PReD-Bench/PRed-Bench huggingface dataset:
Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase
Authors: Patricio Rojas
Lisette Leyton
Andrew F G Quest
Claudio A Hetz
Martin Hunn
Vicente Torres
Journal: Journal of Cell Science (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Fas receptor; apoptosis; caspases; lipid orientation; ceramide levels
Affiliations: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Abstract:  Engagement of the Fas receptor promotes apoptosis by activation of caspases. In addition, alterations in plasma membrane lipid orientation and intracellular ceramide levels are often observed. In A20 B-lymphoma cells, FasL-induced cell death and phosphatidylserine (PS) externalization were completely prevented by the generic caspase inhibitor z-VAD-fmk. By contrast, the caspase-3 inhibitor Ac-DEVD-cho only partially restored cell viability and had no effect on surface exposure of PS. Flow cytometric analysis after FasL treatment identified two populations of dead cells. In one, death was dependent on caspase-3 and paralleled by DNA fragmentation and cell shrinkage. In the second, death occurred in the absence of caspase-3 activity and apoptotic features but was also blocked by zVAD-fmk. By morphological criteria these were identified as apoptotic and necrotic cells, respectively. Using fluorescent substrates, caspase-3 activity was detected only in the apoptotic cell population, whereas caspase-8 activity was detected in both. Both forms of caspase-8-dependent cell death were also detected downstream of Fas in Jurkat T-cells, where Fas-dependent PS externalization and delayed ceramide production, which is similar to results shown here in A20 cells, have been reported. However, for Raji B-cells, lacking lipid scrambling and ceramide production in response to Fas activation, only apoptosis was detected. Short-chain C2- or C6-ceramides, but not the respective inactive dihydro compounds or treatment with bacterial sphingomyelinase, induced predominantly necrotic rather than apoptotic cell death in A20 B-, Raji B- and Jurkat T-cells. Thus, delayed elevation of ceramide is proposed to promote necrosis in those Fas-stimulated cells where caspase-8 activation was insufficient to trigger caspase-3-dependent apoptosis. 

Retracted: No

PubPeer comments:
 Figure 4D: NT and R1 bands are more similar than expected. ![file] , 
 Regions are more similar than expected. Can authors check please? ![file] , 
 Figure 4E: Background is different around some cells. Could authors provide an explanation? ![file] , 
 Figure 9A: the area next to some cells seem different. Could the authors please provide an explanation? ![file] ,
Pleiotropic functions of pituitary adenylyl cyclase-activating polypeptide on retinal ontogenesis: involvement of KLF4 in the control of progenitor cell proliferation
Authors: Maurício Rocha-Martins
Luiz D Barbosa De-Melo
Mariana S Silveira
Karen Braas
Brian Njaine
Rodrigo A P Martins
Rafael Linden
Victor May
Carlos H Vieira-Vieira
Journal: Journal of Molecular Neuroscience (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: neuropeptide; PACAP; proliferation; retinal progenitor cells; cyclin D1
Affiliations: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Edifício do Centro de Ciencias da Saude, Bloco G, Cidade Universitaria, Ilha do Fundão, 21941-902, Rio de Janeiro, Brazil.

Abstract:  We showed previously that the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP) negatively regulates proliferation of postnatal rat retinal progenitor cells through the downregulation of cyclin D1 in a cAMP/protein kinase A dependent manner. In the present study, we describe by microarray analysis several putative PACAP targets regulated by different transcription factor families. One of these families is the Sp/Klf family of transcriptional factors capable of regulating cyclin D1, and among members, we demonstrate by immunocytochemistry that KLF4 is expressed throughout rat retinal development by retinal progenitor cells and in most differentiated cell types. Using retinal explants preparations, PACAP treatment can transiently increase Klf4 mRNA levels; from electrophoretic mobility shift assays, PACAP is also able to increase the nuclear KLF4 content. From these results, we suggest that KLF4 may be involved in the anti-proliferative effects of PACAP as one mechanism regulating progenitor cell transition from proliferation to differentiation throughout retinal development. 

Retracted: No

PubPeer comments:
 Fig. 2a: Same Actin bands that were previously used in other publication (Fig. 1a; Njaine et al., 2010). ![file] Fig. 2c: Same Erk2 bands that were used in a previous publication (Fig. 1a; Rocha-Martins et al., 2012). ![file] , 
 Thanks for bringing the issue to our attention. To clarify, the same cDNA and protein extracts were used in the different studies to analyse different target genes, and for this reason the same actin result was used. In the case of the RT-PCR there was an additional misidentification of the samples in the last manuscript, published at the J Mol Neuroscience. Although we believe these issues do not impact the conclusions of the study, we will get in contact with the Editors of the Journal of Molecular Neuroscience to make all necessary amendments. ,
Combined effects of a thymic peptide, thymopoietin and myasthenic patient sera in rat myotube culture
Authors: E Morel
C Cottin
C Aimé
B Eymard
G Goldstein
S Berrih-Aknin
J F Bach
Journal: Journal of the neurological sciences (1992)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: rat; myotube assay; myasthenic; MG patient sera; thymic peptide

Abstract:  We investigated in a rat myotube assay the combined effect of 26 myasthenic (MG) patient sera and a thymic peptide, thymopoietin (Tpo) which had previously been shown to bind Torpedo and human AChR and to compete with alpha-bungarotoxin (alpha-Bgt) binding. Cultures were first exposed to Tpo alone for 3 h (0.3, 7.5, 15 nM), then MG sera (5% final dilution) were added for an additional 18 h. Reduction in the amount of 125I-alpha-Bgt binding sites in the presence of various concentrations of Tpo were similar with control sera and in all the patients with low or undetectable anti-AChR Ab (11 cases). In cultures exposed to Tpo and sera with high anti-AChR Ab titre (15 cases), Tpo and anti-AChR Ab have an additive capacity to reduce the number of alpha-Bgt binding sites. The results are compatible with the hypothesis that anti-AChR Ab and Tpo could impair neuromuscular transmission by complementary mechanisms. 

