PReD-Bench/PRed-Bench huggingface dataset:
Up-regulated ENO1 promotes the bladder cancer cell growth and proliferation via regulating β-catenin
Authors: Jie Chen
Yelei Ding
Liqiong Gu
Mingfei Ji
Ming Chen
Tao Liu
Zhijun Wang
Journal: Bioscience Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ENO1; apoptosis; bladder cancer; cell cycle; β-catenin.
Affiliations: Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai, China., Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai, China ., Department of Ophthalmology, Shanghai East Hospital, Tongji University, Shanghai, China.

Abstract:  Bladder cancer (BC) is the ninth most common malignancy throughout the world. The molecular mechanisms of this disease remain largely unclear. The glycolytic enzyme enolase 1 (ENO1) has been shown to regulate the development of various cancers. However, the significance of ENO1 in BC is underdetermined. In this study, we found that ENO1 was highly expressed in BC tissues and cells. High expression of ENO1 was associated with the poor survival of BC patients. Using lentivirus-mediated knockdown and over-expression, we revealed that ENO1 was critical for the growth and proliferation of BC cells. ENO1 over-expression also promoted the proliferation of SV-HUC-1 cells. At the molecular level, the cell cycle and apoptosis related genes were regulated by ENO1. β-catenin expression was positively regulated by ENO1. Furthermore, ectopic expression of β-catenin reversed the effect of ENO1 knockdown on T24 cell proliferation and growth. Opposite results were observed in β-catenin knockdown T24 cells. Our findings suggested that ENO1 functioned as an oncogene in BC through regulating cell cycle, apoptosis and β-catenin. Targeting ENO1/β-catenin cascade may benefit for BC patients. 

Retracted: No

PubPeer comments:
 The GAPDH band for patient 6 in Figure 1 seems to include an u201cunnaturalu201d rectangular shape. Could the authors please share the uncropped original blot? *** Closeup ![file] *** Full figure ![file] , 
 EXPRESSION OF CONCERN| FEBRUARY 16 2021 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 CORRECTION OCTOBER 29 2021 This Correction follows an Expression of Concern relating to this article previously published by Portland Press. The authors of the original article u201cUp-regulated ENO1 promotes the bladder cancer cell growth and proliferation via regulating u03b2-cateninu201d (Biosci Rep (2019) 39(9); https: doi.org 10.1042 BSR20190503) would like to correct the western blots in their figures. The authors state that in their original Figures 1-5, the western blot bands were obscure due to the chemiluminescence machine used. They have repeated the whole experiment on request by the Editorial Board, with a higher resolution setting. The authors declare that the results of their new experiment do not affect the results and conclusions of their original article. *** ![file] *** ![file] *** ![file] *** ![file] *** ![file] ,
Review of recent advances in the management of hypertrophic cardiomyopathy
Authors: P-Y Zhang
Y Cao
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Hypertrophic cardiomyopathy; monogenic cardiovascular disorder; left ventricular thickening; genetic disorder; sarcomeric proteins
Affiliations: Department of Cardiology, Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou, Jiangsu, China. .

Abstract:  Hypertrophic cardiomyopathy (HCM) is a complex but common monogenic cardiovascular disorder characterized by unexplained non dilated left ventricular (LV) thickening in the absence of another cardiac or systemic disease. The condition is associated with sudden and unexpected death in young individuals including trained athletes. HCM represents a genetic disorder caused by mutations in genes encoding sarcomeric proteins of the cardiac myocyte. This review article discusses the genetics behind HCM, its clinical presentation, and diagnosis and the present-day pharmacological management of HCM. 

Retracted: No

PubPeer comments:
 The Figure you used appears to be copied from a Medcsape article by Butany et al Geriatrics and Aging. 2008;11(1):22-26. https: www.medscape.com viewarticle 573857_5 ![file] ![file] ,
Developing imprinted polymer nanoparticles for the selective separation of antidiabetic drugs
Authors: Sadia Zafar Bajwa
Adnan Mujahid
Isma Haq
Hadia Ashraf
Tajamal Hussain
Adeel Afzal
Khurram Shehzad
Naseer Iqbal
Journal: Journal of Separation Science (2015)
Discipline: CHEMISTRY
Keywords: Antidiabetic drugs; Metformin; Molecularly imprinted polymers; Sitagliptin.
Affiliations: Institute of Chemistry, University of the Punjab, Quaid-e-Azam Campus, Lahore, Pakistan., King Fahd University of Petroleum and Minerals, Affiliated Colleges at Hafr Al Batin and Department of Chemistry, University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia., Department of Biosciences, COMSATS Institute of Information Technology, ChakShahzad, Islamabad, Pakistan., National Institute of Biotechnology and Genetic Engineering, Faisalabad, Pakistan.

