PReD-Bench/PRed-Bench huggingface dataset:
Steroids and Œ≤2-agonists regulate hyaluronan metabolism in asthmatic airway smooth muscle cells
Authors: Katrin Hostettler
Ioannis Klagas
Eleni Papakonstantinou
George Karakiulakis
Michael Tamm
Vassiliki Kotoula
Chong Teck S&#x27;ng
Michael Roth
Spasenija Savic
Journal: American Journal of Respiratory Cell and Molecular Biology (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Glycosaminoglycans; Hyaluronic acid; Airway smooth muscle cells; Asthma; Glucocorticoids
Affiliations: Department of Pharmacology, School of Medicine, Aristotle University, Thessaloniki, Greece.

Abstract:  Glycosaminoglycans (GAGs), especially hyaluronic acid (HA), regulate tissue flexibility, cell motility, and inflammation. Airway smooth muscle cells (ASMCs) of patients with asthma exhibit abnormal HA metabolism, which contributes to inflammation and remodeling. Here, we investigated the effects of glucocorticoids and long-acting Œ≤(2)-agonists (LABAs) on GAG synthesis and HA metabolism by human primary ASMCs. ASMCs were isolated from airway specimens of 10 patients without asthma and 11 patients with asthma. ASMCs were incubated with glucocorticoids, LABAs, or their combination, as well as with their specific receptor antagonists. Secreted and deposited total GAGs were measured by [(3)H]-glucosamine incorporation. The expression of specific GAGs was determined by ELISA and electrophoresis. The expression of HA synthases (HAS), of hyaluronidases (HYALs), and of the HA receptor CD44 was determined by RT-PCR, immunoblotting in cell cultures, and immunohistochemistry in tissue sections of asthmatic lungs. In serum-activated asthmatic ASMCs, glucocorticoids and LABAs significantly inhibited the increased secretion and deposition of total GAGs, but they stimulated secreted and deposited HA of high molecular mass. This effect was attributed to increased mRNA and protein expression of HAS-1 and to the reduced expression of HYAL-1. Furthermore, drug treatment stimulated the expression of CD44 receptors in asthmatic ASMCs. These effects of the drugs were eliminated by their respective receptor inhibitors. Our findings indicate that the combination of glucocorticoids with LABAs counteracts the pathologic degradation of HA, and thereby may reduce the proinflammatory potential of asthmatic ASMCs. 

Retracted: No

PubPeer comments:
 Figure 2C appears to include the same lane twice, after flipping horizontally and adjusting size (green boxes). Difficult to understand how these transformations could occur by accident during figure assembly. *** Original 2C and false color  *** Juxtaposed and flipped, high contrast  *** Full figure 2  ,
Stability of angiogenic agents, ginsenoside Rg1 and Re, isolated from Panax ginseng: in vitro and in vivo studies
Authors: Lin-Chien Yu
Sung-Ching Chen
Ya-Chun Huang
Kurt M Lin
Hsing-Wen Sung
Po-Hong Lai
Wei-Chun Chang
Journal: International Journal of Pharmaceutics (2007)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ginsenoside Rg(1); Re; angiogenesis; Panax ginseng; stability
Affiliations: Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.

Abstract:  The study was designed to investigate the stability of ginsenoside Rg(1) (Rg(1)) and Re (Re), two natural herbal compounds isolated from Panax ginseng, based on their activity to promote angiogenesis in vitro and in vivo. After being treated at different temperatures, pHs, and solvent species for distinct durations, the remaining activities of Rg(1) and Re on human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation were examined in vitro. Additionally, the remaining activity of each treated test agent, mixed in a growth factor-reduced Matrigel, in stimulating angiogenesis was evaluated subcutaneously in a mouse model. Basic fibroblast growth factor (bFGF) was used as a control. It was found in vitro that HUVEC proliferation, migration in a Transwell plate, and tube formation on Matrigel were all significantly enhanced in the presence of bFGF, Rg(1), or Re. However, after being treated at different temperatures, pHs, or solvent species, the remaining activity of bFGF on HUVEC behaviors reduced significantly. This observation was more significant with increasing the duration of treatment. In contrast, the activities of Rg(1) and Re remained unchanged throughout the entire course of the study. The in vivo results observed on day 7 after implantation showed that the blank control (Matrigel alone) was slightly vascularized. In contrast, the density of neo-vessels in the Matrigel plug mixed with bFGF, Rg(1), or Re was significantly enhanced. However, after being treated, the density of neo-vessels was significantly reduced in the Matrigel plug mixed with bFGF, while those of Rg(1) and Re remained unchanged. The aforementioned results suggested that Rg(1) and Re could be a novel group of nonpeptide angiogenic agents with a superior stability and may be used for the management of tissue regeneration. 

Retracted: No

PubPeer comments:
  Repetitive pattern in Figure 5 ,
Long circulating lectin conjugated paclitaxel loaded magnetic nanoparticles: a new theranostic avenue for leukemia therapy
Authors: Abhalaxmi Singh
Fahima Dilnawaz
Sanjeeb Kumar Sahoo
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: Bcr-Abl positive chronic myelogenous leukemia; paclitaxel; magnetic nanoparticles; targeted therapy; lectin glycoprotein
Affiliations: Laboratory of Nanomedicine, Institute of Life Sciences, Bhubaneswar, Orissa, India.

