PReD-Bench/PRed-Bench huggingface dataset:
Filamin-A and Myosin VI colocalize with fibrillary Tau protein in Alzheimer's disease and FTDP-17 brains
Authors: Annie Laquerriere
Dominique Campion
Thierry Frébourg
Charles Duyckaerts
Vincent Deramecourt
Luc Buée
Sébastien Feuillette
Magalie Lecourtois
Claude-Alain Maurage
David Blum
Marie-Bernadette Delisle
Journal: Brain Research (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Tauopathies; Alzheimer's disease; fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17); Pick's disease; progressive supranuclear palsy
Affiliations: Inserm U614, Institute for Biomedical Research, Faculty of Medicine, University of Rouen, Rouen, France.

Abstract:  Tauopathies, including Alzheimer's disease (AD), fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Pick's disease and progressive supranuclear palsy, are neurodegenerative disorders neuropathologically characterized by the presence of intraneuronal fibrillary inclusions composed of abnormally phosphorylated-Tau. Tau protein is a neuronal microtubule-associated protein (MAP) involved in microtubules polymerization and stabilization. So far, the molecular mechanisms underlying Tau-mediated cellular toxicity remain elusive. To address the determinants of Tau neurotoxicity, we previously performed a misexpression screening in a Drosophila tauopathy model to identify genetic modifiers of the human Tau-induced neurodegeneration. We identified several components of the actin network as modifiers of Tau V337M-induced neurodegeneration, i.e. Filamin-A, Myosin VI, Paxillin and Transgelin-3. The aim of this study was to assess whether these genetic interactions were associated with a colocalization of the proteins (i) in the brains of patients with Tau pathologies, and (ii) in the brain of transgenic mice overexpressing human mutant Tau. We found that Filamin-A and Myosin VI indeed colocalize with fibrillary Tau protein in AD and FTDP-17 and in Thy-Tau22 transgenic mice. 

Retracted: No

PubPeer comments:
 Figures 1 and 3: * Red boxes: Two fluorescence panels look remarkably similar. Both represent  PiD but should be displaying the profiles of a different cell, as well as a different signal combination (filamin-A vs myosin VI) ![file] ,
An optimized CRISPR/Cas9 approach for precise genome editing in neurons
Authors: Richard L Huganir
Richard C Johnson
Richard H Roth
Alexei M Bygrave
Huaqiang Fang
Journal: eLife (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: AMPA receptor; CRISPR/Cas9; NMDA receptor; endogenous protein tagging; genome editing
Affiliations: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States, Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, United States, PKU-Nanjing Institute of Translational Medicine, Nanjing, China, Research Unit of Mitochondria in Brain Diseases, Chinese Academy of Medical Sciences, Nanjing, China

Abstract:  The efficient knock-in of large DNA fragments to label endogenous proteins remains especially challenging in non-dividing cells such as neurons. We developed Targeted Knock-In with Two (TKIT) guides as a novel CRISPR/Cas9 based approach for efficient, and precise, genomic knock-in. Through targeting non-coding regions TKIT is resistant to INDEL mutations. We demonstrate TKIT labeling of endogenous synaptic proteins with various tags, with efficiencies up to 42% in mouse primary cultured neurons. Utilizing in utero electroporation or viral injections in mice TKIT can label AMPAR subunits with Super Ecliptic pHluorin, enabling visualization of endogenous AMPARs in vivo using two-photon microscopy. We further use TKIT to assess the mobility of endogenous AMPARs using fluorescence recovery after photobleaching. Finally, we show that TKIT can be used to tag AMPARs in rat neurons, demonstrating precise genome editing in another model organism and highlighting the broad potential of TKIT as a method to visualize endogenous proteins. 

Retracted: No

PubPeer comments:
 In Fig. 2-supplement 6D ![file] the authors correlate two different methods for labelling knocked-in glutamate receptors. Spine measurements are nested within neurones. The source data do not distinguish the neurones, so it is likely that the potential loss of independence of spine measurements from the same neurone is not taken into account when performing the regression and, more importantly, when calculating the p-value; a form of pseudoreplication. ,
Long noncoding RNA MIAT acts as an oncogene in Wilms' tumor through regulation of DGCR8
Authors: C-Y Dong
C Zhang
N Tao
X-S Zhao
C-M Gong
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNAs; MIAT; Wilms' tumor; RT-qPCR; cell proliferation
Affiliations: Department of Pediatric Surgery, The First Hospital of Jilin University, Changchun, China. .

Abstract:  Objective: Recent researches have proved that long noncoding RNAs (lncRNAs) cover an important role in malignant tumors. Our study showed how lncRNA myocardial infarction-associated transcript (MIAT) functions in the development of Wilms' tumor. Patients and methods: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect the MIAT expression in Wilms' tumor patients. The MIAT expression level and the patients' overall survival time were analyzed. Then, we conducted functional experiments to identify the changes in the biological behaviors of Wilms' tumor cells due to the loss of MIAT. Moreover, further experiments were performed to explore the potential mechanism. Results: By comparing with MIAT expression in adjacent tissues, the MIAT expression level was significantly higher in Wilms' tumor samples. Moreover, the cell growth ability of Wilms' tumor cells was inhibited due to the loss of MIAT. The migrated and invaded ability of the Wilms' tumor cells was inhibited due to the loss of MIAT. Furthermore, the expression of DGCR8 was downregulated due to the loss of MIAT. In addition, it was found that the DGCR8 expression was positively correlated to MIAT expression in Wilms' tumor tissues. Conclusions: The above results suggested that MIAT could promote the cell proliferation and the metastasis of Wilms' tumor by upregulating DGCR8, which indicated that MIAT might be a potential target for the diagnosis and therapy of Wilms' tumor. 