Abstract:  In this study, new molecularly imprinted polymer (MIP) nanoparticles are designed for selective recognition of different drugs used for the treatment of type 2 diabetes mellitus, i.e. sitagliptin (SG) and metformin (MF). The SG- and MF-imprinted polymer nanoparticles are synthesized by free-radical initiated polymerization of the functional monomers: methacrylic acid and methyl methacrylate; and the crosslinker: ethylene glycol dimethacrylate. The surface morphology of resultant MIP nanoparticles is studied by atomic force microscopy. Fourier transform infrared spectra of MIP nanoparticles suggest the presence of reversible, non-covalent interactions between the template and the polymer. The effect of pH on the rebinding of antidiabetic drugs with SG- and MF-imprinted polymers is investigated to determine the optimal experimental conditions. The molecular recognition characteristics of SG- and MF-imprinted polymers for the respective drug targets are determined at low concentrations of SG (50-150 ppm) and MF (5-100 ppm). In both cases, the MIP nanoparticles exhibit higher binding response compared to non-imprinted polymers. Furthermore, the MIPs demonstrate high selectivity with four fold higher responses toward imprinted drugs targets, respectively. Recycled MIP nanoparticles retain 90% of their drug-binding efficiency, which makes them suitable for successive analyses with significantly preserved recognition features. 

Retracted: No

PubPeer comments:
 Figure 3A. * Some particles in this AFM image appear to be visible multiple times. ![file] ,
Alkaline Cytosolic pH and High Sodium Hydrogen Exchanger 1 (NHE1) Activity in Th9 Cells
Authors: Yogesh Singh
Xiaolong Shi
Karl S Lang
Florian Lang
Anja T Umbach
Madhuri S Salker
Shaqiu Zhang
Yuetao Zhou
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NHE1; T helper cells; Th9 cells; cancer; cellular regulation
Affiliations: From the Departments of Cardiology, Cardiovascular Medicine and Physiology, Eberhard-Karls-Tübingen University, Tübingen, Gmelinstraße5, D-72076 Tübingen, Germany, ., From the Departments of Cardiology, Cardiovascular Medicine and Physiology, Eberhard-Karls-Tübingen University, Tübingen, Gmelinstraße5, D-72076 Tübingen, Germany., the Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan 611130, China, and., the Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.

Abstract:  CD4+ T helper 9 (Th9) cells are a newly discovered Th cell subset that produce the pleiotropic cytokine IL-9. Th9 cells can protect against tumors and provide resistance against helminth infections. Given their pivotal role in the adaptive immune system, understanding Th9 cell development and the regulation of IL-9 production could open novel immunotherapeutic opportunities. The Na+/H+ exchanger 1 (NHE1; gene name Slc9α1)) is critically important for regulating intracellular pH (pHi), cell volume, migration, and cell survival. The pHi influences cytokine secretion, activities of membrane-associated enzymes, ion transport, and other effector signaling molecules such as ATP and Ca2+ levels. However, whether NHE1 regulates Th9 cell development or IL-9 secretion has not yet been defined. The present study explored the role of NHE1 in Th9 cell development and function. Th cell subsets were characterized by flow cytometry and pHi was measured using 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-acetoxymethyl ester (BCECF-AM) dye. NHE1 functional activity was estimated from the rate of realkalinization following an ammonium pulse. Surprisingly, in Th9 cells pHi and NHE1 activity were significantly higher than in all other Th cell subsets (Th1/Th2/Th17 and induced regulatory T cells (iTregs)). NHE1 transcript levels and protein abundance were significantly higher in Th9 cells than in other Th cell subsets. Inhibition of NHE1 by siRNA-NHE1 or with cariporide in Th9 cells down-regulated IL-9 and ATP production. NHE1 activity, Th9 cell development, and IL-9 production were further blunted by pharmacological inhibition of protein kinase Akt1/Akt2. Our findings reveal that Akt1/Akt2 control of NHE1 could be an important physiological regulator of Th9 cell differentiation, IL-9 secretion, and ATP production. 

Retracted: No

PubPeer comments:
 The flow cytometry dot plots in red box appear to look similar in Fig 6C. ![file] ,
MicroRNA-30a Mediates Cell Migration and Invasion by Targeting Metadherin in Colorectal Cancer
Authors: Yanteng Zhao
Mengle Peng
Huifang Jin
Yongkui Kong
Xiaoqing Shi
Xianping Lv
Dongchun Qin
Journal: Technology in Cancer Research & Treatment (2018)
Discipline: CLINICAL MEDICINE
Keywords: colorectal cancer; invasion; metadherin; miR-30a; migration.
Affiliations: 1 Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., 2 Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., 3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Abstract:  MicroRNAs play critical roles in the occurrence and progression in various cancers including colorectal cancer. Here, we found that microRNA-30a expression was significantly downregulated in colorectal cancer tissues compared to adjacent noncancerous tissues, and the suppression levels of microRNA-30a were significantly associated with tumor differentiation and lymph node metastasis. We also discovered that the expression level of microRNA-30a was inversely proportional to the invasive potential of several colorectal cancer cell lines. Moreover, overexpression of microRNA-30a in colorectal cancer cells inhibited activity of cell migration and invasion. Luciferase reporter assay confirmed metadherin could be a direct target of microRNA-30a, as the overexpression of microRNA-30a decreased metadherin expression at both the protein and messenger RNA levels. Furthermore, the knockdown of metadherin expression in SW620 significantly decreased cell metastasis and invasion. The upregulation of metadherin at the protein level negatively correlated with the expression of microRNA-30a in colorectal cancer tissues, and this upregulation could partially attenuate the effect induced by microRNA-30a. These findings indicate that microRNA-30a may act as a tumor suppressor in colorectal cancer and that microRNA-30a represses cell migration and invasion by decreasing metadherin, highlighting the therapeutic potential of microRNA-30a and metadherin in colorectal cancer treatment. 

