PReD-Bench/PRed-Bench huggingface dataset:
Quercetin attenuates myocardial ischemia-reperfusion injury via downregulation of the HMGB1-TLR4-NF-κB signaling pathway
Authors: Yu Zhuang
Li-Ya Dong
Feng Chen
Li-Ping Yao
Min Xu
Yun-Jiao Zhang
Journal: American journal of translational research (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Quercetin; inflammation; myocardial ischemia-reperfusion.
Affiliations: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200092, China., Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University Nanjing 210018, China., Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200080, China.

Abstract:  The goal of this study was to assess the ability of quercetin (Qu) to protect against myocardial ischemia-reperfusion injury. Cardiac injury was assessed in the context of global ischemia of isolated hearts, coronary artery ligated rats, and H9C2 cells. Qu was shown to significantly inhibit inflammatory cytokine production in coronary artery occlusion-induced rats, isolated hearts, and H9C2 cells. Electrocardiographic analysis revealed a restoration of the ST segment to normal levels following treatment of Qu. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that Qu could significantly alleviate myocardial injury in vivo. Furthermore, ex vivo analyses showed improved recovery of heart function in response to Qu, characterized by enhanced myocardial contractility and coronary flow in isolated hearts. From a mechanistic standpoint, these effects appeared to be mediated through the HMGB1-related pathway, with expression of downstream targets significantly downregulated in rats, isolated hearts, and H9C2 cells following Qu treatment. Taken together, these data demonstrate the protective effects of Qu against myocardial injury via inhibition of the HMGB1 pathway in a myocardial ischemia-reperfusion injury (I/R) model. 

Retracted: No

PubPeer comments:
 Figure 2.  Effect of Qu on myocardial histology (A)... in I R-induced isolated heart . ![file] I cannot endorse the integrity of these images. I ran out of enthusiasm before marking all the repeated areas of wallpaper. The other two panels are left as an exercise for the reader. ![file] , 
 Figure 6.  Effects of Qu on HMGB1, TLR4 and p-NF-u03baB protein expression by immunohistochemistry . ![file] I cannot vouch for the integrity of these images. ![file] ,
Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation
Authors: Ian R Logan
David E Neal
Luke Gaughan
Craig N Robson
Journal: Nucleic Acids Research (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Androgen receptor; AR regulation; Mdm2; HDAC1; transcription factors
Affiliations: Prostate Research Group, Northern Institute for Cancer Research Paul, O'Gorman Building University of Newcastle Upon Tyne, Medical School Framlington Place, Newcastle Upon Tyne NE2 4HH, UK.

Abstract:  The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors and plays a critical role in regulating the expression of genes involved in androgen-dependent and -independent tumour formation. Regulation of the AR is achieved by alternate binding of either histone acetyltransferase (HAT)-containing co-activator proteins, or histone deacetylase 1 (HDAC1). Factors that control AR stability may also constitute an important regulatory mechanism, a notion that has been confirmed with the finding that the AR is a direct target for Mdm2-mediated ubiquitylation and proteolysis. Using chromatin immunoprecipitation (ChIP) and re-ChIP analyses, we show that Mdm2 associates with AR and HDAC1 at the active androgen-responsive PSA promoter in LNCaP prostate cancer cells. Furthermore, we demonstrate that Mdm2-mediated modification of AR and HDAC1 catalyses protein destabilization and attenuates AR sactivity, suggesting that ubiquitylation of the AR and HDAC1 may constitute an additional mechanism for regulating AR function. We also show that HDAC1 and Mdm2 function co-operatively to reduce AR-mediated transcription that is attenuated by the HAT activity of the AR co-activator Tip60, suggesting interplay between acetylation status and receptor ubiquitylation in AR regulation. In all, our data indicates a novel role for Mdm2 in regulating components of the AR transcriptosome. 

Retracted: No

PubPeer comments:
 Figure 2B. Much more similar than expected. ![file] ![file] , 
 2021 correction. https: academic.oup.com nar advance-article doi 10.1093 nar gkab741 6362076 The authors report several errors in the construction of Figures 1 and 2 of their original publication, as described below (1). Figure 1B: Input samples in panel (ii) were duplicated from panel (i). The original data and corrected Figure 1B(ii) are provided below. Figure 2B and 2D: Several panels were duplicates. The original data and corrected Figure 2B and 2D are provided below. The interpretation of the figures and the conclusions of the article are unaffected. However the authors wish to unreservedly apologise to the readers and publisher for these mistakes. ,
The effect of platelet rich plasma on chondrogenic differentiation of human adipose derived stem cells in transwell culture
Authors: Abbasali Pourazar
Malekmassoud Ansar
Ebrahim Esfandiari
Batool Hashemibeni
Abolghasem Esmaeili
Mohammad Mardani
Azadeh Kabiri
Journal: Iranian journal of basic medical sciences (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Adipose-derived stem cells; Platelet-rich plasma; Transwell culture.
Affiliations: Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran., Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Anatomical Sciences, Paramedical school, Guilan University of Medical Sciences, Langeroud, Iran., Cell, Molecular and Developmental Biology Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran., Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan Iran., Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Anatomical Sciences, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.