Retracted: Yes

PubPeer comments:
 Fig 5A.  Western blot analysis for AR, HIF2u03b1, VEGF, CCND1 and MMP9 of total lysates of SW-839 cells with sh-AR and scr control; OSRC-2 and ACHN cells with over-expressed AR (OE-AR) and Vector (Vec) with GAPDH used to determine equal loading. ![file] Two slices appear to be the same. An error during figure assembly, perhaps? Could the authors check? , 
 It would be good if the authors could also check Figs 5A and 5C. ![file] , 
 The confusion seems to extend to Figure 6E, although the images seem differently colored, the two images appear to overlap. *** ![file] This work was supported by NIH grants (CA155477 and CA156700), George Whipple Professorship Endowment and Taiwan Department of Health Clinical Trial, Research Center of Excellence (DOH99- TD-B-111-004 to China Medical University, Taichung, Taiwan) and The National High Technology Research and Development Program of China (863 Program, NO. SS2014AA020607). ,
Accumulated cytotoxicity of CDK inhibitor dinaciclib with first-line chemotherapy drugs in salivary adenoid cystic carcinoma cells
Authors: Lingzhi Li
Wenping Cai
Shangfeng Liu
Shouliang Zhao
Jun Zhang
Laijun Xu
Journal: Odontology (2020)
Discipline: CLINICAL MEDICINE
Keywords: Apoptosis; Chemotherapy; Dinaciclib; Proliferating; Salivary adenoid cystic carcinoma.
Affiliations: Department of Stomatology, Huashan Hospital, Fudan University, 12 Urumqi Road, Shanghai, 200040, People's Republic of China., Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China., Department of Stomatology, Huashan Hospital, Fudan University, 12 Urumqi Road, Shanghai, 200040, People's Republic of China. ., Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, No. 2, Tianjing Road, Shanghai, 200001, People's Republic of China. .

Abstract:  Adenoid cystic carcinoma (ACC) is one of the most common salivary gland malignant tumors. Its treatment failure is partly due to the limitations of chemotherapeutic agents and their adverse effects. The objective of this study was to determine the potential additive anti-cancer effect of a novel CDK inhibitor dinaciclib with first-line chemotherapy drugs in ACC. Protein expression of phosphorylated CDK2 (p-CDK2) in paraffin-embedded tissue specimens of ACC from 17 patients was investigated by immunohistochemistry (IHC). Cell Counting Kit (CCK-8), clone formation assay, and flow cytometry were used to test the proliferation and apoptosis of ACC-2 cells treated with dinaciclib with or without other first-line chemotherapy drugs. Protein expression was also determined by Western blot. Interestingly, we discovered that p-CDK2 protein was expressed in both cytoplasmic and nucleus in salivary ACC tissues, which was higher than that in normal salivary tissues, indicating that agents targeting CDK2 may be potential therapeutic strategies against this type of tumor. As expected, CDK inhibitor dinaciclib significantly induced ACC-2 cells apoptosis. Moreover, it sensitized cells to the chemotherapeutic agents such as cisplatin, pemetrexed, and etoposide (VP-16), and this effect by dinaciclib may induce cell cycle arrest via abrogating CDK2 activity. Therefore, combinational therapy of CDK inhibitor dinaciclib with first-line chemotherapy drugs may be a promising strategy in the treatment of salivary ACC. 

Retracted: No

PubPeer comments:
 The cell line used in this papert is ACC-2. It is used as a model of salivary adenoid cystic carcinoma (ACC). But it is widely known since 2009 that it is a HeLa contaminated cell line. Thus all conclusions of this paper has applied to adenoid cystic carcinoma are irrelevant. See: * [The relevant Cellosaurus entry] * The article showing that the cell line is contaminated: [PMID:19557180] ,
Long noncoding RNA GAS5 regulates the proliferation, migration, and invasion of glioma cells by negatively regulating miR-18a-5p
Authors: Shanquan Sun
Qian Liu
Juan Huang
Ke Cheng
Hong Xu
Xuan Long
Yalan Lv
Kejian Wang
Shujuan Zhu
Wei Yu
Lan Ma
Journal: Journal of Cellular Physiology (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: human glioma cells; lncRNA GAS5; miR-18a-5p.
Affiliations: Department of Anatomy, Institute of Neuroscience, Chongqing Medical University, Chongqing, China., Department of Epidemiology, School of Public Health and Management, Chongqing Medical University, Chongqing, China., Department of Medical Information Management and Decision Making, School of Medical Informatics, Chongqing Medical University, Chongqing, China., Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China.

