PReD-Bench/PRed-Bench huggingface dataset:
Activation of mammalian target of rapamycin in transformed B lymphocytes is nutrient dependent but independent of Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, insulin growth factor-I, and serum
Authors: Xiaobin Liu
Michal Marzec
Mariusz A Wasik
Erle S Robertson
Monika Kasprzycka
Pawel Wlodarski
Artur Slupianek
Journal: Cancer research (2005)
Discipline: CLINICAL MEDICINE
Keywords: mTOR activation; B lymphocytes; EBV genome; signaling pathway; PI3K/Akt pathway
Affiliations: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.

Abstract:  The study examines the preponderance and mechanism of mammalian target of rapamycin (mTOR) activation in three distinct types of transformed B lymphocytes that differ in expression of the EBV genome. All three types [EBV-immortalized cells that express a broad spectrum of the virus-encoded genes (type III latency; EBV+/III), EBV-positive cells that express only a subset of the EBV-encoded genes (EBV+/I), and EBV-negative, germinal center-derived cells (EBV-)] universally displayed activation of the mTOR signaling pathway. However, only the EBV+/III transformed B cells displayed also activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway that is considered to be the key activator of mTOR and of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway that coactivates one of the immediate targets of mTOR, p70 S6K1. Activation of the PI3K/Akt and MEK/ERK, but not of the mTOR pathway, was inhibited by serum withdrawal and restored by insulin growth factor-I. In contrast, activation of mTOR, but not PI3K/Akt and MEK/ERK, was sensitive to nutrient depletion. Both direct Akt (Akt inhibitors I-III) and a PI3K inhibitor (wortmannin at 1 nmol/L) suppressed Akt phosphorylation without significantly affecting mTOR activation. Furthermore, rapamycin, a potent and specific mTOR inhibitor, suppressed profoundly proliferation of cells from all three types of transformed B cells. U0126, a MEK inhibitor, had a moderate antiproliferative effect only on the EBV+/III cells. These results indicate that mTOR kinase activation is mediated in the transformed B cells by the mechanism(s) independent of the PI3K/Akt signaling pathway. They also suggest that inhibition of mTOR signaling might be effective in therapy of the large spectrum of B-cell lymphomas. 

Retracted: No

PubPeer comments:
  The hypothesis is that peopleu2019s nutritional and oxidative scavenging capacity may provide fundamental data to predict severe and acute pulmonary distress following SARS-Cov2 infection. Consequently, the scientific community has addressed the role of balanced diets, nutritional supplements, and micronutrients, including folk herbal formulations, in reducing hospitalization and the severity of pulmonary impact in COVID-19 by preventing the most serious forms of the infection. This publication only presents speculations without any scientific proof. The publications from China promoting Traditional Chinese Medicine is highly flawed. ,
A novel DNA intercalator, butylamino-pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells
Authors: Gopal M Advirao
Bibha Choudhary
Mridula Nambiar
M S Shahabuddin
Sathees C Raghavan
Journal: Investigational New Drugs (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: DNA intercalators; chemotherapeutic agents; pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series; BPSQ; PPSQ
Affiliations: Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India.

Abstract:  DNA intercalators are one of the most commonly used chemotherapeutic agents. Novel intercalating compounds of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having a butylamino or piperazino group at fourth position (BPSQ and PPSQ, respectively) are studied. Our results showed that BPSQ induced cytotoxicity whereas PPSQ was cytostatic. The cytotoxicity induced by BPSQ was concentration- and time-dependent. Cell cycle analysis and tritiated thymidine assay revealed that BPSQ affects the cell cycle progression by arresting at S phase. The absence of p-histone H3 and reduction in the levels of PCNA in the cells treated with BPSQ further confirmed the cell cycle arrest. Further, annexin V staining, DNA fragmentation, nuclear condensation and changes in the expression levels of BCL2/BAD confirmed the activation of apoptosis. Activation of caspase 8 and lack of cleavage of caspase 9, caspase 3 and PARP suggest the possibility of BPSQ triggering extrinsic pathway for induction of apoptosis, which is discussed. Hence, we have identified a novel compound which would have clinical relevance in cancer chemotherapeutics. 

Retracted: No

PubPeer comments:
 ![file] , 
 Thank you for the observation. We are in the process of doing the needful. ,
Combining sensory information: mandatory fusion within, but not between, senses
Authors: M S Landy
M O Ernst
J M Hillis
M S Banks
Journal: Science (2002)
Discipline: Multidisciplinary
Keywords: sensory information; environmental properties; shape estimation; binocular disparity; perspective projection
Affiliations: Vision Science Program, School of Optometry, University of California, Berkeley, CA 94720-2020, USA. 

Abstract:  Humans use multiple sources of sensory information to estimate environmental properties. For example, the eyes and hands both provide relevant information about an object's shape. The eyes estimate shape using binocular disparity, perspective projection, etc. The hands supply haptic shape information by means of tactile and proprioceptive cues. Combining information across cues can improve estimation of object properties but may come at a cost: loss of single-cue information. We report that single-cue information is indeed lost when cues from within the same sensory modality (disparity and texture gradients in vision) are combined, but not when different modalities (vision and haptics) are combined. 

