PReD-Bench/PRed-Bench huggingface dataset:
Immunoprotection against influenza H5N1 virus by oral administration of enteric-coated recombinant Lactococcus lactis mini-capsules
Authors: Xiaohui Wei
Han Lei
Yuhong Xu
Jian Chen
Dominic Man-Kit Lam
Journal: Virology (2010)
Discipline: MICROBIOLOGY
Keywords: Edible vaccines; pandemic viral infections; vaccination; recombinant Lactococcus lactis; influenza H5N1
Affiliations: School of Life Science and Technology, Shanghai Jiao Tong University, Shanghai, 200240, PR China.

Abstract:  Edible vaccines that can be made widely available and easily administered could bring great benefit to the worldwide battle against pandemic viral infections. They can be used not only for the vaccination of humans and domesticated animals, but also for wild herds and live stock which are otherwise difficult to vaccinate. In this study, we report the development of an edible mini-capsule form of live, non-persisting, recombinant Lactococcus lactis (L. lactis) vaccine against the highly virulent influenza H5N1 strain. Recombinant L. lactis-based H5N1 HA antigen expression constructs were made and shown to be able to induce higher levels of HA-specific serum IgG and fecal IgA antibody production after oral administration. The vectors were then formulated into a mini-capsule dosage form and fed to mouse. Four doses of oral administration rendered complete protection of the mouse against lethal challenges of H5N1 virus. 

Retracted: No

PubPeer comments:
 Fig. 6A, Fig. 6D and Fig. 7B. Two sets of WB bands appear more similar than expected. ![file] , 
 #1 Thank you very much for your correction. We rechecked the original data and found that there was indeed an inadvertence error in clipping, but this error would not affect the correctness of the results of our paper. We have contacted the editorial department to request correction of this error. We apologise for these errors and any inconvenience this may have caused. , 
 Could the authors please provide the update about the correcrion? , 
 #3 ![file] This is the modified Fig.6A and Fig.6D.We have filled in the errata template provided by the magazine and sent it back to the magazine , 
 #3 Thank you very much for point out the mistake. After self - examination, the journal agreed to our corrigendum publication. The email is as follows. Dear Dr. Li, Thank you for checking with me. The Editor-in-chief has approved the corrigendum and we will be sending the typeset proofs to you soon. Please let me know if I can be of any further assistance. Kind regards, Rajashri Ravindranathan Journal Manager Tel: +91 44 42994880 , 
 #5 Could the authors please post the original scans? , 
 #5 Thank you for your reply, and the effort to correct the scientific records. , 
 #6 The original scan is shown below ![file] ![file] ,
Selective Inhibitors of Nuclear Export Block Pancreatic Cancer Cell Proliferation and Reduce Tumor Growth in Mice
Authors: Fazlul H Sarkar
Bin Bao
Asfar S Azmi
Sharon Shacham
Philip A Philip
Ramzi M Mohammad
Michael Kauffman
Amro Aboukameel
Journal: Gastroenterology (2013)
Discipline: CLINICAL MEDICINE
Keywords: Tumor-suppressor proteins; CRM-1; SINEs; pancreatic cancer cells; proliferation
Affiliations: Department of Pathology, Wayne State University, Detroit, Michigan 48201, USA.

Abstract:  Background &amp; aims: Tumor-suppressor proteins are inactivated by many different mechanisms, including nuclear exclusion by chromosome region maintenance (CRM)-1. Increased tumor levels of CRM-1 have been correlated with poor prognosis of patients with pancreatic cancer, making it a therapeutic target. Selective inhibitors of nuclear export (SINEs) bind to CRM-1 to irreversibly inhibit its ability to export proteins; we investigated a new class of SINEs in pancreatic cancer cells. Methods: We studied the effects of SINE analogs in a panel of pancreatic cancer cell lines and nontransformed human pancreatic ductal epithelial cells using proliferation, apoptosis, immunoblot, co-immunoprecipitation, small inhibitor RNA, and fluorescence microscopy analyses. The effects of the SINEs also were investigated in mice with subcutaneous and orthotopic tumors. Results: SINEs (KPT-185, KPT-127, KPT-205, and KPT-227) inhibited proliferation and promoted apoptosis of pancreatic cancer cells, but did not affect human pancreatic ductal epithelial cells. The nuclei of cells incubated with KPT-185 accumulated tumor-suppressor proteins (p27, FOXO, p73, and prostate apoptosis response-4 [PAR-4]) and inhibited interactions between CRM-1 and these proteins. Mutations in the region of CRM-1 that bind to SINEs (Cys-528), or small inhibitor RNA knockdown of PAR-4, prevented the ability of KPT-185 to block proliferation and induce apoptosis of pancreatic cancer cells. Oral administration of KPT-330 to mice reduced growth of subcutaneous and orthotopic xenograft tumors without major toxicity. Analysis of tumor remnants showed that KPT-330 disrupted the interaction between CRM-1 and PAR-4, activated PAR-4 signaling, and reduced proliferation of tumor cells. Conclusions: We identified SINEs that inhibit CRM-1 and promote nuclear accumulation of tumor-suppressor proteins in pancreatic cancer cells. Oral administration of the drug to mice reduces growth of xenograft tumors. 