Abstract:  Intention: Long noncoding RNAs, transcribed from a recently discovered class of noncoding genes, may play a critical role in regulating cellular processes, such as cell proliferation and apoptosis, as well as in cancer progression and metastasis. We previously detected the induction of growth arrest-specific 5 (GAS5) during glioma cell death. However, the function and underlying mechanism of GAS5 in human gliomas remain to be elucidated. Methods: Cell proliferation was detected using CellTiter 96® AQueous Non-Radioactive Cell Proliferation Assay (MTS) and tumorigenicity assay in nude mice. Wound-healing assay and transwell assay were utilized to examine the effects of GAS5 expression on glioma cells migration and invasion. In situ hybridization (ISH) was performed to evaluate GAS5 and microRNA (miR)-18a-5p levels in tissue microarrays. The relationship between GAS5 and miR-18a-5p was evaluated by quantitative reverse-transcription polymerase chain reaction and RNA precipitation. Results: In this study, we demonstrated that overexpression of GAS5 inhibits malignant phenotypes in glioma cells, including proliferation, migration, and invasion, whereas GAS5 knockdown enhances these phenotypes. We further observed Argonaute 2-dependent reciprocal repression between GAS5 and miR-18a-5p in glioma cells. Downregulation of GAS5 and upregulation of miR-18a-5p were observed in glioma tissue microarrays relative to normal brain tissue by ISH. By deletion analysis, we identified one miR-18a-5p-binding site within exon 2 of GAS5 that is partially responsible for the tumor-suppressor functions of GAS5. Conclusion: Taken together, our findings suggest that GAS5 is a tumor suppressor in human gliomas that acts in part by repressing miR-18a-5p. 

Retracted: No

PubPeer comments:
 Figure 4 appears to have an overlapping image ![file] ,
Rescue of MHC-1 antigen processing machinery by down-regulation in expression of IGF-1 in human glioblastoma cells
Authors: Donald D Anthony
Yajun Guo
Jerzy Trojan
Yuexin Pan
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: immune recognition; carcinogenesis; MHC class 1; antigen processing; TAP-1
Affiliations: Division of General Medical Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.

Abstract:  Escape from immune recognition has been hypothesized to be a factor in carcinogenesis. It may be mediated for many cancers through down-regulation in the MHC class 1 antigen processing and presentation pathway. TAP-1, TAP-2, tightly linked to LMP-2 and LMP-7 are multiple components of the endogenous, antigen presentation pathway machinery. We addressed the question of alterations in this pathway in human Glioblastoma (HGB) and of its relationship to modulation in expression of IGF-1 that is highly expressed in this cancer. Deficiencies in expression of TAP-1 were demonstrated by RT-PCR and/or by immuno-flow cytometry in the HGB cell line T98G obtained from ATCC, and in 3 of 4 human cell lines established from patients with Glioblastoma Multiforme. Deficiencies in expression of TAP-2 were observed in 3 of 4, deficiencies in expression of LMP-2 in 4 of 4 and deficiencies in LMP-7 in 3 of 4 HGB cell lines examined by RT-PCR and Western blot. Following down-regulation of IGF-1 by transfection with the pAnti IGF-1 vector that expresses IGF-1 RNA in antisense orientation, or by the exogenous addition of IGF-1 receptor monoclonal antibody to cell culture media, the deficiencies in components of the MHC-1 antigen presentation pathway were up-regulated and/or rescued in all HGB cell lines tested. Moreover, this up-regulation in expression was aborted by addition of 100 ng/ml of IGF-1 to the culture media. Unlike in the case of IFN-γ, the restoration of TAP-1 and LMP-2 by down-regulation of IGF-1 in Glioblastoma cells was not correlated to the tyrosine phosphorylation of STAT 1. In summary, the simultaneous reversion in expression of the multiple constituents of MHC-1 antigen processing path and up-regulation in expression of MHC-1 occurring with down-regulation in IGF-1 may have a role in reinforcement of immunity against tumor antigen(s) in some animal cancers and in humans with Glioblastoma Multiforme. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: Panel A looks unexpectedly similar to panel C. Reported to the journal in September 2014, but no action as of today. ![file] ,
Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells into the Testes of Infertile Male Rats and New Germ Cell Formation
Authors: Mohamadreza Baghaban Eslaminejad
Foroughazam Sayahpour
Roozali Batavani
Mohammad Ghasemzadeh-Hasankolaei
Journal: International Journal of Stem Cells (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Autologous; Bone marrow mesenchymal stem cells; Germ cells; Infertile male rats; Testis
Affiliations: Infertility and Reproductive Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran., Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran., Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Abstract:  Background: Mesenchymal stem cells (MSCs), have been suggested as a potential choice for treatment of male infertility. Yet, the effects of MSCs on regeneration of germinal epithelium of seminiferous tubules and recovery of spermatogenesis have remained controversial. In this research, we have evaluated and compared the fate of autologous bone marrow (BM)-MSCs during three different periods of time- 4, 6 and 8 weeks after transplantation into the testes of busulfan-induced infertile male rats. Methods: Rats BM samples were collected from tibia bone under anesthesia. The samples were directly cultured in culture medium. Isolated, characterized and purified BM-MSCs were labeled with PKH26, and transplanted into the testes of infertile rats. After 4, 6 and 8 weeks, the testes were removed and underwent histological evaluations. Results: Immunohistochemical analysis showed that transplanted BM-MSCs survived in all three groups. Some of the cells homed at the germinal epithelium and expressed spermatogonia markers (Dazl and Stella). The number of homed spermatogonia-like cells in 4-week testes, was more than the 6-week testes. The 8-week testes had the least numbers of homed cells (p&lt;0.05). Immunostaining for vimentin showed that BM-MSCs did not differentiate into the sertoli cells in the testes. Conclusions: From our results, it could be concluded that, autologous BM-MSCs could survive in the testis, migrate onto the seminiferous tubules basement membrane and differentiate into spermatogonia. Although, no more differentiation was observed in the produced spermatogonia, generation of such endogenous GCs would be a really promising achievement for treatment of male infertility using autologous stem cells. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have two sets of repeated images. It is not clear to me that this should be the case. Could the authors please comment? *** Contrast enhanced ![file] *** Full figure ![file] ,
LncRNA CDKN2B-AS1 promotes tumor growth and metastasis of human hepatocellular carcinoma by targeting let-7c-5p/NAP1L1 axis
Authors: Yu Wang
Yuqi Huang
Yuanhua Liu
Bo Xiang
Heping Kan
Journal: Cancer Letters (2018)
Discipline: CLINICAL MEDICINE
Keywords: CDKN2B antisense RNA 1; Liver cancer; Long non-coding RNA; Nucleosome assembly protein 1 like 1; Tumor progression.
Affiliations: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Ave, Guangzhou, Guangdong Province, 510515, China. Electronic address: .