Retracted: No

PubPeer comments:
  The eyes estimate shape using...perspective projection.... For a discussion of why the rules of perspective or projective geometry are, counterintuitively, not relevant to the perception of shape, please see: https: psyarxiv.com n5mbf ,
Optokinetic stimulation induces illusory movement of both out-of-the-body and on-the-body hand-held visual objects
Authors: P Revol
A Farnè
N P Holmes
Y Rossetti
K Koga
L Pisella
A Imai
K Susami
Journal: Experimental Brain Research (2009)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: body part location; visual; proprioceptive; multisensory conflict; optokinetic stimulation
Affiliations: Inserm UMR-S 864, Bron, et Hospices Civils de Lyon, Service de Médecine Physique et Réadaptation, Hôpital Henry Gabrielle, Université de Lyon, Université Lyon 1, Saint-Genis-Laval, France. 

Abstract:  The coding of body part location may depend upon both visual and proprioceptive information, and allows targets to be localized with respect to the body. The present study investigates the interaction between visual and proprioceptive localization systems under conditions of multisensory conflict induced by optokinetic stimulation (OKS). Healthy subjects were asked to estimate the apparent motion speed of a visual target (LED) that could be located either in the extrapersonal space (visual encoding only, V), or at the same distance, but stuck on the subject's right index finger-tip (visual and proprioceptive encoding, V-P). Additionally, the multisensory condition was performed with the index finger kept in position both passively (V-P passive) and actively (V-P active). Results showed that the visual stimulus was always perceived to move, irrespective of its out- or on-the-body location. Moreover, this apparent motion speed varied consistently with the speed of the moving OKS background in all conditions. Surprisingly, no differences were found between V-P active and V-P passive conditions in the speed of apparent motion. The persistence of the visual illusion during the active posture maintenance reveals a novel condition in which vision totally dominates over proprioceptive information, suggesting that the hand-held visual stimulus was perceived as a purely visual, external object despite its contact with the hand. 

Retracted: No

PubPeer comments:
 This paper was criticised as part of a self-reflection posted on Twitter on 2nd-3rd April, 2021 (twitter TheHandLab status 1377760796130869248) Criticism: I am undeservedly a middle author on this paper. These days, I would not accept authorship based on such a small contribution. I would happily defend the paper though! ,
Novel function of PERK as a mediator of force-induced apoptosis
Authors: Qin Wang
David Ron
Donalyn Scheuner
Richard C Austin
Baldwin C Mak
Carol Laschinger
Heather P Harding
Wilson Lee
Randal J Kaufman
Christopher A McCulloch
Journal: Journal of Biological Chemistry (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: apoptosis; tensile forces; connective tissue destruction; osteoarthritis; periodontal diseases
Affiliations: Canadian Institutes of Health Research Group in Matrix Dynamics, University of Toronto, Toronto, Ontario M5S 3E2, Canada.

Abstract:  Induction of apoptosis by tensile forces is an important determinant of connective tissue destruction in osteoarthritis and periodontal diseases. We examined the role of molecular components of the unfolded protein response in force-induced apoptosis. Magnetic fields were used to apply tensile force through integrins to cultured fibroblasts bound with collagen-coated magnetite beads. Tensile force induced caspase 3 cleavage, DNA fragmentation, depolarization of mitochondria, and induction of CHOP10, all indicative of activation of apoptosis. Immunoblotting, immunocytochemistry, and release of Ca(2+) from the endoplasmic reticulum showed evidence for both physical and functional associations between bound beads and the endoplasmic reticulum. Force-induced apoptosis was not detected in PERK null cells, but reconstitution of wild-type PERK in PERK null cells restored the apoptotic response. Force-induced apoptosis did not require PKR, GCN2, eIF2alpha, or CHOP10. Furthermore, force more than 24 h did not activate other initiators of the unfolded protein response including IRE-1 and ATF6. However, force-induced activation of caspase 3 was dependent on caspase 9 but was independent of mitochondria. We conclude that force-induced apoptosis depends on a novel function of PERK that occurs in addition to its canonical role in the unfolded protein response. 

Retracted: No

PubPeer comments:
 Figure 4A u2013 Possible differential splicing (contrast enhanced). Could authors check it please? ![file] ,
Circular RNA cZNF292 silence alleviates OGD/R-induced injury through up-regulation of miR-22 in rat neural stem cells (NSCs)
Authors: Jun Zhang
Yubin Dong
Yaqin Cao
Hui Liu
Journal: Artificial Cells Nanomedicine and Biotechnology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Oxygen-glucose deprivation/reperfusion; Wnt/β-catenin and PKC/ERK pathways; cZNF292; miR-22.
Affiliations: Neonatal Intensive Care Unit, Zhoukou Central Hospital, Zhoukou, China.