Retracted: No

PubPeer comments:
 **Duplicate figures** All the figures of this paper have duplicates and can be found in a [previous paper] by the same two authors Tim Chen and J.C.Y Chen alias John Chen. Fig. 2 (see below) is a recycled Fig.2 of a [paper] published in the journal _Natural Hazards_ where [Cheng-Wu Chen] is the corresponding author. ![file] [Fig. 2] in _Natural Hazards_ journal: ![file] ,
Retracted : High expression of TCF12 contributes to gastric cancer development via being target regulated by miR‐183 and activating PI3K/AKT pathway
Authors: Shen Gao
Ning Yan
Wei Li
Miyang Li
Xuekui Wang
Ling Fang
Feng Xie
Tiehe Gao
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: gastric cancer; miR-183; phosphatidylinositol 3-kinase/AKT pathway; prognosis; transcription factor 12.
Affiliations: Department of Breast and Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

Abstract:  This study aimed to explore the role of transcription factor 12 (TCF12) in the process of gastric cancer (GC) and to elucidate its possible regulatory mechanism. The expression data of GC tissues and matched normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Survival analysis for GC patients with different levels of TCF12 was performed by the Kaplan-Meier analysis. In addition, TCF12 was suppressed in human GC cell lines AGS and MKN-45, followed by detecting cell biological processes (proliferation, apoptosis, migration, and invasion). Moreover, the association between TCF12 and the phosphatidylinositol 3-kinase (PI3K)/AKT signal was elucidated. Besides, the potential micro RNAs that could target TCF12 expression were explored. The results showed that TCF12 was highly expressed in GC tissues and TCF12 upregulation was associated with poor prognosis of GC patients. In addition, suppression of TCF12 significantly inhibited the proliferation, migration, and invasion of both AGS and MKN45 cells, as well as induced apoptosis of the two cell lines. Moreover, suppression of TCF12 significantly decreased the expression of p-AKT, cyclin D1, p-P70, and β-catenin in both AGS and MKN45 cells. Besides, TCF12 was target regulated by miR-183 in GC cells. Our findings reveal that TCF12 is upregulated in GC and its upregulation is associated with poor prognosis of GC patients. To sum up, downregulation of TCF12 may inhibit GC development via being target regulated by miR-183 and inhibiting the PI3K/AKT signal. TCF12 may function as a potential therapeutic target for GC. 

Retracted: Yes

PubPeer comments:
 Retracted [30 June 2021] . ---------------------------------------- The above article, published online on 15 April 2019 in Wiley Online Library , has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed after the authors asked to retract their article due to flawed data. A detailed investigation revealed multiple inappropriate modifications especially in the backgrounds of blots. Since original data could not be provided, the overall validity of the results could not be confirmed. The authors were not available for a final confirmation of the retraction. ,
A new medical imaging technique for diagnosing dermatologic diseases: A clue to treatment choices
Authors: Alireza Sepehri
Maria Grazia Roccia
Iva Binic
Masa Golubovic
Massimo Fioranelli
Julia Sigova
Aracena Jahaira Carolina
Nguyen Van Thuong
Michael Tirant
Torello Lotti
Aroonkumar Beesham
Journal: Dermatologic Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: DNA; electromagnetic waves; melanocytes.
Affiliations: Department of Nuclear, Sub-Nuclear and Radiation Physics, Guglielmo Marconi University, Rome, Italy., Department of NuclearSub‐nuclear and Radiation Physics, Guglielmo Marconi University Via Plinio 44‐00193 Rome Italy, Faculty of Natural Sciences, Mangosuthu University of Technology, Jacobs, South Africa.

Abstract:  Recently, it has been shown that DNA could emit some waves which carry main information about its evolution. Using this idea, we design a new method to image the behavior of skin cells, especially melanocytes, and diagnose their damage. In this method, we make use of a circuit which is formed from DNAs within the damaged melanocytes, a graphene sheet, DNAs within the healthy cells, and a scope. To amplify exchanged waves between hexagonal and pentagonal manifolds of DNAs, we induce some defects in the graphene sheets and replace some hexagonal molecules by pentagonal ones to build a structure similar to the structure of DNAs. We show that unprotected exposure to UVA and UVB damages the DNA in melanocyte cells, producing genetic defects, or mutations, that can lead to exchanged waves between cells and the emergence of a current in our circuit. By analyzing the evolution of this current, we can estimate the rate of destruction in melanocytes, and predict the emergence of cancer. 

Retracted: No

PubPeer comments:
 **Replication and cropping (Kazem Jeddi and Pu Chen are the two common co-authors)!** ![file] ![file] ,
Early-life short-term environmental enrichment counteracts the effects of stress on anxiety-like behavior, brain-derived neurotrophic factor and nuclear translocation of glucocorticoid receptors in the basolateral amygdala
Authors: Rupshi Mitra
Akshaya Hegde
Shruti Suresh
Journal: Scientific Reports (2020)
Discipline: Multidisciplinary
Keywords: early life; stress; environmental enrichment; rat pups; maternal separation
Affiliations: School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore., School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore. .