Retracted: No

PubPeer comments:
 See retraction notice: https: doi.org 10.1016 0022-510X(93)90036-X The decision to retract a paper when a suspicion arises regarding the experimental material used is to be recommended! ,
Adsorption of Cu(II) ions from aqueous solution using pyridine-2,6-dicarboxylic acid crosslinked chitosan as a green biopolymer adsorbent
Authors: Reinout Meijboom
Ibraheem Olayiwola Bisiriyu
Journal: International Journal of Biological Macromolecules (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Adsorption; Crosslinked chitosan; Density functional theory.
Affiliations: Department of Chemical Sciences, University of Johannesburg, PO Box 524, Auckland Park, Johannesburg 2006, South Africa., Department of Chemical Sciences, University of Johannesburg, PO Box 524, Auckland Park, Johannesburg 2006, South Africa. Electronic address: .

Abstract:  In this study, crosslinked chitosan (CCS) has been synthesized by anchoring a bifunctional ligand, namely pyridine-2,6-dicarboxylic acid (PDC) with chitosan through ion exchange. The functionalized biopolymer has been characterized using different instrumental analyses including elemental (CHN), spectroscopic (UV-visible, NMR, powder XRD, and FTIR), thermal analyses (TGA and DSC), surface and morphological (BET and SEM) analyses. The PDC-CCS was utilized for the recovery of Cu(II) from water contaminated with Cu. The adsorption limit/capacity of PDC-CCS has been examined for solution pH, temperature, Cu(II) ion concentration, and the contact time of the adsorbent. An extreme adsorption limit of 2186 mmol·g-1 has been found for the PDC-CCS. Equilibrium was quickly attained within 60 min from the start of adsorption. Also, it was discovered that the adsorption limit/capacity exceedingly relies upon temperature and pH. On testing the experimental data with the two most popular adsorption models (fundamentally, Freundlich and Langmuir), we found that Cu(II) ion adsorption suit both models. Similarly, the experimental adsorption kinetics is in reality, second-order. Thermodynamic studies also revealed that the adsorption process was spontaneous and enthalpy driven. DFT calculations suggest that the main adsorption mechanism is by chelation through charge transfer from the adsorbent to the Cu(II) ions in solution. 

Retracted: No

PubPeer comments:
 From here: * The Langmuir isotherm model accepts that adsorption happens in a monolayer or that adsorption may just happen superficially at a fixed number of limited sites with all adsorption sites indistinguishable and vivaciously proportionate. Also from here: * The Freundlich equation is an observational equation used to portray heterogeneous frameworks where $1 n$ is used to describe the heterogeneity of the adsorption surface. Compare with [Paulino et al., 2008] - not the only, but probably the earliest source of non-tortured versions of the same sentences. * The Langmuir isotherm model assumes that adsorption occurs in a monolayer or that adsorption may only occur at a fixed number of localized sites on the surface with all adsorption sites identical and energetically equivalent. * The Freundlich equation is an empirical equation employed to describe heterogeneous systems characterized by the heterogeneity factor 1 n. Why do the authors alter descriptions of standard notions to the degree that they are barely interpretable? ,
NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression
Authors: Yan Li
Ming Shi
Qiang Liu
Qinyou Ren
Libo Yao
Wenchao Liu
Jin Zheng
Hang Guo
Jiandong Yang
Yan Xue
Hengjun Shi
Yurong Tao
Rui Zhang
Ji Ma
Ning Jiang
Journal: BMC Cancer (2011)
Discipline: CLINICAL MEDICINE
Keywords: Hepatocellular carcinoma; HCC; CD24; NDRG2; metastasis
Affiliations: State Key Discipline of Cell Biology, Department of Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.

Abstract:  Background: The prognosis of most hepatocellular carcinoma (HCC) patients is poor due to the high metastatic rate of the disease. Understanding the molecular mechanisms underlying HCC metastasis is extremely urgent. The role of CD24 and NDRG2 (N-myc downstream-regulated gene 2), a candidate tumor suppressor gene, has not yet been explored in HCC. Methods: The mRNA and protein expression of CD24 and NDRG2 was analyzed in MHCC97H, Huh7 and L-02 cells. Changes in cell adhesion, migration and invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. The expression pattern of NDRG2 and CD24 in HCC tissues and the relationship between NDRG2 and HCC clinical features was analyzed by immunohistochemical and western blotting analysis. Results: NDRG2 expression was negatively correlated with malignancy in HCC. NDRG2 exerted anti-tumor activity by regulating CD24, a molecule that mediates cell-cell interaction, tumor proliferation and adhesion. NDRG2 up-regulation decreased CD24 expression and cell adhesion, migration and invasion. By contrast, NDRG2 down-regulation enhanced CD24 expression and cell adhesion, migration and invasion. Immunohistochemical analysis of 50 human HCC clinical specimens showed a strong correlation between NDRG2 down-regulation and CD24 overexpression (P = 0.04). In addition, increased frequency of NDRG2 down-regulation was observed in patients with elevated AFP serum level (P = 0.006), late TNM stage (P = 0.009), poor differentiation grade (P = 0.002), tumor invasion (P = 0.004) and recurrence (P = 0.024). Conclusions: Our findings indicate that NDRG2 and CD24 regulate HCC adhesion, migration and invasion. The expression level of NDRG2 is closely related to the clinical features of HCC. Thus, NDRG2 plays an important physiological role in HCC metastasis. 