Retracted: No

PubPeer comments:
 Two images in figure 2C appear to overlap. *** ![file] *** Showing location in figure ![file] , 
 Some additional concerns. *** 2D ![file] *** 4C ![file] *** 5C ![file] ,
RETRACTED ARTICLE: Carboxypeptidase E: Elevated Expression Correlated with Tumor Growth and Metastasis in Pheochromocytomas and Other Cancers
Authors: Karel Pacak
Saravana R K Murthy
Y Peng Loh
Journal: Cellular and Molecular Neurobiology (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: carboxypeptidase E; CPE; cancer types; metastatic; mRNA expression
Affiliations: Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bldg. 49, Rm. 5A22, 49 Convent Drive, MSC 4480, Bethesda, MD 20892, USA.

Abstract:  Expression of carboxypeptidase E (CPE), a prohormone processing enzyme in different cancer types, was analyzed from data in the GEO profile database (http://www.ncbi.nlm.nih.gov/geo/) and experimentally in pheochromocytomas. Analysis of microarray data demonstrated that significantly elevated levels of CPE mRNA was found in many metastatic non-endocrine cancers: cervical, colon rectal, renal cancers, Ewing sarcomas (bone cancer), and various types of astrocytomas and oligodendrogliomas, whereas expression of CPE mRNA was virtually absent in their respective counterpart normal tissues. Moreover, there was higher CPE mRNA expression in cells from the metastatic tumor compared to those from the primary tumor in colorectal cancer. Elevated CPE mRNA expression was found in neuroendocrine tumors in lung and pituitary adenomas, although the significance is unclear since endocrine and neuroendocrine cells normally express CPE. However, studies of neuroendocrine tumors, pheochromocytomas, revealed expression of not only wild-type CPE, but a variant which was correlated with tumor behavior. Extremely high CPE mRNA copy numbers of the variant were found in very large or invasive tumors, both of which usually indicate poor prognosis. Thus, collectively the data suggest that CPE may play a role in promoting tumor growth and invasion. CPE could potentially serve as a diagnostic and prognostic biomarker for metastasis in different cancer types. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: link.springer.com article 10.1007 s10571-020-00838-x The Editor and the Publisher have retracted this article [1] following an investigation by the National Institutes of Health (NIH) into the primary data used to construct Table 2. This investigation concluded that the data in Table 2 are unreliable. Reference 1. Murthy SRK, Pacak K, Loh YP (2010) Carboxypeptidase E: elevated expression correlated with tumor growth and metastasis in pheochromocytomas and other cancers. Cell Mol Neurobiol 30:1377u20131381. https: doi.org 10.1007 s10571-010-9592-y ,
Elucidate genetic diversity and population structure of Olea europaea L. germplasm in Iran using AFLP and IRAP molecular markers
Authors: Karim Sorkheh
Esmaeil Khaleghi
Sezai Ercisli
Maryam Hosseni Chaleshtori
Journal: 3 Biotech (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: AFLP; Genetic diversity; IRAP; Olea europaea L.; Population structure.
Affiliations: Department of Horticultural Science, Faculty of Agriculture, Shahid Chamran University of Ahvaz, P.O. Box 61355/144, Ahvaz, Iran., Department of Agronomy and Plant Breeding, Faculty of Agriculture, Shahid Chamran University of Ahvaz, P.O. Box 61355/144, Ahvaz, Iran. ., Rice Research Institute of Iran (RRII), Agriculture Research Education and Extension Organization (AREEO), P. O. Box 1658, Rasht, Iran., Department of Horticulture, Agricultural Faculty, Ataturk University, 25240, Erzurum, Turkey.

Abstract:  Currently, study of the inter and the intra-population genetic disparity was done by use of the 200 Olea europaea L. which is found growing naturally in the nation of Iran, and this study was carried out by AFLP and IRAP markers. The fingerprints that were similar to the AFLP and the IRAP markers were evidence of high concentrations of heterozygosity and this shows that O. europaea L. is primarily the out crossing species. The average percentage of polymorphism is as shown below: 87.15 and 87.38% of the information used in regard to the AFLP and the IRAP, respectively. The gene disparity numerals on the population researched were 1.087 for HT and 0.871 for HS in regard to AFLP. For the IRAP it was 1.084 for HT and 0.860 for HS. The general values for genetic variations that are found in the O. europaea L. germplasm in the nation of Iran were then assessed through putting together the AFLP and the IRAP information so as to cover a larger genome. Arguing from the AFLP and the IRAP studies, it can be concluded that there are more levels of genetic variation at inter and the intra-population level for the O. europaea. 