Abstract:  Early life is a decisive stage for the development of physiological and psychological characteristics of an individual. Any stress or disruption of healthy development at this stage has serious long-lasting consequences for the remaining life. Unfortunately, early life stress is a common occurrence in humans and other animals. In this context, we investigated if the provision of environmental enrichment during the pre-weaning phase of rat pups and dams could alter the consequences of early-life maternal-separation stress. Pre-weaning enrichment rescued the effects of maternal separation on the excess secretion of adrenal stress hormones and anxiety-like behavior during adulthood. Enrichment also reduced the effect of stress on the spine density of basolateral amygdala neurons, a brain region critical for stress-induced facilitation of emotional behaviors. Pre-weaning enrichment, provided during early-life, blunted the effects of maternal separation stress on decreased intra-nuclear translocation of glucocorticoid receptors within the amygdala neurons when tested later in adulthood. Early-life, pre-weaning environmental enrichment also increased the amount of brain-derived neurotrophic factor within adult basolateral amygdala. Our observations showed that environmental manipulation during early formative years could be utilized to build lifelong resilience to stress. Complex naturalistic housing and sensory enrichment is, thus, an useful buffer against an impoverished and stressful childhood. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 7: * The AFR and MS panels appear to be identical, as highlighted with green boxes. * In the MSEE row, the DAPI and MERGE panels do not appear to match. Could the authors please check? It looks like some panels were put in the wrong place. ![file] , 
 Hi Yes, we noticed this immediately postproduction and we are already working with ScRep Production office to replace the duplicated panels with the correct ones. Thank You Rupshi Mitra , 
 Awesome! Thank you Dr. Mitra for your fast reply and for setting the record straight. Much appreciated. , 
 October 2020 correction, found here: https: www.nature.com articles s41598-020-74322-3 It reads:  This Article contains an error in Figure 7 where the representative images for MS group are duplicates of the representative AFR images and MSEE DAPI does not match the Merge panel. The correct Figure 7 appears below as Figure 1. I thank the authors and the journal for correcting this error. ,
Gadd45 expression correlates with age dependent neurodegeneration in Drosophila melanogaster
Authors: Tatiana Dubatolova
Leonid Omelyanchuk
Alexey Moskalev
Mikhail Shaposhnikov
Natalia Bgatova
Ekaterina Plyusnina
Journal: Biogerontology (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: neurodegeneration; aging; antiaging interventions; D-GADD45; Drosophila neurons
Affiliations: Research Institute of Clinical and Experimental Lymphology Siberian Branch of RAMS, Novosibirsk, Russia.

Abstract:  The neurodegeneration is one of the features of aging and age-related disorders. Yet, only several antiaging interventions are known to affect the processes of neurodegeneration. Here we show that overexpression of the pro-longevity gene D-GADD45 in Drosophila neurons leads to a postponed manifestation of histological and ultrastructural features of age-dependent neurodegeneration, such as decrease in the packing density of neurons, increasing the degree of neuron cytoplasmic vacuolization, and morphological defects of mitochondrial cristae. Thus, the previously observed (Plyusnina, Biogerontology 12: 211-226, 2011) life extending effect of D-GADD45 overexpression in the nervous system is associated with delayed neurodegeneration. 

Retracted: No

PubPeer comments:
 Perhaps I m reading the legend incorrectly, but it appears that an image in Figure 6 overlaps with an image in Figure 8 (magenta boxes), but these are intending to illustrate untreated tissue (Fig 6) and treated tissue (Fig 8). Could the authors please clarify? Thank you. *** ![file] ,
miR-137 inhibits renal cell carcinoma growth in vitro and in vivo
Authors: Hongxia Zhang
Hongjun Li
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: miR-137; phosphoinositide 3 kinase/protein kinase B; proliferation; renal cell carcinoma.
Affiliations: Health Examination Center, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.

Abstract:  MicroRNA (miR)-137 has been reported to be underexpressed and involved in various cell processes and to have antitumor effects in a range of tumors, but so far not in renal cell carcinoma (RCC). The aim of the present study was to investigate the clinical significance and role of miR-137 in RCC. The expression levels of miR-137 were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in 50 cases of paired RCC tissues and adjacent normal tissues, and in RCC cell lines. The role of miR-137 in the growth and survival of RCC cells was assessed with several in vitro approaches and in nude mice models. The results of the RT-qPCR showed that the miR-137 expression was downregulated in the RCC tissues and cell lines. The in vitro assay showed that ectopic expression of miR-137 robustly impaired RCC cell proliferation, migratory and invasive properties, and increased the induction of cell apoptosis properties. The in vivo assay demonstrated that enforced miR-137 suppressed tumor growth in xenograft nude mice models. In addition, miR-137 was indicated to inhibit the activation of phosphoinositide 3 kinase/protein kinase B signal pathway, which contributes to the inhibition of RCC growth. These findings indicate that miR-137 functions as tumor suppressor in RCC, suggesting that miR-137 may be a potential therapeutic target for RCC. 