Abstract:  Long non-coding RNAs (lncRNAs) show great potential as therapeutic targets in many diseases including hepatocellular carcinoma (HCC). Here, we aimed to investigate the clinical significance and function of lncRNA CDKN2B antisense RNA 1 (CDKN2B-AS1) in HCC. Here, we identified a novel oncogenic lncRNA CDKN2B-AS1, which was highly expressed in HCC and positively associated with large tumor size, microvascular invasion, high tumor grade, advanced tumor stage and reduced survival of HCC patients. CDKN2B-AS1 knockdown inhibited cell proliferation, migration and invasion, and induced G1 arrest and apoptosis of HCC cells in vitro, and CDKN2B-AS1 silencing suppressed tumor growth and metastasis of HCC in vivo. In accordance, CDKN2B-AS1 overexpression accelerated HCC cell growth and metastasis. Mechanistically, CDKN2B-AS1 promoted nucleosome assembly protein 1 like 1 (NAP1L1) expression by sponging let-7c-5p, thereby activated PI3K/AKT/mTOR signaling in HCC cells. Notably, NAP1L1 restoration abolished the effects of CDKN2B-AS1 silencing on HCC cell growth and metastasis. CDKN2B-AS1, an oncogenic lncRNA of HCC, promoted NAP1L1-mediated PI3K/AKT/mTOR signaling by acting as a molecular sponge of let-7c-5p. Our findings indicate that CDKN2B-AS1 may be a potential prognostic biomarker and a candidate target for HCC therapy. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
null, 
null, 
null, 
null, 
 2020 retraction. https: www.liebertpub.com doi 10.1089 ten.tea.2010.0385.retract Dr. Charles A. Vacanti, the senior author of the article entitled, u201cThe Potential of Stem Cells in Adult Tissues Representative of the Three Germ Layers,u201d (vol. 17, nos. 5 6, pages 607u2013615), published in the March 2011 issue of Tissue Engineering: Part A contacted the Journal to request a formal retraction of the article following an investigation by a Harvard Medical School Committee on Scientific Integrity evaluating a published erratum of the original work presented. The reader is directed to the published correction notice to the article in 2014.1 While the authors maintained that the published erratum was accurate, the committee could not validate the accuracy of the corrections. Consequently, the authors agreed to request a formal retraction. Tissue Engineering, its editors, and its publisher are committed to upholding the strictest standards of the scientific record and the community it serves. ,
A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box–binding protein-1 to modulate the unfolded protein response
Authors: Jeremie Boucher
Marcelo A Mori
Jonathon N Winnay
C Ronald Kahn
Kohjiro Ueki
Journal: Nature Medicine (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PI3K; p85alphaalpha; X-box-binding protein-1; unfolded protein response; ER stress

Abstract:  Class Ia phosphoinositide 3-kinase (PI3K), an essential mediator of the metabolic actions of insulin, is composed of a catalytic (p110alpha or p110beta) and regulatory (p85alphaalpha, p85betaalpha or p55alpha) subunit. Here we show that p85alphaalpha interacts with X-box-binding protein-1 (XBP-1), a transcriptional mediator of the unfolded protein response (UPR), in an endoplasmic reticulum (ER) stress-dependent manner. Cell lines with knockout or knockdown of p85alphaalpha show marked alterations in the UPR, including reduced ER stress-dependent accumulation of nuclear XBP-1, decreased induction of UPR target genes and increased rates of apoptosis. This is associated with a decreased activation of inositol-requiring protein-1alpha (IRE1alpha) and activating transcription factor-6alphaalpha (ATF6alpha). Mice with deletion of p85alpha in liver (L-Pik3r1(-/-)) show a similar attenuated UPR after tunicamycin administration, leading to an increased inflammatory response. Thus, p85alphaalpha forms a previously unrecognized link between the PI3K pathway, which is central to insulin action, and the regulation of the cellular response to ER stress, a state that when unresolved leads to insulin resistance. 

