PReD-Bench/PRed-Bench huggingface dataset:
Ferroptosis-related Genes for Overall Survival Prediction in Patients with Colorectal Cancer can be Inhibited by Gallic acid
Authors: Peili Tang
Chongwang Ran
Chong Yuan
Yanfang Yang
Hezhen Wu
Ying Zhang
Zongchao Hong
Bo Liu
Yi Lu
Xueyun Duan
Journal: International Journal of Biological Sciences (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Colorectal cancer; Ferroptosis; Gallic acid; Natural product..
Affiliations: Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China., Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China.

Abstract:  Colorectal cancer (CRC) is one of the most deadly malignant tumors, which seriously threatens human health. Ferroptosis, a new type of iron-dependent cell regulatory necrosis. Inducing ferroptosis of tumor cells is regarded as a potential treatment strategy. However, the prognostic value of ferroptosis-related genes in CRC remains to be further elucidated. Gallic acid, widely used in the chemical, pharmaceutical, and food fields, is a dietary supplement with potential prescription significance. In this study, the mRNA expression profiles and corresponding clinical data of CRC patients were downloaded from public databases. Gene Expression Profiling Interactive Analysis (GEPIA) was used to evaluate the expression levels of ferroptosis-related genes. In addition, bioinformatics analysis showed the prognostic value of ferroptosis-related genes in CRC. Molecular docking predicts the binding status of gallic acid and ferroptosis-related genes. The experiment confirmed the correctness of the predicted results. Our results show that in the TCGA cohort, 30 ferroptosis-related genes are differentially expressed between CRC and adjacent normal tissues. Among them, eight differentially expressed genes are related to overall survival. Gallic acid can bind to ferroptosis-related targets and regulate the expression of corresponding proteins, and ferroptosis inhibitors reversed the experimental results. In summary, eight new ferroptosis-related genes can be used to predict the prognosis of CRC. Gallic acid can improve CRC by regulating ferroptosis. 

Retracted: No

PubPeer comments:
 I think some of the survival analyses in Figure 4 use clinical data from other cancers. Specifically, a total of 364 samples were used for SLC7A11 and TFRC survival analysis, while only 270 samples were used for other genes analysis. At the same time, the maximum survival time of SLC7A11 and TFRC is 120 months, while that of other genes are 150 months. ![file] In addition, I have performed survival analysis for Colorectal Cancer in GEPIA and found that the expression of SLC7A11 and TFRC does not shows any statistical significance(P 0.6 for both). ![file] ,
An ERK-dependent pathway to Noxa expression regulates apoptosis by platinum-based chemotherapeutic drugs
Authors: S J Martin
G Brumatti
M Elgendy
M Brunet
C Sheridan
Journal: Oncogene (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cisplatin; DNA damage; apoptosis; BH3-only protein; Noxa
Affiliations: Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin, Ireland.

Abstract:  Cisplatin is a widely used cancer chemotherapeutic that promotes DNA damage-associated apoptosis. Although platinum compounds are known to form DNA adducts and provoke DNA damage, the molecular mechanism of cisplatin-induced cell death remains unclear. In this article, we show that the BH3-only protein Noxa is strongly transcriptionally upregulated in response to cisplatin and related platinum compounds. Cisplatin-induced Noxa expression was ERK dependent, but p53 independent, and inhibition of ERK activation markedly attenuated cisplatin-induced cell death, as well as Noxa expression. Furthermore, siRNA-mediated ablation of Noxa expression also inhibited cisplatin-induced cell death and permitted clonogenic survival. These observations reveal a novel ERK-regulated route to Noxa expression that is important for the cell killing activity of platinum-based chemotherapeutic drugs. 

Retracted: No

PubPeer comments:
 Figure 7c. Much more similar than you would expect. https: imgur.com 0xasfIC ,
A DNA-based nanocarrier for efficient cancer therapy
Authors: Hai-Liang Zhu
Yaliang Zhang
Yu-Shun Yang
Zhong-Chang Wang
Mirza Muhammad Faran Ashraf Baig
Songyu Wu
Yiqiao Hu
Muhammad Abbas
Journal: Journal of Pharmaceutical Analysis (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Caveolae; Cisplatin; DNA-nanothread; Drug delivery; HeLa cell line
Affiliations: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, PR China., State Key Laboratory of Analytical Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, PR China.

Abstract:  The study aimed to achieve enhanced targeted cytotoxicity and cell-internalization of cisplatin-loaded deoxyribonucleic acid-nanothread (CPT-DNA-NT), mediated by scavenger receptors into HeLa cells. DNA-NT was developed with stiff-topology utilizing circular-scaffold to encapsulate CPT. Atomic force microscopy (AFM) characterization of the DNA-NT showed uniformity in the structure with a diameter of 50-150 nm and length of 300-600 nm. The successful fabrication of the DNA-NT was confirmed through native-polyacrylamide gel electrophoresis analysis, as large the molecular-weight (polymeric) DNA-NT did not split into constituting strands under applied current and voltage. The results of cell viability confirmed that blank DNA-NT had the least cytotoxicity at the highest concentration (512 nM) with a viability of 92% as evidence of its biocompatibility for drug delivery. MTT assay showed superior cytotoxicity of CPT-DNA-NT than that of the free CPT due to the depot release of CPT after DNA-NT internalization. The DNA-NT exhibited targeted cell internalizations with the controlled intracellular release of CPT (from DNA-NT), as illustrated in confocal images. Therefore, in vitro cytotoxicity assessment through flow cytometry showed enhanced apoptosis (72.7%) with CPT-DNA-NT (compared to free CPT; 64.4%). CPT-DNA-NT, being poly-anionic, showed enhanced endocytosis via scavenger receptors. 