Abstract:  Platelet-rich plasma (PRP) has recently emerged as a promising strategy in regenerative medicine due to its multiple endogenous growth factors. Little is known about the role of PRP as a promoter in chondrogenesis of human adipose derived stem cells (hADSCs). The aim of this study was to determine whether PRP may be considered as a natural and easy achievable source of growth factors to promote the chondrogenic differentiation of hADSCs in Transwell culture. Materials and Methods : Biochemical, immunohistological and molecular assays were used to evaluate the effect of different concentrations (5%, 10%, and 15%) of PRP on chondrogenic differentiation of hADSCs in Transwell culture. Results : The cells in the presence of 10% PRP produced markedly higher amounts of GAG and DNA, in comparison to the control group. PRP also increased chondrogenic markers in these cells, such as sox-9, aggrecan and collagen type II. A high expression level of collagen type X as a hypertrophic marker was observed in cartilage produced by using either PRP or TGF-β1. Conclusion : Our findings indicate that autologous PRP at an optimum concentration had beneficial effects on differentiation of hADSCs in Transwell culture. Further, in vivo studies are necessary to fully define the clinical implications of PRP. 

Retracted: No

PubPeer comments:
 image duplications ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase
Authors: Rakesh Kumar
Christopher J Barnes
Anupama Gururaj
Ratna K Vadlamudi
Journal: Oncogene (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cell signaling; metabolic pathways; p21-activated kinase 1 (Pak1); phosphoglucomutase 1 (PGM); glucose utilization
Affiliations: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract:  We have identified a novel mechanism of cross-talk between cell signaling and metabolic pathways, whereby the signaling kinase p21-activated kinase 1 (Pak1) binds to, phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 (PGM), an important regulatory enzyme in cellular glucose utilization and energy homeostasis. Pak1 and PGM were colocalized in model cell systems and showed functional interactions in a physiological setting. Strong direct interaction of PGM with Pak1 but not Pak2, Pak3, or Pak4 was observed. PGM binding was within 75-149 amino acids (aa) of Pak1, while Pak1 binding to PGM was in the N-terminal 96 aa. Pak1-mediated phosphorylation of PGM selectively on threonine 466 significantly increased PGM enzymatic activity and could be blocked by transfection with a dominant-negative Pak1 expression vector and by Pak1-specific small inhibitory RNA. Stable transfection of PGM into PGM-deficient K562 leukemia cells further demonstrated the role of Pak1 in regulating PGM activity. The results presented here provide new evidence that the cell signaling kinase Pak1 is a novel regulator of glucose metabolism through its phosphorylation and regulation of PGM activity. These findings suggest a new mechanism whereby growth factor signaling may coordinately integrate metabolic regulation with established signaling functions of cell cycle regulation and cell growth. 

Retracted: No

PubPeer comments:
 Figure 2b. Much more similar than expected. https: imgur.com KL2NO3X ,
Ox-LDL induces endothelial cell apoptosis and macrophage migration by regulating caveolin-1 phosphorylation
Authors: Weizhong Han
Likai Pei
Lianqun Cui
Shiliang Jiang
Bo Dong
Min Li
Fei Lin
Yanliang Lin
Qingbin Zhang
Journal: Journal of Cellular Physiology (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HMGB1; caveolin-1; endothelial injury; macrophage; oxidative low-density lipoprotein.
Affiliations: Department of Cardiology; Shandong Energy Zibo Mining Group Co., Ltd Central Hospital; Zibo China, Department of Cardiology; Shandong Provincial Hospital Affiliated to Shandong University; Jinan China, Department of Center Laboratory; Shandong Provincial Hospital Affiliated to Shandong University; Jinan China

Abstract:  Oxidative low-density lipoprotein (ox-LDL) is a risk factor for atherosclerosis. Ox-LDL leads to endothelial injury in the initial stage of atherosclerosis. In this study, we investigated the role of ox-LDL in endothelial injury and macrophage recruitment. We demonstrated that ox-LDL promoted a dose-dependent phosphorylation of caveolin-1 in human umbilical vein endothelial cells. Phosphorylated caveolin-1 increased ox-LDL uptake. Intracellular accumulation of ox-LDL induced NF-κB p65 phosphorylation, promoted HMGB1 translocation from nucleus to cytoplasm and cytochrome C release from mitochondria to cytoplasm, and activated caspase 3, resulting in cell apoptosis. NF-κB activation also facilitated cavolin-1 phosphorylation and HMGB1 expression. In addition, caveolin-1 phosphorylation favored HMGB1 release and nuclear translocation of EGR1. Nuclear translocation of EGR1 contributed to cytoplasmic translocation of HMGB1. The extracellular HMGB1 induced the migration of PMBC-derived macrophages toward HUVECs in a TLR4-dependent manner. Our results suggested that ox-LDL promoted HUVECs apoptosis and macrophage recruitment by regulating caveolin-1 phosphorylation. 