Retracted: No

PubPeer comments:
 Fig. 1: More similar than expected. Different conditions ![file] Supplemental Fig. 6: More similar than expected. ![file] , 
 #1 Shouldn t that be figure 2 instead of figure 1? , 
 #2 Yes, that should be figure 2 instead of figure 1. ,
IRAK-M Is a Negative Regulator of Toll-like Receptor Signaling
Authors: Koichi Kobayashi
Jorge E Galán
Richard A Flavell
Ruslan Medzhitov
Lorraine D Hernandez
Charles A Janeway Jr
Journal: Cell (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Toll-like receptors; TLRs; MyD88; IRAK; IRAK-4

Abstract:  Toll-like receptors (TLRs) detect microorganisms and protect multicellular organisms from infection. TLRs transduce their signals through MyD88 and the serine/threonine kinase IRAK. The IRAK family consists of two active kinases, IRAK and IRAK-4, and two inactive kinases, IRAK-2 and IRAK-M. IRAK-M expression is restricted to monocytes/macrophages, whereas other IRAKs are ubiquitous. We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. IRAK-M(-/-) cells exhibited increased cytokine production upon TLR/IL-1 stimulation and bacterial challenge, and IRAK-M(-/-) mice showed increased inflammatory responses to bacterial infection. Endotoxin tolerance, a protection mechanism against endotoxin shock, was significantly reduced in IRAK-M(-/-) cells. Thus, IRAK-M regulates TLR signaling and innate immune homeostasis. 

Retracted: No

PubPeer comments:
 Figure 4C. Much more similar than expected. https: imgur.com sCDkdua ,
Transgenically expressed rice germin-like protein1 in tobacco causes hyper-accumulation of H2O2 and reinforcement of the cell wall components
Authors: Prabuddha Dey
Mrinal K Maiti
Joydeep Banerjee
Natasha Das
Journal: Biochemical and Biophysical Research Communications (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: rice; germin-like protein1; OsGLP1; superoxide dismutase; SOD activity
Affiliations: Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, India.

Abstract:  Our recent report documented that the rice germin-like protein1 (OsGLP1), being a cell wall-associated protein involves in disease resistance in rice and possesses superoxide dismutase (SOD) activity as recognized by heterologous expression in tobacco. In the present study, the transgenic tobacco plants were analyzed further to decipher the detailed physiological and biochemical functions of the OsGLP1 and its associated SOD activity. The transgenic tobacco lines expressing SOD-active OsGLP1 showed tolerance against biotic and abiotic stresses mitigated by hyper-accumulating H(2)O(2) upon infection by fungal pathogen (Fusarium solani) and treatment to chemical oxidizing agent (ammonium persulfate), respectively. Histological staining revealed enhanced cross-linking of the cell wall components in the stem tissues of the transgenic plants. Fourier transform infrared spectroscopy (FTIR) analysis of the biopolymer from the stem tissues of the transgenic and untransformed plants revealed differential banding pattern of the spectra corresponding to various functional groups. Our findings demonstrate that the OsGLP1 with its inherent SOD activity is responsible for hyper-accumulation of H(2)O(2) and reinforcement of the cell wall components. 

Retracted: No

PubPeer comments:
 Figure 2A. There appears to have an overlap in two images. Could the authors please check? ![file] ,
Measuring Energy Metabolism in the Mouse – Theoretical, Practical, and Analytical Considerations
Authors: John R Speakman
Journal: Frontiers in physiology (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: basal metabolic rate; energy balance; energy expenditure; energy metabolism; indirect calorimetry
Affiliations: Key State Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences Beijing, China ; Institute of Biological and Environmental Sciences, University of Aberdeen Aberdeen, Scotland, UK.

Abstract:  The mouse is one of the most important model organisms for understanding human genetic function and disease. This includes characterization of the factors that influence energy expenditure and dysregulation of energy balance leading to obesity and its sequelae. Measuring energy metabolism in the mouse presents a challenge because the animals are small, and in this respect it presents similar challenges to measuring energy demands in many other species of small mammal. This paper considers some theoretical, practical, and analytical considerations to be considered when measuring energy expenditure in mice. Theoretically total daily energy expenditure is comprised of several different components: basal or resting expenditure, physical activity, thermoregulation, and the thermic effect of food. Energy expenditure in mice is normally measured using open flow indirect calorimetry apparatus. Two types of system are available - one of which involves a single small Spartan chamber linked to a single analyzer, which is ideal for measuring the individual components of energy demand. The other type of system involves a large chamber which mimics the home cage environment and is generally configured with several chambers/analyzer. These latter systems are ideal for measuring total daily energy expenditure but at present do not allow accurate decomposition of the total expenditure into its components. The greatest analytical challenge for mouse expenditure data is how to account for body size differences between individuals. This has been a matter of some discussion for at least 120 years. The statistically most appropriate approach is to use analysis of covariance with individual aspects of body composition as independent predictors. 

Retracted: No

PubPeer comments:
 Image duplication self plagiarism from [doi.org 10.1038 nmeth.1806](doi.org 10.1038 nmeth.1806) ![file] , 
 Thanks for your comment. You are correct I wrote this text and drew the figure and it was published in two places. The second instance was a review paper that includes many figures form previous work, some of which are mine and others not. In all these other figures I included the reference to the original source but for the figure in question I forgot to include the details of the original source of the figure. Sorry for that. I hope that it helped you to understand how to analyse mouse data in the correct way. If you have any problems following the method then do get in touch at j.speakman@abdn.ac.uk ,
Dickkopf-1-promoted vasculogenic mimicry in non-small cell lung cancer is associated with EMT and development of a cancer stem-like cell phenotype
Authors: Fang Liu
Yong Wang
Xueming Zhao
Jie Meng
Danfang Zhang
Qiang Gu
Na Che
Baocun Sun
Yanrong Liu
Yanhui Zhang
Lingli Yao
Xiulan Zhao
Yanjun Zheng
Journal: Journal of Cellular and Molecular Medicine (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DKK1; cancer stem-like cell; epithelial-mesenchymal transition; non-small cell lung cancer; vasculogenic mimicry.
Affiliations: Department of Pathology, Tianjin Medical University, Tianjin, China., Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin, China., Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China.