Retracted: No

PubPeer comments:
 Fig 4A,  PAGE analysis . At right, Fig 3a from [Baig et al (2019)] . ![file] Fig 4A from [Baig et al (2019b)] . ![] , 
 Another version of that PAGE gel! Now at right, Fig 4b from [Baig et al (2020)] . ![file] ,
The three RelE homologs of Mycobacterium tuberculosis have individual, drug-specific effects on bacterial antibiotic tolerance
Authors: Helena I M Boshoff
Clifton E Barry 3rd
Ramandeep Singh
Journal: Journal of Bacteriology (2010)
Discipline: MICROBIOLOGY
Keywords: Escherichia coli; Mycobacterium tuberculosis; persisters; toxins; antitoxins
Affiliations: 33 North Drive, Bldg. 33, Rm. 2W20G, Bethesda, MD 20892, USA.

Abstract:  In Escherichia coli, expression of the RelE and HipA toxins in the absence of their cognate antitoxins has been associated with generating multidrug-tolerant "persisters." Here we show that unlike persisters of E. coli, persisters of Mycobacterium tuberculosis selected with one drug do not acquire cross-resistance to other classes of drugs. M. tuberculosis has three homologs of RelE arranged in operons with their apparent antitoxins. Each toxin individually arrests growth of both M. tuberculosis and E. coli, an effect that is neutralized by coexpression of the cognate antitoxin. Overexpression or deletion of each of the RelE toxins had a toxin- and drug-specific effect on the proportion of bacilli surviving antibiotic killing. All three toxins were upregulated in vivo, but none of the deletions affected survival during murine infection. RelE2 overexpression increased bacterial survival rates in the presence of rifampin in vitro, while deletion significantly decreased survival rates. Strikingly, deletion of this toxin had no discernible effect on the level of persisters seen in rifampin-treated mice. Our results suggest that, in vivo, RelE-generated persisters are unlikely to play a significant role in the generation of bacilli that survive in the face of multidrug therapy or in the generation of multidrug-resistant M. tuberculosis. 

Retracted: No

PubPeer comments:
 ![file] Figure 2 : the highlighted bacterial growths appear identical. , 
 We are investigating this now. We will update this post once we get to the bottom of this duplicated image. We will also contact the journal as soon as we can figure out why this happened. , 
 We thank the reviewer for noticing this panel duplication. The original images are lost. However, we repeated this experiment in two independent labs with the same results. A representative image is attached. The strains remain available to the research community.![file] , 
 We have also submitted a  Correction to J. Bact. that will appear shortly noting this and stating this does not affect the conclusions of the manuscript ,
A Mo5N6 electrocatalyst for efficient Na2S electrodeposition in room-temperature sodium-sulfur batteries
Authors: Yan Jiao
Shi-Zhang Qiao
Chao Ye
Haihui Wang
Huanyu Jin
Kenneth Davey
Huan Li
Qinfen Gu
Jieqiong Shan
Journal: Nature Communications (2021)
Discipline: Multidisciplinary
Keywords: Metal sulfides; electrodeposition; sulfur cathodes; shuttle effect; polysulfides
Affiliations: School of Chemical Engineering & Advanced Materials, The University of Adelaide, Adelaide, SA, 5005, Australia., Australian Synchrotron (ANSTO), 800 Blackburn Rd, Clayton, VIC, 3168, Australia., Beijing Key Laboratory of Membrane Materials and Engineering, Department of Chemical Engineering, Tsinghua University, 100084, Beijing, China. ., School of Chemical Engineering & Advanced Materials, The University of Adelaide, Adelaide, SA, 5005, Australia. .

Abstract:  Metal sulfides electrodeposition in sulfur cathodes mitigates the shuttle effect of polysulfides to achieve high Coulombic efficiency in secondary metal-sulfur batteries. However, fundamental understanding of metal sulfides electrodeposition and kinetics mechanism remains limited. Here using room-temperature sodium-sulfur cells as a model system, we report a Mo5N6 cathode material that enables efficient Na2S electrodeposition to achieve an initial discharge capacity of 512 mAh g-1 at a specific current of 1 675 mA g-1, and a final discharge capacity of 186 mAh g-1 after 10,000 cycles. Combined analyses from synchrotron-based spectroscopic characterizations, electrochemical kinetics measurements and density functional theory computations confirm that the high d-band position results in a low Na2S2 dissociation free energy for Mo5N6. This promotes Na2S electrodeposition, and thereby favours long-term cell cycling performance. 