Retracted: No

PubPeer comments:
 Figures 4 and 5. * Red boxes: The Con panel in Figure 4C looks very similar to the Anti-HMGB1 panel in Figure 5E, if one of the two is mirrored. ![file] , 
 #1 Thank you very much for your correction. This is indeed our mistake. We accidentally placed the wrong picture. We have contacted the mag![file] ![file] ![file] azine for correction. Thanks again for your letter! , 
 Dear Dr. Li, Has there been a correction issued yet? It has been over a year since we discussed this duplication. ,
The mitospecific domain of Mrp7 (bL27) supports mitochondrial translation during fermentation and is required for effective adaptation to respiration
Authors: Jessica M Anderson
Jodie M Box
Rosemary A Stuart
Journal: Molecular Biology of the Cell (2022)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mitoribosomal protein synthesis; oxidative phosphorylation; fermentation; OXPHOS complex assembly; Mrp7
Affiliations: Department of Biological Sciences, Marquette University, Milwaukee, WI 53233

Abstract:  We demonstrate here that mitoribosomal protein synthesis, responsible for the synthesis of oxidative phosphorylation (OXPHOS) subunits encoded by the mitochondrial genome, occurs at high levels during glycolysis fermentation and in a manner uncoupled from OXPHOS complex assembly regulation. Furthermore, we provide evidence that the mitospecific domain of Mrp7 (bL27), a mitoribosomal component, is required to maintain mitochondrial protein synthesis during fermentation but is not required under respiration growth conditions. Maintaining mitotranslation under high-glucose-fermentation conditions also involves Mam33 (p32/gC1qR homologue), a binding partner of Mrp7's mitospecific domain, and together they confer a competitive advantage for a cell's ability to adapt to respiration-based metabolism when glucose becomes limiting. Furthermore, our findings support that the mitoribosome, and specifically the central protuberance region, may be differentially regulated and/or assembled, under the different metabolic conditions of fermentation and respiration. On the basis of our findings, we propose that the purpose of mitotranslation is not limited to the assembly of OXPHOS complexes, but also plays a role in mitochondrial signaling critical for switching cellular metabolism from a glycolysis- to a respiration-based state. 

Retracted: No

PubPeer comments:
 In Figure 2B, two of the blots appear highly similar to each other (marked with red boxes): ![file] Enlarged sections of the figure, notice for example similar  notches on the 6th and 7th band from the left. ![file] Could the authors please check and if possible, provide the original uncropped images? ,
Cyclin-dependent kinase 8 regulates mitotic commitment in fission yeast
Authors: Christopher J McInerny
Marcela Davila Lopez
Zsolt Szilagyi
Gabor Banyai
Claes M Gustafsson
Journal: Molecular and Cellular Biology (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Transcription programs; cell growth; cell division; Mediator; regulatory pathway
Affiliations: Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden. 

Abstract:  Temporal changes in transcription programs are coupled to control of cell growth and division. We here report that Mediator, a conserved coregulator of eukaryotic transcription, is part of a regulatory pathway that controls mitotic entry in fission yeast. The Mediator subunit cyclin-dependent kinase 8 (Cdk8) phosphorylates the forkhead 2 (Fkh2) protein in a periodic manner that coincides with gene activation during mitosis. Phosphorylation prevents degradation of the Fkh2 transcription factor by the proteasome, thus ensuring cell cycle-dependent variations in Fkh2 levels. Interestingly, Cdk8-dependent phosphorylation of Fkh2 controls mitotic entry, and mitotic entry is delayed by inactivation of the Cdk8 kinase activity or mutations replacing the phosphorylated serine residues of Fkh2. In addition, mutations in Fkh2, which mimic protein phosphorylation, lead to premature mitotic entry. Therefore, Fkh2 regulates not only the onset of mitotic transcription but also the correct timing of mitotic entry via effects on the Wee1 kinase. Our findings thus establish a new pathway linking the Mediator complex to control of mitotic transcription and regulation of mitotic entry in fission yeast. 

Retracted: No

PubPeer comments:
 This paper has a corrigendum for Figure 4, which reads:  Volume 32, no. 11, p. 2099 u20132109, 2012, https: doi.org 10.1128 MCB.06316-11. Page 2105, Fig. 4: Due to the way the original figure was arranged, the Coomassie-stained proteins displayed in panels D to F could be misinterpreted as loading controls. To avoid misinterpretation, the CBB blots in these panels should be removed and a new panel G should be added as shown below. We are sorry for any confusion this may have caused. It is worth pointing out how the original figure looked like. The correction completely removed a figure that contained potential repeating elements. Here is the original figure, highlighted with colored arrows to show bands that look unexpectedly similar. One could wonder how such a figure could be  misinterpreted , and whether this would warrant a simple correction. ![file] ,
The kinases aurora B and mTOR regulate the G1–S cell cycle progression of T lymphocytes
Authors: Shahram Salek-Ardakani
Michael Croft
Takanori So
Jianxun Song
Journal: Nature Immunology (2007)
Discipline: IMMUNOLOGY
Keywords: CD28-deficient T cells; G1-S transition; aurora B; survivin; mammalian target of rapamycin (mTOR)
Affiliations: Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.

