PReD-Bench/PRed-Bench huggingface dataset:
RFP represses transcriptional activation by bHLH transcription factors
Authors: Brian R Champion
Penny Hayward
Ekaterina Kotsopoulou
Anthony R Green
Adrian J C Bloor
Journal: Oncogene (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: bHLH transcription factors; tumorigenesis; Ret finger protein (RFP); TRIM family; interaction partner
Affiliations: Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Hills Road, Cambridge CB2 2XY, UK.

Abstract:  Basic helix-loop-helix (bHLH) transcription factors play a pivotal role in the regulation of tumorigenesis, and also in a wide range of other developmental processes in diverse species from yeast to humans. Here we demonstrate for the first time that Ret finger protein (RFP), a member of the TRIM family of proteins initially identified as a recombined transforming gene from a human lymphoma, is a novel interaction partner for four different bHLH proteins (SCL, E47, MyoD and mASH-1), but does not interact with GATA-1 or PU.1. Interaction with SCL required the B-box and first coiled-coil region of RFP together with the bHLH domain of SCL. RFP was able to repress transcriptional activation by E47, MyoD and mASH-1, but not by members of several other transcription factor families. Transcriptional repression by RFP was trichostatin A sensitive and did not involve an Id-like mechanism or ubiquitination with subsequent degradation of bHLH proteins. Instead, our results suggest that bHLH transcription factors are regulated by a previously undescribed interaction with RFP, which functions to recruit HDAC and/or Polycomb proteins and thus repress target genes of bHLH proteins. These results reveal an unexpected link between the bHLH and TRIM protein families. 

Retracted: No

PubPeer comments:
 Figure 1b. Undeclared splice one panel, not splice in the other panel. ![file] ,
Synergistic Effects of the Green Tea Extract Epigallocatechin-3-gallate and Taxane in Eradication of Malignant Human Prostate Tumors
Authors: Min Wang
Mark E Stearns
Journal: Translational Oncology (2011)
Discipline: CLINICAL MEDICINE
Keywords: EGCG; taxane; prostate cancer; apoptosis; tumor growth
Affiliations: Department of Pathology, Drexel University College of Medicine, Philadelphia, PA, USA.

Abstract:  We have examined whether epigallocatechin-3-gallate (EGCG), and extract of green tea, in combination with taxane (i.e., paclitaxel and docetaxel), exerts a synergistic activity in blocking human prostate PC-3ML tumor cell growth in vitro and in vivo. Growth assays in vitro revealed that the IC(50) values were ∼30 µM, ∼3 nM, and ∼6 nM, for EGCG, paclitaxel and docetaxel, respectively. Isobolograms generated from the data clearly indicated that EGCG in combination with paclitaxel or docetaxel had an additive effect in blocking tumor cell growth. EGCG combined with taxane also had an additive effect to increase the expression of apoptotic genes, (p53, p73, p21, and caspase 3) and the percent apoptosis observed in vitro and in tumor modeling studies in severe combined immunodeficient mice. The tumor modeling studies clearly showed that EGCG plus taxane injected intraperitoneally (i.p.) induced a significant increase in apoptosis rates (TUNEL assays) and eliminated preexisting tumors generated from PC-3ML cells implanted i.p., increasing disease-free survival rates to greater than 90%. More importantly, the combination therapy (i.p. biweekly) blocked metastases after intravenous injection of PC-3ML cells through the tail vein. In mice treated with EGCG plus taxane, the disease-free survival rates increased from 0% (in untreated mice) to more than 70% to 80% in treated mice. Taken together, these data demonstrate for the first time that EGCG in combination with taxane may provide a novel therapeutic treatment of advanced prostate cancer. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,
Alliin Attenuated RANKL-Induced Osteoclastogenesis by Scavenging Reactive Oxygen Species through Inhibiting Nox1
Authors: Yueqi Chen
Zhen Cao
Jingjing Sun
Yuan Wang
Nan Li
Ce Dou
Fei Kang
Shiwu Dong
Xiaochao Yang
Journal: International Journal of Molecular Sciences (2016)
Discipline: CHEMISTRY
Keywords: Nox1; alliin; osteoclast; reactive oxygen species.
Affiliations: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Gaotanyan Street No. 30, Chongqing 400038, China. ., Student Camp Four, Third Military Medical University, Chongqing 400038, China. .

Abstract:  The healthy skeleton requires a perfect coordination of the formation and degradation of bone. Metabolic bone disease like osteoporosis is resulted from the imbalance of bone formation and/or bone resorption. Osteoporosis also reflects lower level of bone matrix, which is contributed by up-regulated osteoclast-mediated bone resorption. It is reported that monocytes/macrophage progenitor cells or either hematopoietic stem cells (HSCs) gave rise to multinucleated osteoclasts. Thus, inhibition of osteoclastic bone resorption generally seems to be a predominant therapy for treating osteoporosis. Recently, more and more natural compounds have been discovered, which have the ability of inhibiting osteoclast differentiation and fusion. Alliin (S-allyl-l-cysteine sulfoxides, SACSO) is the major component of aged garlic extract (AGE), bearing broad-spectrum natural antioxidant properties. However, its effects on bone health have not yet been explored. Hence, we designed the current study to explore its effects and role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast fusion and differentiation. It was revealed that alliin had an inhibitory effect in osteoclasteogenesis with a dose-dependent manner via blocking the c-Fos-NFATc1 signaling pathway. In addition, alliin decreased the generation of reactive oxygen species (ROS) and down-regulated the expression of NADPH oxidase 1 (Nox1). The overall results revealed that alliin could be a potential therapeutic agent in the treatment of osteoporosis. 