Retracted: No

PubPeer comments:
 Figure 1(a)  TEM photomicrograph of developed nanocarriers: (a) chitosan nanoparticles . ![file] Fig 1 from [Zakir et al (2011)] .  TEM of Amp B nano-suspension . ![file] They seem to be the same image. ,
Synthesis of Graphene Oxide-FeO Based Nanocomposites Using the Mechanochemical Method and in Vitro Magnetic Hyperthermia
Authors: Aleksandr S Kamzin
Shilpee Jain
Hemant Kumar
Bashar Issa
Venkatesha Narayanaswamy
Chandan Srivastava
Ihab M Obaidat
Sachin Latiyan
Sulaiman Alaabed
Journal: International journal of molecular sciences (2019)
Discipline: CHEMISTRY
Keywords: graphene oxide; hyperthermia; mechanochemical method.
Affiliations: Department of Physics, United Arab Emirates University, Al-Ain 15551, United Arab Emirates., Department of Physics, United Arab Emirates University, Al-Ain 15551, United Arab Emirates. ., Ioffe Physical Technical Institute, St. Petersburg 194021, Russia., Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India., Materials Engineering, Indian Institute of Science, Bangalore 560012, India., Department of Geology, United Arab Emirates University, Al-Ain 15551, United Arab Emirates., Department of Medical Diagnostic Imaging, College of Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.

Abstract:  The study presented in this work consists of two parts: The first part is the synthesis of Graphene oxide-Fe3O4 nanocomposites by a mechanochemical method which, is a mechanical process that is likely to yield extremely heterogeneous particles. The second part includes a study on the efficacy of these Graphene oxide-Fe3O4 nanocomposites to kill cancerous cells. Iron powder, ball milled along with graphene oxide in a toluene medium, underwent a controlled oxidation process. Different phases of GO-Fe3O4 nanocomposites were obtained based on the composition used for milling. As synthesized nanocomposites were characterized by x-ray diffraction (XRD), alternating magnetic field (AFM), Raman spectroscopy, and a vibrating sample magnetometer (VSM). Additionally, the magnetic properties required to obtain high SAR values (Specific Absorption Rate-Power absorbed per unit mass of the magnetic nanocomposite in the presence of an applied magnetic field) for the composite were optimized by varying the milling time. Nanocomposites milled for different extents of time have shown differential behavior for magneto thermic heating. The magnetic composites synthesized by the ball milled method were able to retain the functional groups of graphene oxide. The efficacy of the magnetic nanocomposites for killing of cancerous cells is studied in vitro using HeLa cells in the presence of an AC (Alternating Current) magnetic field. The morphology of the HeLa cells subjected to 10 min of AC magnetic field changed considerably, indicating the death of the cells. 

Retracted: No

PubPeer comments:
 Two identical XRD patterns for different samples ![file] ,
Regulation of AMPK-related glycolipid metabolism imbalances redox homeostasis and inhibits anchorage independent growth in human breast cancer cells
Authors: Zihao He
Yejin Zhu
Zhiyu Li
Renxiang Tan
Lin Yang
Libin Wei
Qinglong Guo
Jingyue Yao
Journal: Redox biology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Anti-metastasis; Fatty acid oxidation; GL-V9; Pentose phosphate pathway; Redox homeostasis.
Affiliations: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China., State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, 138 Xinlin Road, Nanjing 210023, People's Republic of China., State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. Electronic address: .

Abstract:  Breast cancer is one of the most lethal tumors in the world, among which 15% are triple-negative breast cancers (TNBCs) with higher metastasis and lower survival rate. Anoikis resistance is a key process during tumor metastasis, which is usually accompanied with metabolism reprogram. In this study, we established an anchorage independent growth model for MDA-MB-231 cells and investigated the changes in metabolism and redox homeostasis. Results showed that during detached-growth, MDA-MB-231 cells tend to generate ATP through fatty acid oxidation (FAO), instead of glycolysis. Amount of glucose was used for pentose phosphate pathway (PPP) to keep redox balance. Moreover, we discovered that a synthesized flavonoid derivative GL-V9, exhibited a potent inhibitory effect on the anchorage independent growth of TNBCs in vitro and anti-metastasis effect in vivo. In terms of the mechanism, GL-V9 could promote the expression and activity of AMPK, leading to the decrease of G6PD and the increase of p-ACC. Thus, the level of PPP was suppressed, whereas FAO was highly enhanced. The reprogram of glycolipid metabolism destroyed the redox balance ultimately and induced cell death. This paper indicated a novel regulating mechanism of redox homeostasis involving with glycolipid metabolism, and provided a potential candidate for the anti-metastatic therapy of TNBCs. 

Retracted: No

PubPeer comments:
 Figure 1A: Duplication of data: ![file] , 
 #1 Looks like almost a perfect cancellation if superimposed one on top of another with 50% transparency, with some scaling job. ![file] , 
 Corrigendum issued Nov 20 2019 [January 2020] :  The authors regretted because there were an amount of pictures for each group in different time, we copied incorrect pictures and misused the data for 36 h as the data for 48 h. This error caused some vision of the cell morphology photo in 36 h group and 48 h group in Figure 1A are same. We have to apologise for this error, and would like to correct the photo of 48 h group. The corrected figure appears below. Corrected Figure 1A ![] ,
Description of a late miscarriage case at 16 Weeks of Gestation associated with a SARS-CoV-2 infection
Authors: Aurélie Schnuriger
Mathilde Lefebvre
Anne-Sophie Michel
Emeline Maisonneuve
Victoire De Logiviere
Gilles Kayem
Journal: Journal of Gynecology Obstetrics and Human Reproduction (2021)
Discipline: CLINICAL MEDICINE
Keywords: Late miscarriage; Obstetric outcomes; Placental colonization; SARS-CoV-2.
Affiliations: Department of Obstetrics and Gynecology, FHU PREMA, Trousseau Hospital, Paris, France; Sorbonne University, Paris, France., Department of Obstetrics and Gynecology, FHU PREMA, Trousseau Hospital, Paris, France., Sorbonne University, Paris, France; Department of Virology, Trousseau Hospital, Paris, France., Sorbonne University, Paris, France; Department of Foetopathology, Trousseau Hospital, Paris, France., Department of Fetal Medicine, Trousseau Hospital, Paris, France., Department of Obstetrics and Gynecology, FHU PREMA, Trousseau Hospital, Paris, France; Sorbonne University, Paris, France. Electronic address: .