Abstract:  Background: Hypoxic-ischaemic encephalopathy (HIE) is a prevailing severe brain damage disease in newborns, and caused by perinatal asphyxia cerebral ischaemia and reperfusion. Here, we investigated the role of cZNF292 in oxygen-glucose deprivation/reperfusion (OGD/R)-induced neural stem cells (NSCs) injury, and explored the underlying molecular mechanism.Methods: Before NSCs were subjected to OGD/R treatment, NSCs were transfected with or without overexpressing cZNF292, si-cZNF292 or miR-22 inhibitor. Viability, apoptosis and potential molecular mechanism were examined. Cell viability and apoptotic rate were evaluated utilizing cell counting kit-8 (CCK-8) and flow cytometry. The cZNF292 and miR-22 expression was determined utilizing quantitative reverse transcription-PCR (qRT-PCR). Moreover, apoptosis and Wnt/β-catenin and PKC/ERK pathways-associated proteins were quantified applying western blot.Results: OGD/R repressed viability and promoted apoptosis of NSCs. Also, cZNF292 expression was promoted by OGD/R treatment. Moreover, cZNF292 overexpression further caused OGD/R-stimulated damage. Inversely, silencing cZNF292 alleviated OGD/R-stimulated damage in NSCs. In addition, miR-22 expression was negatively regulated by cZNF292. It was confirmed that silencing cZNF292 attenuated OGD/R-induced NSCs injury and promoted the activation of Wnt/β-catenin and PKC/ERK pathways via the up-regulation of miR-22.Conclusions: The cZNF292 silence alleviated OGD/R-induced injury through the up-regulation of miR-22 in NSCs, and which furnished the theoretical basis for further research on HIE progression. 

Retracted: No

PubPeer comments:
 The Western Blots in this paper all display the curious, stylised form, like tadpoles or performing sardines, familiar from products of the celebrated  Tadpole Papermill. Here, Fig 6A C. ![file] Is it possible for the authors to upload or link to scans of the original gels? ,
Glutathione regulates telomerase activity in 3T3 fibroblasts
Authors: Juan Sastre
Federico V Pallardó
Juan M Esteve
Juan R Viña
Consuelo Borrás
José Viña
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: telomerase activity; glutathione; cell cycle; cancer; antioxidant
Affiliations: Department of Physiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain.

Abstract:  Changes in telomerase activity have been associated either with cancer, when activity is increased, or with cell cycle arrest when it is decreased. We report that glutathione, a physiological antioxidant present at high intracellular concentrations, regulates telomerase activity in cells in culture. Telomerase activity increases in 3T3 fibroblasts before exponential cell growth. The peak of telomerase activity takes place 24 h after plating and coincides with the maximum levels of glutathione in the cells. When cells are treated with buthionine sulfoximine, which decreases glutathione levels in cells, telomerase activity decreases by 60%, and cell growth is delayed. Glutathione depletion inhibits expression of E2F4 and Id2, which regulate the cell cycle. When glutathione levels are restored after incubation with glutathione monoethylester, telomerase activity and the cell cycle-related proteins return to control values. To discover the effect of glutathione redox status on the telomerase multicomplex structure, we incubated protein extracts from fibroblasts with different glutathione redox buffers. Telomerase activity is maximal under reduced conditions i.e. when the reduced/oxidized glutathione ratio is high. Consequently glutathione concentration parallels telomerase activity. These results underscore the main role of glutathione in the control of telomerase activity and of the cell cycle. 

Retracted: No

PubPeer comments:
 Figure 4A. Much more similar than you would expect. https: imgur.com DKmUjgC , 
 Figure 4B. Much more similar than you would expect. https: imgur.com rxATES5 , 
 Figure 4A. Much more similar than you would expect. https: imgur.com OKLN08B ,
The effects of sericin in recovering spermatogenesis and sexual hormone levels in diabetic rats
Authors: F Martínez-Pastor
A Olfati
Journal: Physiology International (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: antioxidant; diabetes; sericin; sex hormones; sperm parameters.
Affiliations: Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran, INDEGSAL and Department of Molecular Biology (Cell Biology), Universidad de León, León, Spain

Abstract:  Sericin-S (a hydrolysate from the silk protein sericin) is a natural antioxidant, which may improve spermatogenesis while having high biological safety, thus potentially useful for the treatment of male infertility. Our objective was to determine the effects of sericin-S on the sperm parameters and sexual hormone levels in a diabetic rat model. Thirty-six adult male rats were randomly divided in two groups, inducing diabetes in one of them by intraperitoneal administration of streptozotocin (STZ; 65 mg/kg). Both groups were randomly assigned to three subgroups, receiving oral gavage of saline, 1% or 2% sericin extract for 60 days. Therefore, the experimental design was a 2 × 3 factorial design of STZ and sericin treatments. One day after the last treatment, the rats were euthanized, weighed, the testes were processed (weigh, volume, and histology), and serum samples were processed for measuring sex hormone levels [testosterone, follicle-stimulating hormone, and luteinizing hormone (LH)]. STZ treatment decreased LH concentration and counts of spermatogonia, spermatocytes, and spermatids. Body and testis weights were significantly (p &lt; 0.05) lower in the control group (non-diabetic saline) compared to the treated groups. In non-diabetic rats, sericin treatments increased (p &lt; 0.05) the number of testicular cells (spermatogonia, spermatocytes, spermatids, Sertoli, and Leydig cells) and sex hormone concentrations. In diabetic rats, administration of sericin significantly (p &lt; 0.05) improved sperm cell number and sex hormones levels. In nutshell, sericin can clearly modify sperm parameters and overall sex hormone function, and could improve spermatogenesis in normal and diabetic rats. 