Abstract:  To characterize the contributions of Dickkopf-1 (DKK1) towards the induction of vasculogenic mimicry (VM) in non-small cell lung cancer (NSCLC), we evaluated cohorts of primary tumours, performed in vitro functional studies and generated xenograft mouse models. Vasculogenic mimicry was observed in 28 of 205 NSCLC tumours, while DKK1 was detected in 133 cases. Notably, DKK1 was positively associated with VM. Statistical analysis showed that VM and DKK1 were both related to aggressive clinical course and thus were indicators of a poor prognosis. Moreover, expression of epithelial-mesenchymal transition (EMT)-related proteins (vimentin, Slug, and Twist), cancer stem-like cell (CSC)-related proteins (nestin and CD44), VM-related proteins (MMP2, MMP9, and vascular endothelial-cadherin), and β-catenin-nu were all elevated in VM-positive and DKK1-positive tumours, whereas the epithelial marker (E-cadherin) was reduced in the VM-positive and DKK1-positive groups. Non-small cell lung cancer cell lines with overexpressed or silenced DKK1 highlighted its role in the restoration of mesenchymal phenotypes and development of CSC characteristics. Moreover, DKK1 significantly promotes NSCLC tumour cells to migrate, invade and proliferate. In vivo animal studies demonstrated that DKK1 enhances the growth of transplanted human tumours cells, as well as increased VM formation, mesenthymal phenotypes and CSC properties. Our results suggest that DKK1 can promote VM formation via induction of the expression of EMT and CSC-related proteins. As such, we feel that DKK1 may represent a novel target of NSCLC therapy. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have an image duplication ![file]  Immunofluorescence analysis showed changes in u03b2u2010catenin, Eu2010cadherin and vimentin expressions between transfection and control groups (u00d7400).  HT: H460 transfaected with a pcDNA3.1u2010DKK1 vector; HC: H460 cells transfected with an empty vector. ,
MiR-30e-5p inhibits the migration and invasion of nasopharyngeal carcinoma via regulating the expression of MTA1
Authors: Weiqun Hu
Li Chen
Wenfeng Yao
Haolin Li
Journal: Bioscience Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Invasion; MTA1; MiR-30e-5p; Migration; Nasopharyngeal carcinoma.
Affiliations: Department of Otorhinolaryngology, The Affiliated Hospital of Putian University, China, Department of Otorhinolaryngology, Xinxiang First People’s Hospital, China, Department of Otorhinolaryngology, Zaozhuang Municipal Hospital, China

Abstract:  The study explored the effect of miR-30e-5p on nasopharyngeal carcinoma (NPC). MiR-30e-5p levels in NPC cancer and adjacent normal samples, in metastatic and non-metastatic cancer samples of NPC, and in NP69 cell and five NPC cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between miR-30e-5p and MTA1 was confirmed by dual-luciferase reporter assay, Western blot and qRT-PCR. The viability, migration and invasion of 5-8F and 6-10B cells were determined by CCK-8, scratch test and transwell assays, respectively. The levels of migration-related proteins (vimentin and Snail) and invasion-related proteins (MMP2 and MMP3) in NPC cells were detected by Western blot. The results showed that low expression of miR-30e-5p was associated with HNSC cancer, NPC, metastasis of NPC and NPC cell lines. Overexpressed miR-30e-5p in HNSC cancer and NPC was predictive of a better prognosis of patients. In addition, the viability, migration and invasion were reduced by up-regulating miR-30e-5p in 5-8F cells, but promoted by down-regulated miR-30e-5p in 6-10B cells. MiR-30e-5p reversed the migration and invasion of NPC cells regulated by MTA1, and inhibited migration and invasion of NPC cells via regulating MTA1 expression. 

