PReD-Bench/PRed-Bench huggingface dataset:
MDM2 promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma protein
Authors: Robert Touitou
Patima Sdek
Donny L F Chang
Martin J Allday
Hongwu Zheng
Zhi-Xiong Jim Xiao
Wei Qiu
Haoqiang Ying
Journal: Molecular Cell (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: retinoblastoma protein; Rb; MDM2; proteasome; ubiquitin-independent
Affiliations: Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.

Abstract:  Inactivation of retinoblastoma protein (Rb) plays a critical role in the development of human malignancies. It has been shown that Rb is degraded through a proteasome-dependent pathway, yet the mechanism is largely unclear. MDM2 is frequently found amplified and overexpressed in a variety of human tumors. In this study, we find that MDM2 promotes Rb degradation in a proteasome-dependent and ubiquitin-independent manner. We show that Rb, MDM2, and the C8 subunit of the 20S proteasome interact in vitro and in vivo and that MDM2 promotes Rb-C8 interaction. Expression of wild-type MDM2, but not the mutant MDM2 defective either in Rb interaction or in RING finger domain, promotes cell cycle S phase entry independent of p53. Furthermore, MDM2 ablation results in Rb accumulation and inhibition of DNA synthesis. Taken together, these findings demonstrate that MDM2 is a critical negative regulator for Rb and suggest that MDM2 overexpression contributes to cancer development by destabilizing Rb. 

Retracted: No

PubPeer comments:
 Figure 4C. Much more similar inside yellow rectangles than expected. ![file] ,
EphA3 promotes the proliferation of NPC cells through negatively regulating the ability of FOG2
Authors: Y Wang
Z Song
C Liu
Y-M Liu
S Gao
Z-X Sun
D Bao
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: EphA3; nasopharyngeal carcinoma; proliferation capacity; clinical indicators; prognosis
Affiliations: Department of ENT, Qingdao Central Hospital, Qingdao University, Qingdao, China. .

Abstract:  Objective: The purpose of this study was to investigate the expression level of EphA3 in nasopharyngeal carcinoma (NPC) and its effect on the proliferative capacity of NPC. Meanwhile, the underlying mechanism by which EphA3 prompts NPC malignant progression was further explored. Patients and methods: In this study, the expression of EphA3 in 42 pairs of tumor tissue specimens and paracancerous ones collected from NPC patients was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the interplay between EphA3 expression and clinical indicators, as well as prognosis of NPC patients was analyzed. Meanwhile, qRT-PCR was also applied to further verify EphA expression in NPC cell lines. In addition, EphA knockdown model was constructed in NPC cell lines, CNE2, and 6-10B, and the impacts of EphA on NPC cell functions was assessed through Cell Counting Kit-8 (CCK-8), cell colony formation, as well as 5-Ethynyl-2'- deoxyuridine (EdU) assays. Finally, a potential interplay between EphA3 and FOG2 was also investigated. Results: In this study, qRT-PCR results revealed that EphA3 expression levels in tumor tissues of patients with NPC were markedly higher than those in adjacent tissues. Compared with patients with low expression of EphA3, those with highly expressed EphA3 had a more advanced pathological stage. In addition, in vitro experiments showed that knocking down EphA3 notably attenuated the proliferation capacity of NPC cells. Subsequently, it was found that the expression of FOG2 in NPC cells was remarkably decreased both in NPC cell lines and tissues, which had a negative correlation with EphA3. Finally, cell recovery experiment revealed a mutual regulation between EphA3 and FOG2, which then together affected the malignant progression of NPC. Conclusions: EphA3 is significantly relevant to pathological staging and poor prognosis of patients with NPC and may enhance the proliferation ability of NPC cells by modulating FOG2. 

Retracted: No

PubPeer comments:
 Fig 3D.  There is a significant negative correlation between the expression levels of EphA3 and FOG2 in NPC. Rescaled slightly for ease of comparison with (right) a superimposition of 20 versions of the same correlation scatterplot, from different papers. Data-points are darker if they appear in more of those 20 variants. ![file] Here, 3D (in red) superimposed on that composite, to emphasise how many points line up. Clearly Fig 3D came from the same source. ![file] ,
RETRACTED: Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake
Authors: Jayaraj Ravindran
Madan M Chaturvedi
Ramaswamy Kannappan
Lauri Vaahtera
Jaakko Parkkinen
Bharat B Aggarwal
Sahdeo Prasad
Vivek R Yadav
Journal: Biochemical Pharmacology (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Curcumin; Cyclodextrin complex; Anti-inflammatory; Antiproliferative effects; NF-kappaB
Affiliations: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 143, Houston, TX 77030, USA.