Abstract:  Background: Data about obstetric complications of maternal infection by SARS-CoV-2 remain sparse. Case: A 40-year-old pregnant woman, gravida 3 para 1 with no previous obstetric complications, presented a late miscarriage at 16 weeks of gestation on day 9 of COVID-19 disease. The results of her nasopharyngeal swab for SARS-CoV-2, tested the same day, were negative, but the placenta was infected by SARS-CoV-2 and serology was positive 11 days later. No other obstetric or infectious cause was found to explain this outcome. Conclusion: This case strongly suggests that SARS-CoV-2 may lead to a late miscarriage. 

Retracted: No

PubPeer comments:
 A single case report. Late miscarriage and SARS-CoV-2 infection. This is a correlation but the authors cannot prove causality. In their abstract: ![file] In discussion: ![file] A potential impact cannot be summarized as a strong suggestion. ,
Development of protein-based inhibitors of the proprotein of convertase SKI-1/S1P: processing of SREBP-2, ATF6, and a viral glycoprotein
Authors: Stuart T Nichol
Philomena Pullikotil
Nabil G Seidah
Martin Vincent
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: membrane-bound transcription factors; sterol regulatory element-binding proteins; ER-stress response factor; proprotein convertase; SKI-1/S1P
Affiliations: Laboratories of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada.

Abstract:  Processing of membrane-bound transcription factors such as sterol regulatory element-binding proteins (SREBPs) and the ER-stress response factor ATF6, and glycoproteins of some hemorrhagic fever viruses are initiated by the proprotein convertase SKI-1/S1P. So far, no cellular protein-based inhibitor of the hydrophobic-amino acid specific SKI-1 is known. The prosegment of the basic-amino acid specific convertases (e.g. furin and PC5) or alpha(1)-PDX, a variant of alpha(1)-antitrypsin (alpha(1)-AT) exhibiting an RIPR(358) sequence at the reactive site loop, were shown to potently inhibit these secretory proteinases. Accordingly, we tested the SKI-1-inhibitory potential of various point mutants of either the 198 amino acid preprosegment of SKI-1-(1-198) or alpha(1)-AT. Transient transfections data showed that, out of numerous mutants studied, the R134E prosegment mutant or the alpha(1)-AT reactive site loop variants RRVL(358), RRYL(358) and RRIL(358) are the best specific cellular inhibitors of SKI-1. The observed inhibition of the processing of endogenous SREBP-2, exogenous ATF6 and a PDGF-A (RRLL(86)) variant were &gt;55% and reach approximately 80% in stable transfectants. We also show that SKI-1 forms SDS-stable complexes with these alpha(1)-AT variants, but not with wild-type alpha(1)-AT or alpha(1)-PDX. Finally, these inhibitors were also shown to affect the processing and stability of the Crimean-Congo hemorrhagic fever virus glycoprotein. 

Retracted: No

PubPeer comments:
 ![file] ,
Long Noncoding RNA AFAP1-AS1 Promotes Cell Proliferation and Metastasis via the miR-155-5p/FGF7 Axis and Predicts Poor Prognosis in Gastric Cancer
Authors: Chang-An Guo
Li Ma
Pei-Wu Li
Dong-Hong Ma
Jian-Zhong Ma
Hong-Wu Ma
Da-Yong Xi
Min Guo
Journal: Disease Markers (2020)
Discipline: CLINICAL MEDICINE
Keywords: AFAP1-AS1; gastric cancer; oncogene; miR-155-5p; FGF7
Affiliations: Department of Emergency Medicine, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Department of Gastroenterology, The Second Provincial People's Hospital of Gansu, Lanzhou, Gansu, China., Department of Hepatology, Linxia People's Hospital, Linxia, Gansu, China., Department of Emergency Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China., Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou, Gansu, China.

Abstract:  Background: Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown. Methods: We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development. Results: AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC. Conclusions: AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC. 

Retracted: No

PubPeer comments:
 Figure 2E contains a duplicated image: ![file] ,
Pyroptosis of HUVECs can be induced by heat stroke
Authors: Yan Geng
Lei Su
Yanfang Pei
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: GSDMD; Heat stress; Heat stroke; Pyroptosis; Vascular endothelial cells.
Affiliations: The First School of Clinical Medicine, Southern Medical University, Guangzhou, China; Department of Emergency, Hunan Provincial People's Hospital, No. 61, Jefang West Road, Changsha, Hunan, China., Department of Gastroenterology, 303 Hospital of People's Liberation Army, Nanning, Guangxi, China., The First School of Clinical Medicine, Southern Medical University, Guangzhou, China; Department of Intensive Care Unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Trauma Care and Tissue Repair of PLA, Guangzhou, China. Electronic address: .