Retracted: No

PubPeer comments:
 Figure 3A. * Yellow boxes: The  0 and  0.5 panels appear to show an overlap. * Geen boxes: The  1 and  5 panels appear to show an overlap. The red signal is different, though, between the panels. Similarities also present in DAPI and Merged panels. ![file] , 
 Figure 5A. * Pink boxes: In the DAPI channel, the  R- and  0 panels appear to show a similar group of blue dots. The surrounding areas are different, though. ![file] ,
Non‐canonical Raf‐1/p70S6K signalling in non–small‐cell lung cancer
Authors: Bingwei Ye
Xin Li
Lei Li
Shuang Zhao
Ximing Mo
Weimin Li
Zhixin Qiu
Journal: Journal of Cellular and Molecular Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Raf-1; non-canonical; non-small-cell lung cancer; p70S6K; signaling.
Affiliations: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China., Georgia Cancer Center, Augusta University, Augusta, GA, USA., Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA., Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Abstract:  Lung cancer is the leading cause of cancer-related death globally, with non-small-cell lung cancer (NSCLC) being the predominant subtype. Overall survival remains low for NSCLC patients, and novel targets are needed to improve outcome. Raf-1 is a key component of the Ras/Raf/MEK signalling pathway, but its role and downstream targets in NSCLC are not completely understood. Our previous study indicated a possible correlation between Raf-1 levels and ribosomal protein S6 kinase (p70S6K) function. In this study, we aimed to investigate whether p70S6K is a downstream target of Raf-1 in NSCLC. Raf-1 was silenced in NSCLC cell lines by using small hairpin RNA, and Raf-1 and p70S6K protein levels were measured via Western blot. p70S6K was then overexpressed following Raf-1 knock-down; then, cell proliferation, apoptosis and the cell cycle in NSCLC cell lines were examined. Tumour xenografts with NSCLC cells were then transplanted for in vivo study. Tumours were measured and weighed, and Raf-1 and p70S6K expression, cell proliferation and apoptosis were examined in tumour tissues by Western blot, Ki-67 staining and TUNEL staining, respectively. When Raf-1 was silenced, p70S6K protein levels were markedly decreased in the A549 and H1299 NSCLC cell lines. A significant decrease in NSCLC cell proliferation, a profound increase in apoptosis and cell cycle arrest were observed in vitro following Raf-1 knock-down. Overexpression of p70S6K after Raf-1 depletion effectively reversed these effects. Xenograft studies confirmed these results in vivo. In conclusion, Raf-1 targets p70S6K as its downstream effector to regulate NSCLC tumorigenicity, making Raf-1/p70S6K signalling a promising target for NSCLC treatment. 

Retracted: No

PubPeer comments:
 1. Fig 1C show very similar band compared to Fig 2A after shape change ![file] 2. Fig 1D show very similar band compared to Fig 2A after shape change ![file] 3. Fig 2A show duplicated pictures ![file] 4.Fig 5D show duplicated pictures ![file] ,
MicroRNA-424-5p inhibits the development of non-small cell LCa by binding to ITGB1
Authors: J-W Du X-Q Li
S-X Chen
M Qiu
Q Zhang
Z-L Xu
M Zhang
L-P Gao
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-424-5p; NSCLC; proliferation; apoptosis; ITGB1
Affiliations: Department of Respiratory Medicine, The First People's Hospital of Fuyang, Hangzhou, China. .

Abstract:  Objective: The aim of this study was to explore the effect of microRNA-424-5p on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells, and to investigate its influence on the expression of ITGB1 and potential regulatory mechanism. Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the level of microRNA-424-5p in 44 paired NSCLC tissues and adjacent tissues. The relation between microRNA-424-5p expression and NSCLC clinical indicators was analyzed. Subsequently, microRNA-424-5p mimics and inhibitors were transfected into NSCLC cells to construct microRNA-424-5p overexpression or knockdown models, respectively. QRT-PCR was used to further verify the transfection efficiency. A series of experiments, including cell counting kit-8 (CCK-8) assay, colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), and flow cytometry were used to analyze the effect of microRNA-424-5p on the biological function of NSCLC A549 and H358 cells. Finally, the potential association between microRNA-424-5p and its downstream gene ITGB1 was explored through luciferase reporter gene assay and cell recovery experiment. Results: QRT-PCR results showed that microRNA-424-5p level was significantly lower in NSCLC tissues than that of adjacent normal tissues. Compared with patients with high expression of microRNA-424-5p, the pathological stage of those with low expression of microRNA-424-5p was significantly higher. In vitro experiments showed that microRNA-424-5p overexpression remarkably decreased cell proliferation and increased cell apoptosis, which were further validated in microRNA-424-5p inhibitor group. Subsequently, ITGB1 expression was found significantly up-regulated in NSCLC cell lines and tissues. Meanwhile, ITGB1 expression was negatively correlated with microRNA-424-5p level. In addition, a recovery experiment indicated that overexpression of ITGB1 could counteract the effect of microRNA-424-5p mimics on the proliferation and apoptosis of NSCLC cells. All these findings revealed that microRNA-424-5p and ITGB1 affected the malignant progression of NSCLC. Conclusions: MicroRNA-424-5p was closely correlated with the pathological stage and poor prognosis of NSCLC, thereby inhibiting the occurrence and development of NSCLC. 