Retracted: No

PubPeer comments:
 Seems to be overlapping areas in the images used in Figure 3E (top) and 4E (bottom), including resizing and rotation. Very difficult to understand what errors could have caused this assortment of possible issues. Aided here by pattern recognition tool. *** ![file] ,
Calpain-1-sensitive myofibrillar proteins of the human myocardium
Authors: Judit Barta
Miklós Vaszily
Attila Tóth
András Varró
Zoltán Papp
Julius Gy Papp
István Edes
Journal: Molecular and Cellular Biochemistry (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Calpain-1; myocardial depression; myofibrillar proteins; protein degradation; human myocardium
Affiliations: Division of Clinical Physiology, Institute of Cardiology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.

Abstract:  Calpain-1 is a ubiquitous intracellular Ca2+-activated protease, which has been implicated in the pathogenesis of reversible myocardial depression (i.e. myocardial stunning) that follows ischemia and reperfusion via myofibrillar protein degradation. However, the target proteins of this degradative process in the human myocardium have not yet been identified. In order to compare the levels of Calpain-1 susceptibility within a set of human myofibrillar proteins (titin, alpha-fodrin, desmin, troponin T (cTnT), troponin I (cTnI) and alpha-actinin), crude left ventricular tissue homogenates were incubated for 0.5, 15, 30, 60 or 120 min in the presence of Calpain-1 (1 U or 5 U). Differences in the kinetics and extents of protein degradation were subsequently evaluated by using silver-stained SDS-polyacrylamide gels and Western immunoblot analyses. These assays revealed myofibrillar proteins with high (titin and alpha-fodrin), moderate (desmin and cTnT), or low (cTnI and alpha-actinin) relative Calpain-1 susceptibilities. The level of phosphorylation of cTnI did not explain its relatively low Calpain-1 susceptibility. Moreover, the molecular mass distributions of the truncated alpha-fodrin, desmin and cTnI fragments resulting from Ca2+-dependent autoproteolysis exhibited marked similarities with those of their Calpain-1-clipped products. These in vitro results shed light on a number of structural (titin, alpha-fodrin, desmin and alpha-actinin) and regulatory (cTnT and cTnI) proteins within the contractile apparatus as potential targets of Calpain-1. Their degradation may contribute to the development of postischemic stunning in the human myocardium. 

Retracted: No

PubPeer comments:
 Figure 2 and 4. * Several lanes appear to look similar to each other, as marked with green, blue, and red boxes. These lanes appear to represent different experiments. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. ![file] ,
Long non-coding RNA CRNDE promotes heptaocellular carcinoma cell proliferation by regulating PI3K/Akt /β-catenin signaling
Authors: Junkai Zhang
Qiling Tang
Xiaoli Zheng
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: CRNDE; HCC; Long non-coding RNA; PI3K/Akt/GSK3β; Proliferation and growth
Affiliations: Department of pharmacy, Yuhuangding Hospital, Yantai, China., Department of Hepatobiliary Surgery, Affiliated 1st Hospital of Dalian Medical University, No.222, Zhongshan Road, Dalian, China. Electronic address: .

Abstract:  Hepatocellular carcinoma (HCC) is one of the common malignant cancer worldwide, and its molecular pathogenesis remains elusive and recently long non-coding RNAs (lncRNAs) have been reported that play divergent roles in HCC tumorigenesis and development. In current study, we found a lncRNA, CRNDE is more commonly up-regulated in HCC malignant tissues and associated with poor clinical outcomes. Furthermore, both loss- and gain-functions assays revealed that CRNDE promotes HCC cell proliferation and growth in vitro and in vivo. In addition, we found that CRNDE regulates PI3K/Akt/GSK3β-Wnt/β-catenin axis to exert its oncogenic role in HCC cell proliferation and growth. In conclusion, our findings enlarged our knowledge in the roles of lncRNAs in the progression of HCC and CRNDE as a lncRNA could be a novel target for HCC treatment. 

Retracted: No

PubPeer comments:
 *[above]* Fig. 3.  Knockdown of CRNDE inhibits HCC cell proliferation in vivo. (A) The representative images of tumors which formed by indicated stable cell lines, scale bar, 1 cm . There are no scale bars, only rulers with cm and inches. *[below]* Fig. 2 from [Ma et al (2018)] .  Overexpression of LINC01510 inhibits RCC cell proliferation and invasion. .... (E) Xenograft tumor formation assays showed that heightening the expression of LINC01510 significantly inhibits the ability of subcutaneous tumor formation in 786-O. ![file] Could the authors of either paper comment on the duplication? ,
Beta-actin is required for proper mouse neural crest ontogeny
Authors: Davina Tondeleir
Karima Bakkali
Christophe Ampe
Rivka Noelanders
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: mouse genome; actin genes; beta-actin; neural crest; apoptosis
Affiliations: Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

