PReD-Bench/PRed-Bench huggingface dataset:
Nanoscale metal-organic frameworks for mitochondria-targeted radiotherapy-radiodynamic therapy
Authors: Samuel S Veroneau
Wenbin Lin
Xiaopin Duan
Kaiyuan Ni
Guangxu Lan
Yang Song
Journal: Nature Communications (2018)
Discipline: Multidisciplinary
Keywords: Mitochondria; Cancer cells; Photosensitizers; Photodynamic therapy; X-ray therapy
Affiliations: Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA., Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA. ., Department of Radiation and Cellular Oncology, Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, 60637, USA. .

Abstract:  Selective delivery of photosensitizers to mitochondria of cancer cells can enhance the efficacy of photodynamic therapy (PDT). Though cationic Ru-based photosensitizers accumulate in mitochondria, they require excitation with less penetrating short-wavelength photons, limiting their application in PDT. We recently discovered X-ray based cancer therapy by nanoscale metal-organic frameworks (nMOFs) via enhancing radiotherapy (RT) and enabling radiodynamic therapy (RDT). Herein we report Hf-DBB-Ru as a mitochondria-targeted nMOF for RT-RDT. Constructed from Ru-based photosensitizers, the cationic framework exhibits strong mitochondria-targeting property. Upon X-ray irradiation, Hf-DBB-Ru efficiently generates hydroxyl radicals from the Hf6 SBUs and singlet oxygen from the DBB-Ru photosensitizers to lead to RT-RDT effects. Mitochondria-targeted RT-RDT depolarizes the mitochondrial membrane to initiate apoptosis of cancer cells, leading to significant regression of colorectal tumors in mouse models. Our work establishes an effective strategy to selectively target mitochondria with cationic nMOFs for enhanced cancer therapy via RT-RDT with low doses of deeply penetrating X-rays. 

Retracted: No

PubPeer comments:
 In Supplementary Figure 17, duplicated images were observed from H2DBB-Ru under (-) and (+) conditions, while other samples all show differences. ![file] ,
Protein kinase catalytic subunit (PKAcat) from bovine lens: purification, characterization and phosphorylation of lens crystallins
Authors: Bhaswati Samanta
Kalipada Das
Parimal Chandra Sen
Subir Kumar Nagdas
Journal: Molecular and cellular biochemistry (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Protein kinase A; Purification; Functional characterization; Bovine lens; Catalytic subunit
Affiliations: Department of Chemistry, Bose Institute, 93/1, A.P.C. Road, Kolkata 700009, India.

Abstract:  The purification and functional characterization of protein kinase A catalytic subunit (PKAcat) from bovine lens cytosol has been described. Purification to homogeneity has been achieved by using 100 kDa cut-off membrane filtration followed by Sephacryl S-300 chromatography and finally fractionating on High Q anion exchange column. The purified protein migrates as a single band of molecular mass approximately 41 kDa on 12.5% SDS-PAGE. Proteomic data from ion trap LC-MS when analyzed through NCBI blast program reveals significant homology (52%) with bovine zeta-crystallin and also some homology with pig casein kinase I alpha chain (38%) and SLA-DR1 beta 1 domain (38%). The search does not indicate homology with any known catalytic subunit of PKA. Inspite of the significant homology with the zeta-crystallin, our protein is different from it in terms of molecular mass. pI value of the kinase (5.3) obtained from 2D analysis is also different from zeta-crystallin (8.5). The protein is found to contain 17% alpha-helix, 26.5% beta-sheet, 21.4% turn and 34.7% random coil. The active catalytic subunit of the bovine lens cAMP-dependent kinase belongs to Type I Calpha subtype. The enzyme shows maximum activity at 30 min incubation in presence of 5 mM MgCl(2 )and 50 microM ATP. The kinase shows broad substrate specificity. It prefers Ser over Thr as phosphorylating residue. Phosphorylation of crystallin proteins, major protein fraction of bovine lens and phosphorylation of chaperone protein alpha crystallin by the kinase suggests that the kinase plays some crucial role in regulation of chaperone function within lens. 

Retracted: No

PubPeer comments:
 Figure 5. * Red boxes: Lanes 2 and 7 look very similar. * Blue arrows: The 20 kDa and 50 kDa bands in lane 3 have very different shapes Reported to the journal in October 2015, but no response as of today. ![file] ,
TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus
Authors: Agnès Billecocq
Luca Proietti De Santis
Jean-Marc Egly
Michèle Bouloy
Nicolas Le May
Sandy Dubaele
Journal: Cell (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Rift Valley fever virus; RVFV; hemorrhagic fever; RNA synthesis; TFIIH transcription factor
Affiliations: Unité de Génétique Moléculaire des Bunyaviridés, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, Cedex 15, France.

Abstract:  The Rift Valley fever virus (RVFV) is the causative agent of fatal hemorrhagic fever in humans and acute hepatitis in ruminants. We found that infection by RVFV leads to a rapid and drastic suppression of host cellular RNA synthesis that parallels a decrease of the TFIIH transcription factor cellular concentration. Using yeast two hybrid system, recombinant technology, and confocal microscopy, we further demonstrated that the nonstructural viral NSs protein interacts with the p44 component of TFIIH to form nuclear filamentous structures that also contain XPB subunit of TFIIH. By competing with XPD, the natural partner of p44 within TFIIH, and sequestering p44 and XPB subunits, NSs prevents the assembly of TFIIH subunits, thus destabilizing the normal host cell life. These observations shed light on the mechanism utilized by RVFV to evade the host response. 