Retracted: No

PubPeer comments:
 Fig 3.  Effects of miRu2011137 on the activation of PI3K AKT signaling pathways in renal cell carcinoma cells. PI3K, p-PI3K, AKT and p-AKT protein expression were determined in 786-O cells after transfection with miR-137 mimic or miR-NC by western blotting . ![file] Green and blue boxes mark bands which appear in a number of other papers, e.g. Figs 3C,E of [Liu et al (2015)] .  The ... (C) protein expression levels of PTEN were detected in the HCC cells after transfection with miR-494 mimic or inhibitor. The PTEN protein expression level was detected in... (E) HCC cell lines by western blotting. ![] For the blue-boxed band (here  AKT ) a 180-deg flip is involved. Other manifestations are linked in the other thread. , 
 *[left]* Fig 4B.  Images of the tumor specimens of xenograft models at day 28. *[right]* Fig 6A from [Zhang et al (2015)] .  Representative graphs of tumor masses harvested from nude mice 30 days after inoculation are shown . ![file] Could the authors of either paper comment on the appearance of so many tumors in both? ,
Unifying candidate gene and GWAS Approaches in Asthma
Authors: Andreas Ruether
Albrecht Bufe
Burkhard Simma
Thomas Frischer
Andrea von Berg
Ivo G Gut
Otto Laub
Andrea Heinzmann
Ernst Rietschel
Christian Vogelberg
Sven Michel
Martin Depner
Ashish Kumar
Michaela Schedel
Michael Kabesch
Jon Genuneit
Norman Klopp
Erika von Mutius
Mark Lathrop
Thomas Illig
Liming Liang
Stefan Schreiber
Journal: PloS one (2010)
Discipline: Multidisciplinary
Keywords: GWAS; childhood asthma; susceptibility locus; chromosome 17q21; ORMDL3 gene
Affiliations: Center for Pediatrics, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.

Abstract:  The first genome wide association study (GWAS) for childhood asthma identified a novel major susceptibility locus on chromosome 17q21 harboring the ORMDL3 gene, but the role of previous asthma candidate genes was not specifically analyzed in this GWAS. We systematically identified 89 SNPs in 14 candidate genes previously associated with asthma in &gt;3 independent study populations. We re-genotyped 39 SNPs in these genes not covered by GWAS performed in 703 asthmatics and 658 reference children. Genotyping data were compared to imputation data derived from Illumina HumanHap300 chip genotyping. Results were combined to analyze 566 SNPs covering all 14 candidate gene loci. Genotyped polymorphisms in ADAM33, GSTP1 and VDR showed effects with p-values &lt;0.0035 (corrected for multiple testing). Combining genotyping and imputation, polymorphisms in DPP10, EDN1, IL12B, IL13, IL4, IL4R and TNF showed associations at a significance level between p = 0.05 and p = 0.0035. These data indicate that (a) GWAS coverage is insufficient for many asthma candidate genes, (b) imputation based on these data is reliable but incomplete, and (c) SNPs in three previously identified asthma candidate genes replicate in our GWAS population with significance after correction for multiple testing in 14 genes. 

Retracted: No

PubPeer comments:
 Rhee cites and extensively discusses findings from a 2008 paper by Paterna et al published in Clinical Science that has shown to contain data duplicated in a later study from the same author group published in the Journal of Cardiac Failure (Parinnello 2009). Data from both these studies were contained in a 2012 systematic review published in BMJ Heart journal that was later retracted (Aug 21, 2012) due to the inability of the study group to provide the original data to verify the duplicate data issues due to a u201ccomputer failureu201d. u2028Additional PubPeer posts for the specific studies are available: https: pubpeer.com publications E03BB72DBAA939C61082F4608D558B https: pubpeer.com publications B24491C479E0C003418D1F1CBECE07 A complete blog of the story leading to retraction of the BMJ Heart systematic review is available here: https: www.cebm.net 2019 02 salt-reduction-in-heart-failure-where-has-the-uncertainty-come-from ,
Blockade of ONECUT2 expression in ovarian cancer inhibited tumor cell proliferation, migration, invasion and angiogenesis
Authors: Simin Zhang
Jiaying Guo
Wenhui Zhu
Binhua Wu
Ning Deng
Yunfei Yu
Yinmei Zhang
Tongyi Lu
Journal: Cancer Science (2018)
Discipline: CLINICAL MEDICINE
Keywords: EMT; ONECUT2; ovarian cancer; siRNA; tumor angiogenesis.
Affiliations: Guangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Department of Biology, Jinan University, Guangzhou, China.

Abstract:  One cut homeobox 2 (ONECUT2 or OC-2) is a newly discovered transcription factor. Aberrant expression of OC-2 is closely related to cell proliferation, migration, invasion, and angiogenesis. In this study, we found that OC-2 expression was upregulated in ovarian adenocarcinoma cells, by Western blot analysis. The results of immunohistochemistry showed that the expression of OC-2 was also increased in malignant ovarian cancer tissue. In order to explore the role of OC-2 in the development of ovarian cancer, siRNAs that specifically targets OC-2 were designed. The siRNA targeting OC-2 could effectively inhibit the vascular endothelial growth factor A (VEGFA) expression, but silence and overexpression of VEGFA did not affect OC-2 expression. In addition, OC2-siRNA could block the proliferation, migration, and invasion, and inhibit epithelial-mesenchymal transition and the AKT/ERK signaling pathway, of human ovarian cancer cells in vitro. In a mouse model of ovarian cancer xenograft tumors, OC2-siRNA could significantly inhibit tumor cell growth and the tumor inhibition rate reached approximately 73%. The results of immunohistochemistry showed that the densities of microvessels stained with CD31, the expression of OC-2 and VEGFA were significantly decreased in tumors. These data indicated that OC-2 was an upstream regulator of VEGFA and silencing OC-2 could inhibit ovarian cancer angiogenesis and tumor growth. 