Abstract:  The mouse genome consists of six functional actin genes of which the expression patterns are temporally and spatially regulated during development and in the adult organism. Deletion of beta-actin in mouse is lethal during embryonic development, although there is compensatory expression of other actin isoforms. This suggests different isoform specific functions and, more in particular, an important function for beta-actin during early mammalian development. We here report a role for beta-actin during neural crest ontogeny. Although beta-actin null neural crest cells show expression of neural crest markers, less cells delaminate and their migration arrests shortly after. These phenotypes were associated with elevated apoptosis levels in neural crest cells, whereas proliferation levels were unchanged. Specifically the pre-migratory neural crest cells displayed higher levels of apoptosis, suggesting increased apoptosis in the neural tube accounts for the decreased amount of migrating neural crest cells seen in the beta-actin null embryos. These cells additionally displayed a lack of membrane bound N-cadherin and dramatic decrease in cadherin-11 expression which was more pronounced in the pre-migratory neural crest population, potentially indicating linkage between the cadherin-11 expression and apoptosis. By inhibiting ROCK ex vivo, the knockout neural crest cells regained migratory capacity and cadherin-11 expression was upregulated. We conclude that the presence of beta-actin is vital for survival, specifically of pre-migratory neural crest cells, their proper emigration from the neural tube and their subsequent migration. Furthermore, the absence of beta-actin affects cadherin-11 and N-cadherin function, which could partly be alleviated by ROCK inhibition, situating the Rho-ROCK signaling in a feedback loop with cadherin-11. 

Retracted: No

PubPeer comments:
 Figure 1C: The Alpha-Tubulin band in the 4th lane (Actb- -) looks very similar to the Alpha-Tubulin band in the 2nd lane (Actb+ +). Then, the 2 GFP bands in the 3rd and 4th lane are surrounded by what appears to be a rectangular area with a different background shading than the rest of the blot (see green arrows). ![file] , 
 This issue has been reported to the journal more than four years ago. ,
High performance piezoelectric devices based on aligned arrays of nanofibers of poly(vinylidenefluoride-co-trifluoroethylene)
Authors: Salvatore Girardo
Yonggang Huang
John A Rogers
Canan Dagdeviren
Yewang Su
Dario Pisignano
Luana Persano
Yihui Zhang
Journal: Nature communications (2013)
Discipline: Multidisciplinary
Keywords: Multifunctional capability; flexible design; rugged lightweight construction; self-powered operation; piezoelectric materials
Affiliations: National Nanotechnology Laboratory of Istituto Nanoscienze-CNR, Arnesano, Italy.

Abstract:  Multifunctional capability, flexible design, rugged lightweight construction and self-powered operation are desired attributes for electronics that directly interface with the human body or with advanced robotic systems. For these applications, piezoelectric materials, in forms that offer the ability to bend and stretch, are attractive for pressure/force sensors and mechanical energy harvesters. Here, we introduce a large area, flexible piezoelectric material that consists of sheets of electrospun fibres of the polymer poly[(vinylidenefluoride-co-trifluoroethylene]. The flow and mechanical conditions associated with the spinning process yield free-standing, three-dimensional architectures of aligned arrangements of such fibres, in which the polymer chains adopt strongly preferential orientations. The resulting material offers exceptional piezoelectric characteristics, to enable ultra-high sensitivity for measuring pressure, even at exceptionally small values (0.1 Pa). Quantitative analysis provides detailed insights into the pressure sensing mechanisms, and establishes engineering design rules. Potential applications range from self-powered micro-mechanical elements, to self-balancing robots and sensitive impact detectors. 

Retracted: No

PubPeer comments:
  LST data of the study area were derived from the thermal infrared bands (TIR) of Landsat 8 TM images acquired on 10 July 2017, 2:53 p.m. (row32 path123), with a spatial resolution of 30 m (resampled from 120 m). (p. 6) This statement is really confusing because: Landsat 8 does not have a sensor called Thematic Mapper (TM) but a (thermal) sensor called Thermal Infrared Sensor (TIRS), which has a spatial resolution of 100 m. Landsat 5 has a sensor called Thematic Mapper (TM) at 120 m spatial resolution, but it stopped working in 2011. The authors here say they acquired images from 2017, so it cannot be the TM sensor. But Landsat 8 has no TM sensor. So which sensor was really used here? , 
 #1 Dear Madam or Sir, I appreciate you and your comment. The comment is on merit. it should be corrected as below:  LST data of the study area were derived from the thermal infrared bands (TIRS) of Landsat 8 images acquired on 10 July 2017, 2:53 p.m. (row32 path123), with a spatial resolution of 100 m. Sincerely yours ,
Knockdown of LncRNA PVT1 inhibits tumorigenesis in non-small-cell lung cancer by regulating miR-497 expression
Authors: Dong Guo
Yanli Wang
Xinwei Han
Kewei Ren
Journal: Experimental Cell Research (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Apoptosis; Invasion; MiR-497; NSCLC; PVT1
Affiliations: Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Νo. 1 Jianshe East Road, Zhengzhou 450052, Henan, PR China., Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Νo. 1 Jianshe East Road, Zhengzhou 450052, Henan, PR China. Electronic address: .

Abstract:  Plasmacytoma variant translocation1 (PVT1) was reported to be upregulated in non-small-cell lung cancer (NSCLC) tissues, serve as a promising biomarker for diagnosis and prognosis of NSCLC, and promoted NSCLC cell proliferation. However, the detailed molecular mechanism of PVT1 involved in the pathogenesis and development of NSCLC remains largely unknown. In this study, the expression levels of PVT1 and miR-497 in NSCLC cells were determined by qRT-PCR. Cell viability, invasion and apoptosis were detected by MTT assay, cell invasion assay and flow cytometry analysis, respectively. RNA immunoprecipitation (RIP) and luciferase reporter assay were performed to confirm whether PVT1 directly interacts with miR-497. A xenograft mouse model was established to confirm the effect of PVT1 on tumor growth in vivo and the underlying molecular mechanism. Our findings indicated that PVT1 was significantly upregulated and miR-497 was markedly downregulated in NSCLC cell lines. si-PVT1 effectively decreased the expression of PVT1 and increased the expression of miR-497. PVT1 knockdown remarkably inhibited cell viability, invasion and promoted apoptosis in NSCLC cells. RIP and luciferase reporter assay demonstrated that PVT1 could directly interact with miR-497. Moreover, PVT1 overexpression reversed the inhibitory effect of miR-497 on cell viability, invasion and promotion effect on apoptosis of NSCLC cells. Furthermore, in vivo experiment showed that knockdown of PVT1 inhibited tumor growth in vivo and promoted miR-497 expression. In conclusion, knockdown of PVT1 inhibited cell viability, invasion and induced apoptosis in NSCLC by regulating miR-497 expression, elucidating the molecular mechanism of the oncogenic role of PVT1 in NSCLC and providing an lncRNA-directed target for NSCLC. 