Retracted: No

PubPeer comments:
 Figure 2c. Much more similar than you would expect. ![file] , 
 WBs have been inverted and we apologize for this mistake. The NI fractions (lane 1 and 7) came from the same WB image. This modification does not affect the result. Indeed, in pCI-NSsZH transfected cells, the presence (and the concentration) of transcription factor TBP remains unchanged contrary to what is observed for the p62 subunit of TFIIH. Similarly, in a 2nd experiments, TBP remains unchanged while p62 concentration decreases rapidly in ZH infected extracts ![file] ,
Tissue transglutaminase is a multifunctional BH3-only protein
Authors: Mauro Piacentini
Gian Maria Fimia
Elvira Garofano
Maria Grazia Farrace
Elisabetta Mormone
Lucia Piredda
Fabiola Ciccosanti
Walter Malorni
Carlo Rodolfo
Paola Matarrese
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Tissue transglutaminase; apoptosis; BH3 domain; Bax; mitochondria
Affiliations: Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.

Abstract:  Tissue transglutaminase (TG2) protein accumulates to high levels in cells during early stages of apoptosis both in vivo and in vitro. The analysis of the TG2 primary sequence showed the presence of an eight amino acid domain, sharing 70% identity with the Bcl-2 family BH3 domain. Cell-permeable peptides, mimicking the domain sequence, were able to induce Bax conformational change and translocation to mitochondria, mitochondrial depolarization, release of cytochrome c, and cell death. Moreover, we found that the TG2-BH3 peptides as well as TG2 itself were able to interact with the pro-apoptotic Bcl-2 family member Bax, but not with anti-apoptotic members Bcl-2 and Bcl-X(L). Mutants in the TG2-BH3 domain failed to sensitize cells toward apoptosis. In TG2-overexpressing cells about half of the protein is localized on the outer mitochondrial membrane where, upon cell death induction, it cross-links many protein substrates including Bax. TG2 is the first member of a new subgroup of multifunctional BH3-only proteins showing a large mass size (80 kDa) and enzymatic activity. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar than you would expect. https: imgur.com 7P8w3pi ,
Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-kappaB-regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-kappaBalpha kinase, leading to potentiation of apoptosis
Authors: Bokyung Sung
Bharat B Aggarwal
Tingfang Yi
Manoj K Pandey
Mingyao Liu
Kwang Seok Ahn
Madan M Chaturvedi
Journal: Blood (2008)
Discipline: CLINICAL MEDICINE
Keywords: Anacardic acid; NF-kappaB; apoptosis; gene regulation; cancer
Affiliations: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, USA., Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston; and, Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University System Health Science Center, Houston

Abstract:  Anacardic acid (6-pentadecylsalicylic acid) is derived from traditional medicinal plants, such as cashew nuts, and has been linked to anticancer, anti-inflammatory, and radiosensitization activities through a mechanism that is not yet fully understood. Because of the role of nuclear factor-kappaB (NF-kappaB) activation in these cellular responses, we postulated that anacardic acid might interfere with this pathway. We found that this salicylic acid potentiated the apoptosis induced by cytokine and chemotherapeutic agents, which correlated with the down-regulation of various gene products that mediate proliferation (cyclin D1 and cyclooxygenase-2), survival (Bcl-2, Bcl-xL, cFLIP, cIAP-1, and survivin), invasion (matrix metalloproteinase-9 and intercellular adhesion molecule-1), and angiogenesis (vascular endothelial growth factor), all known to be regulated by the NF-kappaB. We found that anacardic acid inhibited both inducible and constitutive NF-kappaB activation; suppressed the activation of IkappaBalpha kinase that led to abrogation of phosphorylation and degradation of IkappaBalpha; inhibited acetylation and nuclear translocation of p65; and suppressed NF-kappaB-dependent reporter gene expression. Down-regulation of the p300 histone acetyltransferase gene by RNA interference abrogated the effect of anacardic acid on NF-kappaB suppression, suggesting the critical role of this enzyme. Overall, our results demonstrate a novel role for anacardic acid in potentially preventing or treating cancer through modulation of NF-kappaB signaling pathway. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,
Multisensory integration: space, time and superadditivity
Authors: Charles Spence
Nicholas P Holmes
Journal: Current Biology (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Superior colliculus; eye movements; head movements; signals; senses
Affiliations: Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK. 

Abstract:  The superior colliculus generates and controls eye and head movements based on signals from different senses. The latest research on this structure enhances our understanding of the mechanisms of multisensory integration in the brain. 

Retracted: No

PubPeer comments:
 This paper was criticised as part of a self-reflection posted on Twitter on 2nd-3rd April, 2021 (twitter TheHandLab status 1377760796130869248) Criticism: I actually love this one, but there s a typo on p763, 1st col:  was should be  wasn t . It has bugged me forever. In writing this paper I started to realise that the law of #InverseEffectiveness was a #DoubleDip ,
Anticancer effect of Tamarix gallica extracts on human colon cancer cells involves Erk1/2 and p38 action on G2/M cell cycle arrest
Authors: Kiyokazu Kawada
Hiroko Isoda
Soninkhishig Tsolmon
Chedly Abdelly
Junkyu Han
Riadh Ksouri
Mondher Boulaaba
Abderrazak Smaoui
Journal: Cytotechnology (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: oxidative stress; cancer; chemoprevention; antioxidant substances; phenolics

Abstract:  Taking into account that oxidative stress is among the factors causing cancer-related death; chemoprevention which consists in using antioxidant substances such as phenolics could prevent cancer formation and progression. In the present study, phenolic contents and antioxidant activities of methanolic extracts from the halophyte Tamarix gallica shoots were determined. Moreover, the anticancer effect of this species on human colon cancer cells and the likely underlying mechanisms were also investigated. Shoot extracts showed an appreciable total phenolic content (85 mg GAE/g DW) and a high antioxidant activity (IC50 = 3.3 μg/ml for DPPH test). At 50 and 100 μg/ml, shoot, leaf, and flower extracts significantly inhibited Caco-2 cell growth. For instance, almost all plant part extracts inhibited cell growth by 62 % at the concentration 100 μg/ml. DAPI staining results revealed that these extracts decrease DNA synthesis and confirm their effect on Caco-2 cells proliferation, principally at 100 μg/ml. More importantly, cell mitosis was arrested at G2/M phase. The changes in the cell-cycle-associated proteins (cyclin B1, p38, Erk1/2, Chk1, and Chk2) are correlated with the changes in cell cycle distribution. Taken together, our data suggest that T. gallica is a promising candidate species to be used as a source of anticancer biomolecules. 