Retracted: No

PubPeer comments:
 Splice in Western blot in Figure 2A but not in loading control in 2B. Figure 5A and 7A: untreated controls are the same (red boxes). Were arsenate and cadmium (Cd) experiments done simultaneously? And were experiments done more than once? ![file] ,
Overlapping and distinct roles of Aspergillus fumigatus UDP-glucose 4-epimerases in galactose metabolism and the synthesis of galactose-containing cell wall polysaccharides
Authors: Albert M Berghuis
Carole Creuzenet
Paolo V Campoli
Thierry Fontaine
Evgeny Vinogradov
Mark J Lee
Jean-Paul Latgé
Stefanie D Baptista
Donald C Sheppard
Fabrice N Gravelat
Ilia Kravtsov
Hong Liu
Scott G Filler
Se-In Choe
Robert P Cerone
Journal: Journal of Biological Chemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Carbohydrate Biosynthesis; Cell Wall; Galactose Metabolism; Glycobiology; Mycology
Affiliations: From the Department of Microbiology and Immunology, McGill University, Montréal, Québec H3A 2B4, Canada.

Abstract:  The cell wall of Aspergillus fumigatus contains two galactose-containing polysaccharides, galactomannan and galactosaminogalactan, whose biosynthetic pathways are not well understood. The A. fumigatus genome contains three genes encoding putative UDP-glucose 4-epimerases, uge3, uge4, and uge5. We undertook this study to elucidate the function of these epimerases. We found that uge4 is minimally expressed and is not required for the synthesis of galactose-containing exopolysaccharides or galactose metabolism. Uge5 is the dominant UDP-glucose 4-epimerase in A. fumigatus and is essential for normal growth in galactose-based medium. Uge5 is required for synthesis of the galactofuranose (Galf) component of galactomannan and contributes galactose to the synthesis of galactosaminogalactan. Uge3 can mediate production of both UDP-galactose and UDP-N-acetylgalactosamine (GalNAc) and is required for the production of galactosaminogalactan but not galactomannan. In the absence of Uge5, Uge3 activity is sufficient for growth on galactose and the synthesis of galactosaminogalactan containing lower levels of galactose but not the synthesis of Galf. A double deletion of uge5 and uge3 blocked growth on galactose and synthesis of both Galf and galactosaminogalactan. This study is the first survey of glucose epimerases in A. fumigatus and contributes to our understanding of the role of these enzymes in metabolism and cell wall synthesis. 

Retracted: No

PubPeer comments:
 The cell morphology of different groups in red box appear to look similar in Fig 2. ![file] ,
Vitamin D, parathyroid hormone, and cardiovascular events among older adults
Authors: Ian de Boer
Ronit Katz
Mark J Sarnak
Andy Hoofnagle
Michael G Shlipak
Nancy S Jenny
Bryan Kestenbaum
David S Siscovick
Journal: Journal of the American College of Cardiology (2011)
Discipline: CLINICAL MEDICINE
Keywords: 25-hydroxyvitamin D; parathyroid hormone; cardiovascular events; mortality; older adults
Affiliations: Kidney Research Institute, University of Washington, Seattle, WA, USA. 

Abstract:  Objectives: The aim of this study was to evaluate associations of 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentrations separately and in combination with incident cardiovascular events and mortality during 14 years of follow-up in the CHS (Cardiovascular Health Study). Background: Vitamin D deficiency and PTH excess are common in older adults and may adversely affect cardiovascular health. Methods: A total of 2,312 participants who were free of cardiovascular disease at baseline were studied. Vitamin D and intact PTH were measured from previously frozen serum using mass spectrometry and a 2-site immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart failure, cardiovascular death, and all-cause mortality. Results: There were 384 participants (17%) with serum 25-OHD concentrations &lt;15 ng/ml and 570 (25%) with serum PTH concentrations ≥ 65 pg/ml. After adjustment, each 10 ng/ml lower 25-OHD concentration was associated with a 9% greater (95% confidence interval [CI]: 2% to 17% greater) relative hazard of mortality and a 25% greater (95% CI: 8% to 44% greater) relative hazard of myocardial infarction. Serum 25-OHD concentrations &lt;15 ng/ml were associated with a 29% greater (95% CI: 5% to 55% greater) risk for mortality. Serum PTH concentrations ≥ 65 pg/ml were associated with a 30% greater risk for heart failure (95% CI: 6% to 61% greater) but not other outcomes. There was no evidence of an interaction between serum 25-OHD and PTH concentrations and cardiovascular events. Conclusions: Among older adults, 25-OHD deficiency is associated with myocardial infarction and mortality; PTH excess is associated with heart failure. Vitamin D and PTH might influence cardiovascular risk through divergent pathways. 

Retracted: No

PubPeer comments:
 In Table 2 the values for Incident heart failure are wrong ( copied from Cardiovascular mortality). The number of events should sum up to 504 and not to 389 as it is in Cardiovascular mortality. The risks of Model 1 to Model 3 need to be corrected as well ,
SIK2 Promotes Cisplatin Resistance Induced by Aerobic Glycolysis in Breast Cancer Cells through PI3K/AKT/mTOR Signaling Pathway
Authors: Wei Dai
Wencheng Fang
Xiangting Guo
Shoukai Zong
Kai Wang
Journal: Bioscience reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PI3K/AKT/mTOR; SIK2; breast cancer cells; cisplatin; drug resistance
Affiliations: People's Hospital of Rizhao, Rizhao, China.