Retracted: No

PubPeer comments:
 *[left]* Fig. 3.  PVT1 directly interacted with miR-497. (A) A negative correlation between PVT1 and miR-497 expression in NSCLC cells . *[right]* Fig 1C from [Mei et al (2017)] .  The correlation between GAS5 and miR-23a expression in NSCLC tissues was observed . ![file] The two scatterplots have implausibly many points in common. Dramatised by black-white reversing 1C and superimposing it on 3A. Could the authors comment? ,
LncRNA LACAT1 promotes proliferation of oral squamous cell carcinoma cells by inhibiting microRNA-4301
Authors: J Wang
F Huo
X-R Wang
Y-Y Xu
Journal: European Review for Medical and Pharmacological Sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA LACAT1; oral squamous cell carcinoma (OSCC); prognosis; clinicopathology; qRT-PCR
Affiliations: Department of Stomatology, Affiliated Hospital of Chengde Medical College, Chengde, China. .

Abstract:  Objective: To investigate the expression of lncRNA LACAT1 in oral squamous cell carcinoma (OSCC) tissues, and to further investigate its potential mechanism in OSCC as well as its relationship with clinicopathology and prognosis. Patients and methods: Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to analyze LACAT1 level in 78 pairs of OSCC tumor tissues and adjacent tissues, and the interplay between LACAT1 level and OSCC clinical indices along with patient's prognosis was analyzed. Further, the expression level of LACAT1 in OSCC cell line was verified by qRT-PCR. In addition, after LACAT1 knockdown model was constructed using lentivirus and transfected into OSCC cell lines, cell cloning assay and flow cytometry were used to analyze the impact of LACAT1 on biological functions of OSCC cells, and finally its association with microRNA-4301 was explored. Results: In this experiment, qRT-PCR results revealed that LACAT1 level in OSCC tumor tissue specimens was significantly higher than that in paracancerous tissues. In addition, the pathology stage in patients with higher level of LACAT1 was also higher while the overall survival rate was lower. Compared with sh-NC group, the cell proliferation ability of sh-LACAT1 group was significantly decreased while cell apoptosis was oppositely increased. QRT-PCR results showed that microRNA-4301 level was significantly elevated in cells of sh-LACAT1 group, suggesting that the expression of above two molecules was negatively correlated. Meanwhile, cell reverse experiment also demonstrated that LACAT1 and microRNA-4301 can be mutually regulated, and thereby promote the malignant progression of OSCC. Conclusions: The LACAT1 level was found significantly increased in OSCC tissues and cells, which resulted in an advanced OSCC pathological stage and a poor prognosis of patients. In addition, it was found that LACAT1 may promote the malignant progression of OSCC by modulating microRNA-4301 activity. 

Retracted: No

PubPeer comments:
 ![file] ,
Melatonin alters cell death processes in response to age-related oxidative stress in the brain of senescence-accelerated mice
Authors: Mercé Pallás
David De Gonzalo-Calvo
Ana Coto-Montes
Delio Tolivia
María Josefa Rodríguez-Colunga
Clara Soria-Valles
Beatriz Caballero
Covadonga Huidobro-Fernández
Antonio Camins
Ignacio Vega-Naredo
Verónica Sierra
Journal: Journal of Pineal Research (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: age; melatonin; cell death; brain aging; neurodegeneration
Affiliations: Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.

Abstract:  We studied the effect of age and melatonin on cell death processes in brain aging. Senescence-accelerated prone mice 8 (SAMP8) and senescence-accelerated resistant mice (SAMR1) at 5 and 10 months of age were used as models of the study. Melatonin (10 mg/kg) or its vehicle (ethanol at 0.066%) was administered in the drinking water from 1 to 9 months of age. Neurodegeneration, previously shown in the aged brain of SAMP8 and SAMR1 at 10 months of age, may be due to a drop in age-related proteolytic activities (cathepsin D, calpains, and caspase-3). Likewise, lack of apoptotic and macroautophagic processes were found, without apparent modification by melatonin. However, the caspase-independent cell death, owing to high p53 and apoptosis-inducing factor (AIF) levels, might be an alternative pathway of cell death in the aged brain. The main effects of melatonin treatment were observed in the aged SAMR1 mice; in this strain we observed a marked increase in antioxidant activity (catalase and superoxide dismutase). Likewise, a key antioxidant role of apoptosis-related proteins, Bcl-2 and AIF, was suggested in the aged brain of SAM mice, which was clearly influenced by melatonin. Moreover, the age-related increase of lysosomal activity of cathepsin B and a lysosomal membrane-associated protein 2 supports the possibility of the maintenance of lysosomal viability in addition to age-related impairments of the proteolytic or macroautophagic activities. The effectiveness of melatonin against the oxidative stress-related impairments and apoptosis during the aging process is, once more, corroborated in this article. 