Abstract:  Amongst all leukemias, Bcr-Abl positive chronic myelogenous leukemia (CML) confers resistance to native drug due to multi drug resistance and also resistance to p53 and fas ligand pathways. In the present study, we have investigated the efficacy of microtubule stabilizing paclitaxel loaded magnetic nanoparticles (pac-MNPs) to ascertain its cytotoxic effect on Bcr-Abl positive K562 cells. For active targeted therapy, pac-MNPs were functionalized with lectin glycoprotein which resulted in higher cellular uptake and lower IC(50) value suggesting the efficacy of targeted delivery of paclitaxel. Both pac-MNPs and lectin conjugated pac-MNPs have a prolonged circulation time in serum suggesting increased bioavailability and therapeutics index of paclitaxel in vivo. Further, the molecular mechanism pertaining to pac-induced cytotoxicity was analyzed by studying the involvement of different apoptotic pathway proteins by immunoblotting and quantitative PCR. Our study revealed simultaneous activation of JNK pathway leading to Bcr-Abl instability and the extrinsic apoptotic pathway after pac-MNPs treatment in two Bcr-Abl positive cell lines. In addition, the MRI data suggested the potential application of MNPs as imaging agent. Thus our in vitro and in vivo results strongly suggested the pac-MNPs as a future prospective theranostic tool for leukemia therapy. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
null, 
 This paper was the subject of [an anonymous blogpost in 2013](http: sk-sahoo.blogspot.com 2013 05 plos-one-2011611e26803.html) which documented two of the concerns raised above.   , 
 #2 Fig 2:  ,
Long Noncoding RNA MALAT1 Promotes the Development of Colon Cancer by Regulating /STC1 Axis
Authors: Cunxin Zhao
Yongzhu Li
Chunyan Luan
Zhigang Liu
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: MALAT1; apoptosis; colon cancer; invasion; miR-101-3p
Affiliations: Department of Gastroenterology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, People's Republic of China., Department of Cardiology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, People's Republic of China.

Abstract:  Purpose: Colon cancer (CC) is a leading cause of cancer-related deaths worldwide. This study aimed to clarify the effect of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on CC progression and the potential mechanism. Methods: CC cell lines HCT116 and HT29 were selected for functional analysis. The expression of MALAT1, microRNA (miR)-101-3p, and stanniocalcin 1 (STC1) in CC tissues and cells were measured by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were measured by Cell Counting Kit-8 (CCK-8), Ôªøflow cytometry, wound scratch and Ôªøtranswell assay, respectively. The target relationships (MALAT1 and miR-101-3p, miR-101-3p and STC1) were validated by dual-luciferase reporter and RNA pull-down assay. Results: The expression of MALAT1 was elevated in CC tissues compared with adjacent normal tissues and was associated with lymph node metastasis, depth of invasion and tumor-node-metastasis (TNM) stage. Up-regulation of MALAT1 promoted the proliferation, migration, and invasion and inhibited the apoptosis of CC cells; while MALAT1 knockdown exhibited opposite results. MiR-101-3p was a target of MALAT1, which was negatively regulated by MALAT1. Silencing of miR-101-3p reverses the anti-tumor effect of MALAT1 knockdown on CC cells. STC1 was a target of miR-101-3p, which was negatively regulated by miR-101-3p. Silencing of STC1 reverses the tumor promoting effects of MALAT1 up-regulation and miR-101-3p down-regulation on CC cells. Conclusion: MALAT1 may function as an oncogene in CC progression by affecting the miR-101-3p/STC1 axis, providing a hopeful therapeutic option for CC. 

Retracted: No

PubPeer comments:
 Figure 3 and figure 5 s scratch assay appear to reuse images or portions of images several times. Sometimes the same portion of an image appears to be reused in the same figure. For example, the image in the light blue box, blank HCT116 appears to have been flipped, resized, edited slightly, and reused for the si-MALAT1 treated HT29. It appears to have been used again in figure 5D.   ,
AP-1 imprints a reversible transcriptional programme of senescent cells
Authors: Pierre-Fran√ßois Roux
Dimitri Belenki
Bin Sun
Lucas Robinson
Ricardo Iv√°n Mart√≠nez-Zamudio
Jes√∫s Gil
Clemens A Schmitt
Utz Herbig
Gregory Dor√©
Oliver Bischof
Jos√© Am√©rico N L F de Freitas
Maja Milanovic
Journal: Nature Cell Biology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Senescent cells; epigenetic mechanisms; regulatory networks; enhancers; senescence competence
Affiliations: Institut Pasteur, Paris, France., INSERM U993, Paris, France., Center for Cell Signaling, Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School of Rutgers Biomedical and Health Sciences, Rutgers University, Newark, NJ, USA., Johnson & Johnson, Upstream Skin Research, Issy-les-Moulineaux, France., Universit√© de Paris, Sorbonne Paris Cit√©, Paris, France., MRC London Institute of Medical Sciences (LMS), London, UK., Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK., Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molekulares Krebsforschungszentrum, Charit√©-University Medical Center, Berlin, Germany., Max-Delbr√ºck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany., Deutsches Konsortium f√ºr Translationale Krebsforschung (German Cancer Consortium), Berlin, Germany., Department of Hematology and Oncology, Kepler University Hospital, Johannes Kepler University, Linz, Austria., Institut Pasteur, Paris, France. ., INSERM U993, Paris, France. .