Abstract:  This study aimed to investigate the effect of SIK2 on cisplatin resistance induced by aerobic glycolysis in breast cancer cells and its potential mechanism. qRt-PCR and Western blot were used to detect SIK2 mRNA and protein levels, and cisplatin (DDP) resistant cell lines of breast cancer cells were established. Viability was measured and evaluated via CCK-8, cell invasion capability was evaluated via Transwell, and apoptosis rate was assessed via Flow cytometry. The glycolysis level was evaluated by measuring glucose consumption and lactic acid production. The protein levels of p-PI3K, p- protein kinase B (Akt) and p-mTOR were determined by western blot. SIK2 was highly expressed in breast cancer tissues and cells compared with adjacent tissues and normal human breast epithelial cells, and it had higher diagnostic value for breast cancer. Silencing SIK2 expression can inhibit proliferation and invasion of breast cancer cells and induce their apoptosis. In addition, SIK2 knockdown inhibits glycolysis, reverses the resistance of drug-resistant cells to cisplatin, and inhibits PI3K/AKT/mTOR signaling pathway. When LY294002 was used to inhibit PI3K/AKT/mTOR signaling pathway, the effect of pcDNA3.1-SIK2 on aerobic glycolysis of breast cancer cells could be reversed. SIK2 can promote cisplatin resistance caused by aerobic glycolysis of breast cancer cells through PI3K/AKT/mTOR signaling pathway, which may be a new target to improve cisplatin resistance of breast cancer cells. 

Retracted: No

PubPeer comments:
 WITHDRAWN ARTICLE WITHDRAWN: SIK2 Promotes Cisplatin Resistance Induced by Aerobic Glycolysis in Breast Cancer Cells through PI3K AKT mTOR Signaling Pathway Shoukai Zong, Wei Dai, Wencheng Fang, Xiangting Guo, Kai Wang Bioscience Reports (2020), BSR20201302; DOI: 10.1042 BSR20201302 The Accepted Manuscript version of this article (published on 27 May 2020) was withdrawn on 12 June 2020 due to concerns over authorship. ,
Cryo-shocked cancer cells for targeted drug delivery and vaccination
Authors: Tianyuan Ci
Zejun Wang
Gianpietro Dotti
Guojun Chen
Jinqiang Wang
Yiming Tu
Hongjun Li
Zhen Gu
Peter Abdou
Journal: Science Advances (2020)
Discipline: Multidisciplinary
Keywords: Live cells; drug delivery vehicles; targeting capability; cargo release behavior; dead cells
Affiliations: Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA., Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA., California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA., Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China., College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P.R. China., Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Raleigh, NC 27599, USA., Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. ., Center for Minimally Invasive Therapeutics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract:  Live cells have been vastly engineered into drug delivery vehicles to leverage their targeting capability and cargo release behavior. Here, we describe a simple method to obtain therapeutics-containing "dead cells" by shocking live cancer cells in liquid nitrogen to eliminate pathogenicity while preserving their major structure and chemotaxis toward the lesion site. In an acute myeloid leukemia (AML) mouse model, we demonstrated that the liquid nitrogen-treated AML cells (LNT cells) can augment targeted delivery of doxorubicin (DOX) toward the bone marrow. Moreover, LNT cells serve as a cancer vaccine and promote antitumor immune responses that prolong the survival of tumor-bearing mice. Preimmunization with LNT cells along with an adjuvant also protected healthy mice from AML cell challenge. 

Retracted: No

PubPeer comments:
 It s very intresting. The homing of lymphocytes require the cascade reaction induced by chemokine. Is it possible for a dead cell to react as a living cell to migrate through the capillary wall to the bone marrow? Can anyone comment? ,
High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-&kappa;B signaling pathway in non-small cell lung cancer cells
Authors: Youjun Luo
Xue Chen
Caixia Gao
Guoxiong Xu
Tiankui Qiao
Qi Zhang
Xibing Zhuang
Journal: OncoTargets and Therapy (2016)
Discipline: CLINICAL MEDICINE
Keywords: CpG ODN; NF-κB; PD-L1; immune escape; irradiation
Affiliations: Department of Oncology, Jinshan Hospital, Medical Center of Fudan University., Department of Center laboratory, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.

Abstract:  Objectives: Irradiation resistance appears as local recurrence and distant metastasis in advanced stages of non-small cell lung cancer (NSCLC). High-dose irradiation combined with immunotherapy improved overall survival and local control of NSCLC. This study explored the underlying molecular mechanism by which the effect of high-dose irradiation plus toll-like receptor 9 (TLR9) agonist CpG oligodeoxynucleotide (CpG ODN) 7909 on NSCLC. Materials and methods: NSCLC H460 cells were exposed to constant high-dose irradiation (6.37 Gy) in irradiation (IR) group and the irradiation plus CpG group. Gene expression was assessed using quantitative reverse transcriptase-polymerase chain reaction and Western blot. Knockdown of nuclear factor kappa B (NF-κB) p65 expression was conducted using p65 siRNA. Results: Expression of programmed death-ligand 1 (PD-L1) mRNA was significantly decreased in IR combined with CpG ODN 7909 group compared with the control or IR-alone groups (P&lt;0.05). TLR9 expression was also obviously increased in the combination group compared with the control (P&lt;0.05). Moreover, expression of NF-κB p65 was apparently reduced in the combination group compared with the control (P&lt;0.05). However, expression of PD-L1 was significantly decreased after knockdown of p65 in IR group (P&lt;0.05), but increased in the combination group (P&lt;0.05) and slightly increased in CpG ODN-alone group (P&lt;0.05), which was opposite to that without p65 knockdown group. Conclusion: This study demonstrated that radiotherapy combined with CpG ODN 7909 was able to downregulate PD-L1 expression through inhibition via the NF-κB signaling pathway. 