Retracted: No

PubPeer comments:
 Actin lanes are different from LC-3 lanes in number and pattern of blot. They are supposed to run 6 samples, but Actin has 7 lanes. ![file] , 
 #1 Argiope Bruennichi, So, what is your point? One could run same proteins in two different gels and probe for LC3 and actin. Nothing wrong in it. , 
 Could the authors match actin bands with which samples? ![file] , 
 Actually a good discussion about running same proteins in two different gels. https: forbetterscience.com 2018 12 06 western-blot-loading-control-libraries-and-beyond But actin bands cannot correspond with samples is a real profound issue here. , 
 #2  One could run same proteins in two different gels and probe for LC3 and actin. Nothing wrong in it. What s that got to do with  Actin lanes are different from LC-3 lanes in number and pattern of blot. They are supposed to run 6 samples, but Actin has 7 lanes. , which is from comment #1? ,
The Amyloid Inhibitor CLR01 Relieves Autophagy and Ameliorates Neuropathology in a Severe Lysosomal Storage Disease
Authors: Vincenzo Cacace
Veronica Maffia
Thomas Schrader
Teresa Giuliano
Yulia Ezhova
Gal Bitan
Irene Sambri
Maria De Risi
Nicolina Cristina Sorrentino
Alessandro Fraldi
Antonio Monaco
Elvira De Leonibus
Edoardo Nusco
Frank-Gerrit Klärner
Journal: Molecular Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: amyloid aggregation; autophagy; lysosomal storage disease; molecular tweezers; mucopolysaccharidosis type IIIA.
Affiliations: Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy., Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy; Institute of Cellular Biology and Biochemistry, CNR, Via Ramarini 33, 00015 Monterotondo Scalo, Rome, Italy., Department of Chemistry, University of Duisburg-Essen, Universitaetsstrasse 7, 45117 Essen, Germany., Department of Neurology, David Geffen School of Medicine, Brain Research Institute, University of California, Los Angeles, 635 Charles E. Young Drive South, Los Angeles, CA 90095-7334, USA; Molecular Biology Institute, University of California, Los Angeles, 635 Charles E. Young Drive South, Los Angeles, CA 90095-7334, USA., Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy; Department of Translational Medicine, University of Naples "Federico II," Via Sergio Pansini 5, 80131, Naples, Italy. Electronic address: .

Abstract:  Lysosomal storage diseases (LSDs) are inherited disorders caused by lysosomal deficiencies and characterized by dysfunction of the autophagy-lysosomal pathway (ALP) often associated with neurodegeneration. No cure is currently available to treat neuropathology in LSDs. By studying a mouse model of mucopolysaccharidosis (MPS) type IIIA, one of the most common and severe forms of LSDs, we found that multiple amyloid proteins including α-synuclein, prion protein (PrP), Tau, and amyloid β progressively aggregate in the brain. The amyloid deposits mostly build up in neuronal cell bodies concomitantly with neurodegeneration. Treating MPS-IIIA mice with CLR01, a "molecular tweezer" that acts as a broad-spectrum inhibitor of amyloid protein self-assembly reduced lysosomal enlargement and re-activates autophagy flux. Restoration of the ALP was associated with reduced neuroinflammation and amelioration of memory deficits. Together, these data provide evidence that brain deposition of amyloid proteins plays a gain of neurotoxic function in a severe LSD by affecting the ALP and identify CLR01 as new potent drug candidate for MPS-IIIA and likely for other LSDs. 

Retracted: No

PubPeer comments:
 Figure 4A appears to have 2 images which overlap. *** ![file] ,
Helicobacter pylori infection leads to KLF4 inactivation in gastric cancer through a TET1‐mediated DNA methylation mechanism
Authors: Yang Ou
Siying Wang
Yakun Liu
Haifeng Ren
Wenting Xu
Zhengxia Liu
Rongrong Zhao
Le Song
Journal: Cancer Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: H pylori; CagA; KLF4; TET1; gastric cancer.
Affiliations: Department of Physiopathology, Anhui Medical University, Hefei, Anhui, China., Department of Pathology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Abstract:  Krüppel-like factor 4 (KLF4) has a tumor suppressor role in the progression of gastric cancer (GC), and inhibition or loss of KLF4 expression was identified in GC. The aim of this study was to explore the new molecular mechanism of KLF4 inactivation in gastric cancer. Herein, we report that Helicobacter pylori infection or Cag pathogenicity island protein A (CagA) gene transduction resulted in KLF4 expression downregulation and promoted gastric epithelial cell and gastric cancel cell proliferation, migration, and colony formation. Mechanistically, we found that CagA gene transduction led to DNA methylation of the KLF4 promoter, an effect that was relevant to the significant downregulation of TET1 expression. Causally, knockdown of TET1 expression decreased KLF4 expression, whereas overexpression of TET1 had the opposite effect. Clinically, we found that KLF4 expression and the 5-hmC levels were lower in GC cells with H pylori infection than in GC cells without H pylori infection. Thus, our study not only sheds new light on how H pylori infection promotes the progression of GC but also elucidates a novel mechanism of KLF4 inactivation in GC pathogenesis. During pathogenesis, an alteration in the H pylori/CagA-TET1-KLF4 signaling pathway plays a critical role, suggesting that this pathway may be a prospective target for gastric carcinoma intervention and therapy. 

Retracted: No

PubPeer comments:
 In Fig. 5H, two figures overlap ![file] ,
Invasiveness and anchorage independent growth ability augmented by PTEN inactivation through the PI3K/AKT/NFkB pathway in lung cancer cells
Authors: Hakan Akca
Jun Yokota
Onur Tokgun
Aydin Demiray
Journal: Lung Cancer (2011)
Discipline: CLINICAL MEDICINE
Keywords: PTEN; lung cancer; invasiveness; AKT; NFkB
Affiliations: Medical Biology Department, School of Medicine, Pamukkale University, Kinikli, Denizli, Turkey. 