Abstract:  CD28-deficient T cells arrest at the G1-S transition of the cell cycle. Here we show that this is controlled by the kinase aurora B, which exists in a complex with survivin and mammalian target of rapamycin (mTOR). Expression of aurora B in Cd28-/- T cells augmented phosphorylation of mTOR substrates, expression of cyclin A, hyperphosphorylation of retinoblastoma protein and activation of cyclin-dependent kinases 1 and 2 and promoted cell cycle progression. Interleukin 2 enhanced aurora B activity, and inactive aurora B prevented interleukin 2-induced proliferation. Moreover, expression of aurora B restored Cd28-/- T cell proliferation and promoted inflammation in vivo. These data identify aurora B, along with survivin and mTOR, as a regulator of the G1-S checkpoint in T cells. 

Retracted: No

PubPeer comments:
 Supplemental Fig. 1 u2013 more similar than expected ![file] ,
Novel pyochelin-based PEGylated liposomes for enhanced delivery of antibiotics against resistant clinical isolates of Pseudomonas aeruginosa
Authors: Malathy Balaraman Ravindrran
Jayshree Nellore
Uma Sekar
Pradeep Pushparaj Selvadoss
Journal: Artificial Cells Nanomedicine and Biotechnology (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Liposome; Pseudomonas aeruginosa; drug delivery; multi-drug resistance; pyochelin.
Affiliations: a Faculty of Bioengineering , Sathyabama University , Chennai , India., b Department of Biotechnology , Sathyabama University , Chennai , India., c Department of Microbiology , Sathyabama University Dental College and Hospital , Chennai , India., d Department of Microbiology , Sri Ramachandra University , Chennai , India.

Abstract:  Pseudomonas aeruginosa is a problematic human pathogen resistant to almost all available antibiotics. The important prerequisite for these drugs to target this bacterium is an efficient delivery system. Siderophore-mediated drug delivery system is a promising approach to carry out antibiotics to the cells. Pyochelin, a siderophore of P. aeruginosa, was successfully synthesized in a five-step procedure. PEGylated liposomal pyochelin-antibiotic (L-Pch-Ab) carrier was fabricated by thin-film hydration method. L-Pch-Ab had an average size of 90.31 ± 0.11 nm holding a negative zeta potential at -54.12 ± 0.03 mV (PDI &lt;2). The MIC determined by broth dilution method against three clinical strains isolated from burn wounds showed that L-Pch-Ab significantly reduced (≤16 µg/ml) the MIC values than those of free antibiotics. In the time kill assay, L-Pch-Ab was bactericidal against all strains at most time intervals at 2 × and 4 × MIC up to 24 h. TEM observations revealed that L-Pch-Ab was actively taken up by P. aeruginosa and exhibited membrane deformation within 2 h. Developed L-Pch-Ab fused intimately with the outer membrane of MDRPa and exhibited effective antibacterial activity than free Ab. Furthermore, L-Pch-Ab kills MDRPa within infected HaCaT keratinocytes without any cytotoxic effects at 4× MIC concentrations after 72 h. Thus, the specific targeting of L-Pch-Ab with its higher efficacy to deliver drug by limiting the toxicity will be a novel approach to fight infections caused by P. aeruginosa. 

Retracted: No

PubPeer comments:
 Scheme 1 : many errors : aromatic ring without double bonds, reaction between nor-pyochelin and 3-tert-butoxycarbonylamino-propyl ester (false structure) cannot give the compound described. Scheme 3 : a nucleus in a prokaryotic cell, really ?!!! ,
Protein kinase C Inhibitors selectively modulate dynamics of cell adhesion molecules and cell death in human colon cancer cells
Authors: Hulya Ayar Kayali
Duygu Erdogan
Muzaffer Dükel
Deniz Erkan Gök
Zehra Tavsan
Journal: Cell Adhesion & Migration (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Colon cancer; cell adhesion molecules; cell death; protein kinase C; reactive oxygen species.
Affiliations: Moleculer Biology and Genetic Department, Faculty of Art and Science, Mehmet Akif Ersoy University, Burdur, Turkey, Izmir Biomedicine and Genome Center, Izmir, Turkey, Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey, Biochemistry Division, Chemistry Department, Science Faculty, Dokuz Eylul University, Izmir, Turkey

Abstract:  During development of colon cancer, Protein Kinase Cs (PKCs) are involved in regulation of many genes controlling several cellular mechanisms. Here, we examined the changes in cell adhesion molecules and PKCs for colorectal cancer progression. We identified that PKCs affected expression of EpCAM, claudins, tetraspanins. Treatment with low concentrations of PKC inhibitors resulted in decreased cell viability. In addition, immunoblotting and qRT-PCR analysis showed that apoptosis was inhibited while autophagy was induced by PKC inhibition in colon cancer cells. Furthermore, we observed decreased levels of intracellular Reactive Oxygen Species (ROS), lipid peroxidation and protein carbonyl, confirming the ROS-induced apoptosis. Taken together, our results reveal that PKC signalling modulates not only cell adhesion dynamics but also cell death-related mechanisms. Abbreviations: PKC: Protein Kinase C; EpCAM: Epithelial cell adhesion molecule; FBS: fetal bovine serum; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide); CAM: cell adhesion molecule; ROS: reactive oxygen species. 

