against nucleosomes (ANuA) are known to be sensitive markers for systemic lupus erythematosus (SLE), but their clinical relevance seemed to be limited because sera from patients with progressive systemic sclerosis (PSS) also showed positive reactions with conventional ANuA ELISA test systems (anti-Nu1 ELISA). It was generally assumed thatANuA were associated with both diseases. Using discontinuous sucrose gradient centrifugation to generate pure nucleosomes, we discovered by chance that at the 30-50% sucrose interface an antigen (Nu2) banded which was demonstrably free of non-histone components and histone H1. The two different nucleosome preparations, Nu1 and Nu2, were used in parallel as antigenic substrates in standardised ELISA tests to analyse sera from SLE (295 patients), PSS (119) and patients with other rheumatic diseases (101). With Nu1, 62% of the SLE and 52% of the PSS sera showed positive reactions. Two sera from patients suffering from Sjögren's syndrome (SS) and one from polymyositis were also positive. Using the Nu2 preparation, 58% of the SLE but none of the PSS sera showed a positive reaction. One serum from a patient with SS was also positive. It could be shown that it was the PSS-specific autoantigen Scl-70 in the nucleosome preparation (Nu1) which contributed to the positive reactions of the PSS sera in conventional ANuA test systems, whereas in the Nu2 preparation no remaining Scl-70 was detectable. The present study definitely proved that ANuA are highly and specifically associated with SLE but not with PSS. 

Retracted: No

PubPeer comments:
 Concern about Figure 1. In the  Nu2 (native) lane, a completely blank (no background) area appears to be visible in the very relevant  Nucleosomal DNA area. Image made a bit lighter to bring out the background. Shown with a thin red box. Could the authors please clarify? ![file] ,
A novel long noncoding RNA, LINC00483 promotes proliferation and metastasis via modulating of FMNL2 in CRC
Authors: Zhongmiao Wang
Baoli Qin
Yan Yan
Journal: Biochemical and Biophysical Research Communications (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Colorectal cancer; FMNL2; LINC00483; Proliferation/metastasis; ceRNA.
Affiliations: Department of Internal Medicine, Cancer Hospital of China Medical University/Liaoning Cancer Hospital & Institute, Shenyang, PR China. Electronic address: .

Abstract:  Long non-coding RNAs (lncRNAs) are extensively involved in multiple malignancies including colorectal cancer (CRC). In the present study, we found a novel lncRNA, long intergenic non-protein coding RNA 483 (LINC00483), which was upregulated in CRC. We also illustrated that upregulated LINC00483 was correlated with poor clinicopathological features of patients with CRC. Functionally, we displayed that a knockdown of LINC00483 suppressed LOVO and HT29 cells proliferation and metastatic ability. We further illustrated that miR-204-3p was involved in LINC00483 induced proliferation and metastasis. An overexpression of miR-204-3p could attenuate the facilitative effect which LINC00483 presented. Through a luciferase assay, we showed the direct binding effect between LINC00483 and miR-204-3p. Even further, we revealed that LINC00483 and formin like 2 (FMNL2) shared a similar miR-204-3p response elements (MREs-204-3p). FMNL2 was a direct target of miR-204-3p. FMNL2 was a downstream gene of LINC00483 and participated in LINC00483 mediated proliferation and metastasis. Lastly, we proved that LINC00483 promoted proliferation and metastasis via modulating of FMNL2 in LOVO and HT29 cells. In summary, the outcomes of this study illustrated that LINC00483 promoted CRC cells proliferation and metastasis via modulating of FMNL2 by acting as a ceRNA of miR-204-3p. LINC00483/miR-204-3p/FMNL2 axial might be a novel target in molecular treatment of CRC. 