Abstract:  Heat stroke is a serious pathological condition with high mortality. Vascular endothelial cell injury is a key feature in the pathogenesis of heat stroke, but the specific pathophysiological process whereby this occurs is still unclear. Currently, relevant studies are primarily based upon examination of apoptosis. Recently, pyroptosis, a new form of inflammation-related programmed cell death, was also demonstrated to be involved in heat stroke pathophysiology. Herein, we present evidence that vascular endothelial cell pyroptosis can be induced by heat stress in a time- and temperature-dependent manner. Furthermore, this process can be significantly inhibited by GSDMD siRNA. These findings suggest a new therapeutic target for heat stroke. 

Retracted: No

PubPeer comments:
 The control lane in Figure 3B appears to be spliced onto the remaining lanes. Could the authors please post the original uncropped scans? More easily seen with enhanced contrast. *** ![file] ,
The ubiquitin ligase UBR5 suppresses proteostasis collapse in pluripotent stem cells from Huntington’s disease patients
Authors: Isabel Saez
Thorsten Hoppe
Hyun Ju Lee
Seda Koyuncu
Wojciech Pokrzywa
David Vilchez
Ricardo Gutierrez-Garcia
Azra Fatima
Journal: Nature Communications (2018)
Discipline: Multidisciplinary
Keywords: Induced pluripotent stem cells; iPSCs; proteasome activity; UBR5; polyQ-expanded aggregation
Affiliations: Institute for Genetics and Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph Stelzmann Strasse 26, 50931, Cologne, Germany., Laboratory of Protein Metabolism in Development and Aging, International Institute of Molecular and Cell Biology, Trojdena Street 4, 02-109, Warsaw, Poland., Institute for Genetics and Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph Stelzmann Strasse 26, 50931, Cologne, Germany. .

Abstract:  Induced pluripotent stem cells (iPSCs) undergo unlimited self-renewal while maintaining their potential to differentiate into post-mitotic cells with an intact proteome. As such, iPSCs suppress the aggregation of polyQ-expanded huntingtin (HTT), the mutant protein underlying Huntington's disease (HD). Here we show that proteasome activity determines HTT levels, preventing polyQ-expanded aggregation in iPSCs from HD patients (HD-iPSCs). iPSCs exhibit high levels of UBR5, a ubiquitin ligase required for proteasomal degradation of both normal and mutant HTT. Conversely, loss of UBR5 increases HTT levels and triggers polyQ-expanded aggregation in HD-iPSCs. Moreover, UBR5 knockdown hastens polyQ-expanded aggregation and neurotoxicity in invertebrate models. Notably, UBR5 overexpression induces polyubiquitination and degradation of mutant HTT, reducing polyQ-expanded aggregates in HD-cell models. Besides HTT levels, intrinsic enhanced UBR5 expression determines global proteostasis of iPSCs preventing the aggregation of misfolded proteins ensued from normal metabolism. Thus, our findings indicate UBR5 as a modulator of super-vigilant proteostasis of iPSCs. 

Retracted: No

PubPeer comments:
 Figure 2e: Possible image duplication ![file] , 
 Dear Colleague, this is David Vilchez, the corresponding author of the article. I thank you so much for noticing this. I m really sorry about this mistake. When I assembled the figure in Illustrator, it seems that I inserted by mistake twice the image corresponding to Control #2 (Q33) treated with MG-132. I have now included the right image corresponding to the Control #2 treated with DMSO (please see image below). I take full responsibility because I was the one who assembled Figure 2 in Illustrator and made this mistake, but my student provided me the right images . Again, I really apologize for this. I will contact the journal right ASAP to correct this mistake.![file] ,
Sepsis-induced inhibition of neutrophil chemotaxis is mediated by activation of peroxisome proliferator-activated receptor-{gamma}
Authors: Raju C Reddy
Venkateshwar G Keshamouni
Theodore J Standiford
Michael W Newstead
Venkata R Narala
Jami E Milam
Journal: Blood (2008)
Discipline: CLINICAL MEDICINE
Keywords: Neutrophils; PMNs; sepsis; PPAR-gamma; chemotaxis
Affiliations: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor, USA. 

Abstract:  Neutrophils (polymorphonuclear leukocytes [PMNs]) are critical to the immune response, including clearance of infectious pathogens. Sepsis is associated with impaired PMN function, including chemotaxis. PMNs express peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a ligand-activated nuclear transcription factor involved in immune and inflammatory regulation. The role of PPAR-gamma in PMN responses, however, is not well characterized. We report that freshly isolated human PMNs constitutively express PPAR-gamma, which is up-regulated by the sepsis-induced cytokines TNF-alpha and IL-4. PMN chemotactic responses to formylmethionyl-leucyl-phenylalanine (fMLP) and IL-8 were dose-dependently inhibited by treatment with the PPAR-gamma ligands troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and by transfection of PMN-like HL-60 cells with a constitutively active PPAR-gamma construct. Inhibition of chemotaxis by PPAR-gamma ligands correlated with decreases in extracellular signal-regulated kinase-1 and -2 activation, actin polymerization, and adherence to a fibrinogen substrate. Furthermore, PMN expression of PPAR-gamma was increased in sepsis patients and mice with either of 2 models of sepsis. Finally, treatment with the PPAR-gamma antagonist GW9662 significantly reversed the inhibition of PMN chemotaxis and increased peritoneal PMN recruitment in murine sepsis. This study indicates that PPAR-gamma activation is involved in PMN chemotactic responses in vitro and may play a role in the migration of these cells in vivo. 