Retracted: No

PubPeer comments:
  Six-two NPC and adjacent normal samples were obtained from the Affiliated Hospital of Putian University between **02 14 2017 and 02 14 2019** . Fig 1:  (F) The relationship between miR-30e-5p expression and overall survival of NPC patients was analyzed by Kaplanu2013Meier. (G) The relationship between miR-330e expression and disease-free survival of NPC patients was analyzed by Kaplanu2013Meier. ![file] When this paper was submitted to the journal on 12 Dec 2019, the authors had followed the patients survival for five years, i.e. through to the date range **Feb 2022 to Feb 2024**. Am I missing something? , 
 April 7, 2021 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 While the journal s investigation proceeds, is it possible for the authors to upload or link to scans of the original blots for their curiously stylised string-of-sausages Western Blots? ![file] ,
Combinatorial effects of lapatinib and rapamycin in triple-negative breast cancer cells
Authors: Mourad Tighiouart
Ruth M O&#x27;Regan
Tisheeka R Graham
Shi-Yong Sun
Christine Lobo
Ryan Dolan
Lily Yang
Amy Adams
Rami Yacoub
LaTonia D Taliaferro-Smith
Tongrui Liu
Journal: Molecular Cancer Therapeutics (2011)
Discipline: CLINICAL MEDICINE
Keywords: Triple-negative breast cancers; African Americans; therapeutic targets; Epidermal growth factor receptor (EGFR); mTOR inhibition
Affiliations: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Abstract:  Triple-negative breast cancers, which lack estrogen receptor, progesterone receptor, and HER2/neu overexpression, account for approximately 15% of breast cancers, but occur more commonly in African Americans. The poor survival outcomes seen with triple-negative breast cancers patients are, in part, due to a lack of therapeutic targets. Epidermal growth factor receptor (EGFR) is overexpressed in 50% of triple-negative breast cancers, but EGFR inhibitors have not been effective in patients with metastatic breast cancers. However, mTOR inhibition has been shown to reverse resistance to EGFR inhibitors. We examined the combination effects of mTOR inhibition with EGFR inhibition in triple-negative breast cancer in vitro and in vivo. The combination of EGFR inhibition by using lapatinib and mTOR inhibition with rapamycin resulted in significantly greater cytotoxicity than the single agents alone and these effects were synergistic in vitro. The combination of rapamycin and lapatinib significantly decreased growth of triple-negative breast cancers in vivo compared with either agent alone. EGFR inhibition abrogated the expression of rapamycin-induced activated Akt in triple-negative breast cancer cells in vitro. The combination of EGFR and mTOR inhibition resulted in increased apoptosis in some, but not all, triple-negative cell lines, and these apoptotic effects correlated with a decrease in activated eukaryotic translation initiation factor (eIF4E). These results suggest that mTOR inhibitors could sensitize a subset of triple-negative breast cancers to EGFR inhibitors. Given the paucity of effective targeted agents in triple-negative breast cancers, these results warrant further evaluation. 

Retracted: No

PubPeer comments:
 Two images in figure 5 appear to overlap, with different magnification and descriptions. *** ![file] *** Full figure and caption ![file] ,
Phorbol ester treatment of K562 cells regulates the transcriptional activity of AML1c through phosphorylation
Authors: Youhong Zhang
Andrew S Kraft
Joseph R Biggs
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: phorbol ester; K562 cells; AML1 transcription factor; phosphorylation; transcriptional activity
Affiliations: Hollings Cancer Center, the Medical University of South Carolina, 86 Jonathan Lucas St., Charleston, SC 29425, USA.

Abstract:  We find that phorbol ester (PE) treatment of K562 cells greatly stimulates promoters (T cell receptor beta, myeloperoxidase, macrophage colony-stimulating factor receptor, and granulocyte macrophage colony-stimulating factor receptor) containing AML1 transcription factor binding sites. This stimulation of AML1c transcriptional activity is mediated by direct phosphorylation of the AML1c molecule on multiple phosphorylation sites. Eleven AML1c (S/T)P sites in the transcriptional activating domain are phosphorylated at a basal level in untreated K562 cells; treatment of the K562 cells with PE results in increased phosphorylation at five of these sites (serines 276, 293, 303, 462, and threonine 300). Mutation of these five sites to alanine inhibits PE-induced transcriptional activity; mutation of the sites to an acidic amino acid, aspartic acid, stimulates constitutive activity. Single mutations in four amino acids or double mutations (serines 276 and 293 or threonine 300 and serine 303) have little effect on AML1c transcriptional activity. Inhibitor assays suggest that the ERK family of protein kinases is activated by PEs to phosphorylate the (S/T)P sites within the AML1c molecule and markedly enhance the transcriptional activity of AML1c. 

Retracted: No

PubPeer comments:
 ![file] ,
DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation
Authors: Adam Antebi
Moritz Horn
Corinna Klein
Ben Becker
Michele Pagano
Christoph Geisen
Shuhei Nakamura
Lukas Cermak
Journal: Developmental cell (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Developmental timing genes; stem cell progression; animal maturation programs; Caenorhabditis elegans; DRE-1/FBXO11
Affiliations: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, 50674 Cologne, Germany., Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany., Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA; Howard Hughes Medical Institute, Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA., Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, 50674 Cologne, Germany; Department of Molecular and Cellular Biology, Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: .

Abstract:  Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF(DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1. blmp-1 also opposed dre-1 for other life history traits, including entry into the dauer diapause and longevity. BLMP-1 protein was strikingly elevated upon dre-1 depletion and dysregulated in a stage- and tissue-specific manner. The role of DRE-1 in regulating BLMP-1 stability is evolutionary conserved, as we observed direct protein interaction and degradation function for worm and human counterparts. Taken together, posttranslational regulation of BLMP-1/BLIMP-1 by DRE-1/FBXO11 coordinates C. elegans developmental timing and other life history traits, suggesting that this two-protein module mediates metazoan maturation processes. 

Retracted: No

PubPeer comments:
 Figure 9. Much more similar than expected. https: imgur.com NCLGjL8 ,
Micro RNA -214,-150,-146a and-125b target Huntingtin gene
Authors: Mithun Sinha
Nitai P Bhattarcharyya
Jayeeta Ghose
Journal: RNA Biology (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: miRNA; Huntington's disease; HTT gene; neurodegenerative diseases; luciferase reporter vectors
Affiliations: Stuctural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India.