Retracted: No

PubPeer comments:
 In Fig I, the alpha-Tubulin in C appears exceptionally similar to that in A, after vertical compression, marked with red boxes. ![file] ,
Direct inhibition of RNA polymerase II transcription by RECQL5
Authors: Ronald C Conaway
Stephanie E Kong
Ozan Aygün
Hidehisa Takahashi
Joan W Conaway
Xiaohua Xu
Yilun Liu
Jesper Q Svejstrup
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: DNA helicases; RECQ family; RECQL5; RNA polymerase II; transcription
Affiliations: Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK, London Research Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom.

Abstract:  DNA helicases of the RECQ family are important for maintaining genome integrity, from bacteria to humans. Although progress has been made in understanding the biochemical role of some human RECQ helicases, that of RECQL5 remains elusive. We recently reported that RECQL5 interacts with RNA polymerase II (RNAPII), pointing to a role for the protein in transcription. Here, we show that RECQL5 inhibits both initiation and elongation in transcription assays reconstituted with highly purified general transcription factors and RNAPII. Such inhibition is not observed with the related, much more active RECQL1 helicase or with a version of RECQL5 that has normal helicase activity but is impaired in its ability to interact with RNAPII. Indeed, RECQL5 helicase activity is not required for inhibition. We discuss our findings in light of the fact that RECQ5(-/-) mice have elevated levels of DNA recombination and a higher incidence of cancer. 

Retracted: No

PubPeer comments:
 Images in this paper appear very similar to images in another paper with shared authors. I did not see either paper referenced in the other. Apologies if I missed that. I did not look elsewhere. Other thread: https: pubpeer.com publications 2361C297E380F3301C4C7650B938F8 *** ![file] ,
MiR-99a-5p regulates proliferation, migration and invasion abilities of human oral carcinoma cells by targeting NOX4
Authors: Y Ma
X Qu
Z Bo
Y Shi
G Pang
L Yang
W Bao
Journal: Neoplasma (2017)
Discipline: CLINICAL MEDICINE
Keywords: miR-99a-5p NOX4.; oral carcinoma.

Abstract:  Previous research has showed that miR-99a-5p was a tumor suppressor. The aim of our study was to explore the effect of miR-99a-5p on the vitality and proliferation, migration together with the invasion of oral tumor cells via inhibiting the expression of NOX4. QRT-PCR and Western blot were applied to examine the expression level of miR-99a-5p and NOX4 in human oral tumorous and adjacent tissues. Dual luciferase reporter gene assay was applied to confirm that miR-99a-5p negatively regulated directly on NOX4 in TSCC1 cells. Cell transfection and lentiviral vectors were used to up-regulate expression of miR-99a-5p and NOX4, respectively. Cell proliferation, cell cycle, apoptosis and invasion along with the migration in different groups were assessed using MTT assay, colony formation assay, the flow cytometry, transwell assay and the wound healing assay, respectively. MiR-99a-5p was under-expressed in human oral tumor, while NOX4 was over-expressed. There was a negative relationship between miR-99a-5p and NOX4. Up-regulating miR-99a-5p or down-regulating NOX4 suppressed the vitality, proliferation, migration together with invasion of TSCC1 cells. MiR-99a-5p affected the vitality and proliferation, migration together with the invasion of oral tumor cells through targeting NOX4. 

Retracted: No

PubPeer comments:
 I am questioning the quality control and peer-reviewing process for publishing in Neoplasma. Here is everything displayed: duplication of data, different cases of data manipulation and falsification. ![file] ,
Genetically targeted magnetic control of the nervous system
Authors: Sarah Kucenas
Bryan S Barker
Michael A Wheeler
Matteo Ottolini
Ryan M Grippo
Ronald P Gaykema
Cody J Smith
Christopher D Deppmann
Aarti M Purohit
Manoj K Patel
Mark P Beenhakker
Ali D Güler
Anthony J Spano
Journal: Nature Neuroscience (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Optogenetic; chemogenetic; actuators; neural correlates; behavior
Affiliations: Department of Biology, University of Virginia, Charlottesville, Virginia, USA., Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, USA., Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA., Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA., Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA., Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.

Abstract:  Optogenetic and chemogenetic actuators are critical for deconstructing the neural correlates of behavior. However, these tools have several limitations, including invasive modes of stimulation or slow on/off kinetics. We have overcome these disadvantages by synthesizing a single-component, magnetically sensitive actuator, "Magneto," comprising the cation channel TRPV4 fused to the paramagnetic protein ferritin. We validated noninvasive magnetic control over neuronal activity by demonstrating remote stimulation of cells using in vitro calcium imaging assays, electrophysiological recordings in brain slices, in vivo electrophysiological recordings in the brains of freely moving mice, and behavioral outputs in zebrafish and mice. As proof of concept, we used Magneto to delineate a causal role of striatal dopamine receptor 1 neurons in mediating reward behavior in mice. Together our results present Magneto as an actuator capable of remotely controlling circuits associated with complex animal behaviors. 