Abstract:  Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with multiple beneficial activities, but its optimum potential is limited by poor bioavailability, in part due to the lack of solubility in aqueous solvents. To overcome the solubility problem, we have recently developed a novel cyclodextrin complex of curcumin (CDC) and examined here this compound for anti-inflammatory and antiproliferative effects. Using the electrophoretic mobility shift assay, we found that CDC was more active than free curcumin in inhibiting TNF-induced activation of the inflammatory transcription factor NF-kappaB and in suppressing gene products regulated by NF-kappaB, including those involved in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF). CDC was also more active than free curcumin in inducing the death receptors DR4 and DR5. Annexin V staining, cleavage of caspase-3 and PARP, and DNA fragmentation showed that CDC was more potent than free curcumin in inducing apoptosis of leukemic cells. Antiproliferative assays also demonstrated that CDC was more active than free curcumin in suppressing proliferation of various cancer cell lines. The cyclodextrin vehicle had no effect in these assays. Compared with free curcumin, CDC had a greater cellular uptake and longer half-life in the cells. Overall we demonstrated that CDC had superior attributes compared with free curcumin for cellular uptake and for antiproliferative and anti-inflammatory activities. 

Retracted: Yes

PubPeer comments:
null, 
null, 
 An illustration of some of the problems noted in the Retraction Notice:  Images in Fig. 5A were reused to represent different experimental conditions: curcumin uptake by KBM-5 cells treated with curcumin alone at 30 min, and curcumin uptake by KBM-5 cells treated with cyclodextrin-complexed curcumin (CDC) at 45 min. Images from Fig. 5A were reused in Fig. 2A of Ref. [2] to represent different experimental conditions: four of the control images of cellular uptake of curcumin shown in Fig. 5A (45, 60, 120 and 180 min) are also shown in Fig. 2A (45, 60, 120 and 180 min) of Ref. [2]. ![file] ,
Synthesis, characterization, and debromination reactivity of cellulose-stabilized Pd/Fe nanoparticles for 2,2',4,4'-tretrabromodiphenyl ether
Authors: Sihao Lv
Changfang Li
Yongyou Hu
Guofu Huang
Mianmian Wang
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: cellulose derivatives; Pd/Fe nanoparticles; debromination; stabilizers; antioxidative abilities
Affiliations: School of Environment and Energy, South China University of Technology, the Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, Guangzhou, PR China., State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou, PR China., School of Environment and Civil Engineering, Dongguan University of Technology, Dongguan, PR China., Dongguan Cleaner Production Center, Dongguan, PR China.

Abstract:  In this study, two kinds of cellulose derivatives (polyanionic cellulose (PAC) and hydroxypropylmethyl cellulose (HPMC)) were selected as stabilizers of Pd/Fe nanoparticles (NPs) to investigate their influences on the debromination performances of 2,2',4,4'-tretrabromodiphenyl ether (BDE47). Field emission scanning electron microscope (FE-SEM) images revealed that the cellulose-stabilized Pd/Fe NPs were smaller and more uniform than the bare-Pd/Fe NPs. X-ray diffractometer (XRD) and X-ray photoelectron spectroscopy (XPS) results suggested that cellulose coatings found on Pd/Fe NPs surfaces featured some antioxidation abilities, which followed the order of HPMC &lt; PAC. Sedimentation tests demonstrated that the stabilizing power of PAC for Pd/Fe NPs was higher than that of HPMC. Fourier transfer infrared spectrometer (FTIR) results indicated that PAC molecules were bound to the Pd/Fe NPs surfaces by polar covalent bonds and hydrogen bonds, while HPMC molecules interacted with the nanoparticles by hydrogen bonds. Batch debromination test for BDE47 demonstrated that the catalytic debromination rate with cellulose-stabilized Pd/Fe NPs was higher than that with bare-Pd/Fe NPs during reaction period of 15 min. Overall, this study indicated that both celluloses are beneficial to forming smaller, more regular, stable and antioxidative Pd/Fe NPs, leading to higher debromination reactivity for BDE47 compared with the bare-Pd/Fe NPs. Therefore Pd/Fe NPs can be utilized as a promising remediation technology for the contaminated groundwater and soils. 

Retracted: No

PubPeer comments:
 ![file] Unexpected similarity for some parts of XRD patterns and strong difference for main peaks. ,
The transcription factor FOXO3a is a crucial cellular target of gefitinib (Iressa) in breast cancer cells
Authors: R Charles Coombes
Richard E Francis
Eric W-F Lam
André Albergaria
Andreas Polychronis
Andrew Sunters
Janna Krol
Journal: Molecular Cancer Therapeutics (2007)
Discipline: CLINICAL MEDICINE
Keywords: Gefitinib; EGFR; FOXO3a; breast cancer; cell cycle arrest
Affiliations: Cancer Research UK Labs and Department of Cancer Medicine, Imperial College London, MRC Cyclotron Building, Imperial College School of Medicine at Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.