Retracted: No

PubPeer comments:
 This paper is flawed according to the comments in https: pubpeer.com publications C0B047951E52EE8B4A351646172A55 ![file] ![file] , 
 Regarding the ranking method, it seems that you were clear based on the discussion in: https: pubpeer.com publications 763257B958790969FC1AF53012DD5B#20 ,
Nanobubbles for enhanced ultrasound imaging of tumors
Authors: Du Cheng
Tinghui Yin
Rongqin Zheng
Bowen Zheng
Ping Wang
Xinling Zhang
Xintao Shuai
Journal: International Journal of Nanomedicine (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: contrast agent; phospholipids; tumor-targeted; ultrasound.

Abstract:  The fabrication and initial applications of nanobubbles (NBs) have shown promising results in recent years. A small particle size is a basic requirement for ultrasound contrast-enhanced agents that penetrate tumor blood vessel pores to allow for targeted imaging and therapy. However, the nanoscale size of the particles used has the disadvantage of weakening the imaging ability of clinical diagnostic ultrasound. In this work, we fabricated a lipid NBs contrast-enhanced ultrasound agent and evaluated its passive targeting ability in vivo. The results showed that the NBs were small (436.8 ± 5.7 nm), and in vitro ultrasound imaging suggested that the ultrasonic imaging ability is comparable to that of microbubbles (MBs). In vivo experiments confirmed the ability of NBs to passively target tumor tissues. The NBs remained in the tumor area for a longer period because they exhibited enhanced permeability and retention. Direct evidence was obtained by direct observation of red fluorescence-dyed NBs in tumor tissue using confocal laser scanning microscopy. We have demonstrated the ability to fabricate NBs that can be used for the in vivo contrast-enhanced imaging of tumor tissue and that have potential for drug/gene delivery. 

Retracted: No

PubPeer comments:
 Overlapping images were found in this article. ![file] , 
 ![file] , 
 #1 Thank you for your questions. Since there are many pictures of traswell experiment results in the article,We uploaded the wrong pictures due to our careless. We apologize for the adverse effects caused. We will actively communicate with the magazine and make corrections in time. Thank you for your suggestions. ,
Selective induction of apoptosis through the FADD/caspase-8 pathway by a p53 c-terminal peptide in human pre-malignant and malignant cells
Authors: Yuehua Mao
Paul W Brandt-Rauf
Ramon V Rosal
Richard D Dinnen
Yin Li
Ann C Williams
Robert L Fine
Journal: International Journal of Cancer (2005)
Discipline: CLINICAL MEDICINE
Keywords: p53 C-terminal peptide; Antennapedia; apoptosis; Fas pathway; cancer cells
Affiliations: Experimental Therapeutics Program, Division of Medical Oncology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY 10032, USA.

Abstract:  A p53 C-terminal peptide (aa 361-382, p53p), fused at its C-terminus to the minimal carrier peptide of antennapedia (17 aa, Ant; p53p-Ant), induced rapid apoptosis in human cancer cells, via activation of the Fas pathway. We examined p53p-Ant mechanism of action, toxicity in various human normal, non-malignant, pre-malignant and malignant cancer cells and investigated its biophysical characteristics. p53p-Ant selectively induced cell death in only pre-malignant or malignant cells in a p53-dependent manner and was not toxic to normal and non-malignant cells. p53p-Ant was more toxic to the mutant p53 than wild-type p53 phenotype in H1299 lung cancer cells stably expressing human temperature-sensitive p53 mutant 143Ala. Surface plasmon resonance (BIACORE) analysis demonstrated that this peptide had higher binding affinity to mutant p53 as compared to wild-type p53. p53p-Ant induced-cell death had the classical morphological characteristics of apoptosis and had no features of necrosis. The mechanism of cell death by p53p-Ant was through the FADD/caspase-8-dependent pathway without the involvement of the TRAIL pathway, Bcl-2 family and cell cycle changes. Blocking Fas with antibody did not alter the peptide's effect, suggesting that Fas itself did not interact with the peptide. Transfection with a dominant-negative FADD with a deleted N-terminus inhibited p53p-Ant-induced apoptosis. Its mechanism of action is related to the FADD-induced pathway without restoration of other p53 functions. p53p-Ant is a novel anticancer agent with unique selectivity for human cancer cells and could be useful as a prototype for the development of new anti-cancer agents. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar than you would expect, although the cell lines are different. https: imgur.com qeLaxEw ,
Repeated caffeine administration aggravates post-traumatic stress disorder-like symptoms in rats
Authors: Durgesh Singh Dangi
Santosh Kumar Prajapati
Sairam Krishnamurthy
Journal: Physiology & Behavior (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Anxiety; Caffeine; Corticosterone; Depression; Serotonin
Affiliations: Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, U.P., India., Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, U.P., India. Electronic address: .