Abstract:  Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) 'pioneers' the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications. 

Retracted: No

PubPeer comments:
 There is a typo in the metadata of this _Nature_ u2018News and Views Articleu2019:  The word **u2018Bonku2019** should be written **u2018Banku2019** as it refers to the [Jodrell Bank Observatory] .  ,
Inter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling
Authors: Zoey Zhou
Brian Birditt
Roman Gulati
Margaret Hoang
Martine Roudier
Peter S Nelson
Gary Geiss
Stephen R Plymate
Rhonda Meredith
Michelle Kriner
Colm Morrissey
Lawrence D True
Ilsa Coleman
Joseph Beechem
Lauren Brady
Journal: Nature Communications (2021)
Discipline: Multidisciplinary
Keywords: Metastatic prostate cancer; digital spatial profiling; tumor phenotype; intra-tumor heterogeneity; androgen receptor
Affiliations: Fred Hutchinson Cancer Research Center, Seattle, WA, USA., NanoString Technologies, Inc., Seattle, WA, USA., University of Washington, Seattle, WA, USA., VAPSHCS-GRECC, Seattle, WA, USA., Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ., University of Washington, Seattle, WA, USA. .

Abstract:  Metastatic prostate cancer (mPC) comprises a spectrum of diverse phenotypes. However, the extent of inter- and intra-tumor heterogeneity is not established. Here we use digital spatial profiling (DSP) technology to quantitate transcript and protein abundance in spatially-distinct regions of mPCs. By assessing multiple discrete areas across multiple metastases, we find a high level of intra-patient homogeneity with respect to tumor phenotype. However, there are notable exceptions including tumors comprised of regions with high and low androgen receptor (AR) and neuroendocrine activity. While the vast majority of metastases examined are devoid of significant inflammatory infiltrates and lack PD1, PD-L1 and CTLA4, the B7-H3/CD276 immune checkpoint protein is highly expressed, particularly in mPCs with high AR activity. Our results demonstrate the utility of DSP for accurately classifying tumor phenotype, assessing tumor heterogeneity, and identifying aspects of tumor biology involving the immunological composition of metastases. 

Retracted: No

PubPeer comments:
 Hello, I enjoyed this paper. However, I do believe that the incorrect figure or data was used in figures 3b and 3c. The caption indicates that each each box and whisker is describing the z scores (with median and IQRs) of all tumor ROIs for each of individuals to support the idea that inter-tumor (intra-individual) variation is often low. However, the symmetrical box and whisker plots that terminate at each of the two points indicates that they were generated from the tumor averaged z-scores (usually 2 per sample), rather than ROIs (usually 3 per tumor). If this is the case, most box an whisker plots are based on two points only. If all ROIs are averaged (pictured in 4d), you would not always have symmetrical boxes. The points pictured on this plot would then be the mean z score (as indicated by the y-axis) of two points each- which would t be described by a box and whisker plot. Rather than points as those outside the 1.5 IQR, points are the mean z-score of each tumor. Thanks- I hope this is helpful. ,
A Randomized Controlled Clinical Trial Investigating the Effect of Synbiotic Administration on Markers of Insulin Metabolism and Lipid Profiles in Overweight Type 2 Diabetic Patients with Coronary Heart Disease
Authors: M Tajabadi-Ebrahimi
A Farrokhian
Z Asemi
N Sharifi
F Raygan
S Taheri
F Karamali
R Razzaghi
Journal: Experimental and Clinical Endocrinology & Diabetes (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: synbiotic administration; metabolic profiles; overweight diabetic patients; coronary heart disease; probiotic bacteria
Affiliations: Faculty Member of Science Department, Science Faculty, Islamic Azad University, Tehran Central branch, Tehran, Iran., Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R. Iran., Department of Cardiology, School of Medicine, Kashan University of Medical Sciences, Kashan, I.R. Iran., Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran., Department of Infectious Disease, school of medicine, Kashan University of Medical Sciences, Kashan, I.R. Iran.

Abstract:  Objective: The current study was performed to evaluate the effects of synbiotic administration on metabolic profiles in overweight diabetic patients with coronary heart disease (CHD). Methods: This randomized, double-blind, placebo-controlled trial was done among 60 diabetic patients with CHD. Participants were randomly divided into 2 groups: group A (n=30) received synbiotic supplements containing 3 probiotic bacteria spices Lactobacillus acidophilus 2√ó109, Lactobacillus casei 2√ó109, Bifidobacterium bifidum 2√ó109 CFU/g plus 800 mg inulin and group B (n=30) received placebo for 12 weeks. Fasting blood samples were taken at baseline and after 12-week intervention to determine metabolic profiles. Results: After 12 weeks of intervention, patients who consumed synbiotic capsule had significantly decreased fasting plasma glucose (- 19.6¬±74.6 vs.+19.2¬±66.9 mg/dL, P=0.03), serum insulin concentrations (- 0.7¬±5.1 vs.+3.3¬±6.3 ¬µIU/mL, P=0.01), the homeostasis model of assessment-estimated b cell function (- 3.4¬±19.5 vs.+11.5¬±21.0, P=0.006) and increased the quantitative insulin sensitivity check index (+ 0.002¬±0.01 vs.-0.01¬±0.02, P=0.03) compared with the placebo. In addition, changes in HLDL-cholesterol levels (+ 1.8¬±5.7 vs.-2.2¬±6.0 mg/dL, P=0.01) in supplemented patients were significantly different from those of patients in the placebo group. Conclusion: Synbiotic supplementation for 12 weeks among diabetic patients with CHD had beneficial effects on markers of insulin metabolism and HDL-cholesterol levels. 