Abstract:  PTEN is inactivated in a subset of lung cancer; therefore, we investigated the involvement of PTEN inactivation in invasiveness of lung cancer cells. AKT at Ser473 was phosphorylated in several lung cancer cell lines with loss of PTEN expression. Therefore, we created a tetracycline inducible expression system of wild-type PTEN (PTEN-WT) as well as catalytically (PTEN-G129R) and lipid phosphatase (PTEN-G129E) inactive PTEN mutants using the PC14, PC9 and PC3 lung adenocarcinoma cell lines, in which endogenous PTEN expression was not detected and AKT at Ser473 was phosphorylated by Western blot analysis. Induction of PTEN-WT reduced phosphorylation of AKT and inhibited the transcriptional activity of NFkB, whereas PTEN mutants did not, suggesting that PTEN inactivation results in the activation of the AKT/NFkB pathway in PC14, PC9 and PC3 cells. Furthermore, overexpression of PTEN-WT suppressed anchorage independent growth in soft agar and reduced invasiveness in a trans-well chamber assay of PC14 cells. Neither PTEN-G129R nor PTEN-G129E had suppressive effects on anchorage independent growth and invasiveness. Augmentation of invasiveness by constitutively active AKT was also shown in mouse NIH3T3 cells. Therefore, it was strongly indicated that activation of the PI3K/AKT/NFkB pathway by PTEN inactivation results in augmented invasiveness in lung cancer cells and lipid phosphatase activity of PTEN plays a key role in this process. 

Retracted: No

PubPeer comments:
 May 2016 correction, found here: https: www.lungcancerjournal.info article S0169-5002(16)30319-1 fulltext (but not visible from the paper s landing page). It reads:  The publisher regrets that the authors mistakenly inserted the incorrect GAPDH line on Fig. 2A. All densitometric analyses and values were calculated correctly with using correct GAPDH line in previously figure too. Mistake was just put wrong GAPDH on figure. A corrected Fig. 2A with the correct GAPDH line is now below. Unfortunately, several issues in Figures 1 and 2 appear to remain. I reported these issues to the journal in November 2016, but the journal took no further action. ![file] ,
Long noncoding RNA ITGB1 promotes migration and invasion of clear cell renal cell carcinoma by downregulating Mcl-1
Authors: W-G Lv
Y-Y Zhang
X-L Zheng
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; linc-ITGB1; clear cell renal cell carcinoma (ccRCC); tumorigenesis; Real Time-quantitative Polymerase Chain Reaction (RT-qPCR)
Affiliations: Department of Pharmacy, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. .

Abstract:  Objective: Researchers have discovered the important role of long noncoding RNA (lncRNAs) in tumorigenesis recently. In this work, we aimed to explore whether lncRNA linc-ITGB1 affected the development of clear cell renal cell carcinoma (ccRCC), and to elucidate the possible underlying mechanism. Patients and methods: Linc-ITGB1 expression in both ccRCC cells and tissue samples was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Moreover, the association between linc-ITGB1 expression level and patients' disease-free survival rate was explored. Then, wound healing and transwell assays were conducted. Furthermore, the underlying mechanism was explored through RT-qPCR and Western blot assay. Results: Linc-ITGB1 expression level in ccRCC samples was markedly higher than that of the adjacent ones. The expression of linc-ITGB1 was closely related to the disease-free survival time of ccRCC patients. Moreover, the migration and invasion of ccRCC cells were remarkably enhanced after linc-ITGB1 upregulation in vitro. In addition, the mRNA and protein expression of Mcl-1 were significantly downregulated after linc-ITGB1 overexpression. Furthermore, the expression level of Mcl-1 was negatively correlated with the linc-ITGB1 expression in ccRCC tissues. Conclusions: Our findings suggested that linc-ITGB1 could enhance ccRCC cell migration and invasion via downregulating Mcl-1. In addition, linc-ITGB1 might be a potential therapeutic target for ccRCC. 

Retracted: No

PubPeer comments:
 The article by Mandeep Mehra and his colleagues (Lancet May 22nd 2020) has been retracted because the data on which it is based are not certain. This article was accompanied by a commentary by Dr Christian Funck-Brentano and Dr Joe-Elie Salem from Paris (France) who praised the results obtained by Mehra et al. These two authors did not see that the results were not valid. It seems to me that their comments should be removed at their request. It would be more honest. ,
LncRNA FLJ33360 accelerates the metastasis in hepatocellular carcinoma by targeting miRNA-140/MMP9 axis
Authors: Yingzi Yu
Yu Zhou
Yaqin He
Dong Jin
Li Na
Qi Wang
Yongzhao Zhu
Genwang Wang
Xiangchun Ding
Zhenhui Lu
Journal: American journal of translational research (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: FLJ33360; hepatocellular carcinoma (HCC); metastasis; miRNA-140.
Affiliations: Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University Yinchuan, Ningxia, China., Department of Infection Control, General Hospital of Ningxia Medical University Yinchuan, Ningxia, China., Department of Infectious Disease, General Hospital of Ningxia Medical University Yinchuan, Ningxia, China., Department of Surgical Research Laborator, General Hospital of Ningxia Medical University Yinchuan, Ningxia, China.