Retracted: No

PubPeer comments:
 This article is retracted: https: akjournals.com view journals 2060 aop article-10.1556-2060.106.2019.0001 article-10.1556-2060.106.2019.0001.xml But the PubMed page indicates no such status: https: pubmed.ncbi.nlm.nih.gov 31564119 ,
Clinical significance of CD146 and latexin during different stages of thyroid cancer
Authors: Emad Kandil
Zakaria Y Abd Elmageed
Krzysztof Moroz
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Thyroid tumorigenesis; CD146; Lxn; therapeutic targets; thyroid cancer
Affiliations: Tulane University Health Sciences Center, New Orleans, LA 70112, USA. 

Abstract:  Molecular mechanisms underlying thyroid tumorigenesis and identifying new therapeutic targets are still under investigation. We aim to investigate the role of CD146 and latexin (Lxn) and examine whether they have any clinical significance in thyroid cancer. Human thyroid papillary (PTC), follicular (FTC), anaplastic (ATC) cancer cells, and other control cells were used in this study. Western blot, cell proliferation, invasion assay, and shRNA were applied to study the expression levels and functional significances of CD146 and Lxn in thyroid cells. The protein expression was evaluated by immunohistochemistry using human tissue microarray (TMA) slides. Multivariate analysis was used to examine whether these proteins have any clinical significance in patients with thyroid cancer. The protein expressions of CD146 and Lxn were detected in most thyroid cancer cell lines when compared with normal cells. Notably, knockdown of CD146 reduced the migration and invasion in K1 (PTC) and OCUT-1 (ATC) cells. TMAs showed more immunoreactivity against CD146 and Lxn in PTC cores compared with FTC, ATC, and normal tissues. A positive correlation was established between CD146 and both Lxn (r = 0.421, p = 0.045) and age (r = 0.566, p = 0.012); however, it showed a negative correlation with tumor stage (r = -0.231, p = 0.010). In conclusion, CD146 and Lxn increased tumor migration and invasion in vitro and showed a high expression in PTC compared to those in ATC and normal human tissues demonstrating their role in early stage of thyroid tumorigenesis. CD146 was positively correlated with age, but negatively correlated with tumor stage. 

Retracted: No

PubPeer comments:
 Figure 2A and 3A: * Red boxes: three b-actin lanes look similar to each other. ![file] ,
Opposing activities protect against age-onset proteotoxicity
Authors: Ehud Cohen
Jan Bieschke
Andrew Dillin
Jeffery W Kelly
Rhonda M Perciavalle
Journal: Science (2006)
Discipline: Multidisciplinary
Keywords: Protein aggregation; Neurodegenerative diseases; Alzheimer's disease; Abeta(1-42) peptide; Caenorhabditis elegans
Affiliations: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

Abstract:  Aberrant protein aggregation is a common feature of late-onset neurodegenerative diseases, including Alzheimer's disease, which is associated with the misassembly of the Abeta(1-42) peptide. Aggregation-mediated Abeta(1-42) toxicity was reduced in Caenorhabditis elegans when aging was slowed by decreased insulin/insulin growth factor-1-like signaling (IIS). The downstream transcription factors, heat shock factor 1, and DAF-16 regulate opposing disaggregation and aggregation activities to promote cellular survival in response to constitutive toxic protein aggregation. Because the IIS pathway is central to the regulation of longevity and youthfulness in worms, flies, and mammals, these results suggest a mechanistic link between the aging process and aggregation-mediated proteotoxicity. 

Retracted: No

PubPeer comments:
 A more recent publication calls to question the part of the conclusions about the disaggregation of Au03b21u201340 amyloid fibrils by cellular and tissue extracts from this article. Murray et al., 2013 - 10.1002 pro.2339  Recently, we reported the discovery of amyloid disaggregase activities in extracts from mammalian cells and Caenorhabditis elegans. **However, we have discovered a problem with the interpretation of our previous results as Au03b2 disaggregation in vitro. Here, we show that Au03b2 fibrils adsorb to the plastic surface of multiwell plates and Eppendorf tubes.** This adsorption is markedly increased in the presence of complex biological mixtures subjected to a denaturing air-water interface. The time-dependent loss of thioflavin T fluorescence that we interpreted previously as disaggregation is due to increased adsorption of Au03b2 amyloid to the surfaces of multiwell plates and Eppendorf tubes in the presence of biological extracts. As the proteins in biological extracts denature over time at the air-water interface due to agitation shaking, their adsorption increases, in turn promoting adsorption of amyloid fibrils. We delineate important control experiments that quantify the extent of amyloid adsorption to the surface of plastic and quartz containers. **Based on the results described in this article, we conclude that our interpretation of the kinetic fibril disaggregation assay data previously reported in Bieschke et al., Protein Sci 2009;18:2231-2241 and Murray et al., Protein Sci 2010;19:836-846 is invalid when used as evidence for a disaggregase activity. ** Will authors follow with a correction? ,
A novel transcriptional inhibitor induces apoptosis in tumor cells and exhibits antiangiogenic activity
Authors: Senthil K Radhakrishnan
Andrei L Gartel
Journal: Cancer Research (2006)
Discipline: CLINICAL MEDICINE
Keywords: high-throughput cell-based assay; nucleoside analogue; transcriptional inhibitor; RNA polymerase II; p53
Affiliations: Department of Medicine, University of Illinois at Chicago, Illinois 60612, USA.