Retracted: No

PubPeer comments:
 Figure 1A. * Blue boxes: The CD82 panel looks unexpectedly similar to four lanes in the Claudin-1 panel in Figure 9D of another paper by the same research group, i.e. Du00fckel et al., Process Biochemistry (2021), doi: 10.1016 j.procbio.2020.10.002 ![file] , 
 Figure 3. * Pink boxes: Three lanes in the EpCAM panel of Caco-2 cells (C) look similar to lanes in the TSPAN8 panel of Caco-2 cells (C) and to lanes in the EpCAM panel of SSW620 cells (G), albeit in different orientations. ![file] , 
 Thanks for the comments for our work. Those bands are not same, I agree they look similar but they are not same bands. Plus some western blot bands might look very similar , 
 #3 Dear Dr. Dukel: Thank you for your reply. Can you please supply the uncropped original scans? This is the best way to address image concerns of this type. , 
 Dear Dr. Du00fckel, Could you post the original films scans of those blots marked with the pink boxes, in high resolution, please? I mean the complete scans with MW markers and edges of the blot, etc. That might take away any concerns. You can post up to 1 MB files here, or larger files on e.g. Google Drive or Imgur. Thank you! ,
miRNA-21 promotes cell proliferation and invasion via VHL/PI3K/AKT in papillary thyroid carcinoma
Authors: Ruifeng Ge
Chuanshan Zang
Wenyi Liu
Jian Sun
Chunqin Chu
Liwei Jiang
Journal: Human Cell (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EMT; Invasion; Papillary thyroid carcinoma; VHL; miR-21.
Affiliations: Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China., Department of Anesthesia, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, Shandong, People's Republic of China. ., Department of Anesthesia, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, Shandong, People's Republic of China.

Abstract:  Papillary thyroid carcinoma (PTC) is the main kind of thyroid carcinoma, most of which are diagnosed in women. MiR-21 has been reported to be upregulated in multiple cancers to effect tumor growth. However, the role of miR-21 in PTC development remains unclear. In this present study, miR-21 and VHL expressions in PTC tissues and cells were evaluated by RT-qPCR and/or western blot. MTT assay and transwell assay were employed to assess cell proliferative and invasive abilities, respectively. Luciferase reporter assay was carried out to identify the target of miR-21and explore its roles in PTC. MiR-21 was upregulated in PTC tissues and cells. Ectopic of miR-21 expression promoted cell proliferative and invasive abilities, while knockdown miR-21 suppressed these in TPC-1 and BCPAP cells. Overexpression of miR-21 predicted poor prognosis in PTC. What is more, luciferase reporter assays showed miR-21 can directly target VHL in PTC cells. Knockdown of miR-21 expression inhibited TPC-1 and BCPAP cell invasion-mediated EMT and proliferation through the PI3K/AKT pathway. In addition, VHL reverses partial function of miR-21 on PTC cell proliferation and invasion. MiR-21 can inhibit cell proliferation and invasion by regulated VHL in PTC cells. The newly identified miR-21/VHL axis might provide a novel insight into the pathogenesis and therapy of PTC. 

Retracted: No

PubPeer comments:
  The papillary thyroid carcinoma and corresponding adjacent normal tissues were obtained from 52 patients undergoing operation from **January 2015 to December 2017** in the Affiliated Hospital of Qingdao University. According to Fig 1b, the authors followed their patients survival for 12-1 2 years after recruiting them, i.e. through to the date range **July 2027 to June 2030**. Was a time machine involved? ![] , 
 #1 I m sorry, it s a typo.The correct sample collection time was from 2005 to 2007. ,
MiR-202 inhibits the proliferation and invasion of colorectal cancer by targeting UHRF1
Authors: Ji Gao
Shaoqin Chen
Yisu Liu
Yan Zheng
Suyong Lin
Yilin Lin
Zhihua Chen
Journal: Acta Biochimica et Biophysica Sinica (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: UHRF1; colorectal cancer; invasion; miR-202; proliferation.
Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China, Fujian University of Medicine, School of Nursing, Fuzhou, China

Abstract:  The purpose of this study was to investigate the expression of microRNA-202 (miR-202) and its role in colorectal cancer (CRC) in vivo and in vitro. We examined the expression of miR-202 in CRC tissues by quantitative real-time PCR (qRT-PCR) assay. Lentiviral vectors were constructed to overexpress or inhibit the expression of miR-202 in the CRC cell lines HCT116 and SW480 to determine its effects on cell invasion and proliferation. We found that overexpression of miR-202 significantly inhibited the proliferation and invasion of HCT116 cells. MiRNA target gene prediction, dual luciferase assay, and western blot analysis demonstrated that miR-202 regulated ubiquitin-like with PHD and RING finger domain 1 (UHRF1) expression in both cell lines. The effect of miR-202 on cell proliferation and invasion was partially reversed by activating the expression of UHRF1. Furthermore, miR-202 induced tumor formation in HCT116 xenograft BALB/c nude mice. Mice vaccinated with miR-202-overexpressing cells had smaller tumors and lower UHRF1 expression than the control group. These results indicate the possibility that miR-202 is under-expressed in CRC tissues, and that miR-202 inhibits the proliferation and invasion of CRC via targeting UHRF1. MiR-202 is a potential therapeutic target for CRC. 