Retracted: No

PubPeer comments:
 For the supplementary Figure 1, some of the weak peaks presented in Mo5N6 and Mo2N are neglected, which may have a certain role in the following electrochemical battery performance. The presence of impurity will make the modeling results are not accurate convincible. ![file] ,
Knocking down clock control gene CRY1 decreases adipogenesis via canonical Wnt/β-catenin signaling pathway
Authors: Shiwei Sun
Tieqi Zhang
Yueming Yu
Lei Zhou
Minghai Wang
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Adipogenesis; CRY1; Clock gene; Wnt; β-Catenin.
Affiliations: The Fifth People's Hospital of Shanghai, Fudan University, 200240, Shanghai, China., The Fifth People's Hospital of Shanghai, Fudan University, 200240, Shanghai, China. Electronic address: .

Abstract:  Cryptochrome gene 1(CRY1) is a member of circadian clock genes, which play an important role in adipocyte biology. CRY1 was reported to be related with the lipid metabolism, but the molecule mechanism of CRY1 in regulating the adipogenesis remains unclear. Here we report that CRY1 is a key regulator in adipogenic differentiation. We found that the expression levels of CRY1 in 3T3-L1 cells and C3H10T1/2 cells gradually increased during the process of adipogenic differentiation. Knockdown of endogenous CRY1 significantly inhibited the expression of adipogenic markers and lipid droplet formation in cells under adipogenic induction. In addition, knockdown of endogenous CRY1 promoted the expression and nuclear accumulation of β-catenin, the critical signal molecular in the canonical canonical Wnt signaling pathway, suggesting the regulation effect of CRY1 in adipogenesis was mediated by canonical Wnt/β-catenin signaling. Taken together, our study suggests that CRY1 regulates adipogenic differentiation through modulating the canonical Wnt/β-catenin signaling pathway. 

Retracted: No

PubPeer comments:
 Images in Figure 1I and 3A appear to overlap (red and yellow boxes). *** ![file] ,
LncRNA MALAT1 promotes proliferation and metastasis in epithelial ovarian cancer via the PI3K-AKT pathway
Authors: Y Jin
S-J Feng
S Qiu
N Shao
J-H Zheng
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MALAT1; long non-coding RNA; ovarian cancer; metastasis; prognosis
Affiliations: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. .

Abstract:  Objective: The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that plays a key role in the malignant phenotype of tumors. Although abnormal regulation of lncRNA MALAT1 impacts clinical prognostic and tumor metastasis, its function remains unclear in ovarian cancer. Patients and methods: We collected 64 samples of surgical EOC tissues and 30 samples of normal ovarian tissues at the Department of Gynecology of Harbin Medical University (Harbin, China). The 30 control samples of ovarian surface epithelial tissues were obtained from patients diagnosed with uterine fibroids and scheduled hysterectomy with oophorectomy. Results: The present study discovered that MALAT1 was upregulated in tumor tissues and ovarian cancer cell lines. Further, the 5-year overall survival was higher in the lower expression of the MALAT1 group. MALAT1 inhibition impeded cell proliferation, invasion and metastasis, and promoted cell apoptosis in both in vivo and in vitro. Furthermore, silencing of MALAT1 hindered the expression of epithelial-to-mesenchymal transition (EMT)-related genes and MMPS. The evidence showed that MALAT1 induce EMT via PI3K/AKT pathway. Conclusions: Our research suggests that MALAT1 transforms metastasis in EOC and may be a prospective therapeutic target. 

Retracted: No

PubPeer comments:
 Fig 2.  (D) knockdown MALAT1 promoted tumor cells apoptosis in A2780 and HO8910 cell lines by flow cytometry; (E-F) transwell assay testified silencing of MALAT1 restrained cell invasion and metastasis . Two panels of (D) are the same. The 12 panels of (E) are overlapping details of just four images. ![] It may be that I spent more time marking up these figures than the authors spent creating them. , 
 So far cited 149 times. ,
Hydrogen peroxide-mediated downregulation of matrix metalloprotease-2 in indomethacin-induced acute gastric ulceration is blocked by melatonin and other antioxidants
Authors: Krishnendu Ganguly
Russel J Reiter
Snehasikta Swarnakar
Aditi Banerjee
Parag Kundu
Journal: Free Radical Biology and Medicine (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Gastric mucosal damage; extracellular matrix degradation; matrix metalloproteinases (MMPs); inflammatory diseases; gastric ulcer
Affiliations: Department of Physiology, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.

Abstract:  Gastric mucosal damage is directly associated with extracellular matrix degradation in which matrix metalloproteinases (MMPs) play a crucial role. Remodeling of connective tissues and loss of tissue integrity due to the action of MMPs are reported in several inflammatory diseases, including gastric ulcer. Indomethacin-induced gastric ulceration involves the generation of reactive oxygen species (ROS) and a reduction in MMP-2 transcription and translation. Our aim was to identify the mechanism for suppression of MMP-2 activity by ROS during acute ulceration and further to examine the possible actions of antioxidants, especially melatonin, during healing. Melatonin (N-acetyl-5-methoxytryptamine) blocked hydroxyl radical and nitrite anion generation, protein oxidation, mucosal cell disruption, and MMP-2 downregulation. In addition, suppression of MMP-2 activity by H2O2 in a dose- and time-dependent manner in vitro is blocked by melatonin, omeprazole, and curcumin. We observed that melatonin and other antioxidants (e.g., curcumin and omeprazole) offered gastroprotection in vivo by upregulation of suppressed MMP-2 expression and activity at the level of secretion and synthesis. Moreover, antioxidants reversed the suppression of MMP-2 expression by upregulation of MT1-MMP and downregulation of TIMP-2. Hence, we hypothesize that antioxidants exerted protection against H2O2-mediated inactivation and downregulation of MMP-2 expression during onset of indomethacin-induced ulceration. 