Abstract:  Using a high-throughput cell-based assay, we identified a nucleoside analogue 4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo(2,3-d)-pyrimidine-5-carboxamide (ARC), which has the properties of a general transcriptional inhibitor. Specifically, ARC inhibits the phosphorylation of RNA polymerase II by positive transcription elongation factor-b, leading to a block in transcriptional elongation. ARC was able to potently repress p53 targets p21 and hdm2 (human homologue of mdm2) protein levels, but dramatically increased p53 levels similar to other transcriptional inhibitors, including flavopiridol. This increase in p53 corresponded to the down-regulation of short-lived protein hdm2, which is a well-established negative regulator of p53. Remarkably, ARC induced potent apoptosis in human tumor and transformed, but not in normal cells, and possessed strong antiangiogenic activity in vitro. Although ARC promoted the accumulation of p53, ARC-induced apoptosis in tumor cells was p53-independent, suggesting that it may be useful for the treatment of tumors with functionally inactive p53. Furthermore, cell death induced by ARC had a strong correlation with down-regulation of the antiapoptotic gene survivin, which is often overexpressed in human tumors. Taken together, our data suggests that ARC may be an attractive candidate for anticancer drug development. 

Retracted: No

PubPeer comments:
 ![file] ,
The E3 ubiquitin ligase GRAIL regulates T cell tolerance and regulatory T cell function by mediating T cell receptor-CD3 degradation
Authors: Chen Dong
Shuling Zheng
Shao-Cong Sun
Xin Lin
Gustavo J Martinez
Joseph M Reynolds
Roza I Nurieva
Yongliang Zhang
Guillermina Lozano
Sung-Ling Wang
Yeonseok Chung
Wei Jin
Journal: Immunity (2010)
Discipline: IMMUNOLOGY
Keywords: T cell activation; GRAIL; autoimmune diseases; immune tolerance; proliferation
Affiliations: Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030, USA. 

Abstract:  T cell activation is tightly regulated to avoid autoimmunity. Gene related to anergy in lymphocytes (GRAIL, encoded by Rnf128) is an E3 ubiquitin ligase associated with T cell tolerance. Here, we generated and analyzed GRAIL-deficient mice and found they were resistant to immune tolerance induction and exhibited greater susceptibility to autoimmune diseases than wild-type mice. GRAIL-deficient naive T cells, after activation, exhibited increased proliferation and cytokine expression than controls and did not depend on costimulation for effector generation. Moreover, GRAIL-deficient regulatory T (Treg) cells displayed reduced suppressive function, associated with increased Th17 cell-related gene expression. GRAIL-deficient naive and Treg cells were less efficient in downregulating T cell receptor (TCR)-CD3 expression after activation and exhibited increased NFATc1 transcription factor expression; GRAIL expression promoted CD3 ubiquitinylation. Our results indicate that GRAIL, by mediating TCR-CD3 degradation, regulates naive T cell tolerance induction and Treg cell function. 

Retracted: No

PubPeer comments:
 ![file] ![file] , 
 In this experiment, we determined and compared the expression of T cell receptor (TCR) signaling molecules in CD4+ T cells from WT and Grail KO mice, before and after activation with anti-CD3 to trigger TCR activation. The purpose was to see if WT and KO T cells had any difference in their expression, either before or after activation, but NOT to compare one type of T cells, WT or KO, before and after activation. Therefore, we run WT and KO samples side-by-side but samples before and after activation were run on separate gels. One could notice that protein quantitation was made separately on samples before and after activation, and set the lower expressing samples as 1 independently. We do not see any reason for the concern raised by the anonymous commenter. -Roza Nurieva and Chen Dong ,
MicroRNA‑34a inhibits metastasis in liver cancer cells
Authors: Ling Tang
Huihuan Tang
Wei Wei
Journal: Oncology Letters (2018)
Discipline: CLINICAL MEDICINE
Keywords: metastasis; microRNA-34a; tumor suppressor.
Affiliations: Department of General Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China., Department of Pharmacy, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

Abstract:  MicroRNAs (miRNA/miRs) have the ability to target specific mRNAs, resulting in degradation of mRNA or inhibition of translation. Notably, miR-34a is able to regulate cell cycle and tumorigenicity. The level of miR-34a expression is usually low in tumors, and previous studies have indicated miR-34a to be an important tumor suppressor. In order to elucidate the association between miR-34a and metastasis, stable cell lines were established and transfected with miR-34a. Cell invasion assay was subsequently performed. The present study demonstrated that cell invasion was inhibited in cells that were transfected with miR-34a compared with the control group (P&lt;0.05). Therefore, miR-34a was able to inhibit metastasis in liver cancer cells. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have two sets of repeated images (red and green boxes). *** ![file] ![file] ,
Enhancing the dissolution of phenylbutazone using Syloid® based mesoporous silicas for oral equine applications
Authors: Faraj Mohammad
Laura J Waters
John P Hanrahan
Shamsuddeen A Ahmad
Maria Saleem
Catherine V Finch
Joseph M Tobin
Gareth M B Parkes
Journal: Journal of pharmaceutical analysis (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Dissolution; Drug-loading; Phenylbutazone; Solubility; Syloid® silicas.