Retracted: No

PubPeer comments:
 Figure 5. Much more similar than you would expect.  , 
 These two rows with individual panels are definitely different. Any experienced person can see the obvious differences in the minor peaks. ,
Salidroside attenuates lipopolysaccharide (LPS) induced serum cytokines and depressive-like behavior in mice
Authors: Xiayun Chang
Jing Gao
Tingting Wei
Lingpeng Zhu
Mingxing Miao
Tianhua Yan
He He
Journal: Neuroscience Letters (2015)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: BDNF; Depression; Inflammation; Lipopolysaccharide; Salidroside.
Affiliations: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, China., Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, China. Electronic address: .

Abstract:  The aim of the study was to investigate the effects and possible underlying mechanism of salidroside (Sal) on lipopolysaccharide (LPS)-induced depression-like behavior in mice. Sal (12 mg/kg and 24 mg/kg) and fluoxetine (20 mg/kg) were administered intragastrically once daily for 5 days. At the 5th day, LPS (0.5 mg/kg) was injected intraperitoneally 30 min after drug administration. Levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-Œ± in serum were measured by ELISA. Levels of neurotransmitters like norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in the prefrontal cortex were detected by HPLC-MS. Further, brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) and Nuclear factor-Œ∫B (NF-Œ∫B) in hippocampal was determined by western blot analysis. Our data showed that pretreatment with Sal dramatically attenuated LPS-induced inflammatory response, decrease of NE and 5-HT levels in the prefrontal cortex. In addition, Sal increased expression levels of BNDF and TrkB. These results suggested that Sal may play a neuroprotective role through the BDNF/TrkB signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 4. * Red and blue boxes: Some bands look more similar to each other than expected, albeit not always in the same orientation.  ,
Small interfering RNA-induced silencing of galectin-3 inhibits the malignant phenotypes of osteosarcoma in vitro
Authors: Yihe Hu
Zhan Liao
Pengfei Lei
Hongbo He
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Osteosarcoma; Galectin-3; Cell proliferation; Apoptosis; Cell migration
Affiliations: Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

Abstract:  Osteosarcoma (OS) is the most common malignant tumor of bone. It has recently been demonstrated that galectin-3, a multifunctional Œ≤-galactoside-binding, is significantly upregulated in OS tissues, and is correlated with its progression and metastasis. However, the detailed role of galectin‚Ä? in the regulation of cellular biological processes in OS cells has remained to be elucidated. The present study reported that the mRNA and protein levels of galectin‚Ä? were significantly increased in OS tissues compared to those in their matched normal adjacent tissues. Furthermore, galectin‚Ä? was upregulated in three OS cell lines, Saos‚Ä?, MG63 and U2OS, when compared with that in the human osteoblast cell line hFOB1.19. Knockdown of galectin‚Ä? by galectin‚Ä?‚Äëspecific small interfering RNA markedly inhibited OS‚Äëcell proliferation and induced cell apoptosis. Furthermore, silencing of galectin‚Ä? expression significantly inhibited OS cell migration and invasion, accompanied with a marked decrease in the protein expression of matrix metalloproteinase 2 and ‚Ä?. Mechanistic investigation suggested that the mitogen‚Äëactivated protein kinase kinase/extracellular signal‚Äëregulated protein kinase signaling pathway may be involved in the galectin‚Ä?‚Äëmediated OS cell invasion. In conclusion, the present study was the first to report that silencing of galectin‚Ä? inhibited the malignant phenotypes of osteosarcoma in vitro. Therefore, galectin-3 may serve as a potential therapeutic target for OS. 

Retracted: Yes

PubPeer comments:
 This trial suffers from methodological weaknesses and the data should be interpreted with caution. Statin side effects frequently take weeks or months to appear. Patients experiencing side effects in less than two weeks are more likely to be experiencing nocebo effects than the typical patient. This trial selected for inclusion only those patients and also excluded patients with confirmed rise in serum creatine kinase or rhabdomyolysis. These selection criteria essentially guaranteed the result found. The trial design also biased in favor of a null result by limiting the period of statin use to one consecutive month in most cases. This would minimize the side effects that appear on drug and risks some of those side effects continuing after drug cessation because they can take some time to diminish , resulting in increased reports on placebo. Given these limitations, the results of this trial should be interpreted with great caution and are not generally applicable to all statin users. This comment was submitted to NEJM as a letter to the editor, but rejected due to claimed  space limitations . I have added it here for the public record. Ryan Horath ,
A model of neuronal responses in visual area MT
Authors: E P Simoncelli
D J Heeger
Journal: Vision Research (1998)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Electrophysiological studies; neurons; middle temporal area; MT physiology; computational model

Abstract:  Electrophysiological studies indicate that neurons in the middle temporal (MT) area of the primate brain are selective for the velocity of visual stimuli. This paper describes a computational model of MT physiology, in which local image velocities are represented via the distribution of MT neuronal responses. The computation is performed in two stages, corresponding to neurons in cortical areas V1 and MT. Each stage computes a weighted linear sum of inputs, followed by rectification and divisive normalization. V1 receptive field weights are designed for orientation and direction selectivity. MT receptive field weights are designed for velocity (both speed and direction) selectivity. The paper includes computational simulations accounting for a wide range of physiological data, and describes experiments that could be used to further test and refine the model. 