Retracted: No

PubPeer comments:
 As one reader put it, there appear to be u201cvertical discontinuitiesu201d in some of the bands but not on others in Figure 4. Could the authors review and explain please? *** ![file] ,
Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor
Authors: Arnaud Parcellier
Sandeep Gurbuxani
Ilektra Kouranti
Elise Schmitt
Arlette Hammann
Carmen Garrido
Celine Cande
Eric Daugas
Alena Pance
Chris Spahr
Guido Kroemer
Journal: Oncogene (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Heat shock protein 70; HSP70; apoptosis; apoptosis-inducing factor; AIF
Affiliations: INSERM U-517, Faculty of Medicine and Pharmacy, 7 Boulevard Jeanne d'Arc, 21033 Dijon, France.

Abstract:  Heat shock protein 70 (HSP70) can inhibit apoptosis by neutralizing and interacting with apoptosis-inducing factor (AIF), a mitochondrial flavoprotein that translocates upon apoptosis induction to the nucleus, via the cytosol. Here, we show that only members of the HSP70 family interact with AIF. Systematic deletion mapping revealed the existence of three distinct functional regions in the AIF protein: (1) a region between amino acids 150 and 228 that binds HSP70, (2) a domain between residues 367 and 459 that includes a nuclear localization sequence (NLS) and (3) a C-terminal domain beyond residue 567 required for its chromatin-condensing activity. Deletion of the 150-268 domain completely abolished HSP70 binding and facilitated the nuclear import of AIF, resulting in a gain-of-function phenotype with enhanced AIF-mediated chromatin condensation as compared to wild-type AIF. This gain-of-function phenotype was observed in wild-type control cells (which express low but significant levels of HSP70), yet was lost when AIFDelta150-268 was introduced into HSP70 knockout cells, underscoring the functional importance of the AIF-HSP70 interaction. Altogether, our data demonstrate that AIF inhibition by HSP70 involves cytosolic retention of AIF. Moreover, it appears that endogenous HSP70 protein levels are sufficiently elevated to modulate the lethal action of AIF. 

Retracted: No

PubPeer comments:
 Figure 2b. Much more similar than expected. ![file] , 
 #1 After retrieving the corresponding bands and zooming them, it is clear that although there is a resemblance between the bands, they are clearly not identical, neither in the contour nor in the contrast. Carmen Garrido ,
Survivin-mediated therapeutic efficacy of gemcitabine through glucose-regulated protein 78 in hepatocellular carcinoma
Authors: Der-Zen Liu
Po-Li Wei
Feng-Yen Lin
Li-Tzu Li
Hui-Hsiung Liu
Chin-Sheng Hung
Li-Jen Kuo
Yu-Jia Chang
Hou-Yu Su
Shen-Fu Lin
Phui-Ly Liew
Journal: Annals of surgical oncology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Survivin; gemcitabine; hepatocellular carcinoma; knockdown; siRNA
Affiliations: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract:  Background: Survivin is an antiapoptotic molecule that is widely expressed in cancers, including hepatocellular carcinoma (HCC). Survivin has become a general therapeutic target for cancers because of its selective overexpression in a majority of tumors. However, little is known regarding the effect of survivin expression in combination with gemcitabine on HCC. Methods: We generated survivin knockdown cells (survivin-KD) via a short interfering RNA (siRNA) technique. The antiproliferation effects of gemcitabine were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) assay, and cell cycle evaluation. Results: According to the MTT assay, we found that survivin-KD cells were more sensitive than parental cells and scrambled control cells to gemcitabine treatment. The apoptotic cell population increased in survivin-KD cells that were treated with gemcitabine in comparison to scrambled control cells, as observed by the cell cycle distribution and TUNEL assays. We found that survivin knockdown resulted in a reduction of glucose-regulated protein 78 (GRP78), which may be responsible for the observed increased survivin-KD cell sensitivity to gemcitabine. Conclusions: We conclude that survivin knockdown may contribute to a therapeutic effect of gemcitabine through GRP78 on HCC cells. 