Abstract:  Background: Caffeine is the widely consumed central nervous system stimulant in form of coffee and other beverages. However, the repeated administration of caffeine induces anxiety, disturbance in hypothalamic-pituitary-adrenal (HPA) axis and psychiatric symptoms in humans. As much evidence links PTSD to HPA axis dysfunction, and anxiety is a hallmark symptom, repeated and/or large doses of caffeine may exacerbate symptoms of PTSD. Objective: In our present study, we evaluated the effect of repeated administration of caffeine on stress re-stress (SRS) model of PTSD. Methods: As per the protocol, male rats were restrained for 2 h followed by 20 min forced swim and halothane anaesthesia on day 2 (D-2). Then the rats were re-stressed (forced swim) at 6-days interval between D-8 to D-32. After exposure to SRS, depressive, anxiety-like behaviour, and cognitive functions were evaluated by forced swim test (FST), elevated plus maze (EPM) and Y-maze tests respectively. Caffeine (10, 20 and 30 mg/kg, i.p.) dosing was started from D-8 and continued up to D-32. The corticosterone level was measured in plasma followed by serotonin and glucocorticoid receptor (GR) and mineralocorticoid receptors (MR) estimation in hippocampus (HIP), prefrontal cortex (PFC) and amygdala (AMY). Results: SRS-induced depressive and anxiety-like behaviour was aggravated by caffeine at dose of 20 and 30 mg/kg. Caffeine (30 mg/kg) treated control animals showed depressive, anxiety-like behaviour and cognitive impairments. SRS-induced decrease in plasma corticosterone level and increase in serotonin (5HT) levels in the PFC, HIP and AMY were not altered by caffeine. Caffeine did not modulate the SRS-induced decrease in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). In contrast, caffeine per se decreased GR and MR expression and their ratio in unstressed animals. Conclusion: Repeated intake of caffeine aggravates PTSD-like symptoms in stress-exposed rats and induces PTSD-like symptoms in unstressed rats by altering the expression of glucocorticoid receptors. 

Retracted: No

PubPeer comments:
 Figure 4. Some bands within the same panel look unexpectedly similar to each other, although they appear sometimes in mirror image. Arrows of the same color show orientation and similarities across bands. ![file] ,
Amyloid fibril formation by the chain B subunit of monellin occurs by a nucleation-dependent polymerization mechanism
Authors: Jayant B Udgaonkar
A T Sabareesan
Journal: Biochemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Proteins; Amyloid fibrils; Formation mechanism; Model protein system; Reproducibility
Affiliations: National Centre for Biological
Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India

Abstract:  Proteins possessing very different structures, or even no structure, form amyloid fibrils that are very similar in internal structure. This suggests that the mechanisms by which amyloid fibrils form might be very similar, irrespective of whether the fibrils are associated with disease or with normal cellular function, or even if they have no physiological importance. In this context, it is important to have a model protein system whose amyloid fibril formation is robust in its reproducibility, which can reveal the fundamentals of the amyloid fibril reaction that may be applicable to all proteins. In this study, the aggregation mechanism of amyloid fibril formation by chain B of the heterodimeric protein monellin has been elucidated in detail. It is shown that the aggregation reaction meets all the stringent kinetic criteria of a homogeneous nucleation-dependent polymerization mechanism, which is valid over a wide range of protein concentrations. Quantitative analyses of the kinetic data using one approach based on features of the entire kinetic curve, and another based on only the initial rate of aggregation, indicate that the thermodynamic nucleus is a dimer. Spherical oligomers are observed by atomic force microscopy to form transiently early during fibril formation but are off-pathway to the direct fibril formation pathway. It is shown that amyloid fibril formation can be prevented by the addition of chain A of monellin at early stages of chain B aggregation: the two free chains combine to form native monellin, which leads to the dissociation of early aggregates. 

Retracted: No

PubPeer comments:
 ![file] , 
 Figure 1E shows an AFM image taken at the 24 hour time point of aggregation. Inadvertently, an image taken at the 24 houru00a0time point was used in place of a 12 hour time point. Fibril images taken at 12 hours are similar to those taken at 24 hours as the reaction is complete at 12 hoursu00a0(Figures 1A-D). Figure 7 shows AFM images taken at 4 different time points. In Figure 7D, the time point is 24 hours. The images in Figures 1E and 7D are exactly the same because they are from the same experiment (not two independent experiments) at exactly the same time point (24 hours). ,
Fabrication of a multifunctional magnetic-fluorescent material for medical applications
Authors: Fernando Arteaga-Cardona
N Rutilo Silva-González
Ulises Salazar-Kuri
Silvia Hidalgo-Tobón
Miguel A Méndez-Rojas
Pilar Dies-Suarez
Gary N Cherr
J Octavio Estévez
Justo Miguel Gracia Y Jiménez
Journal: Dalton Transactions (2020)
Discipline: CHEMISTRY
Keywords: Multifunctional biocompatible materials; thermal decomposition preparation; fluorescent-magnetic particles; composite structure; CoFe2O4 nanoparticles
Affiliations: Instituto de Física, Departamento de Materia Condensada/Instituto de Física UNAM, Departamento de Ciencias Químico-Biológicas, Departamento de Física, Departamento de Imagenología, Bodega Marine Laboratory