Retracted: No

PubPeer comments:
 Unexpected similarity between bands in Fig 2A ![file] , 
 Some bands from 2005 JBC paper (Fig. 8A) seem like being reused in 2006 Free Radical Biology Medicine (Fig 3B). The bands are labelled as obtained in different experimental conditions. ![file] ,
Combination of mTOR and EGFR kinase inhibitors blocks mTORC1 and mTORC2 kinase activity and suppresses the progression of colorectal carcinoma
Authors: Chunsheng Li
Chunhai Hao
Feng Wei
Quan Wang
Tongjun Liu
Guoyue Lv
Guangyi Wang
Anita C Bellail
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: mTORC1/2; colorectal carcinoma; mTOR inhibitors; PP242; AKT phosphorylation
Affiliations: Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, Jilin, China. 

Abstract:  Mammalian target of rapamycin complex 1 and 2 (mTORC1/2) are overactive in colorectal carcinomas; however, the first generation of mTOR inhibitors such as rapamycin have failed to show clinical benefits in treating colorectal carcinoma in part due to their effects only on mTORC1. The second generation of mTOR inhibitors such as PP242 targets mTOR kinase; thus, they are capable of inhibiting both mTORC1 and mTORC2. To examine the therapeutic potential of the mTOR kinase inhibitors, we treated a panel of colorectal carcinoma cell lines with PP242. Western blotting showed that the PP242 inhibition of mTORC2-mediated AKT phosphorylation at Ser 473 (AKT(S473)) was transient only in the first few hours of the PP242 treatment. Receptor tyrosine kinase arrays further revealed that PP242 treatment increased the phosphorylated epidermal growth factor receptor (EGFR) at Tyr 1068 (EGFR(T1068)). The parallel increase of AKT(S473) and EGFR(T1068) in the cells following PP242 treatment raised the possibility that EGFR phosphorylation might contribute to the PP242 incomplete inhibition of mTORC2. To test this notion, we showed that the combination of PP242 with erlotinib, an EGFR small molecule inhibitor, blocked both mTORC1 and mTORC2 kinase activity. In addition, we showed that the combination treatment inhibited colony formation, blocked cell growth and induced apoptotic cell death. A systemic administration of PP242 and erlotinib resulted in the progression suppression of colorectal carcinoma xenografts in mice. This study suggests that the combination of mTOR kinase and EGFR inhibitors may provide an effective treatment of colorectal carcinoma. 

Retracted: No

PubPeer comments:
 Figure 1C. Some lanes appear to be visible twice or three times, to represent different cell lines or time points. Boxes of the same color depict lanes that look similar. Reported to the journal in October 2015. ![file] ,
miR-21-mediated Radioresistance Occurs via Promoting Repair of DNA Double Strand Breaks
Authors: Ping Wang
Ya Wang
Jian Wang
Shuofeng Hu
Xiaomin Ying
Xiang Wang
Baocheng Hu
Hongyan Wang
Xiangming Zhang
Journal: Journal of Biological Chemistry (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: DNA double strand breaks; DNA repair; DNA-dependent serine/threonine protein kinase (DNA-PK); GSK3β; cellular regulation
Affiliations: From the Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and., the Beijing Institute of Basic Medical Sciences, Beijing 100850, China., From the Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and .

Abstract:  miR-21, as an oncogene that overexpresses in most human tumors, is involved in radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance occurs through promoting repair of DNA double strand breaks, which includes facilitating both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ occurs through targeting GSK3B (a novel target of miR-21), which affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity. The miR-21-promoted HRR occurs through targeting both GSK3B and CDC25A (a known target of miR-21), which neutralizes the effects of targeting GSK3B-induced CDC25A increase because GSK3B promotes degradation of both CDC25A and cyclin D1, but CDC25A and cyclin D1 have an opposite effect on HRR. A negative correlation of expression levels between miR-21 and GSK3β exists in a subset of human tumors. Our results not only elucidate miR-21-mediated radioresistance, but also provide potential new targets for improving radiotherapy. 

Retracted: Yes

PubPeer comments:
 Concern about Figure 5E. * Green boxes: Lanes 7 and 23 look remarkably similar * Red boxes: Lanes 8 and 26 look remarkably similar ![file] , 
 #1 We do apologize for the mistake caused by cropping several lanes from the original agarose gels. Fortunately, during the submission, we submitted also all manuscriptu2018s raw, uncropped versions of all gels and western blots. From these data (see below) is obvious that we did unintentionally inserted the wrong lane. Figure 5e will be corrected. Importantly, this error did not affect the results and conclusions presented in the paper. Also, the EMSA data only supports what was mainly demonstrated by MST. ![file] ,
Yeast-template synthesized Fe-doped cerium oxide hollow microspheres for visible photodegradation of acid orange 7
Authors: Li Zhang
Zhen Liu
Baoqin Zhao
Shengsong Ge
Luhan Hao
Qian Shao
Bing Zhang
Zhanhu Guo
Journal: Journal of Colloid and Interface Science (2018)
Discipline: CHEMISTRY
Keywords: Bio-template; Fe-doped CeO(2); Hollow microspheres; Photocatalytic activity.
Affiliations: College of Chemical and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, PR China., College of Chemical and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, PR China. Electronic address: ., Integrated Composites Laboratory (ICL), Department of Chemical & Biomolecular Engineering, University of Tennessee, Knoxville, TN 37996, USA., School of Environmental and Materials Engineering, Shanghai Second Polytechnic University, Shanghai 201209, PR China. Electronic address: ., Department of Physics and Engineering, Frostburg State University, Frostburg, MD, USA., Integrated Composites Laboratory (ICL), Department of Chemical & Biomolecular Engineering, University of Tennessee, Knoxville, TN 37996, USA. Electronic address: .