Retracted: No

PubPeer comments:
 Erratum Published: 04 December 2013 Figure 1 was incorrect in the original article. The correct figure is as follows: ![file] , 
 Identified by another reader. Other paper: https: pubpeer.com publications 338452DDEA74D79677088F7360A856 *** ![file] ,
Peptidyl-prolyl cis/trans isomerase Pin1 is critical for the regulation of PKB/Akt stability and activation phosphorylation
Authors: Y Wei
X Zhou
N K Agarwal
D Shi
J-Y Yang
D Yu
M-C Hung
C Dai
D Sarbassov
Y-J Chen
Y Liao
Journal: Oncogene (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: serine/threonine protein kinase B; PKB; Akt; Pin1; cancer
Affiliations: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract:  The serine/threonine protein kinase B (PKB, also known as Akt) plays a pivotal role in diverse cellular functions. Elevated expression of activated Akt has been detected in a wide variety of human cancers; however, the mechanism of Akt protein stability regulation remains unclear. In this study, we showed a strong correlation between the expression levels of an oncogenic peptidyl-prolyl cis/trans isomerase Pin1 and levels of Akt phosphorylation at S473 in multiple cancer types (P&lt;0.0001). Akt-pS473 status combined with Pin1 expression levels predicted a poorer prognosis than did either one alone in patients with breast cancer (P=0.0052). We further showed that Pin1 regulated Akt stability and phosphorylation on S473 through the phosphorylated Thr-Pro motifs of Akt. These motifs are conserved evolutionary and are required for the maintenance of Akt stability and its interaction with Pin1. In addition, repressing Pin1 expression through either homologue Pin1 knockout or small interfering RNA-mediated knockingdown compromised its ability to protect Akt from degradation. Our results show how Akt protein stability is regulated by the peptidyl-prolyl cis/trans isomerase Pin1 and highlight the importance of this oncogenic network in human disease pathogenesis. 

Retracted: No

PubPeer comments:
 Figure reuse with CNS Neurosci Ther 10.1111 cns.12002 and PLOS ONE 10.1371 journal.pone.0054841: Part of Figure 2 from the CNS Neurosci Ther and PLOS ONE papers in this manuscript in Figure 2d **J Mol Neurosci** ![file] **CNS Neurosci Ther** ![file] **PLOS ONE** ![file] , 
 2020-03-25 Dear ladies and gentlemen: The two images on the left are our innovative model map, which is used to evaluate the area of demyelination. There is no data and experimental results in it. Our results are shown in the right square, which is totally different from the results of other articles. If you think that s not appropriate, we can draw a new pattern to evaluate the percentage of demyelination. Finally, we sincerely thank you for your serious spirit and scientific attitude. We will learn from this lesson, carefully mapping all figures, so that readers can understand them more easily. Finally, we would like to apologize for our carelessness, and for the confusion we have added to you. Thank you again! Sincerely, Bao-Guo Xiao ,
Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis
Authors: Pouya Pakneshan
Moshe Szyf
Shafaat A Rabbani
Robin Farias-Eisner
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Metastasis; Urokinase (uPA); Hypomethylation; Breast cancer; AdoMet
Affiliations: Department of Medicine, McGill University, Montreal H3A 1A1, Canada.

Abstract:  Metastasis is a leading cause of mortality and morbidity in cancer. Urokinase (uPA), only expressed by the highly invasive cancer cells, has been implicated in invasion, metastases, and angiogenesis of several malignancies including breast cancer. Because uPA expression is strongly correlated with its hypomethylated state, we utilized the uPA gene in the highly invasive MDA-231 human breast cancer cells as a model system to test the hypothesis that pharmacological reversal of the uPA promoter hypomethylation would result in its silencing and inhibition of metastasis. S-Adenosyl-l-methionine (AdoMet) has previously been shown to cause hypermethylation and inhibit demethylation. Treatment of MDA-231 cells with AdoMet, but not its unmethylated analogue S-adenosylhomocysteine, significantly inhibits uPA expression and tumor cell invasion in vitro and tumor growth and metastasis in vivo. The effects of AdoMet on uPA expression were reversed by the demethylating agent 5'-azacytidine, supporting the conclusion that AdoMet effects are caused by hypermethylation. Knockdown of the methyl-binding protein 2 also causes a significant inhibition of uPA expression in vitro and tumor growth and metastasis in vivo. These treatments did not have any effects on estrogen receptor expression, suggesting that inhibition of hypomethylation will not affect genes already silenced by hypermethylation. These data are consistent with the hypothesis that hypomethylation of critical genes like uPA plays a causal role in metastasis. Inhibition of hypomethylation can thus be used as a novel therapeutic approach to silence the pro-metastatic gene uPA and block breast cancer progression into the aggressive and metastatic stages of the disease. 

Retracted: No

PubPeer comments:
 Figure 1B. Much more similar than expected. ![file] , 
 Figure 2. Much more similar than expected. ![file] , 
 Figure 3. Much more similar than expected. ![file] , 
 Figure 4. Much more similar than expected. ![file] , 
 Possibly more similarities in Figure 1B? *** ![file] *** False color ![file] , 
 #4 Figure 4A.Much more similar than expected. ![file] , 
 #5 Figure 1 appears to be drawn from Figure 4-1 in the [2004 PhD thesis ] of the first author. *** Figure 4-1 from thesis ![file] *** Figure 1 from this paper ![file] *** The first author now appears to be at Roche, but I havenu2019t been able to locate her current email address. ![file] ,
Circular RNA circ-ABCB10 promotes non-small cell lung cancer proliferation and inhibits cell apoptosis through repressing KISS1
Authors: T-J Cui
J-P Zheng
Y Zheng
Y-M Dai
Z Chen
Q Chen
X Lin
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: circRNAs; circ-ABCB10; non-small cell lung cancer; NSCLC; RT-qPCR
Affiliations: Department of Oncology, Fujian Provincial Hospital, Fuzhou, China. .