Abstract:  Multifunctional biocompatible materials have evoked considerable interest in the field of medical applications. Here we report the thermal decomposition preparation of homogeneous fluorescent-magnetic particles with a composite structure containing CoFe2O4 nanoparticles as nucleation seeds for fluorescent Gd2-xO3:Eux. The composite exhibited a wide range of fluorescence transitions in the whole visible spectrum, displaying 18 different emission peaks when excited at a 250 nm wavelength. Moreover, at low temperature the peaks of the composite were wider than the peaks of the fluorescent material, which may be attributed to a set of new energy levels due to a combination of Stark splitting with the magnetic field of CoFe2O4. Because this material is intended to be used for biomedical applications, the potential toxicity of the composite was tested using an invertebrate hemocyte cell model. The cells showed slight morphological and biochemical changes upon exposure to the composite; however, there was no increase in cell death at concentrations of up to 40 ppm. In addition, the material could be tracked by its fluorescence inside the cells, when excited at a more bio-friendly and less energetic wavelength of 405 nm. Furthermore, MRI showed T1 and T2 dual contrast with relaxivity values in the range of most reported materials. 

Retracted: No

PubPeer comments:
 Figure 9 was pointed out to me by a reader. * Red boxes: Panels f (hemocytes with GE5) and g (hemocytes with ML5) appear to look identical. ![file] ,
Molecular Basis of LH Action on Breast Cancer Cell Migration and Invasion via Kinase and Scaffold Proteins
Authors: Joselina Magali Mondaca
Ivonne Denise Uzair
Ana Carla Castro Guijarro
Marina Inés Flamini
Angel Matias Sanchez
Journal: Frontiers in Cell and Developmental Biology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LH; N-WASP; breast cancer; cortactin; migration and invasion.
Affiliations: Laboratorio de Transducción de Señales y Movimiento Celular, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Cuyo, Mendoza, Argentina., Laboratorio de Biología Tumoral, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Cuyo, Mendoza, Argentina.

Abstract:  Breast cancer (BC) is a major public health problem affecting women worldwide. Approximately 80% of diagnosed cases are hormone-dependent breast cancers. These hormones are known to stimulate tumor development and progression. In this setting, tentative evidence suggests that luteinizing hormone (LH) may also play a role in tumors. In BC cells that express functional LH receptors (LHR), this hormone regulates cell migration and invasion by controlling several kinases that activate actin cytoskeletal proteins. In this article, we show that LH induces phosphorylation of paxillin and its translocation toward the plasmatic membrane, where focal adhesion complexes are assembled. This process is triggered via a rapid extra-gonadal LHR signaling to Src/FAK/paxillin, which results in the phosphorylation/activation of the nucleation promoter factors cortactin and N-WASP. As a consequence, Arp2/3 complexes induce actin polymerization, essential to promote cell adhesion, migration, and invasion, thus enhancing metastatic spread of tumoral cells. Our findings provide relevant information about how gonadotrophins exert their action in BC. This information helps us understand the extragonadal effects of LH on BC metastasis. It may provide new perspectives for therapeutic treatment, especially for women with high serum levels of gonadotrophins. 

Retracted: No

PubPeer comments:
 Figure 5C appears to have two images which overlap. *** ![file] , 
 Thank you very much for reminding us of the repetition. I checked the original data and reports. Indeed, it is a mistake during figure preparation. Surely, I will ask the journal for the correction soon. Thank you very much for your efforts in making the scientific publication solid and clean. Sincerely, Matias , 
 This figure has been corrected, 2 years ago, by the journal. , 
 #3 Thank you for providing an update. Could the author please point me to the correction? I redownloaded the article today and this overlap still seems to be there. ,
Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway
Authors: Ning Li
Zhiqiao Xu
Zhenying Yi
Yan Zhang
Xiaojing Tie
Fengqian Shen
Journal: IUBMB Life (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ESCC; IL-6; STAT3; circ_0000654; miR-149-5p.
Affiliations: Department of Tumor Center, Kaifeng Central Hospital, Kaifeng, Henan, China.

Abstract:  Circular RNAs (circRNAs) are novel noncoding RNAs (ncRNAs) with covalently closed-loop structures that play an essential regulatory role in diverse malignancies, including esophageal squamous cell cancer (ESCC). Circ_0000654 expression in ESCC and its mechanism of action remains unclear. Real-time PCR (RT-PCR) was employed to detect circ_0000654 and miR-149-5p expression in ESCC tissues. Circ_0000654 and miR-149-5p expression in ESCC cells was selectively regulated. Furthermore, interleukin 6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) expression in cells was detected by RT-PCR and western blot analysis, while CCK8, BrdU, flow cytometry, and transwell assays were used to monitor cell proliferation, apoptosis, migration and invasion, respectively. The dual-luciferase reporter assay and RIP assay were used to verify the targeting relationship between circ_0000654 and miR-149-5p, miR-149-5p and IL-6. The function of circ_0000654 on ESCC cell proliferation and metastasis in vivo was examined using a subcutaneous xenograft model and a tail intravenous injection model in nude mice. Circ_0000654 was significantly upregulated in ESCC tissues and cell lines, and its high expression was remarkably associated with an increased T stage and local lymph node metastasis in ESCC patients. Circ_0000654 overexpression and knockdown experiments revealed that circ_0000654 regulated ESCC cell proliferation, migration, invasion, and apoptosis in vitro. Circ_0000654 was identified as a sponge of miR-149-5p and facilitated ESCC progression by indirectly activating the IL-6/STAT3 signaling pathway. Additionally, knocking down circ_0000654 strikingly repressed ESCC growth and metastasis in vivo. In summary, circ_0000654 functions as an oncogenic circRNA in ESCC and accelerates ESCC progression via adsorbing miR-149-5p and activating the IL-6/STAT3 signaling pathway. 