Abstract:  Three mesoporous silica excipients (Syloid® silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent and rate of drug release for all three forms of Syloid® silica at a 1:1 drug:silica ratio over a period of 30 min. An explanation for this increase was determined to be conversion to the amorphous form and an enhanced drug loading ability within the pores. Differences between the release profiles of the three silicas were concluded to be a consequence of the physicochemical differences between the three forms. Overall, this study confirms that Syloid® silica based excipients can be used to enhance dissolution, and potentially therefore bioavailability, for compounds with poor aqueous solubility such as phenylbutazone. In addition, it has been confirmed that drug release can be carefully tailored based on the choice of Syloid® silica and desired release profile. 

Retracted: No

PubPeer comments:
 For drug loading in mesoprus silica the solvent salection is must be on the solubulity of drug , but here the the drug loading is done in water so drug is only disperse in water and how the drug loading is takes place ..... ,
Stable Upconversion Nanohybrid Particles for Specific Prostate Cancer Cell Immunodetection
Authors: Liisa Kautto
Yiqing Lu
Helena Nevalainen
Arun V Everest Dass
Robert D Willows
Nicolle H Packer
Bradley Walsh
Yu Shi
Bingyang Shi
Roger Chung
Dayong Jin
Nima Sayyadi
James Piper
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Prostate cancer; early detection; upconversion immune-nanohybrids; targeting capability; stable optical properties
Affiliations: International Joint Center for Biomedical Innovation, Henan University, Kaifeng, Henan, 457001, China., Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia., ARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, NSW, 2109, Australia., Minomic International Ltd, Macquarie Park, Sydney, NSW, 2109, Australia.

Abstract:  Prostate cancer is one of the male killing diseases and early detection of prostate cancer is the key for better treatment and lower cost. However, the number of prostate cancer cells is low at the early stage, so it is very challenging to detect. In this study, we successfully designed and developed upconversion immune-nanohybrids (UINBs) with sustainable stability in a physiological environment, stable optical properties and highly specific targeting capability for early-stage prostate cancer cell detection. The developed UINBs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and luminescence spectroscopy. The targeting function of the biotinylated antibody nanohybrids were confirmed by immunofluorescence assay and western blot analysis. The UINB system is able to specifically detect prostate cancer cells with stable and background-free luminescent signals for highly sensitive prostate cancer cell detection. This work demonstrates a versatile strategy to develop UCNPs based sustainably stable UINBs for sensitive diseased cell detection. 

Retracted: No

PubPeer comments:
 Figure S4. * Some luminescence photographs look more similar than expected, as indicated with boxes of the same color. ![file] , 
 Hi Elisabeth, In Figure S4, the samples in the same solution should be extremely similar they are. Because they are the same samples and were tested under the same condition, the only difference is time. The images captured at hour 1 and hour 24 are extremely similar because the dispersibility of our NPs is outstanding and they are super stable, as shown in the size distribution. This is what we want to demonstrate via this figure. ,
Novel method of forming human embryoid bodies in a polystyrene dish surface-coated with a temperature-responsive methylcellulose hydrogel
Authors: Mei-Ju Yang
Hsing-Wen Sung
Wannhsin Chen
Pei-Ju Lin
Chih-Hao Huang
Chun-Hung Chen
Journal: Biomacromolecules (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: temperature-responsive hydrogel; methylcellulose; PBS; sol-gel transition; embryoid bodies
Affiliations: Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan, Republic of China, and Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China

Abstract:  A temperature-responsive hydrogel composed of aqueous methylcellulose (MC) blended with distinct concentrations of PBS was prepared and characterized. The developed MC hydrogel underwent a sol-gel reversible transition upon heating or cooling at approximately 32 degrees C. This temperature-responsive hydrogel was employed to coat the surface of a polystyrene dish and used to cultivate human embryonic stem (hES) cell clumps for the formation of embryoid bodies (EBs) in liquid suspension culture (LSC-MC/PS). The conventional hanging drop culture (HDC) and LSC in the uncoated polystyrene dish (LSC-PS) or in the Corning Ultralow-Attachment plate (LSC-ULAP) were used as controls. The results indicated that LSC-PS failed to generate EBs in an efficient manner, whereas the efficiencies of EB formation observed in LSC-ULAP and LSC-MC/PS were significantly greater than in HDC. The hES cells within the EBs were shown to express molecular markers specific for representative cells from the three embryonic germ layers. These results indicated that the MC-coated dish can be used to produce a large scale of hES cell derivatives through the formation of EBs. 

Retracted: No

PubPeer comments:
 ![file] Figure 4. Some cell clumps look highly similar despite different conditions ,
Novel nano-sized chitosan amphotericin B formulation with considerable improvement against Leishmania major
Authors: Mostafa Haji Molla Hoseini
Mehdi Shafiee Ardestani
Amitis Ramezani
Ali Khamesipour
Tahereh Zadeh Mehrizi
Nariman Mosaffa
Journal: Nanomedicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: increasing effective therapeutic dose; nanochitosan; phase separation; toxicity reduction.
Affiliations: Department of Clinical Research, Pasteur Institute of Iran, Tehran, Iran., Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Department of Medical Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences, Tehran, Iran.