Abstract:  Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR) that causes growth delay in cancer cell lines and human tumor xenografts expressing high levels of EGFR. An understanding of the downstream cellular targets of gefitinib will allow the discovery of biomarkers for predicting outcomes and monitoring anti-EGFR therapies and provide information for key targets for therapeutic intervention. In this study, we investigated the role of FOXO3a in gefitinib action and resistance. Using two gefitinib-sensitive (i.e., BT474 and SKBR3) as well as three other resistant breast carcinoma cell lines (i.e., MCF-7, MDA-MB-231, and MDA-MB-453), we showed that gefitinib targets the transcription factor FOXO3a to mediate cell cycle arrest and cell death in sensitive breast cancer cells. In the sensitive cells, gefitinib treatment causes cell cycle arrest predominantly at the G(0)-G(1) phase and apoptosis, which is associated with FOXO3a dephosphorylation at Akt sites and nuclear translocation, whereas in the resistant cells, FOXO3a stays phosphorylated and remains in the cytoplasm. The nuclear accumulation of FOXO3a in response to gefitinib was confirmed in tumor tissue sections from breast cancer patients presurgically treated with gefitinib as monotherapy. We also showed that knockdown of FOXO3a expression using small interfering RNA (siRNA) can rescue sensitive BT474 cells from gefitinib-induced cell-proliferative arrest, whereas reintroduction of active FOXO3a in resistant MDA-MB-231 cells can at least partially restore cell-proliferative arrest and sensitivity to gefitinib. These results suggest that the FOXO3a dephosphorylation and nuclear localization have a direct role in mediating the gefitinib-induced proliferative arrest and in determining sensitivity to gefitinib. 

Retracted: No

PubPeer comments:
 Figure 1A (this paper) much more similar than expected. ![file] ,
miR-122-5p/KIF5B/AMPK/AKT regulatory network regulates the progression of NAFLD
Authors: Jianling Zhang
Huanjun Huang
Journal: American journal of translational research (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: KIF5B; cell biology; miR-122-5p; non-alcoholic fatty liver disease.
Affiliations: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei, P. R. China., Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei, P. R. China.

Abstract:  Background: Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease, which may develop into end-stage liver disease and endanger human life. miR-122-5p may be related to the progression of NAFLD disease, but the specific regulation mechanism is still unknown. It is helpful for us to optimize the prevention or treatment strategy of NAFLD. Methods: Real-time PCR was applied to test miR-122-5p and KIF5B in serum, rat liver tissue induced by high fat diet (HFD), and primary hepatocytes exposed to oleic acid ester and palmitate (FFA) of NAFLD patients. The role of miR-122-5p on inflammatory factors (MCP-1, TNF-α, IL-10) and liver injury markers (AST, ALT) in vivo and in vitro was analyzed. Results: miR-122-5p and KIF5B were both highly expressed in NAFLD patients' serum, rat liver tissue and primary hepatocytes, while KIF5B was low expressed. miR-122-5p expression enhanced with the increase of HFD feeding time. The dual luciferase reporter gene assay system confirmed that there was a targeting relationship between miR-122-5p and KIF5B, indicating that KIF5B and protein level were evidently up-regulated in primary hepatocytes. Down-regulation of miR-122-5p was helpful to improve the liver weight/body weight ratio (liver index) level of rats, as well as the levels of triglyceride (TG), inflammatory factors and liver injury markers in liver tissues in vivo and in vitro. Phosphorylation of AMPK/AKT pathway-related proteins and fat metabolism-related factors in rat liver tissues and cells in primary hepatocytes were notably reduced, while down-regulation of miR-122-5p was helpful to restore activation of the pathway and increase the level of fat metabolism-related factors. Conclusion: Decrease of miR-122-5p can target and enhance KIF5B, which can be applied for treating NAFLD. 

Retracted: Yes

PubPeer comments:
 [Retracted](http: www.ajtr.org files ajtr0134768.pdf).  In this article, Dr. Huanjun Huang was listed as the corresponding author without being informed and the corresponding e-mail HuangHuanjun6618@163.com was forged. Therefore, this article was requested to be retracted by Dr. Huanjun Huang due to the authorship problem. The authors deeply regret for the inconvenience this has caused to the journal and the scientific community. ,
Metagenomic and culturomic analysis of gut microbiota dysbiosis during Clostridium difficile infection
Authors: Issa Isaac Ngom
Niokhor Dione
Edmond Kuete
Sophie Amrane
Thi-Phuong-Thao Pham
Didier Raoult
Marie Hocquart
Jean Christophe Lagier
Dipankar Bachar
Camille Valles
Pamela Afouda
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: Clostridium difficile infection; bacteriotherapy; gut microbiota; metagenomics; culturomics
Affiliations: Aix Marseille Univ, IRD, MEPHI, IHU-Méditerranée Infection, Marseille, France., Aix Marseille Univ, IRD, MEPHI, IHU-Méditerranée Infection, Marseille, France. .