Retracted: No

PubPeer comments:
 Figure 2C and 5B (updated) * Blue, green, and red boxes: Three panels appear to show an overlap with each other. The blue and green boxes might be showing the same experiment, but the red boxes do not. ![file] ,
dapk1, encoding an activator of a p19ARF-p53-mediated apoptotic checkpoint, is a transcription target of p53
Authors: Alain Martoriati
Myriam Alcalay
Gilles Doumont
Jean-Christophe Marine
Eric Bellefroid
Pier Giuseppe Pelicci
Journal: Oncogene (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p53; tumour suppressor; transcriptional activator; p53-inducible genes; proapoptotic
Affiliations: Laboratory for Molecular Cancer Biology, Flanders Interuniversity Institute for Biotechnology (VIB), Technologiepark, 927, Ghent B-9052, Belgium.

Abstract:  The p53 tumour suppressor functions as a transcriptional activator, and several p53-inducible genes that play a critical proapoptotic role have been described. Moreover, p53 regulates the expression of various proteins participating in autoregulatory feedback loops, including proteins that negatively control p53 stability (Mdm2 and Pirh2) or modulate stress-induced phosphorylation of p53 on Ser-46 (p53DINP1 or Wip1), a key event for p53-induced apoptosis. Here, we describe a new systematic analysis of p53 targets using oligonucleotide chips, and report the identification of dapk1 as a novel p53 target. We demonstrate that dapk1 mRNA levels increase in a p53-dependent manner in various cellular settings. Both human and mouse dapk1 genomic loci contain DNA sequences that bind p53 in vitro and in vivo. Since dapk1 encodes a serine/threonine kinase previously shown to suppress oncogene-induced transformation by activating a p19ARF/p53-dependent apoptotic checkpoint, our results suggest that Dapk1 participates in a new positive feedback loop controlling p53 activation and apoptosis. 

Retracted: No

PubPeer comments:
 Much more similar than expected. ![file] ![file] ,
Identification of a novel circular RNA circZNF652/miR-486-5p/SERPINE1 signaling cascade that regulates cancer aggressiveness in glioblastoma (GBM)
Authors: Shan Xiao
Zifeng Zhu
Yan Wang
Liang Liu
Rongkang Mai
Yiyao Cao
Yong Zheng
Sen Yang
Journal: Bioengineered (2022)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Circznf652; SERPINE1; exosomes; glioblastoma; miR-486-5p.
Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China, Department of Endocrinology, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China, Department of General Practice Medicine, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China

Abstract:  Circular RNAs (circRNAs) are closely associated with cancer development in glioblastoma (GBM), and this study aims to explore the molecular mechanisms of a novel circular RNA circZNF652 in regulating GBM aggressiveness. The present study found that CircZNF652 and SERPINE1 were upregulated, while miR-486-5p was downregulated in GBM tissues and cell lines, and GBM patients with high expression of CircZNF652 and SERPINE1, and patients with low expression of miR-486-5p tended to have a worse prognosis. Further results validated that both silencing of circZNF652 and miR-486-5p overexpression suppressed cell growth, migration, invasion, epithelial-mesenchymal transition (EMT) and tumorigenesis in GBM cells in vitro and in vivo. Next, the underlying mechanisms were investigated, and we found that circZNF652 sponged miR-486-5p to upregulate SERPINE1 in GBM cells. Also, we validated that knock-down of circZNF652 regulated the miR-486-5p/SERPINE1 axis to reverse the malignant phenotypes in GBM cells. Interestingly, we noticed that GBM cells derived exosomes were characterized by high-expressed CircZNF652. Collectively, we concluded that targeting the circular RNA circZNF652/miR-486-5p/SERPINE1 axis was a novel and effective strategy to suppress cancer progression in GBM. 

Retracted: No

PubPeer comments:
 At least three cases of data duplications have been detected in Figure 3g, 4j and 7g. In all cases, data has been presented as something else. With simple tools it is possible to detect data duplications. Therefore it is surprising and sad to see that the publisher, Taylor Francis apparenly do not prioritize quality control of manuscripts. ![file] , 
 Since there is no response from the authors or papermill, I can continue: One qRT-PCR primer sequence appears to be incorrect. Two of the primary antibodies used for Western immunoblotting appear to be incorrect. Xenograft experiment: mismatch between total number of mice presented in Materials and methods (20) and number of mice presented in Figure 8. ![file] ,
CD73-dependent adenosine dampens interleukin-1β-induced CXCL8 production in gingival fibroblasts: Association with heme oxygenase-1 and adenosine monophosphate-activated protein kinase
Authors: Robson Coutinho-Silva
Erivan Schnaider Ramos-Junior
Ana Carolina Morandini
David M Ojcius
Drake Exstrom
Özlem Yilmaz
Renee E Lee
Michael Pedram
Journal: Journal of Periodontology (2020)
Discipline: CLINICAL MEDICINE
Keywords: 5′-nucleotidase; adenosine; adenosine triphosphate; fibroblasts; gingiva
Affiliations: Department of Biomedical SciencesArthur A. Dugoni School of DentistryUniversity of the Pacific San Francisco CA USA, Doctor of Dental Surgery Program, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA, USA., Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA, USA., College of Letters & Sciences, University of California, Berkeley, CA, USA., Department of Oral Health Sciences and Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA., Immunobiology ProgramInstitute of Biophysics Carlos Chagas FilhoFederal University of Rio de Janeiro Rio de Janeiro RJ Brazil