Retracted: No

PubPeer comments:
  The V1 neurons described thus far are not selective for stimulus velocity. Rather, they are selective only for the component of velocity orthogonal to their preferred spatial orientation (Adelson Movshon, 1982). A couple of problems here. First, Adelson and Movshon (1982) were not studying V1 neurons, or any neurons for that matter. Second, the statement reflects Adelson and Movshon s description of the  aperture problem, a description which is false. As discussed in a [blog post] and several related PubPeer comments (the claim has rippled widely through the literature), the orthogonal motion claim is a special case contingent on the shape of the aperture being circular (or radially symmetrical) and does not apply generally. It does not apply, e.g. to rectangular apertures, as illustrated by the barberpole illusion. If founded on a false generalization, the proposed model cannot be a general model. The paper is well-cited, recently by Wallisch Movshon (2019) Journal of Neurophysiology, PubPeer comment [here] . ,
c-Jun NH2-terminal kinase promotes apoptosis by down-regulating the transcriptional co-repressor CtBP
Authors: Mihail Iordanov
Qinghong Zhang
Su-Yan Wang
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Genetic knock out; transcriptional co-repressor; CtBP; apoptosis; HIPK2
Affiliations: Vollum Institute and Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, Oregon 97239, USA.

Abstract:  Genetic knock out of the transcriptional co-repressor carboxyl-terminal-binding protein (CtBP) in mouse embryonic fibroblasts results in up-regulation of several genes involved in apoptosis. We predicted, therefore, that a propensity toward apoptosis might be regulated through changes in cellular CtBP levels. Previously, we have identified the homeodomain-interacting protein kinase 2 as such a regulator and demonstrated that HIPK2 activation causes Ser-422 phosphorylation and degradation of CtBP. In this study, we found that c-Jun NH2-terminal kinase 1 activation triggered CtBP phosphorylation on Ser-422 and subsequent degradation, inducing p53-independent apoptosis in human lung cancer cells. JNK1 has previously been linked to UV-directed apoptosis. Expression of MKK7-JNK1 or exposure to UV irradiation reduced cellular levels of CtBP via a proteasome-mediated pathway. This effect was prevented by JNK1 deficiency. In addition, sustained activation of the JNK1 pathway by cisplatin similarly triggered CtBP degradation. These findings provide a novel target for chemotherapy in cancers lacking p53. 

Retracted: No

PubPeer comments:
  ,
Transducin Œ≤-like 1 X-linked receptor 1 suppresses cisplatin sensitivity in nasopharyngeal carcinoma via activation of NF-Œ∫B pathway
Authors: Shu-Peng Chen
Long-Juan Zhang
Chan-Juan Wang
Qi Yang
Fang-Yong Lei
Yi Fang
Shu Wu
Ling Guo
Xiang Guo
Li-Bing Song
Journal: Molecular Cancer (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: TBL1XR1; transcriptional cofactor; carcinogenesis; tumor progression; nasopharyngeal carcinoma
Affiliations: Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China Guangzhou, Guangdong 510060, People's Republic of China. .

Abstract:  Background: Transducin Œ≤-like 1 X-linked receptor 1 (TBL1XR1) is an important transcriptional cofactor involved in the regulation of many signaling pathways, and is associated with carcinogenesis and tumor progression. However, the precise role of TBL1XR1 in these processes is not well understood. Methods: We detected the expression of TBL1XR1 protein and mRNA in nasopharyngeal carcinoma (NPC) cell lines and biopsies by western blotting, real-time PCR and immunohistochemical staining (IHC). Overexpression of TBL1XR1 in NPC enhanced chemoresistance to cisplatin using two NPC cell lines in vitro and in vivo. Results: TBL1XR1 was upregulated in NPC cell lines and clinical samples. The expression of TBL1XR1 was correlated with several clinicopathological factors including clinical stage, T classification, N classification and patient survival. Univariate and multivariate analysis revealed that TBL1XR1 was an independent prognostic factor for patient survival. In vitro and in vivo studies demonstrated that TBL1XR1 high expression induced resistance to cisplatin-induced apoptosis in NPC cells. Furthermore, we found that TBL1XR1 activated the NF-Œ∫B pathway and promoted transcription of genes downstream of NF-Œ∫B, especially anti-apoptotic genes. Conclusions: Upregulation of TBL1XR1 induces NPC cells resistance to cisplatin by activating the NF-Œ∫B pathway, and correlates with poor overall survival of NPC patients. TBL1XR1 has a pivotal role in NPC and could be a valuable prognostic factor as well as a novel biomarker for tailoring appropriate therapeutic regimes. 

Retracted: No

PubPeer comments:
 Fig. 3D. Two FCS plots have multiple sets of similar regional dots distribution, which seem very irregular.  ,
Inhibition of microRNA-495 suppresses chondrocyte apoptosis through activation of the NF-Œ∫B signaling pathway by regulating CCL4 in osteoarthritis
Authors: Da-Wei Yang
Gui-Bin Qian
Peng Wang
Kun-Zheng Wang
Ming-Jiu Jiang
Journal: Gene Therapy (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Osteoarthritis; microRNAs; miR-495; chemokine ligand 4; CCL4
Affiliations: Department of Orthopaedics, The Fourth Affiliated Hospital of Harbin Medical University, 150001, Harbin, China., Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, 710000, Xi'an, China. .