Abstract:  We observed earlier that expressions of several micro RNAs (miRNAs) are altered in a cell model of Huntington's disease (HD). As genes involved in different neurodegenerative diseases are targeted by miRNAs, we searched databases to find out whether Huntingtin gene (HTT), mutation to which causes HD, is a target of any miRNA. Among many miRNAs that are predicted to target HTT, we showed using various experimental approaches that miR-214, miR-150, miR-146a and miR-125b could target both human HTT and mouse Htt. Luciferase reporter vectors containing 3'-UTRs of mouse and human HTT showed reduction in relative luciferase activities on exogenous expression of cloned miRNAs. Loss of function studies with miRNA inhibitors led to the revival of luciferase activities of cloned 3'-UTR of HTT. Exogenous expression of these miRNAs reduced the expression of endogenous Htt in mouse cells. Expression of miRNAs with mutations at seed sequences neither reduced the reporter luciferase activities nor the endogenous expression of Htt. Taking together, we showed that miR-214, miR-150, miR-146a and miR-125b targeted HTT. Besides, the exogenous expression of wild type miRNAs reduced HTT aggregates formed by the recombinant exon1 of HTT gene that codes for 83Q tagged with 3'-UTR of Htt, as observed by filter retardation assay and confocal microscopy. In summary, regulation of HTT by miRNAs might provide a new mechanism for the modulation of HD. 

Retracted: No

PubPeer comments:
 ![file] ,
<p>The LncRNA XIRP2-AS1 predicts favorable prognosis in colon cancer</p>
Authors: Zhuojun Zheng
Feng Shen
Fengru Zhou
Jincheng Ruan
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: XIRP2-AS1; colon cancer; invasion; proliferation; survival.
Affiliations: Department of Anus and Intestine Surgery, The Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, People's Republic of China., Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, People's Republic of China.

Abstract:  Background: Colorectal cancer is a heterogeneous disease with complex genetic and epigenetic changes. LncRNA has recently been regarded as the biomarker in cancers. Novel biomarkers in colon cancer need to be identified. Purpose: The objective of this study was to identify the differentially expressed lncRNAs between colon cancer tissue and adjacent tissue, as well as to explore its biological functions. Patients and methods: There were 130 colon cancer patients included in this study. Of them, 6 colon cancer samples and 3 normal samples were selected for microarray profiling. Another 121 colon cancer samples with complete clinical information were used for immunohistochemical assay and survival analysis. Microarray analysis was performed to determine the differentially expressed lncRNAs between colon cancer tissue and adjacent tissue. Gain-of-function experiments was conducted in vitro and in vivo. In situ hybridization and survival analysis were applied to determine the prognostic impact on survival. Results: LncRNA XIRP2-AS1 was significantly less expressed in colon cancer tissue. XIRP2-AS1 was remarkably downregulated in colon cancer tissues and cell lines. Functionally, XIRP2-AS1 could inhibit the proliferation and invasion ability of colon cancer cells in vitro and in vivo. Clinical sample analysis showed that XIRP2-AS1 had a favorable impact on the overall survival and progression free survival of patients with colon cancer. miR-182 was validated as the target of XIRP2-AS1 according to luciferase reporter assays, RNA immunoprecipitation and RNA pull down. Conclusions: Our results suggested that XIRP2-AS1 may act as a favorable biomarker for patients with colon cancer. 

Retracted: No

PubPeer comments:
 In Figure 3A, a flow cytometry dot plot has been duplicated and presented as something else. In addition, the tumors presented in Figure 4A are also seen in a later publication (Shi Y et al. 2020; J Cellular Physiology), but manipulated and presented as something else. It is therefore difficult to trust this article. ![file] ,
Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid induces apoptosis and cell cycle arrest in CNE-2Z nasopharyngeal carcinoma cells
Authors: Jianfa Chen
Wende Li
Yi Liu
Yingnian Lv
Nian Ci Liang
Kefeng Wu
Liao Cui
Li Li
Journal: Oncology Reports (2013)
Discipline: CLINICAL MEDICINE
Keywords: Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid; Pteris semipinnata L.; cell proliferation; apoptosis; G2 phase
Affiliations: Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, and Department of General Surgery, 422 Hospital of PLA, Zhanjiang, Guangdong 524023, PR China.

Abstract:  Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), a compound isolated from Pteris semipinnata L. (PsL), inhibits cell proliferation and induces cell apoptosis in several cancer lines. We found that 5F induced apoptosis and G2 phase cell cycle arrest in the CNE-2Z nasopharyngeal carcinoma (NPC) cells, accompanied by a decrease of NF-κB expression. 5F suppressed the viability of CNE-2Z cells in a time- and dose-dependent manner. 5F induced G2/M phase cell cycle arrest, but did not induce p21. Further analysis revealed that CNE-2Z cells harbored two p53 mutations. 5F treatment resulted in mitochondrial apoptosis, associated with increased Bax/Bcl-2 ratio, upregulation of cytochrome c in the cytosol, decreased NF-κB-p65 and increased IκB. Of note, 5F significantly sensitized CNE-2Z cells to cisplatin. 5F did not increase ROS, but reduced ROS production alone or in combination with cisplatin. Our data suggest that 5F is a potential anti-NPC drug for the development of single agent therapy and therapy in combination with cisplatin. 

Retracted: No

PubPeer comments:
 Two images in figure 2A appear to overlap. *** ![file] ,