Abstract:  Background: During inflammation, stressed or infected cells can release adenosine triphosphate (ATP) to the extracellular medium, which can be hydrolyzed to adenosine by ectonucleotidases such as ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and 5'-nucleotidase (CD73). The role of CD73 in the modulation of cytokine release by human gingival fibroblasts (HGFs) remains underexplored. Here, we investigated whether CD73-mediated hydrolysis of extracellular ATP (eATP) could affect interleukin (IL)-1β-induced CXCL8 secretion. Methods: The levels of mRNA expression of adenosine receptors, CD39 and CD73 of periodontitis samples were retrieved from a public database. Moreover, HGF mRNA levels were measured by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) after 3, 6, or 24 hours of IL-1β stimulation. IL-1β-induced CXCL8 protein levels were measured after pretreatment with 100-µM eATP in the presence or absence of CD73 inhibitor. The effect of eATP degradation to adenosine on CXCL8 levels was investigated using agonist and antagonist of adenosine receptors. Results: Levels of CD39, CD73, and adenosine receptor mRNA were differentially modulated by IL-1β. ATP pretreatment impaired IL-1β-induced CXCL8 secretion and required activation of heme oxygenase-1 (HO-1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK). The inhibition of CD73 or the inhibition of adenosine receptors abrogated the ATP effect on CXCL8 secretion. Conclusions: CD73-generated adenosine dampens IL-1β-induced CXCL8 in HGFs and involves HO-1 and pAMPK signaling. These results imply that CD73 is a negative regulator of the inflammatory microenvironment, suggesting that this ectoenzyme could be involved in the generation of deficient CXCL8 gradient in chronic inflammation. 

Retracted: No

PubPeer comments:
 Figures 4B and 5F share the same loading Actin, but they differ in the HO-1 bands. ![file] ,
Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl
Authors: Asok Mukhopadhyay
Bharat B Aggarwal
Kate Denning
Ruby John Anto
Journal: Carcinogenesis (2002)
Discipline: CLINICAL MEDICINE
Keywords: Curcumin; Anticancer agents; Tumor cells; Apoptosis pathway; Caspase-8
Affiliations: Cytokine Research Section, Department of Bioimmunotherapy, Box 143, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.

Abstract:  Pharmacologically safe compounds that can inhibit the proliferation of tumor cells have potential as anticancer agents. Curcumin, a diferuloylmethane, is a major active component of the food flavor turmeric (Curcuma longa) that has been shown to inhibit the proliferation of a wide variety of tumor cells. The apoptotic intermediates through which curcumin exhibits its cytotoxic effects against tumor cells are not known, and the participation of antiapoptotic proteins Bcl-2 or Bcl-xl in the curcumin-induced apoptosis pathway is not established. In the present report we investigated the effect of curcumin on the activation of the apoptotic pathway in human acute myelogenous leukemia HL-60 cells and in established stable cell lines expressing Bcl-2 and Bcl-xl. Curcumin inhibited the growth of HL-60 cells (neo) in a dose- and time-dependent manner, whereas Bcl-2 and Bcl-xl-transfected cells were relatively resistant. Curcumin activated caspase-8 and caspase-3 in HL-60 neo cells but not in Bcl-2 and Bcl-xl-transfected cells. Similarly, time-dependent poly(ADP)ribose polymerase (PARP) cleavage by curcumin was observed in neo cells but not in Bcl-2 and Bcl-xl-transfected cells. Curcumin treatment also induced BID cleavage and mitochondrial cytochrome c release in neo cells but not in Bcl-2 and Bcl-xl-transfected cells. In neo HL-60 cells, curcumin also downregulated the expression of cyclooxygenase-2. Because DN-FLICE blocked curcumin-induced apoptosis, caspase-8 must play a critical role. Overall, our results indicate that curcumin induces apoptosis through mitochondrial pathway involving caspase-8, BID cleavage, cytochrome c release, and caspase-3 activation. Our results also suggest that Bcl-2 and Bcl-xl are critical negative regulators of curcumin-induced apoptosis. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,
Defective TGF-beta signaling sensitizes human cancer cells to rapamycin
Authors: D N Jackson
E Lee
D A Foster
N Gadir
Journal: Oncogene (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mTOR; survival signals; human cancers; apoptosis; serum
Affiliations: Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10021, USA.