Abstract:  As a common form of arthritis, osteoarthritis (OA) represents a degenerative disease, characterized by articular cartilage damage and synovium inflammation. Recently, the role of various microRNAs (miRs) and their specific expression in OA has been highlighted. Therefore, the aim of the current study was to elucidate the role by which miR-495 and chemokine ligand 4 (CCL4) influence the development and progression of OA. OA mice models were established, after which the CCL4 and collagen levels as well as cell apoptosis were determined in cartilage tissue of OA mice. The chondrocytes of the OA mice models were subsequently treated with a series of miR-495 mimic, inhibitor, and siRNA against CCL4. Afterwards, miR-495 expressions as well as the levels of CCL4, p50, p65, and IkBa and the extent of IkBa phosphorylation in addition to the luciferase activity of NF-kB were measured accordingly. Finally, cell apoptosis and cell cycle distribution were detected. miR-495 was highly expressed while NF-Œ∫B, CCL4, and collagen II were poorly expressed. Cell apoptosis was elevated in the cartilage tissue of the OA mice. CCL4 was a potential target gene of miR-495. Downregulation of miR-495 led to accelerated chondrocyte proliferation accompanied by diminished cell apoptosis among the OA mice. Taken together, the results of the current study demonstrated that inhibition of miR-495 suppressed chondrocyte apoptosis and promoted its proliferation through activation of the NF-Œ∫B signaling pathway by up-regulation of CCL4 in OA. 

Retracted: No

PubPeer comments:
 Figure 8B: There are some unusual plots, I don t think there should be bulges in this kind of data (magenta circle), would the authors please comment?  , 
 Who did this to you, Fig 8B??!  , 
 Fig 6(a),  Gray values of CCL4, NF-u03baB, p50, p65, IkBa, and the extent of IkBa phosphorylation in each group .  WBs of this unusual stylised form have appeared in a number of problematic papers. I prepared a montage:  Is it possible for the authors to upload scans of their original gels, to allay any concerns? ,
Ubiquitin/SUMO modification regulates VHL protein stability and nucleocytoplasmic localization
Authors: Erle S Robertson
Qiliang Cai
Journal: PloS one (2010)
Discipline: Multidisciplinary
Keywords: VHL; tumor suppressor protein; cancer; RCC; hypoxia-inducible factor Œ±
Affiliations: Department of Microbiology and Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.

Abstract:  Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor protein is linked to the development of several forms of cancer as well as oncogenic progression like sporadic renal clear-cell carcinomas (RCC). Despite the critical role played by VHL in destruction of hypoxia-inducible factor Œ± (HIFŒ±) via ubiquitin-mediated proteolysis, very little is known about the post-translational modification which regulates VHL activity. Our previous study showed that the SUMO E3 ligase PIASy interacts with VHL and induces VHL SUMOylation on lysine residue 171 (Cai et al, PLoS ONE, 2010, 5(3):e9720). Here we further report that VHL also undergoes ubiquitylation on both lysine residues 171 and 196, which is blocked by PIASy. Moreover, using a VHL-SUMO1 or ubiquitin fusion protein, we found that ubiquitylated VHL is localized predominantly in the cytoplasm, while SUMOylated VHL results in increased VHL protein stability and nuclear redistribution. Interestingly, substitution of lysine 171 and 196 to arginine of VHL abrogates its inhibitory function on the transcriptional activity of HIFŒ±, and tube formation in vitro. This demonstrates that post-translational modifications like ubiquitylation and SUMOylation contributes to VHL protein stability and nucleocytoplasmic shuttling, and that the overall function of VHL in tumor suppression may require a precise and dynamically regulated process which involves protein modification. 

Retracted: Yes

PubPeer comments:
  Because doping graphene with cheap bird droppings produces more electrocatalytic materials than many complex multielemental doping procedures, we do not see any justification for such efforts, and we believe that researchers should focus their energy on other research directions. This might be a must-read paper for those in the field. , 
 This paper made my day. It s so refreshing to read something this well written and quirky. , 
 Yes, this was great! ,
The Interleukin-6/Soluble Interleukin-6 Receptor System Induces Parathyroid Hormone‚ÄìRelated Protein in Human Osteoblastic Cells
Authors: A R de Gort√°zar
P Esbrit
C Guill√©n
Journal: Calcified Tissue International (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: parathyroid hormone-related protein (PTHrP); interleukin-6 (IL-6); soluble receptor (IL-6sR); osteoblasts; mitogen-activated protein kinase (MAPK)
Affiliations: Bone and Mineral Metabolism Laboratory, Research Unit, Fundaci√≥n Jim√©nez D√≠az, 28040, Madrid, Spain.