Abstract:  Fe-doped cerium oxide (CeO2) hollow microspheres were successfully synthesized by a simple co-precipitation route using yeast asa bio-template and nitrate as the oxide precursor. The products were characterized by scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, N2 adsorption-desorption isotherms and UV-Vis diffuse reflectance spectroscopy. It was found that the products had a well-defined ellipsoidal morphology and the size of the hollow microspheres was about 1.5-2.5μm. The formation mechanism of Fe-doped CeO2 hollow microspheres was proposed and discussed as well. The photocatalytic test results showed that the Fe-doped CeO2 hollow microspheres exhibited a higher photocatalytic activity in the degradation of acid orange 7 (AO7) aqueous solutions containing H2O2 under visible irradiation compared with CeO2 hollow microspheres and Fe-doped CeO2 nanoparticles, which was attributed to their more oxygen vacancies, higher specific surface area and lower band gap. The degradation rate of the Fe-doped CeO2 hollow microspheres was found to be 93% after 80min and the degradation reaction followed pseudo-first-order kinetics. 

Retracted: No

PubPeer comments:
 Figure 1. * Pink boxes: Panels C (CeO2 hollow microspheres) and E ( Fe-doped CeO2 hollow microspheres after calcination) appear to show the same sample, but at different magnification. ![file] ,
DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival
Authors: Seong A Kang
W Michael Kuehl
Nathanael S Gray
Yasemin Sancak
Timothy R Peterson
David M Sabatini
Mathieu Laplante
Carson C Thoreen
Journal: Cell (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mTORC1; mTORC2; DEPTOR; S6K1; Akt
Affiliations: Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.

Abstract:  The mTORC1 and mTORC2 pathways regulate cell growth, proliferation, and survival. We identify DEPTOR as an mTOR-interacting protein whose expression is negatively regulated by mTORC1 and mTORC2. Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities. DEPTOR overexpression suppresses S6K1 but, by relieving feedback inhibition from mTORC1 to PI3K signaling, activates Akt. Consistent with many human cancers having activated mTORC1 and mTORC2 pathways, DEPTOR expression is low in most cancers. Surprisingly, DEPTOR is highly overexpressed in a subset of multiple myelomas harboring cyclin D1/D3 or c-MAF/MAFB translocations. In these cells, high DEPTOR expression is necessary to maintain PI3K and Akt activation and a reduction in DEPTOR levels leads to apoptosis. Thus, we identify a novel mTOR-interacting protein whose deregulated overexpression in multiple myeloma cells represents a mechanism for activating PI3K/Akt signaling and promoting cell survival. 

Retracted: No

PubPeer comments:
 Figures 2C and 4C. Flow cytometry panels representing different cell lines or experiments appear to share areas of similarity. Boxes of the same color draw attention to several of these areas. ![file] ![file] , 
 Dear Dr. Elisabeth M Bik. Thanks for your comments. We have noticed this issue and checked through our original work in the study. That is a mistake, we had contacted the editor for correction. Thanks again! Yazhuo Jiang , 
 Dear Dr. Jiang, Thank you for your reply. But could you please clarify how the apparent duplications of parts of quadrant happened? You wrote it was a mistake, but for educational purposes, could you please provide some more details on how such mistake might have happened? ,
Cross-talk between Human Papillomavirus Oncoproteins and Hedgehog Signaling Synergistically Promotes Stemness in Cervical Cancer Cells
Authors: Abhishek Tyagi
Arvind Pandey
Kanchan Vishnoi
Alok C Bharti
Tejveer Singh
Sukh Mahendra Singh
Gaurav Verma
Mohit Jadli
Sutapa Mahata
Journal: Scientific reports (2016)
Discipline: Multidisciplinary
Keywords: Viral oncoproteins; E6/E7; human papillomavirus (HPV); cervical carcinogenesis; GLI-signaling
Affiliations: Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, India., Division of Molecular Oncology, Institute of Cytology &Preventive Oncology (ICMR), Noida, Uttar Pradesh, India., School of Biotechnology, Banaras Hindu University, Varanasi, Uttar Pradesh, India., Molecular Oncology Laboratory, B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, New Delhi, India.