Abstract:  Recently, cocktail of bacteria were proposed in order to treat Clostridium difficile infection (CDI), but these bacteriotherapies were selected more by chance than experimentation. We propose to comprehensively explore the gut microbiota of patients with CDI compared to healthy donors in order to propose a consortium of bacteria for treating C. difficile. We compared stool samples composition from 11 CDI patients and 8 healthy donors using two techniques: metagenomics, 16S V3-V4 region amplification and sequencing and culturomics, high throughout culture using six culture conditions and MALDI-TOF identification. By culturomics, we detected 170 different species in the CDI group and 275 in the control group. Bacteroidetes were significantly underrepresented in the CDI group (p = 0.007). By metagenomics, 452 different operational taxonomic units assigned to the species level were detected in the CDI group compared to 522 in the control group. By these two techniques, we selected 37 bacteria only found in control group in more than 75% of the samples and/or with high relative abundance, 10 of which have already been tested in published bacteriotherapies against CDI, and 3 of which (Bifidobacterium adolescentis, Bifidobacterium longum and Bacteroides ovatus) have been detected by these two techniques. This controlled number of bacteria could be administrated orally in a non-invasive way in order to treat CDI. 

Retracted: No

PubPeer comments:
 This chapter is based on conclusions from several flawed publications on Lie-group symmetry analysis. For details, please see the full review: https: publons.com publon 31812953 #review-7962984 ,
Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization
Authors: Thomas R Cech
Ci Ji Lim
Journal: Nature Reviews Molecular Cell Biology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: telomere length regulation; telomeric protein complexes; ribonucleoprotein telomerase; telomere architecture; telomere maintenance
Affiliations: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA. ., Department of Biochemistry, University of Colorado Boulder, Boulder, CO, USA. ., BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA. ., Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO, USA. .

Abstract:  The regulation of telomere length in mammals is crucial for chromosome end-capping and thus for maintaining genome stability and cellular lifespan. This process requires coordination between telomeric protein complexes and the ribonucleoprotein telomerase, which extends the telomeric DNA. Telomeric proteins modulate telomere architecture, recruit telomerase to accessible telomeres and orchestrate the conversion of the newly synthesized telomeric single-stranded DNA tail into double-stranded DNA. Dysfunctional telomere maintenance leads to telomere shortening, which causes human diseases including bone marrow failure, premature ageing and cancer. Recent studies provide new insights into telomerase-related interactions (the 'telomere replisome') and reveal new challenges for future telomere structural biology endeavours owing to the dynamic nature of telomere architecture and the great number of structures that telomeres form. In this Review, we discuss recently determined structures of the shelterin and CTC1-STN1-TEN1 (CST) complexes, how they may participate in the regulation of telomere replication and chromosome end-capping, and how disease-causing mutations in their encoding genes may affect specific functions. Major outstanding questions in the field include how all of the telomere components assemble relative to each other and how the switching between different telomere structures is achieved. 

Retracted: No

PubPeer comments:
 Erratum for Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization. Lim CJ, Cech TR. Nat Rev Mol Cell Biol. 2021 Feb 9. doi: 10.1038 s41580-021-00328-y. Online ahead of print. PMID: 33564154 Review. Correction to: Nature Reviews Molecular Cell Biology https: doi.org 10.1038 s41580-021-00328-y, published online 09 February 2021. In Figure 2b, the label u2018TRFH-binding motifu2019 has been nudged down, towards the illustration of TIN2, and re-styled to match the other protein-domain labels in the figure. The changes have been made in the HTML and PDF versions of the article. ,
The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis
Authors: Kyung Keun Kim
Jae-Seoun Hur
Jae Hyuk Lee
Kyung Hwa Lee
Rui Zhou
Thanh Thi Nguyen
So-Yeon Park
Hangun Kim
Yi Yang
Young-Woo Seo
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Lichens; secondary metabolites; anti-migratory activity; lung cancer cells; Everniastrum vexans
Affiliations: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea., Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea., Faculty of Natural Science and Technology, Tay Nguyen University, Buon Ma Thuot, Vietnam., Korea Basic Science Institute, Gwangju Center, Gwangju, Republic of Korea., Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea., Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Republic of Korea., College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea. .

Abstract:  Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc. Atranorin decreased KAI1 C-terminal interacting tetraspanin (KITENIN)-mediated AP-1 activity and the activity of the KITENIN 3'-untranslated region. The nuclear distribution of the AP-1 transcriptional factor, including c-jun and c-fos, was suppressed in atranorin-treated cells, and atranorin inhibited the activity of Rho GTPases including Rac1, Cdc42, and RhoA, whereas it had no effect on epithelial-mesenchymal transition markers. STAT-luciferase activity and nuclear STAT levels were decreased, whereas total STAT levels were moderately reduced. The human cell motility and lung cancer RT² Profiler PCR Arrays identified additional atranorin target genes. Atranorin significantly inhibited tumorigenesis in vitro and in vivo. Taken together, our results indicated that E. vexans and its subcomponent atranorin may inhibit lung cancer cell motility and tumorigenesis by affecting AP-1, Wnt, and STAT signaling and suppressing RhoGTPase activity. 