Abstract:  In the present in vitro study, we tested the hypothesis that parathyroid hormone-related protein (PTHrP) might be a mediator of interleukin-6 (IL-6) and its soluble receptor (IL-6sR) in osteoblasts. We found that IL-6, within 1-20 ng/mL, added together with IL-6sR (100 ng/mL), rapidly (1 hour) increased PTHrP mRNA in human osteoblastic osteosarcoma MG-63 cells and human osteoblastic (hOB) cells from trabecular bone. PD098059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, at 10 microM, and two inhibitors of protein prenylation and thus Ras activation, simvastatin (1 microM) and a farnesyltransferase (FTase) inhibitor (100 nM), but not the phosphatidylinositol 3-kinase inhibitor wortmannin, blocked the IL-6/IL-6sR-induced PTHrP expression in these cells. In addition, PD098059 as well as simvastatin and the FTase inhibitor abolished alkaline phosphatase activity and/or osteocalcin mRNA induction by the IL-6/IL-6sR in these cells. Our results support the role of the Ras/MAPK pathway as a major mechanism in the modulation of both PTHrP expression and differentiation in human osteoblasts. 

Retracted: No

PubPeer comments:
 Figure 2A: More similar than expected. Could authors check please?  , 
 Thanks to Tetraponera merita for the comment. This paper was published many years ago when i was in other lab and i have no access to the original images of the corresponding RT-PCRs. In fact, the PI retired several years ago and the laboratory was dismantled. Then, it is impossible to localize the original scanned images from these experiments. Best regards Carlos ,
LncRNA BCAR4 up-regulates EGFR and thus promotes human thyrocyte proliferation
Authors: H Y Zhai
R H Yan
Z H Zhou
L Gao
J Li
T Z Yang
Journal: Neoplasma (2019)
Discipline: CLINICAL MEDICINE
Keywords: withdrawn; authors; Publisher; inconvenience
Affiliations: Department of Nuclear Medicine, Liaocheng People's Hospital, Liaocheng, China., Laboratory of Molecular Medicine, Liaocheng People's Hospital, Liaocheng, China., Department of Endocrinology, Liaocheng People's Hospital, Liaocheng, China.

Abstract:  This article has been withdrawn at the request of the authors. The Publisher apologizes for any inconvenience. 

Retracted: No

PubPeer comments:
 This paper generally is a duplication of the Winshurst machine, which is invented 200 years ago. The authors do not acknowledge Winshurst machine in the paper but claim it as a new invented power management strategy to generate high voltage. ,
Identification of a p65 peptide that selectively inhibits NF-kappa B activation induced by various inflammatory stimuli and its role in down-regulation of NF-kappaB-mediated gene expression and up-regulation of apoptosis
Authors: Bharat B Aggarwal
Sujay Singh
Yasunari Takada
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NF-kappaB; p65; protein transduction domains; inflammation; viral replication
Affiliations: Cytokine Research Laboratory, Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Imgenex, San Diego, California 92121, USA.

Abstract:  Because of the critical role of the nuclear transcription factor NF-kappaB in inflammation, viral replication, carcinogenesis, antiapoptosis, invasion, and metastasis, specific inhibitors of this nuclear factor are being sought and tested as treatments. NF-kappaB activation is known to require p65 phosphorylation at serine residues 276, 529, and 536 before it undergoes nuclear translocation. Small protein domains, termed protein transduction domains (PTDs), which are able to penetrate cell membranes can be used to transport other proteins across the cell membrane. We have identified two peptides from the p65 subunit of NF-kappaB (P1 and P6 were from amino acid residues 271-282 and 525-537, respectively) that, when linked with a PTD derived from the third helix sequence of antennapedia, inhibited tumor necrosis factor (TNF)-induced NF-kappaB activation in vivo. Linkage to the PTD was not, however, required to suppress the binding of the p50-p65-heterodimer to the DNA in vitro. PTD-p65-P1 had no effect on TNF-induced AP-1 activation. PTD-p65-P1 suppressed NF-kappaB activation induced by lipopolysaccharide, interleukin-1, okadaic acid, phorbol 12-myristate 13-acetate, H(2)O(2), and cigarette smoke condensate as well as that induced by TNF. PTD-p65-P1 had no effect on TNF-induced inhibitory subunit of NF-kappaB(IkappaBalpha) phosphorylation, IkappaBalpha degradation, or IkappaBalpha kinase activation, but it blocked TNF-induced p65 phosphorylation and nuclear translocation. NF-kappaB-regulated reporter gene expression induced by TNF, TNF receptor 1, TNF receptor-associated death domain, TNF receptor-associated factor-2, NF-kappaB-inducing kinase, IkappaBalpha kinase, and p65 was also suppressed by these peptides. Suppression of NF-kappaB by PTD-p65-P1 enhanced the apoptosis induced by TNF and chemotherapeutic agents. Overall, our results demonstrate the identification of a p65 peptide that can selectively inhibit NF-kappaB activation induced by various inflammatory stimuli, down-regulate NF-kappaB-mediated gene expression, and up-regulate apoptosis. 

Retracted: No

PubPeer comments:
 Identified by another reader. ***  ,
The chaperoning and assistance roles of the HIV-1 nucleocapsid protein in proviral DNA synthesis and maintenance
Authors: Daniela Lener
Carole Bampi
Sandrine Jacquenet
Didier D√©cimo
Jean-Luc Darlix
Journal: Current HIV Research (2004)
Discipline: IMMUNOLOGY
Keywords: HIV-1; nucleocapsid protein; RNA; proviral DNA; reverse transcriptase
Affiliations: LaboRetro, Unit√© de Virologie Humaine, INSERM #412, Ecole Normale sup√©rieure de Lyon, 46 allee d'Italie, 69 364 Lyon, France.