Retracted: No

PubPeer comments:
null, 
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 The findings of the paper was completely denied by three revaluation papers See https: www.nature.com articles s41593-019-0473-5 ,
Retracted Article: Long noncoding RNA PCA3 regulates glycolysis, viability and apoptosis by mediating the miR-1/CDK4 axis in prostate cancer
Authors: Xiaobing Niu
Zongyuan Xu
Shuo Gu
Fei Mao
Journal: RSC Advances (2018)
Discipline: CHEMISTRY
Keywords: Prostate cancer; long noncoding RNAs; lncRNA; PCA3; aerobic glycolysis
Affiliations: Department of Urology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian City, P. R. China

Abstract:  Prostate cancer is one of the common tumor malignancies in men worldwide. Although long noncoding RNAs (lncRNAs) have been demonstrated to play essential roles in the progression of prostate cancer, the roles and potential mechanism of lncRNA prostate cancer antigen 3 (PCA3) remain poorly understood. In the present study, we investigated the role of PCA3 in aerobic glycolysis, viability and apoptosis in prostate cancer cells and probed the interaction between PCA3 and microRNA-1 (miR-1)/cyclin-dependent kinase 4 (CDK4). Here we found that PCA3 and CDK4 were up-regulated while miR-1 was down-regulated in prostate cancer tissues and cells. Moreover, knockdown of PCA3 inhibited aerobic glycolysis and viability and induced apoptosis in prostate cancer cells. Intriguingly, PCA3 was bound to miR-1 and inhibition of miR-1 reversed the regulatory effect of PCA3 knockdown on aerobic glycolysis, viability and apoptosis in prostate cancer cells. Besides, CDK4 was indicated as a target of miR-1 and it was regulated by PCA3 through functioning as a competing endogenous RNA (ceRNA) of miR-1 in prostate cancer cells. The results indicated that PCA3 might drive aerobic glycolysis, viability and apoptosis by regulating the miR-1/CDK4 axis in prostate cancer cells, providing a promising avenue for treatment of prostate cancer. 

Retracted: Yes

PubPeer comments:
 The Royal Society of Chemistry hereby wholly retracts this RSC Advances article due to concerns with the reliability of the data. The images in the article were screened by an image integrity expert. The backgrounds to the western blot bands do not appear authentic and the blots may not be genuine. Furthermore, the blots and many other features of the article were found to closely resemble the blots and features of other articles, which is highly unexpected given that there are no overlapping authors. The authors were asked to provide the raw data for this article, but did not respond. Given the significance of the concerns about the validity of the data, and the lack of raw data, the findings presented in this paper are not reliable. The authors were informed but have not responded to any correspondence regarding the retraction. Signed: Laura Fisher, Executive Editor, RSC Advances Date: 19th January 2021 ,
A potential alpha-helix motif in the amino terminus of LANA encoded by Kaposi's sarcoma-associated herpesvirus is critical for nuclear accumulation of HIF-1alpha in normoxia
Authors: Erle S Robertson
Huaxin Si
Qiliang Cai
Masanao Murakami
Journal: Journal of virology (2007)
Discipline: MICROBIOLOGY
Keywords: Hypoxia-inducible factor 1 (HIF-1); Kaposi's sarcoma; Latency-associated nuclear antigen (LANA); Kaposi's sarcoma-associated herpesvirus (KSHV); Angiogenesis
Affiliations: Department of Microbiology and the Tumor Virology Program, Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA., Department of Microbiology and the Tumor Virology Program, Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104

Abstract:  Hypoxia-inducible factor 1 (HIF-1) is a ubiquitously expressed transcriptional regulator involved in induction of numerous genes associated with angiogenesis and tumor growth. Kaposi's sarcoma, associated with increased angiogenesis, is a highly vascularized, endothelial cell-derived tumor. Previously, we have shown that the latency-associated nuclear antigen (LANA) encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) targets the HIF-1alpha suppressors von Hippel-Lindau protein and p53 for degradation via its suppressor of cytokine signaling-box motif, which recruits the EC5S ubiquitin complex. Here we further show that HIF-1alpha was aberrantly accumulated in KSHV latently infected primary effusion lymphoma (PEL) cells, as well as HEK293 cells infected with KSHV, and also show that a potential alpha-helical amino-terminal domain of LANA was important for HIF-1alpha nuclear accumulation in normoxic conditions. Moreover, we have now determined that this association was dependent on the residues 46 to 89 of LANA and the oxygen-dependent degradation domain of HIF-1alpha. Introduction of specific small interfering RNA against LANA into PEL cells also resulted in a diminished nuclear accumulation of HIF-1alpha. Therefore, these data show that LANA can function not only as an inhibitor of HIF-1alpha suppressor proteins but can also induce nuclear accumulation of HIF-1alpha during KSHV latent infection. 