Retracted: No

PubPeer comments:
 Figure 2D appears to have a repeated image. *** ![file] , 
 Thank you for informing us about the problem with the picture of Fig 2D in our publication. It is clear that we made an unintentional mistake during the data presentation. We believe this error does not affect the conclusion of this study. Weu2019ll contact the Editorial office to correct this and post the decision as soon as possible. Thank you for your comment. ![file] ,
Relationship between simultaneously recorded spiking activity and fluorescence signal in GCaMP6 transgenic mice
Authors: Christof Koch
Jérôme Lecoq
Jack Waters
Michael A Buice
Lu Li
Lawrence Huang
R Clay Reid
Hongkui Zeng
Ulf Knoblich
Saskia Ej de Vries
Gabe J Murphy
Peter Ledochowitsch
Journal: eLife (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: action potential; calcium imaging; calibration; cell-attached recording; excitatory neurons
Affiliations: Allen Institute for Brain Science, Seattle, United States., Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract:  Fluorescent calcium indicators are often used to investigate neural dynamics, but the relationship between fluorescence and action potentials (APs) remains unclear. Most APs can be detected when the soma almost fills the microscope's field of view, but calcium indicators are used to image populations of neurons, necessitating a large field of view, generating fewer photons per neuron, and compromising AP detection. Here, we characterized the AP-fluorescence transfer function in vivo for 48 layer 2/3 pyramidal neurons in primary visual cortex, with simultaneous calcium imaging and cell-attached recordings from transgenic mice expressing GCaMP6s or GCaMP6f. While most APs were detected under optimal conditions, under conditions typical of population imaging studies, only a minority of 1 AP and 2 AP events were detected (often &lt;10% and ~20-30%, respectively), emphasizing the limits of AP detection under more realistic imaging conditions. 

Retracted: No

PubPeer comments:
 https: twitter.com marius10p status 1370020278235975684 https: twitter.com marius10p status 1370041673460424708 , 
 https: twitter.com marius10p status 1370827047170347011?s=19 ,
JunB mediates enhancer/promoter activity of COL1A2 following TGF-beta induction
Authors: Clare Harvey
Tetsuro Ikeda
Markella Ponticos
David Abraham
George Bou-Gharios
Journal: Nucleic Acids Research (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Transcriptional control; collagen type I; enhancer; promoter; molecular mechanism
Affiliations: Department of Medicine, Centre for Rheumatology, University College London Royal Free Campus, London NW3 2PF, UK.

Abstract:  Transcriptional control of the genes coding for collagen type I is regulated by a complex interaction between a distal enhancer and a proximal promoter. In this study, we have dissected the molecular mechanism of this interaction by defining a specific sequence within the enhancer that respond in fibroblasts to transforming growth factor-beta (TGF-beta). We show that TGF-beta activates COL1A2 gene via a non-canonical (Smad-independent) signalling pathway, which requires enhancer/promoter co-operation. This interaction involves exchange of cJun/Jun B transcription factor occupancy of a critical enhancer site resulting in the stabilization of enhancer/promoter coalescence. Moreover, using transgenesis, we show that interference in this mechanism results in the abolition of COL1A2 fibroblast expression in vivo. These data are therefore relevant to the control of collagen type I in vivo both in embryonic development, in adult connective tissue homeostasis, and in tissue repair and scarring pathologies. 

Retracted: No

PubPeer comments:
 Figure 5A. Differential splicing makes comparison between panels problematic. https: imgur.com FI0ExVy , 
 Figure 5C. Differential splicing makes comparison between panels problematic. https: imgur.com Y2sMHoi ,
Mild endoplasmic reticulum stress ameliorates lipopolysaccharide-induced neuroinflammation and cognitive impairment via regulation of microglial polarization
Authors: Qing-Qing Qian
Yan-Ning Qian
Peng-Fei Ni
Jia-Wen Xu
Xiang Zhang
Yi-Wei Wang
Qin Zhou
Journal: Journal of neuroinflammation (2017)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Endoplasmic reticulum stress; Lipopolysaccharide; Microglia; Neurodegeneration; Neuroinflammation.
Affiliations: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People's Republic of China., Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China., Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People's Republic of China. .

Abstract:  Background: Neuroinflammation, which ultimately leads to neuronal loss, is considered to play a crucial role in numerous neurodegenerative diseases. The neuroinflammatory process is characterized by the activation of glial cells such as microglia. Endoplasmic reticulum (ER) stress is commonly associated with impairments in neuronal function and cognition, but its relationship and role in neurodegeneration is still controversial. Recently, it was confirmed that nonharmful levels of ER stress protected against experimental Parkinson's disease. Here, we investigated mild ER stress-based regulation of lipopolysaccharide (LPS)-driven neuroinflammation in rats and in primary microglia. Methods: Male Sprague-Dawley (SD) rats received the intracerebroventricular injection of the ER stress activator tunicamycin (TM) with or without intraperitoneal injection of the ER stress stabilizer sodium 4-phenylbutyrate (4-PBA) 1 h before LPS administration. The levels of neuroinflammation and memory dysfunction were assessed 24 h after treatment. In addition, the effect of mild ER stress on microglia was determined in vitro. Results: Here, we found that low doses of TM led to mild ER stress without cell or organism lethality. We showed that mild ER stress preconditioning reduced microglia activation and neuronal death as well as improved LPS-induced memory impairment in rats. In addition, pre-exposure to nonlethal doses of TM in microglia showed significant protection against LPS-induced proinflammatory cytokine production and M1/2b polarization. However, sodium 4-PBA, a compound that ameliorates ER stress, ablated this protective effect in vivo and in vitro. Conclusions: Based on our findings, we conclude that the mild ER stress not only limits the accumulation of misfolded proteins but also protects tissues from harmful endotoxemia insults. Therefore, ER stress preconditioning has potential therapeutic value for the treatment of neurodegenerative diseases. 