Abstract:  Objective: Recent researches have proved that circular RNAs (circRNAs) act as an important role in many diseases. Our study aims to uncover the role of circ-ABCB10 in the progression of non-small cell lung cancer (NSCLC). Patients and methods: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect circ-ABCB10 expression in NSCLC patients. Then, we conducted Cell Counting Kit-8 (CCK-8) assay, colony formation assay, Ethynyl deoxyuridine (EdU) incorporation assay, cell cycle assay, and cell apoptosis assay in treated NSCLC cells. Besides, further experiments including RT-qPCR and Western blot assay were performed to explore the potential mechanism in vitro. Results: Circ-ABCB10 expression level was significantly higher in NSCLC samples comparing to that in adjacent tissues. Moreover, functional assays showed that the cell growth ability of NSCLC cells was inhibited after circ-ABCB10 was knocked down. In addition, the cell apoptosis of NSCLC cells was promoted after circ-ABCB10 was knocked down. Also the expression of KISS1 was upregulated by the knockdown of circ-ABCB10. Furthermore, it was found that KISS1 expression was negatively correlated to the circ-ABCB10 expression in NSCLC tissues. Conclusions: Results above indicated that circ-ABCB10 promoted cell proliferation and inhibited cell apoptosis of NSCLC by suppressing KISS1, which suggested that circ-ABCB10 may be a potential therapeutic target in NSCLC. 

Retracted: Yes

PubPeer comments:
null, 
 ![file] !!!!!!! ,
Repression of telomerase reverse transcriptase mRNA and hTERT promoter by gambogic acid in human gastric carcinoma cells
Authors: Zi Tan
Qing-Long Guo
Xiaotang Wang
Hai-Wei Zhang
Hong-Yan Gu
Qi-Dong You
Zhao Li
Sen-Sen Lin
Jun Yu
Journal: Cancer Chemotherapy and Pharmacology (2006)
Discipline: CLINICAL MEDICINE
Keywords: Gambogic acid; Telomerase; Gastric carcinoma; Cell proliferation; hTERT
Affiliations: Department of Physiology, China Pharmaceutical University, 24 Tongjiaxian, 210009, Nanjing, China.

Abstract:  Objectives: To investigate the effects and potential mechanisms of gambogic acid (GA), a naturally occurring anticancer agent, on the expression and regulation of telomerase in human gastric carcinoma cells. Methods: GA-induced inhibition of cell proliferation was evaluated by the commonly employed MTT assay on two human gastric carcinoma cell lines, MGC-803 and SGC-7901. Telomerase activity and hTERT mRNA expression were determined by telomeric repeat amplication protocol-polymerase chain reaction and reverse transcription-polymerase chain reaction, respectively. The hTERT promoter activity was measured by luciferase assay. The expression of c-MYC, an apoptotic gene that modulates the expression of hTERT promoter, was quantified by Western blotting. Results: The proliferation of human gastric carcinoma cell lines, MGC-803 and SGC-7901, was significantly inhibited with GA treatment. Both telomerase activity and hTERT mRNA expression were notably decreased in cells treated with GA. The activity of hTERT promoter and the expression of c-MYC were also remarkably decreased in GA-treated cells. Conclusion: This study demonstrated that GA treatment of human gastric carcinoma cell lines, MGC-803 and SGC-7901, significantly reduced the expression of c-MYC in a time- and concentration-dependent manner accompanied with the down-regulation of the hTERT transcription and the ultimate reduction in telomerase activity. Our results indicate that the hTERT is a target of c-MYC activity and identify a feasible mechanism of GA's potent anticancer activity. 

Retracted: No

PubPeer comments:
 Figure 5. * Rounded red boxes: The GAPDH panels in A (MGC-803 cells) and B (SGC-7901 cells) look similar Figure 7. * Rectangular blue boxes: The Actin panels in A (MGC-803 cells) and B (SGC-7901 cells) look similar * Rounded blue boxes: Two lanes in those actin panels look similar to two lanes in the left c-MYC panel. Note the presence of a small dot Reported to the journal together with 28 other papers in the summer of 2015, with a friendly reminder in April 2017, but no answer. With the exception of one paper, the journal did not correct or retract a single paper from this set. ![file] ,
R115777 (Zarnestra®)/Zoledronic acid (Zometa®) cooperation on inhibition of prostate cancer proliferation is paralleled by Erk/Akt inactivation and reduced Bcl-2 and bad phosphorylation
Authors: Giuseppe Tonini
Anna Maria D&#x27;Alessandro
Michele Caraglia
Giuseppina Meo
Carlo Leonetti
Alfredo Budillon
Monica Marra
Alfonso Baldi
Raffaello Bertieri
Gabriella Zupi
Daniele Santini
Alberto Abbruzzese
Journal: Journal of Cellular Physiology (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Zoledronic acid; R115777; prostate cancer; apoptosis; growth inhibition
Affiliations: Experimental Pharmacology Unit, National Cancer Institute of Naples "Fondazione G. Pascale," Naples, Italy.

Abstract:  Zoledronic acid (ZOL) has proved activity in bone metastases from prostate cancer through inhibition of mevalonate pathway and of prenylation of intracellular proteins. We have reported that ZOL synergizes with R115777 farnesyltransferase inhibitor (FTI, Zarnestra) in inducing apoptosis and growth inhibition on epidermoid cancer cells. Here, we have studied the effects of the combination of these agents in prostate adenocarcinoma models and, specifically, on androgen-independent (PC3 and DU145) and -dependent (LNCaP) prostate cancer cell lines. We have found that ZOL and R115777 were synergistic in inducing both growth inhibition and apoptosis in prostate adenocarcinoma cells. These effects were paralleled by disruption of Ras--&gt;Erk and Akt survival pathways, consequent decreased phosphorylation of both mitochondrial bcl-2 and bad proteins, and caspase activation. Finally, ZOL/R115777 combination induced cooperative effects also in vivo on tumor growth inhibition of prostate cancer xenografts in nude mice with a significant survival increase. These effects were paralleled by enhanced apoptosis and inactivation of both Erk and Akt. In conclusions, the combination between ZOL and FTI leads to enhanced anti-tumor activity in human prostate adenocarcinoma cells likely through a more efficacious inhibition of ras-dependent survival pathways and consequent bcl-related proteins-dependent apoptosis. 