Abstract:  Viral oncoproteins E6/E7 play key oncogenic role in human papillomavirus (HPV)-mediated cervical carcinogenesis in conjunction with aberrant activation of cellular signaling events. GLI-signaling has been implicated in metastasis and tumor recurrence of cervical cancer. However, the interaction of GLI-signaling with HPV oncogenes is unknown. We examined this relationship in established HPV-positive and HPV-negative cervical cancer cell lines using specific GLI inhibitor, cyclopamine and HPVE6/E7 siRNAs. Cervical cancer cell lines showed variable expression of GLI-signaling components. HPV16-positive SiHa cells, overexpressed GLI1, Smo and Patch. Inhibition by cyclopamine resulted in dose-dependent reduction of Smo and GLI1 and loss of cell viability with a higher magnitude in HPV-positive cells. Cyclopamine selectively downregulated HPVE6 expression and resulted in p53 accumulation, whereas HPVE7 and pRb level remained unaffected. siRNA-mediated silencing of HPV16E6 demonstrated reduced GLI1 transcripts in SiHa cells. Cervical cancer stem-like cells isolated by side population analysis, displayed retention of E6 and GLI1 expression. Fraction of SP cells was reduced in cyclopamine-treated cultures. When combined with E6-silencing cyclopamine resulted in loss of SP cell's sphere-forming ability. Co-inhibition of GLI1 and E6 in cervical cancer cells showed additive anti-cancer effects. Overall, our data show existence of a cooperative interaction between GLI signaling and HPVE6. 

Retracted: No

PubPeer comments:
 Image duplication ![file] , 
 Also, image recycled from this paper to another paper. ![file] ,
Functional vascular smooth muscle cells derived from human induced pluripotent stem cells via mesenchymal stem cell intermediates
Authors: Panagiotis Mistriotis
Yuin-Han Loh
George Q Daley
Vivek K Bajpai
Stelios T Andreadis
Journal: Cardiovascular research (2012)
Discipline: CLINICAL MEDICINE
Keywords: Smooth muscle cells; vascular homeostasis; mesenchymal stem cells; human induced pluripotent stem cells; differentiation
Affiliations: Bioengineering Laboratory, Department of Chemical and Biological Engineering,  University of Buffalo, The State University of New York, 908 Furnas Hall, Amherst, NY 14260-4200,  USA.

Abstract:  Aims: Smooth muscle cells (SMC) play an important role in vascular homeostasis and disease. Although adult mesenchymal stem cells (MSC) have been used as a source of contractile SMC, they suffer from limited proliferation potential and culture senescence, particularly when originating from older donors. By comparison, human induced pluripotent stem cells (hiPSC) can provide an unlimited source of functional SMC for autologous cell-based therapies and for creating models of vascular disease. Our goal was to develop an efficient strategy to derive functional, contractile SMC from hiPSC. Methods and results: We developed a robust, stage-wise, feeder-free strategy for hiPSC differentiation into functional SMC through an intermediate stage of multipotent MSC, which could be coaxed to differentiate into fat, bone, cartilage, and muscle. At this stage, the cells were highly proliferative and displayed higher clonogenic potential and reduced senescence when compared with parental hair follicle mesenchymal stem cells. In addition, when exposed to differentiation medium, the myogenic proteins such as α-smooth muscle actin, calponin, and myosin heavy chain were significantly upregulated and displayed robust fibrillar organization, suggesting the development of a contractile phenotype. Indeed, tissue constructs prepared from these cells exhibited high levels of contractility in response to receptor- and non-receptor-mediated agonists. Conclusion: We developed an efficient stage-wise strategy that enabled hiPSC differentiation into contractile SMC through an intermediate population of clonogenic and multipotent MSC. The high yield of MSC and SMC derivation suggests that our strategy may facilitate an acquisition of the large numbers of cells required for regenerative medicine or for studying vascular disease pathophysiology. 

Retracted: No

PubPeer comments:
 Figure 2C. Much more similar than you would expect. https: imgur.com 82obr2e ,
Remote Actuation of Magnetic Nanoparticles For Cancer Cell Selective Treatment Through Cytoskeletal Disruption
Authors: Marina Sokolsky
Alyssa M Master
Judy S Riffle
Alexander V Kabanov
Nipon Pothayee
Nikorn Pothayee
Yuri I Golovin
Rui Zhang
Hemant M Vishwasrao
Philise N Williams
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: magnetic particles; mechanosensitive cellular functions; cancer cells; superparamagnetic nanoparticles; block copolymers
Affiliations: Center for Nanotechnology in Drug Delivery, University of North Carolina, Chapel Hill, NC, USA., Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA., Macromolecules and Interfaces Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA., Nanocenter, G. R. Derzhavin Tambov State University, Tambov, 392000, Russian Federation., Laboratory of Chemical Design of Bionanomaterials, Faculty of Chemistry, M. V. Lomonosov Moscow State University, Moscow, 117234, Russian Federation.

Abstract:  Motion of micron and sub-micron size magnetic particles in alternating magnetic fields can activate mechanosensitive cellular functions or physically destruct cancer cells. However, such effects are usually observed with relatively large magnetic particles (&gt;250 nm) that would be difficult if at all possible to deliver to remote sites in the body to treat disease. Here we show a completely new mechanism of selective toxicity of superparamagnetic nanoparticles (SMNP) of 7 to 8 nm in diameter to cancer cells. These particles are coated by block copolymers, which facilitates their entry into the cells and clustering in the lysosomes, where they are then magneto-mechanically actuated by remotely applied alternating current (AC) magnetic fields of very low frequency (50 Hz). Such fields and treatments are safe for surrounding tissues but produce cytoskeletal disruption and subsequent death of cancer cells while leaving healthy cells intact. 