Retracted: No

PubPeer comments:
 similar bands in figure 3E and 5H ![file] ,
Synthesis, characterization, evaluation and molecular dynamics studies of 5, 6–diphenyl–1,2,4–triazin–3(2 H )–one derivatives bearing 5–substituted 1,3,4–oxadiazole as potential anti–inflammatory and analgesic agents
Authors: Nirupam Das
Sushant Kumar Shrivastava
Radhey Shyam Srivastava
Sushant A Shengule
Anupam G Banerjee
Journal: European Journal of Medicinal Chemistry (2015)
Discipline: CHEMISTRY
Keywords: 1,2,4–triazine; 1,3,4–oxadiazole; Analgesic; Anti–inflammatory; Cyclooxygenase.
Affiliations: Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221 005, India. Electronic address: ., Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221 005, India., National Toxicology Centre, Vadgaon Khurd, Sinhagad Road, Pune, 411 041, India.

Abstract:  A series of triazin-3(2H)-one derivatives bearing 1,3,4-oxadiazole (4a-4o) were synthesized, characterized and evaluated for anti-inflammatory and analgesic activities. Preliminary in vitro anti-inflammatory activity was assessed using an albumin denaturation assay. The promising compounds were further evaluated in acute, sub-chronic and chronic animal models of inflammation. Derivatives 4d, 4e, 4g, 4j and 4l exhibited significant anti-inflammatory activity with reduced ulcerogenic, hepatotoxic and renotoxic liabilities compared to standard indomethacin. These potential derivatives were also evaluated for in vivo analgesic activity using a writhing model and the formalin-induced paw licking response in mice. Compounds 4d, 4e and 4g exhibited comparable analgesic activity, whereas 4j and 4l yielded moderate effects. The specificity of compounds 4d, 4e, 4g, 4j, and 4l to inhibit (cyclooxygenase-1) COX-1 and (cyclooxygenase-2) COX-2 isozymes and their kinetics were also determined via an in vitro COX inhibition assay. In silico docking studies were performed using a molecular dynamics simulation of the most active compound 4d (COX-2 IC50: 3.07 μM) at the COX-2 active site. The outcome of this exercise helped to verify the consensual interaction of these compounds with the enzyme. 

Retracted: No

PubPeer comments:
 This article is using data from two previous publishied articles and presenting them as something different. Figure 6a: One micrographs (HUVEC cbMSC aggregates) is taken from Yeh YC et al., 2010; Biomaterials; Figure 4 a (hAFSC sheet fragments). Another micrograph (Saline) is taken from Lee WY et al., 2012; Biomaterials; Figure 7a (HUVEC bodies) ![file] ![file] ,
Cathepsin L2, a novel human cysteine proteinase produced by breast and colorectal carcinomas
Authors: A Fueyo
C López-Otín
E Campo
I Santamaría
G Velasco
M Cazorla
Journal: Cancer research (1998)
Discipline: CLINICAL MEDICINE
Keywords: papain family; cysteine proteinases; cathepsin L2; amino acid sequence; structural characteristics
Affiliations: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, Spain.

Abstract:  We have identified and cloned a new member of the papain family of cysteine proteinases from a human brain cDNA library. The isolated cDNA codes for a polypeptide of 334 amino acids that exhibits all of the structural features characteristic of cysteine proteinases, including the active site cysteine residue essential for peptide hydrolysis. Pairwise comparisons of this amino acid sequence with the remaining human cysteine proteinases identified to date showed a high percentage of identity (78%) with cathepsin L; the percentage of identity with all other members of the family was much lower (&lt;40%). On the basis of these structural characteristics, we have tentatively called this novel protein cathepsin L2. The cDNA encoding the mature cathepsin L2 was expressed in Escherichia coli, and after purification, the recombinant protein was able to degrade the synthetic peptide benzyloxycarbonyl-L-phenylalanyl-L-arginine-7-amido-4-methylcoumarin, which is commonly used as a substrate for cysteine proteinases. Cathepsin L2 proteolytic activity on this substrate was abolished by trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, an inhibitor of cysteine proteinases, thus providing additional evidence that the isolated cDNA encodes a functional cysteine proteinase. Northern blot analysis of polyadenylated RNAs isolated from a variety of human tissues demonstrated that cathepsin L2 is predominantly expressed in the thymus and testis. This finding is in marked contrast with the wide tissue distribution of most cysteine proteinases characterized to date, including cathepsin L, and suggests that cathepsin L2 may play a specialized role in the thymus and testis. Expression analysis of cathepsin L2 in human tumors revealed a widespread expression in colorectal and breast carcinomas but not in normal colon or mammary gland or in peritumoral tissues. Cathepsin L2 was also expressed by colorectal and breast cancer cell lines as well as by some tumors of diverse origin, including ovarian and renal carcinomas. These results open the possibility that this novel enzyme may be involved in tumor processes, as already reported for other cysteine proteinases, including cathepsin L. 