Abstract:  In the following three sections we will briefly review the seminal roles of the HIV-1 nucleocapsid protein NCp7 in the fate of the HIV-1 full length RNA from genomic RNA in a dimeric form to the proviral DNA. Emphasis will be given to the mechanisms of NC-directed assistance to the genomic RNA and reverse transcriptase in the course of proviral DNA synthesis and to DNA integrity at the end of the polymerization process, and to the NC-assisted repair and recombination reactions fueling the viability and variability of the virus. 

Retracted: No

PubPeer comments:
 Two reviews seem very similar:- 1. Curr HIV Res . 2004 Jan;2(1):79-92. doi: 10.2174 1570162043485022. The Chaperoning and Assistance Roles of the HIV-1 Nucleocapsid Protein in Proviral DNA Synthesis and Maintenance Carole Bampi 1, Sandrine Jacquenet, Daniela Lener, Didier Du00e9cimo, Jean-Luc Darlix Affiliations collapse Affiliation 1LaboRetro, Unitu00e9 de Virologie Humaine, INSERM #412, Ecole Normale supu00e9rieure de Lyon, 46 allee d Italie, 69 364 Lyon, France. PMID: 15053342 DOI: 10.2174 1570162043485022 Abstract In the following three sections we will briefly review the seminal roles of the HIV-1 nucleocapsid protein NCp7 in the fate of the HIV-1 full length RNA from genomic RNA in a dimeric form to the proviral DNA. Emphasis will be given to the mechanisms of NC-directed assistance to the genomic RNA and reverse transcriptase in the course of proviral DNA synthesis and to DNA integrity at the end of the polymerization process, and to the NC-assisted repair and recombination reactions fueling the viability and variability of the virus. 2. Int J Biochem Cell Biol . 2004 Sep;36(9):1668-86. doi: 10.1016 j.biocel.2004.02.024. The Chaperoning and Assistance Roles of the HIV-1 Nucleocapsid Protein in Proviral DNA Synthesis and Maintenance Carole Bampi 1, Sandrine Jacquenet, Daniela Lener, Didier Du00e9cimo, Jean-Luc Darlix Affiliations expand PMID: 15183337 DOI: 10.1016 j.biocel.2004.02.024 Abstract In the following three sections, we will briefly review the seminal roles of the HIV-1 nucleocapsid protein p7 (NCp7) in the fate of the HIV-1 full length RNA from genomic RNA in a dimeric form to the proviral DNA. Emphasis will be given to the mechanisms of NC-directed assistance to the genomic RNA and reverse transcriptase (RT) in the course of proviral DNA synthesis and to DNA integrity at the end of the polymerization process, and to the NC-assisted repair and recombination reactions fueling the viability and variability of the virus. ,
Differential consequences of neurokinin receptor 1 and 2 antagonists in metastatic breast carcinoma cells; Effects independent of Substance P
Authors: Nuray Erin
Esra Nizam
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Breast cancer; MIP-2; Metastasis; NK1 receptor; NK2 receptor
Affiliations: Department of Medical Pharmacology, Akdeniz University, Faculty of Medicine, Antalya, Turkey., Department of Medical Pharmacology, Akdeniz University, Faculty of Medicine, Antalya, Turkey. Electronic address: .

Abstract:  Introduction: The biological action of Substance P (SP) is mediated mainly by NK-1 receptors (NK1R) followed by NK2 receptors (NK2R). Aberrant expression of NK1R and NK2R has been identified in various carcinomas. The role of Substance P and its receptors, especially NK2R in cancer progression is not entirely known and there are conflicting results in the literature demonstrating the need for further investigation. In the current study, we examined the effects of SP and antagonists selective for the NK1R and NK2R in breast carcinoma cells metastasize to vital organs. Methods: The effects of highly potent and selective non-peptide mouse NK1R and NK2R antagonists RP 67,580 and GR 159897, respectively, as well as SP and SP methyl ester, on both metastatic (4THM, 4TBM, 4TLM, 4T1) and non-metastatic (67NR) breast cancer cells were determined. Results: NK1R and NK2R were over expressed in metastatic breast cells compared to non-metastatic cells. The NK1R antagonist at a 30 ŒºM dose inhibited cell growth and induced cell death in metastatic cells while enhancing phosphorylation of Akt, the latter response not observed in the non-metastatic 67NR cells. Blocking the action of SP at the NK2R (30 ŒºM antagonist) suppressed cellular proliferation in all the cell lines examined, with a response less prominent than that of the NK1R antagonist. Differently, the NK2R antagonist increased phosphorylation of p38 and enhanced MIP-2 secretion. SP and the SP methyl ester neither altered cell proliferation nor the effects of NK1R and NK2R antagonists in the metastatic cell lines. Conclusions: Increased sensitivity of metastatic breast carcinoma cells to NK1R and NK2R antagonists suggest potential therapeutic value of antagonists in metastatic disease. NK1R and NK2R in metastatic breast carcinoma cells react differently to agonists and antagonists. These findings together with previously published data demonstrate that differential consequences of receptor antagonists and SP may inhibit breast cancer growth and metastasis. 

Retracted: No

PubPeer comments:
 Would the authors be so kind as to post the original uncropped scans of the western blot in Figure 4B? There appears to be some differential splicing. ***  ,