Retracted: No

PubPeer comments:
 Figure 7D. Much more similar than you would expect. No background. https: imgur.com 33XJrJj , 
 Last author appears to be on this journalu2019s editorial board: https: jvi.asm.org content board-editors ,
Tumor regression by phenethyl isothiocyanate involves DDB2
Authors: Nilotpal Roy
Indira Elangovan
Srilata Bagchi
Pradip Raychaudhuri
Dragana Kopanja
Journal: Cancer Biology & Therapy (2013)
Discipline: CLINICAL MEDICINE
Keywords: DDB2; PEITC; ROS; apoptosis; colon cancer
Affiliations: Department of Biochemistry and Molecular Genetics, Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.

Abstract:  Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive agent commonly found in edible cruciferous vegetables. It has been implicated also for therapy, and is in clinical trial for lung cancer. Here, we provide evidence that the tumor suppressive effect of PEITC is related to its ability to induce expression of damaged DNA binding protein 2 (DDB2), a DNA repair protein involved also in apoptosis and premature senescence. DDB2 expression is attenuated in a wide variety of cancers including the aggressive colon cancers. We show that, in colon cancer cells, reactive oxygen species, which are induced by PEITC, augment expression of DDB2 through the p38MAPK/JNK pathway, independently of p53. PEITC-induced expression of DDB2 is critical for inhibition of tumor progression by PEITC. Tumors derived from DDB2-deficient colon cancer cells are refractory to PEITC-treatments, resulting from deficiencies in apoptosis and senescence. The DDB2-proficient tumors, on the other hand, respond effectively to PEITC. The results show that PEITC can be used to induce expression of DDB2, and that expression of DDB2 is critical for effective response of tumors to PEITC. 

Retracted: No

PubPeer comments:
 April 2017 Corrigendum:  The authors inadvertently supplied an older version of Fig. 5A found on p. 113 of the article indicated above. A correct version of Fig. 5A appears below. The change does not affect any conclusions of the study. The authors apologize for the error. Here is the original Figure 5A, with a duplication marked with green boxes: ![file] ,
Overexpression of long non-coding RNA H19 protects lung fibroblasts from LPS-induced injury by targeting miR-181a and Runx2 via activation of Notch and JNK pathways
Authors: Chunyang Yang
Yu Teng
Lin Wu
Yongqiang Hua
Liping Sun
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Retraction; Long noncoding RNA H19; Lung fibroblasts; Lipopolysaccharide-induced injury; miR-181a
Affiliations: Department of Respiration, Weifang People's Hospital, Weifang 261000, Shandong, China.

Abstract:  Retraction: "Overexpression of long noncoding RNA H19 protects lung fibroblasts from lipopolysaccharide-induced injury by targeting miR-181a and Runx2 via activation of the Notch and c-Jun N-terminal kinases pathways" from the Journal of Cellular Biochemistry by Lin Wu, Liping Sun, Yongqiang Hua, Chunyang Yang, and Yu Teng published online on 8 January 2018 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the journal Editor in Chief Gary S. Stein and John Wiley and Sons, Inc. The retraction has been agreed because the authors are not responding to the requests to finalize their article for publication in the journal as the Version of Record. 

Retracted: No

PubPeer comments:
  The above article, ... published online on 8 January 2018 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the journal Editor in Chief Gary S. Stein and John Wiley and Sons, Inc. The retraction has been agreed because the authors are not responding to the requests to finalize their article for publication in the journal as the Version of Record. There are other issues. Fig 8: ![file] Plagiarising [a comment by Elisabeth Bik] : This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: - https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) - https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: - Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 - Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 ,
Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse models
Authors: Svetlana Komarnitsky
Kelly A Rogers
Nikolay O Bukanov
Bing Wang
Ryan J Russo
Laurie A Smith
Oxana Ibraghimov-Beskrovnaya
Hervé Husson
James A Shayman
John P Leonard
William R Dackowski
Thomas A Natoli
Yeva Budman
Steven R Ledbetter
Alexei Belenky
Journal: Nature Medicine (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Polycystic kidney disease; genetic disorders; renal cystic growth; kidney failure; therapeutic interventions
Affiliations: Department of Cell Biology, Genzyme Corporation, Framingham, Massachusetts, USA.

Abstract:  Polycystic kidney disease (PKD) represents a family of genetic disorders characterized by renal cystic growth and progression to kidney failure. No treatment is currently available for people with PKD, although possible therapeutic interventions are emerging. Despite genetic and clinical heterogeneity, PKDs have in common defects of cystic epithelia, including increased proliferation, apoptosis and activation of growth regulatory pathways. Sphingolipids and glycosphingolipids are emerging as major regulators of these cellular processes. We sought to evaluate the therapeutic potential for glycosphingolipid modulation as a new approach to treat PKD. Here we demonstrate that kidney glucosylceramide (GlcCer) and ganglioside GM3 levels are higher in human and mouse PKD tissue as compared to normal tissue, regardless of the causative mutation. Blockade of GlcCer accumulation with the GlcCer synthase inhibitor Genz-123346 effectively inhibits cystogenesis in mouse models orthologous to human autosomal dominant PKD (Pkd1 conditional knockout mice) and nephronophthisis (jck and pcy mice). Molecular analysis in vitro and in vivo indicates that Genz-123346 acts through inhibition of the two key pathways dysregulated in PKD: Akt protein kinase-mammalian target of rapamycin signaling and cell cycle machinery. Taken together, our data suggest that inhibition of GlcCer synthesis represents a new and effective treatment option for PKD. 