Retracted: No

PubPeer comments:
 Figure 4: More similar than expected. Could authors check it please? ![file] ,
RETRACTED: The role of ATG-7 contributes to pulmonary hypertension by impacting vascular remodeling
Authors: Yu-Mei Li
Xi-Xi Zeng
Li Zhang
Liang-Wan Chen
Jian-Qiang Ye
Xiao-Hui Wu
Xi Yang
Journal: Journal of Molecular and Cellular Cardiology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ATG-7; Pulmonary hypertension; Smooth muscle cell; Vascular remodeling.
Affiliations: School of Pharmacy, Fujian Medical University, Fuzhou 350122, China; Department of Toxicology, Fujian Center for Evaluation of New Drug, Fujian Medical University, Fuzhou, China., Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China; The Key Laboratory of Fujian Province University on Ion Channel and Signal Transduction in Cardiovascular Disease, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China., The Key Laboratory of Fujian Province University on Ion Channel and Signal Transduction in Cardiovascular Disease, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China., Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China. Electronic address: ., Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of Toxicology, Fujian Center for Evaluation of New Drug, Fujian Medical University, Fuzhou, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China. Electronic address: .

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). At the request of the authors, this article has been retracted following questions of data ownership that were brought to the Editor’s attention after publication. Concerns were raised over whether all data were generated in the authors’ lab, and over ownership of the models used. The authors were unable to reach a resolution with other labs involved, and as a result all authors have agreed to a retraction of this article. 

Retracted: Yes

PubPeer comments:
 Retracted, [29 December 2021] .  At the request of the authors, this article has been retracted following questions of data ownership that were brought to the Editor s attention after publication. Concerns were raised over whether all data were generated in the authors lab, and over ownership of the models used. The authors were unable to reach a resolution with other labs involved, and as a result all authors have agreed to a retraction of this article. ,
Inhibition of Sp1 functions by its sequestration into PML nuclear bodies
Authors: Kun-Sang Chang
Wen-Xin Zou
June Li
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Promyelocytic leukemia nuclear bodies; PML; Sp1; gene expression regulation; Chromatin immunoprecipitation
Affiliations: Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.

Abstract:  Promyelocytic leukemia nuclear bodies (PML NBs) are comprised of PML and a striking variety of its associated proteins. Various cellular functions have been attributed to PML NBs, including the regulation of gene expression. We report here that induced expression of PML recruits Sp1 into PML NBs, leading to the reduction of Sp1 transactivation function. Specifically, Chromatin immunoprecipitation (ChIP) assay demonstrated that induced expression of PML significantly diminishes the amount of Sp1 binding to its target gene promoter, immunofluorescence staining showed dramatic increase in the co-localization between PML and Sp1 upon induction of PML expression, moreover, PML and Sp1 co-fractionated in the core nuclear matrix. Our study further showed that PML promotes SUMOylation of Sp1 in a RING-motif-dependent manner, SUMOylation of Sp1 facilitates physical interaction between Sp1 and PML and recruitment of Sp1 into the PML NBs, the SUMO binding motif of PML was also important for its interaction with Sp1. The results of this study demonstrate a novel mechanism by which PML regulates gene expression through sequestration of the transcription factor into PML NBs. 

Retracted: No

PubPeer comments:
 Figure 5A. * Red, green, and blue boxes: In three panels, lanes 1 and 4 appear to look very similar to each other. Reported to the journal in October 2015, but no action taken as of today. ![file] ,
p70S6K is regulated by focal adhesion kinase and is required for Src-selective autophagy
Authors: Margaret C Frame
Christina Schoenherr
Emma Sandilands
Journal: Cellular Signalling (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Akt; Autophagosomes; FAK; PDK1; S6
Affiliations: Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, United Kingdom., Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, United Kingdom. Electronic address: .