Retracted: No

PubPeer comments:
 Figure 4 BT474 panel appear to show the same cells in treatment and no-treatment groups. ![file] Report from Forensically ![file] , 
 Thank you for pointing this out. We are investigating and will take appropriate action. , 
 #1 Supplemental information **figure S12** has unexpected similarities in few flow cytometry panels. Alike areas highlighted in different colors. ![file] , 
 Thank you for pointing this out. An erratum has been published. Master, A.M., Williams, P.N., Pothayee, N. et al. Author Correction: Remote Actuation of Magnetic Nanoparticles For Cancer Cell Selective Treatment Through Cytoskeletal Disruption. Sci Rep 12, 10077 (2022). https: doi.org 10.1038 s41598-022-14288-6 ,
Cotransfection of heme oxygenase-1 prevents the acute inflammation elicited by a second adenovirus
Authors: S D McCarter
J R Scott
P J Lee
X Zhang
C A McLean
R F Potter
A A Dungey
A M K Choi
K A Harris
A Badhwar
A Bihari
Journal: Gene Therapy (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: adenovirus vectors; acute inflammation; gene therapy; anti-inflammatory enzyme; heme oxygenase-1
Affiliations: Department of Medical Biophysics and Surgery, University of Western Ontario and the Lawson Health Research Institute, London, ON, Canada.

Abstract:  The acute inflammatory response elicited by adenovirus vectors results in loss of gene expression and tissue injury in the target organ. This acute inflammation is now believed to be the major limiting factor for the use of adenovirus vectors in gene therapy. While exploring the level of acute inflammation caused by the adenovirus encoding the gene for the anti-inflammatory enzyme heme oxygenase-1, we discovered that this adenovirus not only did not elicit acute inflammation, but could prevent the inflammation caused by a second adenovirus. Here we describe a new approach to gene therapy, which uses the encoding of the potent anti-inflammatory enzyme heme oxygenase-1 to prevent early host inflammatory responses normally associated with adenovirus vectors. 

Retracted: No

PubPeer comments:
 Figure 2. Much more similar than expected. ![file] ,
Retracted : Effect of microRNA‐128 on cisplatin resistance of glioma SHG‐44 cells by targeting JAG1
Authors: Fang-Cheng Zhang
Qing Su
Yong-Cun Cen
Hong-Yang Zhao
Qing Zhang
Dong-Ye Yi
Peng Fu
Wei Xiang
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: SHG-44/DDP cells; antisense oligonucleotides; apoptosis; cell cycle; cisplatin
Affiliations: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

Abstract:  This current study intends to investigate the effect of microRNA-128 (miR-128) on cisplatin (DDP) resistance in glioma SHG-44 cells. SHG-44/DDP cells were transfected with miR-128 antisense oligonucleotide (ASO) and assigned into blank, resistance, NC, anti-miR-128, miR-128 mimic, si-JAG1, and anti-miR-128 + si-JAG1 groups. qRT-PCR and Western blotting were employed for determining expression of miR-128, JAG1, Bax and Bcl-2. MTT assay, Giemsa staining, and flow cytometry were applied to detect DDP resistance, cellular morphology, and cell cycle, respectively. JAG1 is targeted and negatively regulated by miR-128. In in vitro experiments, compared with the blank group, the rest groups exhibited declined miR-28 and Bax expression, lowered cell inhibition rate and apoptosis rate, but elevated JAG1 and Bcl-2 expression with cells arrested in the S phase. Compared with the resistance group, the anti-miR-128 group showed decreasedBax expression along with a lowered cell inhibition rate and apoptosis rate, but increased JAG1 and Bcl-2 expression with reduced cells arrested in the S phase; while the miR-128 mimic group showed an opposite trend; the si-JAG1 group showed decreased Bcl-2 expression and reduced cells in the S phase. In in vivo experiments, compared with the resistance group, the tumor growth rate, tumor volume, and weight as well as JAG1 expression accelerated in the anti-miR-128 group; whereas the miR-128 mimic and si-JAG1 groups exhibited an opposite trend. Our findings demonstrated that miR-128 ASO transfection might down-regulate the expression of miR-128 in SHG-44/DDP and up-regulate the DDP resistance in SHG-44/DDP cells, providing a potential treatment target for glioma. 