Abstract:  This study aims to detect expression level of long non-coding RNA (lncRNA) FLJ33360 in hepatocellular carcinoma (HCC) and its regulatory effects on accelerating malignant progression of HCC. Expression levels of FLJ33360 in 29 matched HCC tissues and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection of sh-FLJ33360#1 in Bel-7402 and HepG2 cells, changes in migratory and invasive capacities were evaluated by Transwell and wound healing assay. Potential miRNAs targeting FLJ33360 were verified. The correlation between expression levels of FLJ33360 and miRNA-140 in HCC tissues was determined. At last, potential influences of FLJ33360/miRNA-140 regulatory loop on HCC phenotypes were determined by rescue experiments. FLJ33360 was upregulated in HCC tissues relative to paracancerous ones. After knockdown of FLJ33360, migratory and invasive capacities in Bel-7402 and HepG2 cells were attenuated. There were five miRNA candidates predicted to bind FLJ33360, and miRNA-140 was the most differentially expressed by FLJ33360 regulation. Dual-luciferase reporter gene assay confirmed the binding between FLJ33360 and miRNA-140. Besides, their expression levels were negatively correlated in HCC tissues. Moreover, knockdown of miRNA-140 could stimulate metastatic ability in HCC. At last, rescue experiments verified the involvement of miRNA-140 in FLJ33360-regulated HCC progression. LncRNA FLJ33360 is upregulated in HCC. It accelerates the metastasis of HCC through targeting miRNA-140/MMP9 axis. 

Retracted: No

PubPeer comments:
 Fig 3E.  A negative correlation between levels of FLJ33360 and miRNA-140 in HCC tissues . Rescaled slightly, for better comparison with (right) a superimposition of 15 versions of a correlation scatterplot, from different papers. Data-points are darker if they appear in more of those 15 variants. ![file] Here, 3E superimposed on that composite. Enough points in common to suggest that it is from the same source. ![file] ,
Long Noncoding RNA PlncRNA-1 Promotes Colorectal Cancer Cell Progression by Regulating the PI3K/Akt Signaling Pathway
Authors: Wei Song
Mingzhi Zhang
Jia-Zhuan Mei
Journal: Oncology research (2018)
Discipline: CLINICAL MEDICINE
Keywords: lncRNA; PlncRNA-1; colorectal cancer; expression; biological functions
Affiliations: The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China., Department of Oncology, The People's Hospital of Zhengzhou, Zhengzhou, Henan, P.R. China., Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.

Abstract:  Accumulating evidence has indicated that long noncoding RNA (lncRNA) PlncRNA-1 plays an important regulatory role in cancers. However, the expression and biological functions of PlncRNA-1 in colorectal cancer (CRC) are still unclear. In the present study, we determined the expression of PlncRNA-1 in CRC and explored the function of PlncRNA-1 on CRC cell progression. The results showed that PlncRNA-1 was significantly increased in CRC tissues and cell lines; high PlncRNA-1 expression was associated with depth of invasion, lymph node metastasis, and TNM stage of CRC patients. Kaplan-Meier curve analysis showed that patients with high PlncRNA-1 expression had a poor overall survival. PlncRNA-1 knockdown remarkably reduced cell proliferation, migration, and invasion and promoted cell apoptosis in vitro. In vivo xenograft experiments showed that PlncRNA-1 inhibition significantly suppressed tumor growth. Finally, we used an agonist (740Y-P) of the PI3K/Akt signaling pathway; function assays showed that PlncRNA-1 exerted its effects by targeting the PI3K/Akt signaling pathway in CRC. Taken together, our data suggested that PlncRNA-1 might act as an oncogene in CRC progression and serve as a potential biomarker and therapeutic target for the treatment of CRC. 

Retracted: No

PubPeer comments:
 Immunoblots in Fig.5 are improperly cut, duplicated and show not the samples announced. # **Fig.5** ![file] , 
 From the Conclusion:  PlncRNA-1 is a potential diagnostic and therapeutic agent for the treatment of CRC patients. NO NO NO Adding some more information why (I did not see your post, Stahnkeus Deserticola, before I made it!): ![file] , 
 Erratum, [Jan 31 2022] .  In the original article Figures 3 and 5 contained some errors that were discovered when the experiments were repeated in 2021. The corrected version of the figures is shown here, and the figures have been replaced with the corrected version in the original published article in the online site . The corrections to the figures do not affect any content or results of the original article. ![file] ![file] ,
Utx is required for proper induction of ectoderm and mesoderm during differentiation of embryonic stem cells
Authors: Kristian Helin
Anne Laugesen
Cristina Morales Torres
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Embryonic development; chromatin remodeling; gene expression; H3K27me3; histone demethylases
Affiliations: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.

Abstract:  Embryonic development requires chromatin remodeling for dynamic regulation of gene expression patterns to ensure silencing of pluripotent transcription factors and activation of developmental regulators. Demethylation of H3K27me3 by the histone demethylases Utx and Jmjd3 is important for the activation of lineage choice genes in response to developmental signals. To further understand the function of Utx in pluripotency and differentiation we generated Utx knockout embryonic stem cells (ESCs). Here we show that Utx is not required for the proliferation of ESCs, however, Utx contributes to the establishment of ectoderm and mesoderm in vitro. Interestingly, this contribution is independent of the catalytic activity of Utx. Furthermore, we provide data showing that the Utx homologue, Uty, which is devoid of detectable demethylase activity, and Jmjd3 partly compensate for the loss of Utx. Taken together our results show that Utx is required for proper formation of ectoderm and mesoderm in vitro, and that Utx, similar to its C.elegans homologue, has demethylase dependent and independent functions. 

Retracted: No

PubPeer comments:
 Figure 1. * Red boxes: Lanes  D02 and  D05 look remarkably similar. * Blue arrows: Some unexpected vertical sharp transitions appear to be visible between lanes ![file] , 
 Figure 7 and Figure S2. * Boxes in green, purple, and blue bring attention to lanes that look similar. ![file] ,