Retracted: No

PubPeer comments:
 Figure 1. https: imgur.com KaXdylL ,
Intrachromosomal tandem duplication and repeat expansion during attempts to inactivate the subtelomeric essential gene GSH1 in Leishmania
Authors: Lance D Langston
Marc Ouellette
Angana Mukherjee
Journal: Nucleic Acids Research (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Gamma-glutamylcysteine synthetase; GSH1; Leishmania; gene disruption; duplication
Affiliations: Département de Microbiologie, Immunologie and Infectiologie, Université Laval, Québec, Canada.

Abstract:  Gamma-glutamylcysteine synthetase encoded by GSH1 is the rate-limiting enzyme in the biosynthesis of glutathione and trypanothione in Leishmania. Attempts to generate GSH1 null mutants by gene disruption failed in Leishmania infantum. Removal of even a single allele invariably led to the generation of an extra copy of GSH1, maintaining two intact wild-type alleles. In the second and even third round of inactivation, the markers integrated at the homologous locus but always preserved two intact copies of GSH1. We probed into the mechanism of GSH1 duplication. GSH1 is subtelomeric on chromosome 18 and Southern blot analysis indicated that a 10-kb fragment flanked by 466-bp direct repeated sequences was duplicated in tandem on the same chromosomal allele each time GSH1 was targeted. Polymerase chain reaction analysis and sequencing confirmed the generation of novel junctions created at the level of the 466-bp repeats consequent to locus duplication. In loss of heterozygosity attempts, the same repeated sequences were utilized for generating extrachromosomal circular amplicons. Our results are consistent with break-induced replication as a mechanism for the generation of this regional polyploidy to compensate for the inactivation of an essential gene. This chromosomal repeat expansion through repeated sequences could be implicated in locus duplication in Leishmania. 

Retracted: No

PubPeer comments:
 Two flow-cytometry plots share most of their points in common and appear to be derived from the same data file, differently gated and filtered. ![file] Left-hand panel is from Figs 2e, 3e. Right-hand panel is from Figs 2C, 5C of [Wang et al (2019)] . Here in context: ![file] ![file] ------------------------------------------- And now, a triad of flow-cytometry plots. Left-hand panel is from Figs 2e, 3e. ![file] Other two panels are from Figs 2C, 5C, 6C of [Cheng et al (2020)] , and Figs 2D, 4D, 5D of [Yang et al (2019)] . Here in context: ![] ![] , 
 #1  Left-hand panel is from Figs 2e, 3e. Right-hand panel is from Figs 2C, 5C of Wang et al (2019). The Wang et al (2019) paper was retracted, [21 July 2021] , as the work of a papermill.  Other two panels are from Figs 2C, 5C, 6C of Cheng et al (2020), and Figs 2D, 4D, 5D of Yang et al (2019). The Chang et al (2020) paper was retracted, [28 September 2021] , as the work of a papermill. The Yang et al (2019) paper was retracted, [28 September 2021] , et cetera. ,
POSTN promotes proliferation and epithelial-mesenchymal transition in renal cell carcinoma through ILK/AKT/mTOR pathway
Authors: Hong-Jun Li
Yuan-Yuan Jia
Yue Yu
Journal: Journal of Cancer (2021)
Discipline: CLINICAL MEDICINE
Keywords: ILK/AKT/mTOR pathway.; POSTN; Renal cell carcinoma; epithelial-mesenchymal transition.
Affiliations: Department of Health Management Medical Center, China-Japan Union Hospital of Jilin University,126 Xiantai Street,Changchun, Jilin, China., Department of endocrinology and metabolism, China-Japan Union Hospital of Jilin University, 126 Xiantai Street,Changchun, Jilin,China.

Abstract:  Periostin (POSTN) is an extracellular matrix (ECM) protein, involved in various diseases. This research focused on the detailed mechanisms study of periostin (POSTN) overexpression in renal cell carcinoma (RCC) invasion and migration. Western blot and RT-PCR were performed to explore POSTN expression in various RCC cells. Cells were transfected with siRNAs or lentivirus to regulate the expression of POSTN. The effects of POSTN on cell viability, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT) of RCC cells were determined by CCK-8, flow cytometry, migration and invasion assay and Western blot analysis. POSTN expression was significantly enhanced in RCC cells compared with renal tubular epithelial cells. In vitro experiments showed that POSTN knockdown could dramatically inhibit RCC cell proliferation, migration and invasion, while overexpression of POSTN could promote these biological behaviors. We further demonstrated that POSTN knockdown suppressed epithelial-mesenchymal transition (EMT), which was mediated via upregulation of E-cadherin and downregulation of N-cadherin and vimentin, through IKL/AKT/mTOR pathway. In contrast, overexpression of POSTN could promote EMT in RCC cells via the activation of IKL /AKT/mTOR pathway. Next, we demonstrated that higher POSTN expression promoted angiogenesis in vivo in an RCC xenograft tumor via activating IKL /AKT/mTOR pathway. Our study showed that POSTN could promote EMT through ILK/AKT/mTOR pathway and might be an alternative therapeutic strategy for RCC treatment. 