Abstract:  mTOR, the mammalian target of rapamycin, is a critical target of survival signals in many human cancers. In the absence of serum, rapamycin induces apoptosis in MDA-MB-231 human breast cancer cells. However, in the presence of serum, rapamycin induces G(1) cell cycle arrest-indicating that a factor(s) in serum suppresses rapamycin-induced apoptosis. We report here that transforming growth factor-beta (TGF-beta) suppresses rapamycin-induced apoptosis in serum-deprived MDA-MB-231 cells in a protein kinase Cdelta (PKCdelta)-dependent manner. Importantly, if TGF-beta signaling or PKCdelta was suppressed, rapamycin induced apoptosis rather than G(1) arrest in the presence of serum. And, if cells were allowed to progress into S phase, rapamycin induced apoptosis in the presence of serum. BT-549 and MDA-MB-468 breast, and SW-480 colon cancer cells have defects in TGF-beta signaling and rapamycin induced apoptosis in these cells in the presence of either serum or TGF-beta. Thus, in the absence of TGF-beta signaling, rapamycin becomes cytotoxic rather than cytostatic. Importantly, this study provides evidence indicating that tumors with defective TGF-beta signaling--common in colon and pancreatic cancers--will be selectively sensitive to rapamycin or other strategies that target mTOR. 

Retracted: No

PubPeer comments:
 I invite you to share your feedback on the present study. Best regards, Pieter VdB ,
Telemedicine in clinical setting
Authors: Peiying Zhang
Xiao-Ying Zhang
Journal: Experimental and Therapeutic Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: information technology; management; telemedicine.
Affiliations: Nanjing University of Chinese Medicine, Information Institute, Nanjing, Jiangsu 221009, P.R. China., Department of Cardiology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China.

Abstract:  The telemedicine department of a hospital is an emerging branch in upcoming hospitals and may become an essential component of every hospital. It basically utilizes the information technologies along with telecommunication systems in order to provide clinical care and assistance. Furthermore, the branch of telemedicine offers significant opportunities for the process of developmental freedom from illness, early death, and preventable diseases. It advances development by providing relevant drugs and the necessary care aimed to alleviate patient suffering. It is also beneficial for patients in rural remote areas who usually do not have adequate access to advanced hospitals. Telemedicine in these remote areas allows for timely treatment of emergency cases. Thus, it contributes towards remote emergency critical care in order to save lives in crucial cases. Additionally, the emerging advances have now enabled telemedicine to transfer large amounts of clinical informatics data including images, and test reports to the specifically specialized health professionals in some serious cases. However, as in the case of many emerging technologies, organizing information and understanding the field has significant challenges. The present review article aimed to discuss important aspects of the field with regard to the better management of patients in clinical settings. 

Retracted: No

PubPeer comments:
 Fig.4:More similar than expected. Could authors check please? ![file] , 
 Thank you for letting us know about this issue. We have rechecked this figure and, indeed, it seems that one of the blots has been duplicated by mistake during the elaboration of the final figure. We have been able to find the original scans from these experiments and have corrected this involuntary mistake. We attach here the new version of figure 4 panel B, in which the mistake has been corrected. Ana Cuenda and Guadalupe Sabio ![file] , 
 We kindly ask you to contact the journal and submit your source data so that we can determine the best way to correct the scientific record. ,
Recovery from rapamycin: drug-insensitive activity of yeast target of rapamycin complex 1 (TORC1) supports residual proliferation that dilutes rapamycin among progeny cells
Authors: Stephanie K Evans
Joseph V Gray
Karl E V Burgess
Journal: Journal of Biological Chemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell Signaling; Drug Metabolism; EGO Complex; Enzyme Inhibitor; Proliferation-dependent Dilution
Affiliations: From the School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ and., Glasgow Polyomics, Translational Cancer Research Centre, University of Glasgow, Glasgow G61 1QH, Scotland, United Kingdom., From the School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ and .

Abstract:  The target of rapamycin complex 1 (TORC1) is a key conserved regulator of eukaryotic cell growth. The xenobiotic rapamycin is a potent inhibitor of the yeast complex. Surprisingly, the EGO complex, a nonessential in vivo activator of TORC1, is somehow required for yeast cells to recover efficiently from a period of treatment with rapamycin. Why? Here, we found that rapamycin is only a partial inhibitor of TORC1. We confirmed that saturating amounts of rapamycin do not fully inhibit proliferation of wild-type cells, and we found that the residual proliferation in the presence of the drug is dependent on the EGO complex and on the activity of TORC1. We found that this residual TORC1-dependent proliferation is key to recovery from rapamycin treatment. First, the residual proliferation rate correlates with the ability of cells to recover from treatment. Second, the residual proliferation rate persists long after washout of the drug and until cells recover. Third, the total observable pool of cell-associated rapamycin is extremely stable and decreases only with increasing cell number after washout of the drug. Finally, consideration of the residual proliferation rate alone accurately and quantitatively accounts for the kinetics of recovery of wild-type cells and for the nature and severity of the ego- mutant defect. Overall, our results revealed that rapamycin is a partial inhibitor of yeast TORC1, that persistence of the drug limits recovery, and that rapamycin is not detoxified by yeast but is passively diluted among progeny cells because of residual proliferation. 

Retracted: No

PubPeer comments:
null, 
 #1 Yes that s precisely the point of the article, isn t it? ,