Retracted: Yes

PubPeer comments:
 Fig 8. ![file] The protein blobs seem to come from the same restricted gamut shown in this montage: ![] , 
 Retracted [30 June 2021] . ----------------------------- The above article, published online on 01 November 2017 in Wiley Online Library has been retracted by agreement between the the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid. ,
The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
Authors: Shao-Cong Sun
Xuhong Cheng
Jae-Hoon Chang
Mikyoung Chang
Jin Jin
Yichuan Xiao
Robyn Starr
Hongbo Hu
Jiayi Yu
George C Brittain
Journal: Nature Immunology (2012)
Discipline: IMMUNOLOGY
Keywords: Immunoglobulin class switching; antibody diversity; humoral immunity; TBK1; IgA isotype
Affiliations: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Abstract:  Immunoglobulin class switching is crucial for the generation of antibody diversity in humoral immunity and, when deregulated, also has severe pathological consequences. How the magnitude of immunoglobulin isotype switching is controlled is still poorly understood. Here we identify the kinase TBK1 as a pivotal negative regulator of class switching to the immunoglobulin A (IgA) isotype. B cell-specific ablation of TBK1 in mice resulted in uncontrolled production of IgA and the development of nephropathy-like disease signs. TBK1 negatively regulated IgA class switching by attenuating noncanonical signaling via the transcription factor NF-κB, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase NIK. Our findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and identify a unique mechanism that controls IgA production. 

Retracted: No

PubPeer comments:
 Figure 5a. Much more similar than expected. https: imgur.com PZUFY86 , 
 #1 Thank you for pointing this mistake in our paper. After checking the record of the manuscript submission and contacting the first author, we found that this error occurred during the paper revision. The originally submitted version was in color and correct. During the revision, we remade Fig. 5a using black white version of the FACS data panels (to avoid color figure charge), and unfortunately, an error was made by mistake during this process. We have already contacted Nature Immunology to make this correction. We apologize for this mistake and will get it corrected as soon as possible. , 
 July 3, 2020 In the version of this article initially published, in Fig. 5a, the flow cytometry plot that is second from the right in the bottom row (+LPS, +TGF-u03b2 + APRIL, +u03b1CD40; NIKKO mice) did not display the correct data. The error occurred when the figure was converted from color to black and white; no changes were made to the data. The original and corrected Fig. 5a are shown below (omitted). The error has not been corrected in the original article. , 
 Thank you for pointing this out. I have contacted Nature Immunology and obtained the following answer.  Unfortunately, your original article was prepared using software that the production company no longer uses. We are only able to correct original articles that were created with the same versions of the software we use currently. The correction notice does state that the correction has not been made in the original article . ,
Effect of miRNA-19a antisense oligonucleotide and Ara-C on the proliferation and apoptosis of HL60 cells
Authors: Shijie Bao
Yanrong Zhang
Jinrong Zeng
Dongmei He
Shengting Chen
Journal: Annals of Translational Medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: Ara-C; HL60 cells; MicroRNA19a (miR-19a); antisense oligonucleotide (ASODN); apoptosis.
Affiliations: Shenzhen Hospital, Southern Medical University, Shenzhen 518110, China., Departmemt of Hematology, The First Affiliated Hospital, Jinan University, Guangzhou 510290, China., Institute of Hematology, School of Medicine, Jinan University, Guangzhou 510290, China.

Abstract:  Background: This study aimed to investigate the effects of microRNA19a (miR-19a) antisense oligonucleotide (ASODN) on the proliferation and apoptosis of acute myeloid leukemia cells (HL60). Methods: In experiment 1, HL60 cells were divided into the blank control group, the blank transfection group, the scrambled oligonucleotide (SODN) group and the ASODN group. MiR-19a ASODN and SODN were independently transferred into HL60 cells. The miR-19a expression was detected by real-time quantitative RT-PCR (qRT-PCR) after 48-h and 72-h transfection; CCK8 assay was used to detect the proliferation inhibition rate at 48 and 72 h; Hoechst 33258 staining was performed to examine apoptotic cells at 48 h; the apoptosis rate was detected by flow cytometry after AnnexinV/PI staining at 48 and 72 h; the protein expression of E2F1 and Bim was detected by Western blotting at 48 h. In experiment 2, cells were divided into the Ara-C group, the SODN + Ara-C group and the ASODN + Ara-C group. The cell proliferation inhibition rate at 48 and 72 h and apoptosis rate at 72 h were assessed as mentioned above. Results: MiR-19a expression in the miR-19a ASODN group was lower than in the SODN group and the blank control group (P&lt;0.05). MiR-19a ASODN significantly inhibited the growth of HL60 cells (P&lt;0.05) and increased their apoptosis, and the apoptosis rate peaked at 48 h. The protein expression of E2F1 and Bim in the ASODN group was higher than in the blank control group, blank transfection group and SODN group. In addition, Ara-C further inhibited the growth and induced the apoptosis of miR-19a ASODN-transfected cells (P&lt;0.05) in a time dependent manner. The growth inhibition rate and apoptosis rate in the ASODN + Ara-C group were higher than the sum of those in both Ara-C group and ASODN group. Conclusions: miRNA-19a ASODN can inhibit the proliferation and induce apoptosis of HL60 cells and may exert synergistic effects with Ara-C on HL60 cells. 

Retracted: No

PubPeer comments:
 Multiple overlaps in Figs 3 4 ![file] ,
Intermediate filament Nestin and the cell motility in cancer - a review
Authors: X Wang
Z-Q Tao
A-M Shi
Y-Q Wang
Journal: European review for medical and pharmacological sciences (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Intermediate filament; Nestin; cell motility; cancer; review

Abstract:  "Intermediate filament Nestin and the cell motility in cancer - a review" by A.-M. Shi, Z.-Q. Tao, X. Wang, Y.-Q. Wang, published in Eur Rev Med Pharmacol Sci 2016; 20 (12): 2598-2602 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,