Abstract:  Here we report that focal adhesion kinase (FAK) is required for optimal signalling to the Akt-p70S6K-S6 pathway in squamous cell carcinoma (SCC) cells. Specifically, in SCCs that are genetically deficient for FAK, there is reduced phosphorylation of Akt, p70S6K and S6, and signalling to Akt-p70S6K-S6 is more sensitive to inhibition by multiple agents that suppress the pathway. By contrast, mTOR is unaffected. Indeed, pharmacological agents that inhibit the Akt-p70S6K-S6 pathway, and PDK1 that lies upstream of Akt, also impair the autophagic targeting of activated c-Src (p-Src) in FAK deficient cells. This is associated with loss of a complex between p-Src and the autophagy protein LC3, a biochemical surrogate of impaired Src-selective autophagy. In keeping with a vital role for p70S6K, inhibition by a selective inhibitor and specific siRNA also impaired Src-selective autophagy. Finally, components of the PDK1-Akt-p70S6K signalling pathway were co-located with p-Src at autophagosomes, and Src and p70S6K co-exist in the same biochemical complex. We therefore deduce that the FAK-regulated signalling module PDK1-Akt-p70S6K that controls Src's intracellular trafficking operates at Src-containing autophagosomes. 

Retracted: No

PubPeer comments:
 Figure 1C. Much more similar than expected. ![file] , 
 ![file] , 
 #2 Signals for modified and unmodified proteins should be similar, but not the same. They do look very similar. Could the authors post the full blot here? The GAPDH loading control panel is a claim that all the panels are from the same bot. , 
 These ones are very similar in left lane but not in right lane which I think confirms it is different. We often find re-probed stripped blot species can be very similar (total antibody and phospho-antibody) with regard to shape of band and bubbles etc. All these are blotted from same lysates but may have been run on different gels. The GAPDH blot is from exactly same cell lysates. , 
 ![file] ![file] ![file] ,
Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis
Authors: Maurizio Moroni
Paolo Pinton
Massimo Marcaccio
Marco Giorgio
Giovanni Pelliccia
Cristina Contursi
Francesca Orsini
Saverio Minucci
Pier Giuseppe Pelicci
Enrica Migliaccio
Demis Paolucci
Lucilla Luzi
Paolo Bernardi
Rosario Rizzuto
Francesco Paolucci
Journal: Cell (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Reactive oxygen species; apoptosis; mitochondria; p66Shc; ROS metabolism
Affiliations: Experimental Oncology Department, European Institute of Oncology, Milan, Italy. 

Abstract:  Reactive oxygen species (ROS) are potent inducers of oxidative damage and have been implicated in the regulation of specific cellular functions, including apoptosis. Mitochondrial ROS increase markedly after proapoptotic signals, though the biological significance and the underlying molecular mechanisms remain undetermined. P66Shc is a genetic determinant of life span in mammals, which regulates ROS metabolism and apoptosis. We report here that p66Shc is a redox enzyme that generates mitochondrial ROS (hydrogen peroxide) as signaling molecules for apoptosis. For this function, p66Shc utilizes reducing equivalents of the mitochondrial electron transfer chain through the oxidation of cytochrome c. Redox-defective mutants of p66Shc are unable to induce mitochondrial ROS generation and swelling in vitro or to mediate mitochondrial apoptosis in vivo. These data demonstrate the existence of alternative redox reactions of the mitochondrial electron transfer chain, which evolved to generate proapoptotic ROS in response to specific stress signals. 

Retracted: No

PubPeer comments:
 Figure 6D. Much more similar than expected. ![file] ,
Scara1 deficiency impairs clearance of soluble amyloid-β by mononuclear phagocytes and accelerates Alzheimer’s-like disease progression
Authors: Terry K Means
Lindsay Puckett
Nathan D Kingery
Kim Wilkinson
Dan Frenkel
Howard L Weiner
Joseph El Khoury
Suzanne E Hickman
Lingzhi Zhao
Dorit Farfara
Journal: Nature Communications (2013)
Discipline: Multidisciplinary
Keywords: Alzheimer's disease; soluble amyloid-β; synaptic dysfunction; neuronal loss; scavenger receptor
Affiliations: Department of Neurobiology, Sagol School of Neuroscience, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 699788, Israel.

Abstract:  In Alzheimer's disease, soluble amyloid-β causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of soluble amyloid-β are not known. Here we use short hairpin RNA screening and identify the scavenger receptor Scara1 as a receptor for soluble amyloid-β expressed on myeloid cells. To determine the role of Scara1 in clearance of soluble amyloid-β in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer's disease, and generate PS1-APP-Scara1-deficient mice. Scara1 deficiency markedly accelerates Aβ accumulation, leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer's disease. 

Retracted: No

PubPeer comments:
 A few concerns with this article 1. It is well known that B6C3-Tg (APPswe, PSEN1dE9)85Dbo J stock number 004462 has a highly variable amount of Abeta levels (measured by ELISA) and amyloid (measured by IHC). With ONLY N=4-6 mice per group, it will be almost impossible to get such a tight error bar shown in Figure 4e and Supplementary Figure S3. 2. Although Abeta levels were measured by ELSIA with 5 months old group (Supplementary Figure S3), why was there no supporting ELISA for 8 months old group used for Figure 4e? 3. This particular mouse model is known to have a HUGE sex difference in Abeta levels. The sex of each mouse was not indicated in this article. If the authors did not know this sex difference and used male and female mixed sex, the tiny error bars reported in Figure 4e and Supplementary Figure S3 are almost impossible to obtain. ,