Retracted: No

PubPeer comments:
 Figure 7. Much more similar than expected. ![file] , 
 Figure 4. Much more similar than expected. ![file] ,
In Vivo Type 2 Diabetes and Wound-Healing Effects of Antioxidant Gold Nanoparticles Synthesized Using the Insulin Plant Chamaecostus cuspidatus in Albino Rats
Authors: MohamedIbrahim Ponnanikajamideen
Gurusamy Annadurai
Mahendran Vanaja
Shanmugam Rajeshkumar
Journal: Canadian Journal of Diabetes (2019)
Discipline: CLINICAL MEDICINE
Keywords: Chamaecostus cuspidatus; antidiabetes; antidiabétique; gold nanoparticles; guérison d'une plaie
Affiliations: Environmental Nanotechnology Division, Sri Paramakalyani Centre for Environmental Sciences Manonmaniam Sundaranar University, Alwarkurichi, Tamilnadu, India., Department of Pharmacology, Saveetha Dental College and Hospitals, SIMATS, Chennai, Tamilnadu, India. Electronic address: .

Abstract:  Background: Gold nanoparticles are known for their many applications in the fields of therapeutics and diagnosis. Methods: This article focuses mainly on the green method of synthesizing gold nanoparticles by using the leaf powder extract of the insulin plant Chamaecostus cuspidatus and on the characterization of developed plant-mediated synthesis of gold nanoparticles. Furthermore, we investigated the free-radical scavenging activity of green-synthesized gold nanoparticles. Results: The free radicals were exhibited in a dose-dependent manner. The 50% inhibition of free radicals by gold nanoparticles showed that it was similar to that of the standard inhibition. Toxicity studies generally examine changes in blood serum chemistry and cell populations in tissue morphology through histologic analysis without inducing any lethal effects in the mouse model, thereby accomplishing sustained control over the progression of diabetes mellitus, which plays a leading role in vascular complications in patients. The treatment by gold nanoparticles of the mice with diabetes for a period of 21 days restored their blood glucose, glycogen and insulin levels. Conclusions: The use of gold nanoparticles as antidiabetes materials has been achieved. Further studies are required before gold nanoparticle-based drugs are more widely used. 

Retracted: No

PubPeer comments:
  Figure 4. Macroscopic appearance of wound repair with positive control, vehicle H2O as control, Chamaecostus cuspidatus extract and gold nanoparticles at differing postwounding days . ![file] I am not entirely convinced that all these treatment healing-time combinations are in fact different. ,
IGF-1 Signalling Regulates Mitochondria Dynamics and Turnover through a Conserved GSK-3β–Nrf2–BNIP3 Pathway
Authors: Sarah Riis
Joss B Murray
Rosemary O&#x27;Connor
Journal: Cells (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: BNIP3; HIF-1α; IGF-1; IGF-1R; NFE2L2/Nrf2
Affiliations: Cell Biology Laboratory, School of Biochemistry and Cell Biology, BioSciences Institute, University College Cork, Cork T12 YT20, Ireland.

Abstract:  The Insulin-like Growth Factor I (IGF-1) signalling pathway is essential for cell growth and facilitates tumourogenic processes. We recently reported that IGF-1 induces a transcriptional programme for mitochondrial biogenesis, while also inducing expression of the mitophagy receptor BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), suggesting that IGF-1 has a key mitochondria-protective role in cancer cells. Here, we investigated this further and delineated the signaling pathway for BNIP3 induction. We established that IGF-1 induced BNIP3 expression through a known AKT serine/threonine kinase 1 (AKT)-mediated inhibitory phosphorylation on Glycogen Synthase Kinase-3β (GSK-3β), leading to activation of Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2/Nrf2) and acting through the downstream transcriptional regulators Nuclear Respiratory Factor-1 (NRF1) and Hypoxia-inducible Factor 1 subunit α (HIF-1α). Suppression of IGF-1 signaling, Nrf2 or BNIP3 caused the accumulation of elongated mitochondria and altered the mitochondrial dynamics. IGF-1R null Mouse Embryonic Fibroblasts (MEFs) were impaired in the BNIP3 expression and in the capacity to mount a cell survival response in response to serum deprivation or mitochondrial stress. IGF-1 signalling enhanced the cellular capacity to induce autophagosomal turnover in response to activation of either general autophagy or mitophagy. Overall, we conclude that IGF-1 mediated a mitochondria-protective signal that was coordinated through the cytoprotective transcription factor Nrf2. This pathway coupled mitochondrial biogenesis with BNIP3 induction, and increased the cellular capacity for autophagosome turnover, whilst enhancing survival under conditions of metabolic or mitochondrial stress. 

Retracted: No

PubPeer comments:
 I think the authers might made a big mistake. The sequence in Supplemental Figure 2A neither belong to the Promoter of NFE2L2 nor BNIP3. The results might just fabricated. ,
Creation of tumorigenic human endometrial epithelial cells with intact chromosomes by introducing defined genetic elements
Authors: M Takakura
M Inoue
J Sakaguchi
S Ohno
Y Mizumoto
Y Maida
M Hashimoto
M Nakamura
T Kiyono
S Kyo
Journal: Oncogene (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: genetic mutations; endometrial cancers; in vitro model; endometrial carcinogenesis; human papillomavirus type 16 E6/E7 gene
Affiliations: Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.