Retracted: No

PubPeer comments:
 ![file] Figures 5, 8 9 : Highlighted organs appear identical despite coming from different specimen. , 
 *Thank you for bringing this to our attention. We are looking for the complete data to get in touch with the Journal and do the needful to address this matter. * ,
Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and beta-catenin/Wnt pathways
Authors: Paola Bendinelli
Paola Maroni
Sara Previdi
Maria Alfonsina Desiderio
Emanuela Matteucci
Massimo Broggini
Journal: European Journal of Cancer (2010)
Discipline: CLINICAL MEDICINE
Keywords: human-breast cancer; metastatic cells; bone microenvironment; HGF/Met system; beta-catenin/Wnt pathway
Affiliations: Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.

Abstract:  To clarify the reciprocal interaction between human-breast cancer metastatic cells and bone microenvironment, we studied the influence of HGF/Met system on a proposed-prognostic marker of aggressiveness, the beta-catenin/Wnt pathway. For in vitro and in vivo experiments we used 1833-bone metastatic clone, derived from human-MDA-MB231 cells. In osteolytic bone metastases and in metastatic cells, Met was expressed in nuclei and at plasma membrane, and abnormally co-localised at nuclear level with beta-catenin and the tyrosine phosphorylated c-Src kinase. Thus, in 1833 cells nuclear-Met COOH-terminal fragment and beta-catenin-TCF were constitutively activated, possibly by receptor and non-receptor tyrosine kinases. The activity of the gene reporter TOPFLASH (containing multiple TCF/LEF-consensus sites) was measured, as index of beta-catenin functionality. In 1833 cells, human and mouse HGF increased Met and beta-catenin tyrosine phosphorylation and expression in nuclear and perinuclear compartments, beta-catenin nuclear translocation via Kank and TOPFLASH transactivation. Human HGF was autocrine/intracrine in bone metastasis, and mouse HGF originating from the adjacent host-bone marrow, was found inside the metastatic nuclei. Parental MDA-MB231 cell nuclei did not show functional beta-catenin, for TCF-transactivating activity, and the regulation by HGF. Our study highlighted the importance of the metastasis-stroma interaction in human-breast cancer metastatisation and first identified the HGF/nuclear Met/phospho-c-Src/beta-catenin-TCF/Wnt pathway as a potential-therapeutic target to delay establishment/progression of bone metastases by affecting the aggressive phenotype. 

Retracted: No

PubPeer comments:
 Fig 1C: ![] Please compare the loading control with that of Fig 4D in [Bendinelli et al (2011)] . ![] ,
PD-L1 regulates tumorigenesis and autophagy of ovarian cancer by activating mTORC signaling
Authors: Hongmin Gao
Xiaohong Ren
Juan Zhang
Journal: Bioscience Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PD-L1; autophagy; mTORC; ovarian cancer.
Affiliations: Department of Obstetrics and Gynecology, Xi'an Fourth Hospital, Xi'an, Shaanxi 710004, China., Department of Obstetrics, Affiliated Hospital of Yan'an University, Yan'an, Shaanxi 716000, China., Department of Gynecology, Shaanxi Nuclear Industry 215 Hospital, Xianyang, Shaanxi 712000, China.

Abstract:  PD-L1 is a well-known immune co-stimulatory molecule that regulates tumour cell escape from immunity by suppressing the immune response. However, the clinical significance of PD-L1 in the progression of ovarian cancer is unclear. Our study demonstrated that PD-L1 is up-regulated in ovarian tumour tissue compared with its expression level in adjacent normal tissue. Furthermore, we confirmed that PD-L1 increases the proliferation of cancer cells by activating the AKT-mTORC signalling pathway, which is also enhanced by the expression of S6K, the substrate of mTORC. In addition, PD-L1 promotes the autophagy of ovarian cancer cells by up-regulating the expression of BECN1, a crucial molecule involved in the regulation of autophagy. In conclusion, PD-L1 may provide a target for the development of a novel strategy for the treatment of ovarian cancer. 

Retracted: No

PubPeer comments:
 Fig. 5B.  Expression of the TLR4 NF-u03baB signaling pathway-related genes (TLR4, NF-u03baB and Iu03baBu03b1) in esophageal mucosal tissues of rats.... B, protein expression of TLR4, NF-u03baB and Iu03baBu03b1 in esophageal mucosal tissues . ![file] I am intrigued by the absence of background on these WBs, and the way the bands remain perfectly linear and retain the shape of the protein blobs as they move up the gel. Is it possible for the authors to upload the original scans of the gels? Numerous other papers have Figures which display the same qualities, hence my curiosity. I compiled a montage: ![file] , 
 Retracted, [3 November 2021] . ---------------------- The article u201cInvolvement of the TLR4 NF-u03baB Signaling Pathway in the Repair of Esophageal Mucosa Injury in Rats with Gastroesophageal Reflux Diseaseu201d [Cell Physiol Biochem 2018;51:1645u20131657; DOI: 10.1159 000495652] by Hai-Xiang Yu, Xiao-Long Wang, Le-Ning Zhang, Ji Zhang and Wei Zhao has been retracted by the current and former Publishers and the Editor. After the publication of this article, concerns were raised about the integrity of some of the data presented. The authors did not respond to requests to comment on the concerns and provide the raw data within the given timeframe despite multiple attempts of contact. The matter has been raised to the corresponding author s institution who did not respond to our request for an investigation. Given the severity of the concerns raised this article is being retracted. The authors have not responded to our correspondence regarding this retraction despite multiple attempts of contact. ,