Retracted: No

PubPeer comments:
 An images seems to appear in both Figure 5B (top) and Figure 8D (bottom), but is described differently. *** ![file] ,
HDAC inhibitors increase NRF2-signaling in tumour cells and blunt the efficacy of co-adminstered cytotoxic agents
Authors: C Roland Wolf
Colin J Henderson
A Kenneth MacLeod
Michael McMahon
Lesley A McLaughlin
Kathryn H Campbell
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: NRF2 signalling cascade; electrophilic chemicals; oxidative stress; cancer; pharmacological activation
Affiliations: Medical Research Institute, University of Dundee, Dundee, United Kingdom.

Abstract:  The NRF2 signalling cascade provides a primary response against electrophilic chemicals and oxidative stress. The activation of NRF2-signaling is anticipated to have adverse clinical consequences; NRF2 is activated in a number of cancers and, additionally, its pharmacological activation by one compound can reduce the toxicity or efficiency of a second agent administered concomitantly. In this work, we have analysed systematically the ability of 152 research, pre-clinical or clinically used drugs to induce an NRF2 response using the MCF7-AREc32 NRF2 reporter. Ten percent of the tested drugs induced an NRF2 response. The NRF2 activators were not restricted to classical cytotoxic alkylating agents but also included a number of emerging anticancer drugs, including an IGF1-R inhibitor (NVP-AEW541), a PIM-1 kinase inhibitor (Pim1 inhibitor 2), a PLK1 inhibitor (BI 2536) and most strikingly seven of nine tested HDAC inhibitors. These findings were further confirmed by demonstrating NRF2-dependent induction of endogenous AKR genes, biomarkers of NRF2 activity. The ability of HDAC inhibitors to stimulate NRF2-signalling did not diminish their own potency as antitumour agents. However, when used to pre-treat cells, they did reduce the efficacy of acrolein. Taken together, our data suggest that the ability of drugs to stimulate NRF2 activity is common and should be investigated as part of the drug-development process. 

Retracted: No

PubPeer comments:
 Figure 5. Much more similar after horizontal re-sizing than expected. ![file] ,
Exercise increases insulin signaling in the hippocampus: physiological effects and pharmacological impact of intracerebroventricular insulin administration in mice
Authors: Ignácio Torres-Aleman
Luis V Portela
Francisco Lulhier
Diogo O Souza
Jussânia Gnoatto
Clarissa B Haas
Alexandre P Muller
Eduardo R Zimmer
Julia D Moreira
Marcos L S Perry
Journal: Hippocampus (2011)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: physical exercise; insulin signaling; hippocampus; memory performance; voluntary exercise
Affiliations: Departamento de Bioquímica, ICBS, UFRGS, Programa de Pós Graduação em Ciências Biológicas-Bioquímica, Rua Ramiro Barcelos, 2600 anexo, CEP 90035-003, Porto Alegre, RS, Brazil.

Abstract:  Increasing evidence indicates that physical exercise induces adaptations at the cellular, molecular, and systemic levels that positively affect the brain. Insulin plays important functional roles within the brain that are mediated by insulin-receptor (IR) signaling. In the hippocampus, insulin improves synaptic plasticity, memory formation, and learning via direct modulation of GABAergic and glutamatergic receptors. Separately, physical exercise and central insulin administration exert relevant roles in cognitive function. We here use CF1 mice to investigate (i) the effects of voluntary exercise on hippocampal insulin signaling and memory performance and (ii) whether central insulin administration alters the effects of exercise on hippocampal insulin signaling and memory performance. Adult mice performed 30 days of voluntary exercise on running wheel and afterward both, sedentary and exercised groups, received intracerebroventricular (icv) injection of saline or insulin (0.5-5 mU). Memory performance was assessed using the inhibitory avoidance and water maze tasks. Hippocampal tissue was measured for [U-(14)C] glucose oxidation and the immunocontent of insulin receptor/signaling (IR, pTyr, pAktser473). Additionally, the phosphorylation of the glutamate NMDA receptor NR2B subunit and the capacity of glutamate uptake were measured, and immunohistochemistry was used to determine glial reactivity. Exercise significantly increased insulin peripheral sensitivity, spatial learning, and hippocampal IR/pTyrIR/pAktser473 immunocontent. Glucose oxidation, glutamate uptake, and astrocyte number also increased relative to the sedentary group. In both memory tasks, 5 mU icv insulin produced amnesia but only in exercised animals. This amnesia was associated a rapid (15 min) and persistent (24 h) increase in hippocampal pNR2B immunocontent that paralleled the increase in glial reactivity. In conclusion, physical exercise thus increased hippocampal insulin signaling and improved water maze performance. Overstimulation of insulin signaling in exercised animals, however, via icv administration impaired behavioral performance. This effect was likely the result of aberrant phosphorylation of the NR2B subunit. 

Retracted: No

PubPeer comments:
 Fig. 4B and Fig.5B: More similar than expected ![file] ,