Abstract:  Several genetic mutations have been identified in human endometrial cancers, but the specific combinations of mutations required to form endometrial cancer cells remain unknown. In the present study, we established an in vitro model of endometrial carcinogenesis, in which defined genetic elements were introduced into endometrial epithelial cells to create transformed endometrial cells at different stages. Introduction of the human papillomavirus type 16 E6/E7 gene and the human telomerase reverse transcriptase (hTERT) gene into human primary endometrial epithelial cells was sufficient to generate immortalized cells. Introduction of hTERT in early passages stabilized telomeres and created immortalized cells with normal karyotype, whereas introduction of hTERT in later passages generated immortalized cells but with widespread chromosome abnormalities. However, neither of those two immortalized cell lines exhibited tumorigenic phenotypes. Tumorigenic endometrial epithelial cells with invasive capacity were created by introducing a mutant K-ras allele into immortalized cells, keeping their chromosomes intact. Inhibiting the PTEN gene and activating Akt pathways did not create tumorigenic phenotypes, although the latter conferred anchorage-independent growth capacity. These findings suggest that neoplastic transformation of human endometrial cells can occur in the absence of widespread chromosomal abnormality, and that the combination of Rb inactivation, telomerase activation and altered K-ras signaling is sufficient for in vitro neoplastic transformation. The present experimental model can help clarify the genetic requirements for endometrial carcinogenesis, and it is useful for testing and developing specific inhibitors of specific oncogenic pathways. 

Retracted: No

PubPeer comments:
 Figure 2. https: imgur.com vDXTMb1 ,
C/EBPepsilon interacts with retinoblastoma and E2F1 during granulopoiesis
Authors: Sigal Gery
Adrian F Gombart
Yuen K Fung
H Phillip Koeffler
Journal: Blood (2004)
Discipline: CLINICAL MEDICINE
Keywords: C/EBPepsilon; Rb; E2F1; granulocytic differentiation; myeloid cells
Affiliations: Cedars-Sinai Medical Center, Davis Bldg 5066, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. , From the Cedars-Sinai Medical Center, Division of Hematology/Oncology, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, CA and the Division of Hematology/Oncology, University of Southern California (USC) School of Medicine, Childrens Hospital Los Angeles, CA.

Abstract:  CCAAT enhancer binding protein epsilon (C/EBPepsilon) is a myeloid specific transcription factor that is essential for terminal granulocytic differentiation. Retinoblastoma (Rb) and E2F1 are critical cell cycle regulators that also have been implicated in several differentiation systems. Here, we demonstrate that C/EBPepsilon interacts with Rb and E2F1 during granulocytic differentiation in NB4 and U937 human myeloid cells and in 32Dcl3 murine myeloid precursor cells. The interaction between C/EBPepsilon and Rb enhances C/EBPepsilon-mediated transcription of myeloid specific genes both in reporter assays and endogenously. The C/EBPepsilon-E2F1 interaction results in repression of E2F1-mediated transcriptional activity. Finally, overexpression of C/EBPepsilon in human myeloid cells leads to down-regulation of c-Myc. We propose that the interactions between C/EBPepsilon, a tissue-specific transcription factor, and the broad-spectrum proteins, Rb and E2F1, are important in C/EBPepsilon-induced terminal granulocytic differentiation. 

Retracted: No

PubPeer comments:
 Figure 7B. Much more similar than expected. https: imgur.com Z4vbfeU ,
Relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to up-regulate matrix metalloproteinases: the additional involvement of iNOS
Authors: Tim D Hewitson
Chrishan S Samuel
Elaine Guo Yan Chew
Ross A D Bathgate
Chongxin Zhao
Bryna Suet Man Chow
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: relaxin; myofibroblast differentiation; collagen deposition; TGF-β1/Smad2 axis; RXFP1
Affiliations: Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria, Australia.

Abstract:  The hormone, relaxin, inhibits aberrant myofibroblast differentiation and collagen deposition by disrupting the TGF-β1/Smad2 axis, via its cognate receptor, Relaxin Family Peptide Receptor 1 (RXFP1), extracellular signal-regulated kinase (ERK)1/2 phosphorylation (pERK) and a neuronal nitric oxide (NO) synthase (nNOS)-NO-cyclic guanosine monophosphate (cGMP)-dependent pathway. However, the signalling pathways involved in its additional ability to increase matrix metalloproteinase (MMP) expression and activity remain unknown. This study investigated the extent to which the NO pathway was involved in human gene-2 (H2) relaxin's ability to positively regulate MMP-1 and its rodent orthologue, MMP-13, MMP-2 and MMP-9 (the main collagen-degrading MMPs) in TGF-β1-stimulated human dermal fibroblasts and primary renal myofibroblasts isolated from injured rats; by gelatin zymography (media) and Western blotting (cell layer). H2 relaxin (10-100 ng/ml) significantly increased MMP-1 (by ~50%), MMP-2 (by ~80%) and MMP-9 (by ~80%) in TGF-β1-stimulated human dermal fibroblasts; and MMP-13 (by ~90%), MMP-2 (by ~130%) and MMP-9 (by ~115%) in rat renal myofibroblasts (all p&lt;0.01 vs untreated cells) over 72 hours. The relaxin-induced up-regulation of these MMPs, however, was significantly blocked by a non-selective NOS inhibitor (L-nitroarginine methyl ester (hydrochloride); L-NAME; 75-100 µM), and specific inhibitors to nNOS (N-propyl-L-arginine; NPLA; 0.2-2 µM), iNOS (1400W; 0.5-1 µM) and guanylyl cyclase (ODQ; 5 µM) (all p&lt;0.05 vs H2 relaxin alone), but not eNOS (L-N-(1-iminoethyl)ornithine dihydrochloride; L-NIO; 0.5-5 µM). However, neither of these inhibitors affected basal MMP expression at the concentrations used. Furthermore, of the NOS isoforms expressed in renal myofibroblasts (nNOS and iNOS), H2 relaxin only stimulated nNOS expression, which in turn, was blocked by the ERK1/2 inhibitor (PD98059; 1 µM). These findings demonstrated that H2 relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to mediate its anti-fibrotic actions, and additionally signals through iNOS to up-regulate MMPs; the latter being suppressed by TGF-β1 in myofibroblasts, but released upon H2 relaxin-induced inhibition of the TGF-β1/Smad2 axis. 