Abstract:  Aim: Improvement in the treatment of Leishmania major's pathological effects through increasing the dose of amphotericin B loaded into nanochitosan. Materials &amp; methods: The phase separation method was used for nanochitosan synthesis and amphotericin loading. Also a novel solvent was designed and the nanodrug efficacy was evaluated in vitro and in vivo (pathology) environments. Results: The drug loading efficiency of 90%, along with slow drug-release with cellular uptake of 98.6% was achieved. The novel solvent was composed of 10% acetic acid, and it was succeeded to dissolve AK10 mg/kg. Also, AK10 mg/kg had no side effects in in vitro and in vivo environments. In addition, the complete wound healing and parasite inhibition were achieved by using AK10 mg/kg in terms of improvement the treatment indicators. Conclusion: Increasing the therapeutic dose of AK to 10 mg/kg caused the successful treatment of L. major's pathological effects in in vitro and in vivo environments. 

Retracted: No

PubPeer comments:
 Some more questionable images by an overlapping group of authors as these: https: pubpeer.com publications 6F91195571CAF273A4DD5D386438A5 https: pubpeer.com publications 7B28C72C50435D3058BB27158D34E0 There could be more papers, others may check if they wish. *** False color ![file] *** Original ![file] ,
In vivo evidence of CHIP up-regulation attenuating tau aggregation
Authors: Akihiko Takashima
Naruhiko Sahara
Miyuki Murayama
Keiji Tanaka
Ryosuke Takahashi
Tatsuya Mizoroki
Makoto Urushitani
Yuzuru Imai
Shigeo Murata
Journal: Journal of Neurochemistry (2005)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: CHIP; Hsp70; tau ubiquitination; NFTs; Alzheimer's disease
Affiliations: Laboratory for Alzheimer's Disease, RIKEN Brain Science Institute, Saitama, Japan.

Abstract:  The carboxyl terminus of heat-shock cognate (Hsc)70-interacting protein (CHIP) is a ubiquitin E3 ligase that can collaborate with molecular chaperones to facilitate protein folding and prevent protein aggregation. Previous studies showed that, together with heat-shock protein (Hsp)70, CHIP can regulate tau ubiquitination and degradation in a cell culture system. Ubiquitinated tau is one component in neurofibrillary tangles (NFTs), which are a major histopathological feature of Alzheimer's disease (AD). However, the precise sequence of events leading to NFT formation and the mechanisms involved remain unclear. To confirm CHIP's role in suppressing NFT formation in vivo, we performed a quantitative analysis of CHIP in human and mouse brains. We found increased levels of CHIP and Hsp70 in AD compared with normal controls. CHIP levels in both AD and controls corresponded directly to Hsp90 levels, but not to Hsp70 or Hsc70 levels. In AD samples, CHIP was inversely proportional to sarkosyl-insoluble tau accumulation. In a JNPL3 mouse brain tauopathy model, CHIP was widely distributed but weakly expressed in spinal cord, which was the most prominent region for tau inclusions and neuronal loss. Protein levels of CHIP in cerebellar regions of JNPL3 mice were significantly higher than in non-transgenic littermates. Human tau was more highly expressed in this region of mouse brains, but only moderate levels of sarkosyl-insoluble tau were detected. This was confirmed when increased insoluble tau accumulation was found in mice lacking CHIP. These findings suggest that increases in CHIP may protect against NFT formation in the early stages of AD. If confirmed, this would indicate that the quality-control machinery in a neuron might play an important role in retarding the pathogenesis of tauopathies. 

Retracted: No

PubPeer comments:
 Biochemical analyses were performed very well in this study. An important landmark paper!!! However, there is no single data justifying the title  In vivo evidence of CHIP up-regulation attenuating tau aggregation in this article. 1) This article included multiple ***association*** experiments. Association is not causation. 2) The authors reported an increase in insoluble Tau level in Chip Knockout mice. However, this finding does NOT necessarily mean that Chip up-regulation will attenuate tau aggregation. To justify the title  In vivo evidence of CHIP up-regulation attenuating tau aggregation , the authors should have overexpressed Chip in the brain and then demonstrate a decrease in tau aggregation. ,
Myc mediates cancer stem-like cells and EMT changes in triple negative breast cancers cells
Authors: Liping Xu
Arun K Rishi
Vino T Cheryan
Shuping Yin
Kaladhar B Reddy
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: Triple negative breast cancer; racial disparity; cancer stem-like cells; c-Myc; chemotherapy
Affiliations: Department of Pathology, Wayne State University, Detroit, Michigan, United States of America., John D. Dingell VA Medical Center, Wayne State University, Detroit, Michigan, United States of America., Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, United States of America., Departments of Oncology, Wayne State University, Detroit, Michigan, United States of America.