Retracted: No

PubPeer comments:
 ![file] ,
Human CNK1 acts as a scaffold protein, linking Rho and Ras signal transduction pathways
Authors: Pontus Aspenström
Alan Hall
Aron B Jaffe
Journal: Molecular and Cellular Biology (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Rho family GTPases; cellular responses; cytoskeletal rearrangements; gene expression; cell transformation
Affiliations: MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Cancer Research UK Oncogene and Signal Transduction Group, and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom., Ludwig Institute for Cancer Research, S-751 24 Uppsala, Sweden, MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Cancer Research UK Oncogene and Signal Transduction Group, and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom

Abstract:  Rho family GTPases act as molecular switches to control a variety of cellular responses, including cytoskeletal rearrangements, changes in gene expression, and cell transformation. In the active, GTP-bound state, Rho interacts with an ever-growing number of effector molecules, which promote distinct biochemical pathways. Here, we describe the isolation of hCNK1, the human homologue of Drosophila connector enhancer of ksr, as an effector for Rho. hCNK1 contains several protein-protein interaction domains, and Rho interacts with one of these, the PH domain, in a GTP-dependent manner. A mutant hCNK1, which is unable to bind to Rho, or depletion of endogenous hCNK1 by using RNA interference inhibits Rho-induced gene expression via serum response factor but has no apparent effect on Rho-induced stress fiber formation, suggesting that it acts as a specific effector for transcriptional, but not cytoskeletal, activation pathways. Finally, hCNK1 associates with Rhophilin and RalGDS, Rho and Ras effector molecules, respectively, suggesting that it acts as a scaffold protein to mediate cross talk between the two pathways. 

Retracted: No

PubPeer comments:
 Figure 4B. Vertical and horizontal splices (sharp, straight changes in signal) in hCNK1 panel, but not in L63Rho panel. Band rightmost lane hCNK1 panel looks like it is on its own rectangle of background. ![file] ,
MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors
Authors: Tim Wang
Amanda W Hutchins
Jan E Carette
Yetis Gultekin
Richard Possemato
Walter W Chen
Omer H Yilmaz
Thijn R Brummelkamp
Kivanç Birsoy
David M Sabatini
Clary B Clish
Catherine E Koch
Tim R Peterson
Journal: Nature Genetics (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: oncogenic transformation; metabolic program; glycolysis; genetic screen; resistance mechanisms
Affiliations: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.

Abstract:  There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA-resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors. 

Retracted: No

PubPeer comments:
 Figure 4a. Much more similar than expected. ![file] ,
c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/β-catenin–ATP-binding cassette G2 signaling
Authors: A S T Wong
C K Ip
A S C Mak
H-C Lai
W K Chau
Journal: Oncogene (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cisplatin; paclitaxel; ovarian cancer; tumor-initiating cells; c-Kit
Affiliations: School of Biological Sciences, University of Hong Kong, HK, Hong Kong.

Abstract:  Cisplatin and paclitaxel are standard chemotherapy for metastatic ovarian cancer, but with limited efficacy. Cancer stem/progenitor cells (or tumor-initiating cells, TICs) are hypothesized to be chemoresistant, and the existence of TICs in ovarian cancer has been previously demonstrated. However, the key signals and molecular events regulating the formation and expansion of ovarian tumor-initiating cells (OTICs) remain elusive. Here, we show that c-Kit is not just a marker of OTICs, but also a critical mediator of the phenotype that can be a viable target for the treatment of ovarian cancer. In contrast to non-OICs, c-Kit was overexpressed in OTICs. Moreover, the use of small interfering RNA to inhibit c-Kit expression markedly attenuated the number and size of OTIC subpopulations, inhibited the expression of stem cell markers and decreased the tumorigenic capabilities of OTICs. Imatinib (Gleevec), a clinical drug that blocks c-Kit kinase activity, also demonstrated its inhibition potency on OTICs. In addition, cisplatin/paclitaxel, which killed non-OTICs, with c-Kit knockdown or imatinib revealed that this was critically required for intervening ovarian cancer progression and recurrence in vitro and in xenograft tumors in vivo. Similar results were obtained with OTICs derived from ovarian carcinoma patients. Studies into the mechanisms suggest an important role for the activation of Wnt/β-catenin and ATP-binding cassette G2 downstream of c-Kit. The tumor-promoting microenvironment, such as hypoxia, could promote OTICs via upregulation of c-Kit expression. These results unravel an integral role for c-Kit in ovarian neoplastic processes and shed light on its mechanisms of action. 

Retracted: No

PubPeer comments:
 Figure 2d and 4a appear to have a repeated image described differently. *** ![file] *** ![file] ,