Retracted: No

PubPeer comments:
 In Figure 6A, the tubulin controls look very similar to those for Figure 6C (if they are stretched vertically), yet the treatment conditions were different. Could the authors please check? ![file] ,
Losartan loaded liposomes improve the antitumor efficacy of liposomal paclitaxel modified with pH sensitive peptides by inhibition of collagen in breast cancer
Authors: Qin He
Yang Wang
Lifang Ma
Li Zhang
Ji Liu
Qianwen Yu
Qianyu Zhang
Tai Xia
Huile Gao
Kairong Shi
Journal: Pharmaceutical Development and Technology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Losartan loaded liposomes; breast cancer; collagen inhibition; combined strategy; enhanced antitumor efficacy.
Affiliations: a School of Chemical Engineering , Sichuan University , Chengdu , People's Republic of China., b Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy , Sichuan University , Chengdu , People's Republic of China., c West China School of Preclinical and Forensic Medicine , Sichuan University , Chengdu , People's Republic of China.

Abstract:  The dense collagen network in tumors restricts the penetration of drugs into tumors. Free losartan could inhibit collagen, but it would cause hypotension at the dosage of 10 mg/kg/d. In this study, losartan was encapsulated in liposomes (LST-Lip) and the collagen inhibition ability of LST-Lip was investigated. Our results showed the blood pressure was not affected by LST-Lip at the dosage of 2.5 mg/kg every other day. The amount of Evans Blue in tumor in LST-Lip group was 1.98 times of that in control group. Confocal laser scanning microscopy images showed that prior injection of LST-Lip could inhibit collagen and further improve the tumorous accumulation of liposomes modified with TH peptides (AGYLLGHINLHHLAHL(Aib)HHIL-NH2) (TH-Lip) in 4T1 tumors. Compared with control group, the tumor inhibition rate of combined strategy of LST-Lip and paclitaxel loaded TH-Lip (PTX-TH-Lip) was 41.73%, while that of group only treated with PTX-TH-Lip was 14.94%. Masson's trichrome staining confirmed that collagen was inhibited in LST-Lip group. Thus, the administration of LST-Lip in advance could inhibit the collagen in tumors effectively and did not affect the blood pressure, then PTX-TH-Lip injected subsequently could exert enhanced antitumor efficacy. In conclusion, this combined strategy might be promising for breast cancer therapy. 

Retracted: No

PubPeer comments:
 There appear to be some images that overlap in this paper (red and green boxes), I believe in Figure 8. Unfortunately the version of the paper I can retrieve isnu2019t entirely clear which figures are which. *** ![file] ,
Glucocorticoid Induces Hepatic Steatosis by Inhibiting Activating Transcription Factor 3 (ATF3)/S100A9 Protein Signaling in Granulocytic Myeloid-derived Suppressor Cells
Authors: Jian-Yang Wei
Jie Zhou
Mao-Hua Shi
Yu-Feng Liu
Hua Jiang
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: S100 proteins; cAMP response element-binding protein; glucocorticoid; immunosuppression; liver metabolism.
Affiliations: From the Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, 9th Jin Sui Road, Guangzhou 510623, and., Institute of Human Virology, Sun Yat-Sen University, 74 Zhongshan 2nd Road, Guangzhou 510080., the Department of Hematology Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9th Jin Sui Road, Guangzhou 510623, China., From the Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, 9th Jin Sui Road, Guangzhou 510623, and ., the Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Chinese Ministry of Education, 74 Zhongshan 2nd Road, Guangzhou 510080, and.

Abstract:  Glucocorticoids (GCs) used as inflammation suppressors have harmful side effects, including induction of hepatic steatosis. The underlying mechanisms of GC-promoted dysregulation of lipid metabolism, however, are not fully understood. GCs could facilitate the accumulation of myeloid-derived suppressor cells (MDSC) in the liver of animals, and the potential role of MDSCs in GC-induced hepatic steatosis was therefore investigated in this study. We demonstrated that granulocytic (G)-MDSC accumulation mediated the effects of GCs on the fatty liver, in which activating transcription factor 3 (ATF3)/S100A9 signaling plays an important role. ATF3-deficient mice developed hepatic steatosis and displayed expansion of G-MDSCs in the liver and multiple immune organs, which shared high similarity with the phenotype observed in GC-treated wild-type littermates. Adoptive transfer of GC-induced or ATF3-deficient G-MDSCs promoted lipid accumulation in the liver, whereas depletion of G-MDSCs alleviated these effects. Mechanistic studies showed that in MDSCs, ATF3 was transrepressed by the GC receptor GR through direct binding to the negative GR-response element. S100A9 is the major transcriptional target of ATF3 in G-MDSCs. Silencing S100A9 clearly alleviated G-MDSCs expansion and hepatic steatosis caused by ATF3 deficiency or GC treatment. Our study uncovers an important role of G-MDSCs in GC-induced hepatic steatosis, in which ATF3 may have potential therapeutic implications. 

Retracted: No

PubPeer comments:
 The flow cytometry dot plots in red boxes appear to look similar in Fig 2A. ![file] ,