Abstract:  Women with triple negative breast cancer (TNBC) have poor prognosis compared to other breast cancer subtypes. There were several reports indicating racial disparity in breast cancer outcomes between African American (AA) and European American (EA) women. For example, the mortality rates of AA breast cancer patients were three times higher than of EA patients, even though, the incidence is lower in AA women. Our in vitro studies indicate that cancer stem-like cells (CSCs) derived from AA TNBC cell lines have significantly higher self-renewal potential (mammosphere formation) than CSCs derived from EA cell lines. TNBC tumors express high levels of Myc compared to luminal A or HER2 expressing breast cancers. We studied the effects of c-Myc overexpression on CSCs and chemotherapy in AA, and EA derived TNBC cell line(s). Overexpression of c-Myc in AA derived MDA-MB-468 (Myc/MDA-468) cells resulted in a significant increase in CSCs and with minimal changes in epithelial-to-mesenchymal transition (EMT) compared to the control group. In contrast, overexpression of c-Myc in EA derived MDA-MB-231(Myc/MDA-231) cells led to increased epithelial-to-mesenchymal transition (EMT), with a minimal increase in CSCs compared to the control group. Myc/MDA-468 cells were resistant to standard chemotherapeutic treatments such as iniparib (PARP inhibitor) plus cisplatin, / iniparib, cisplatin, paclitaxel and docetaxel. However, Myc/MDA-231 cells, which showed EMT changes responded to iniparib with cisplatin, but were resistant to other drugs, such as iniparib, cisplatin, paclitaxel and docetaxel. Collectively, our results indicate that intrinsic differences in the tumor biology may contribute to the breast cancer disparities. 

Retracted: No

PubPeer comments:
 Iniparib is not a PARP inhibitor. This was shown in 2012: https: clincancerres.aacrjournals.org content 18 2 510 https: clincancerres.aacrjournals.org content 18 6 1655 It also failed in an phase 3 study for the treatment of triple negative breast cancer. Why are the authors still calling it a PARP inhibitor and why do they include it in a study related to triple negative breast cancer?! ,
Sex difference in the proliferative response of mouse hepatocytes to treatment with the CAR ligand, TCPOBOP
Authors: Danilo Concas
Francesca Molotzu
Gabriella Simbula
Monica Pibiri
Giovanna M Ledda-Columbano
Amedeo Columbano
Costanza Cossu
Journal: Carcinogenesis (2003)
Discipline: CLINICAL MEDICINE
Keywords: Constitutive Androstane Receptor (CAR); gene transcription; testosterone metabolites; hepatocyte proliferation; CD-1 mice
Affiliations: Department of Toxicology, Oncology and Molecular Pathology Unit, University of Cagliari, Via Porcell 4, 09124 Cagliari, Italy.

Abstract:  The nuclear receptor Constitutive Androstane Receptor (CAR) binds DNA as a heterodimer with the retinoic-X receptor and activates gene transcription. Previously, in vitro studies have shown that the testosterone metabolites, androstenol and androstenol, inhibit the constitutive transcriptional activity of CAR, suggesting that differences might exist in the response to CAR-mediated gene activation between different sexes. In this study, we have analyzed the response of female and male CD-1 mice to stimulation of hepatocyte proliferation caused by the CAR ligand TCPOBOP. Results showed that the labelling index of female hepatocytes at 24, 30 and 36 h after treatment was much higher than that found in males. The higher proliferative activity of female hepatocytes was associated with increased hepatic levels of cyclin D1, cyclin A, E2F and enhanced phosphorylation of pRb and p107. The increased mitogenic response of females was associated with higher mRNA levels of CYP2B10, a known target of CAR. Administration of androstenol to TCPOBOP-treated mice caused a reduction of labelling index, which was accompanied by a decrease of CYP2B10 and CAR mRNA levels. In conclusion, the results show that, in addition to microsomal detoxification, another biological response elicited by the CAR ligand TCPOBOP, namely, hepatocyte proliferation, occurs at higher levels in female than male mice, suggesting that CAR transcriptional activity in males is partially counteracted by physiological higher levels of testosterone metabolites such as androstenol and androstenol. 

Retracted: No

PubPeer comments:
null, 
 #1 Figure 8. 2 lanes much more similar than expected. Figure 5 and 8. Much more similar than expected. https: imgur.com cxqFZwS ,
MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB
Authors: Jia Xu
Yangyang Li
Xiaoming Lu
Jian Zhang
Jiale Zhang
Jie Zhang
Journal: Cancer Cell International (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Glioma; NFIB; Proliferation; miR-346.
Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 Jiangsu China.

Abstract:  Background: Glioma is considered one of the most common tumors and has a poor prognosis. Recently, microRNAs (miRNAs) have been reported to be strongly linked to various human tumors including glioma. In this study, we investigated a new anticancer miRNA, miR-346, to determine the effects and mechanism of miR-346 and its downstream target gene NFIB on tumors. Methods: Lentivirus transfection, real-time PCR, western blotting, immunohistochemistry, cell proliferation assays, and mouse experiments were used to examine the relationship between miR-346 and its regulation of NFIB in glioma cells. Results: The expression of miR-346 was downregulated in glioma cells. Overexpression of miR-346 arrested the cell cycle of glioma cells and inhibited their proliferation in vitro and in vivo. NFIB was a direct target of miR-346, whose expression was reduced by the miRNA. Overexpression of NFIB reversed all tested functions of miR-346. Conclusion: miR-346 inhibited the growth of glioma cells by targeting NFIB and may be a new prognostic and diagnostic biomarker for glioma. 

Retracted: No

PubPeer comments:
 Figure 2C appears to have a repeated image. *** ![file] , 
 #1 The Figure also contains a pair of different DAPI-stain images where the blue contribution to the Merged panel *should* be a duplication. ![file] ,