Retracted: No

PubPeer comments:
 Figure 1D. Much more similar than you expect. https: imgur.com PZnnpRs ,
Anticancer effect of quinacrine on diffuse large B‑cell lymphoma via inhibition of MSI2‑NUMB signaling pathway
Authors: Huiling Zhu
Kaihong Xu
Lixia Sheng
Guifang Ouyang
Yi Wang
Ping Zhang
Shujun Yang
Qitian Mu
Journal: Molecular Medicine Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Diffuse large B-cell lymphoma; quinacrine; cytotoxic effect; cell cycle arrest; apoptosis
Affiliations: Department of Hematology, Ningbo First Hospital, Ningbo, Zhejiang 315010, P.R. China

Abstract:  Diffuse large B‑cell lymphoma (DLBCL) is the most common subtype of non‑Hodgkin's lymphoma. Despite improvements in the clinical outcomes of DLBCL, ~30% of patients will develop relapse/refractory disease. Therefore, novel therapeutic drugs have been investigated to improve disease outcomes. Previous studies have revealed the anticancer effects of quinacrine (QC) on tumor cells in vitro, although its role in human DLBCL is yet to be identified. The present study sought to examine the cytotoxic effect of QC on DLBCL cells. QC induced G0/G1 cell cycle arrest and apoptosis in the DLBCL cell lines SU‑DHL‑8 and OCI‑LY01, in a dose‑dependent manner, in addition to the downregulation of cyclin‑dependent kinase 4/6 and the upregulation of cleaved poly‑ADP ribose polymerase 1. Upon exposure to QC, RNA‑binding protein Musashi homolog 2 inactivation and activation of protein numb homolog were observed. In addition, QC was able to inhibit the expression of Myc proto‑oncogene protein. The results of the present study indicated that QC may be a potential anti‑DLBCL drug. 

Retracted: No

PubPeer comments:
 Figure 1A. * Red boxes: The top and bottom  Control panels appear to show an overlap, even though they represent different cell lines. ![file] , 
 Correction, December 2020: https: www.spandidos-publications.com 10.3892 mmr.2020.11813  Subsequently to the publication of this paper, an interested reader drew to the authors attention that, in Fig. 1A on p. 524, the images selected to represent the Control experiments for the SU-DHL-8 and OCI-Ly01 cell lines bore some striking similarities. After having examined their original data, the authors realized that they uploaded the wrong images during the process of compiling this figure. ,
Rg1 inhibits high glucose-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway
Authors: Li-Wei Zhang
Li-Ping Xue
Ya-Li Peng
Peng Ding
Min Hu
Xiao-Lin Fu
Ya-Di Li
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: High glucose; Mesenchymal activation; RP11-982M15.8; Rg1; miR-2113.

Abstract:  Recent study has showed that Ginsenoside Rg1, the mian active compound of Panax ginseng, could ameliorate oxidative stress and myocardial apoptosis in diabetes mellitus. However, the roles and mechanisms of Rg1 in proliferative diabetic retinopathy (PDR) are still unclear. In the present study, we aimed to investigate the effects of Rg1 on mesenchymal activation of high-glucose (HG) cultured müller cells. High glucose conditions up-regulate MMP-2, MMP-9 and down-regulate TIMP-2, and promote mesenchymal activation in Müller cells. And Rg1 inhibits the HG-induced mesenchymal activation and HG-increased MMP-2 and MMP-9 and HG-decreased TIMP-2 in Müller cells. HG up-regulates Zeb1 and lncRNA RP11-982M15.8, and down-regulates miR-2113, and Rg1 inhibits these effects of HG. Both inhibition of miR-2113 and over-expression of RP11-982M15.8 significantly restored the HG induced mesenchymal activasion. Taken together, our findings suggested that Rg1 inhibited HG-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway. 

Retracted: No

PubPeer comments:
  Fig. 2. Rg1 inhibits the HG-induced mesenchymal activation and HG-increased MMP-2 and MMP-9 and HG-decreased TIMP-2 in Mu00fcller cells. A and B. Using immunofluorescent staining assay to analyze the effects of high glucose and Rg1 on the vimentin expression. and  Fig. 5. Rg1 inhibits the HG-induced mesenchymal activation via regulating miR-2113 RP11-982M15.8 Zeb1 axis in Mu00fcller cells. ... C. Immunofluorescent staining assay was used to assess the Vimentin expression on the conditions of Rg1 treatment, Rg1u00fe RP11-982M15.8 OE (overexpression) treatment and Rg1u00femiR-2113 inhibitor treatment.  ![file] Same cells seem to illustrate the High-Glucose activation **and** Rg1+Inhibitor treatment. Could the authors check? ,