PReD-Bench/PRed-Bench huggingface dataset:
Downregulation of linc00961 contributes to promote proliferation and inhibit apoptosis of vascular smooth muscle cell by sponging miR-367 in patients with coronary heart disease
Authors: M Tang
C-T Wu
S Liu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Atherosclerosis; Long non-coding RNAs; linc00961; CHD patients; VSMCs
Affiliations: Department of Cardiac Surgery, Second Hospital of Hebei Medical University, Shi Jiazhuang, China. .

Abstract:  Objective: Atherosclerosis is one of the most important risk factors for coronary heart disease (CHD), and growing evidence has shown that long non-coding RNAs (lncRNAs) can serve as prospective markers for atherosclerosis. In this study, we mainly focused on the potential roles of linc00961 in CHD patients. Patients and methods: qRT-PCR was used to detect the expressions of linc00961 and miR-367 in CHD patients and ApoE-/-mice, and the correlations were analyzed. Then, HA-VAMC was respectively treated with 5 inflammatory factors and hypoxia conditions to explore the factors that affect linc00961 levels. Furthermore, the linc00961 overexpression lentivirus (LV-linc00961) and linc00961 downregulation lentivirus (LV-sh linc00961) were purchased and transfected into human vascular smooth muscle cells (VSMCs). CCK8 assay was carried out to measure the cell proliferation of VSMC, and the levels of Cyclin D1, Bcl-2, Bax, and cleaved caspase-3 were detected by RT-PCR and Western blot. Moreover, the Luciferase assay was performed to explore the binding site of linc00961 and miR-367. Finally, the miR-367 inhibitor was transfected into LV-sh linc00961 VSMCs to confirm the linc00961 functions via miR-367. Results: We found that linc00961 was significantly decreased in patients with CHD and ApoE-/-mice. Additionally, linc00961 was reduced in VSMCs at the conditions of hypoxia and C-reactive protein (CRP). Most importantly, the overexpression of linc00961 significantly inhibited the VSMCs proliferation, repressed the levels of Cyclin D1 and Bcl-2, and increased the levels of Bax and cleaved caspase-3. However, the downregulation of linc00961 promoted VSMCs proliferation, increased the levels of Cyclin D1 and Bcl-2, and repressed the levels of Bax and cleaved caspase-3. We also found that miR-367 was downregulated following the upregulation of linc00961, while it was upregulated following the downregulation of linc00961. The Luciferase gene reporter assay indicated that linc00961 could directly bind with miR-367 in VSMCs. Finally, we found that linc00961 could inhibit proliferation and promote apoptosis of VSMCs via binding with miR-367. Conclusions: According to the results, our study revealed that linc00961 was significantly decreased in patients with CHD and ApoE-/-mice. Furthermore, our findings firstly uncovered that linc00961 was reduced by hypoxia and CRP in VSMCs. The downregulation of linc00961 contributed to promote proliferation and inhibit apoptosis of VSMCs by sponging miR-367 in CHD patients, which might provide a potential target for treating atherosclerosis. 

Retracted: No

PubPeer comments:
 ![file] ,
CHCHD2 promotes hepatocellular carcinoma and indicates poor prognosis of hepatocellular carcinoma patients
Authors: Shengyu Wang
Rong Li
Lei Zhao
Yang Yao
Kaige Liu
Jie Su
Journal: Journal of Cancer (2019)
Discipline: CLINICAL MEDICINE
Keywords: CD105; CHCHD2; Hepatocellular carcinoma; biomarker.
Affiliations: Department of Central laboratory, The First Affiliated Hospital, Xi'an Medical University, Xi'an, Shaanxi 710077, PR China., Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA., Department of Ophthalmology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, PR China., Department of Gastroenterology, the First Affiliated Hospital, Xi'an Medical University, Xi'an, Shaanxi 710077, PR China., Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, China.

Abstract:  The coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is overexpressed in several types of cancer. This study aimed to investigate the role of CHCHD2 in hepatocellular carcinoma (HCC). The expression of CHCHD2 in HCC and non-tumorous tissues was detected by immunohistochemistry and Western blot analysis, and the correlation between CHCHD2 expression and clinicopathological features of HCC was analyzed. Furthermore, the proliferation, apoptosis and migration of HepG2 cells with CHCHD2 knockdown were examined. We found that CHCHD2 was upregulated in HCC tissues, and high CHCHD2 expression was associated with poor differentiation, lymph node metastasis, local tissue invasion, high TNM grade of HCC and poor patient survival. Depletion of CHCHD2 led to significantly reduced cell proliferation, increased apoptosis and diminished migratory capacity in HepG2 cells. In addition, HCC tissues had high expression of CD105, a microvessel marker, and HepG2 cells depleted of CHCHD2 had low CD105 expression. In conclusion, CHCHD2 may play an oncogenic role in HCC via promoting tumor cell growth and migration while preventing apoptosis. CHCHD2 is a potential biomarker for poor outcome of HCC patients. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: The  Untreated 24h and the  NC siRNA 24h panels appear to look very similar to each other. ![file] ,
WITHDRAWN: Long non-coding RNA HOTAIR promotes LPS-induced inflammatory injury by down-regulation of microRNA-124 in murine chondrogenic ATDC5 cells
Authors: Shiqiang Song
Guoqing Duan
Shuaishuai Niu
Journal: Life Sciences (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Article withdrawal; Author; Editor; Publisher; Elsevier Policy
Affiliations: Department of Bone and Joint Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, China., Department of Bone and Joint Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, China. Electronic address: .

Abstract:  This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal. 

Retracted: No

PubPeer comments:
 This paper was found during a systematic search of papers in this journal with possible duplicated images. Fifteen papers in this journal (n=98 examined) were found to contain inappropriately duplicated images. These papers have all been reported to the journal publisher in 2017. The editors promised to  investigate promptly but no action has been taken as of today. Figure 4B. The flow cytometry panels appear to share similar groups of dots. In the right-most panel, the same group of dots appears to be visible twice. ![file] ,
Dose‐dependent chemopreventive effects of citronellol in DMBA‐induced breast cancer among rats
Authors: Suganthi Subramaniyan
Jayaganesh Rajendran
Pugalendhi Pachaiappan
Journal: Drug development research (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: DMBA; antioxidant; breast cancer; citronellol; detoxification enzymes.
Affiliations: Department of Biochemistry and Biotechnology, Faculty of ScienceAnnamalai University Annamalainagar Tamil Nadu India

Abstract:  Breast cancer is one of the most common cancers among women world wide and its incidence is on tremendous increase. The present study is aimed to analyze the dose-dependent chemopreventive efficacy of citronellol on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinogenesis. The mammary tumor was induced through a single dose of DMBA (25 mg/rat) injected subcutaneously near the mammary gland of rats. In DMBA-injected rats, 100% tumor incidence, increased tumor volume, and tumor burden along with loss of body weight were observed. Biochemical analysis revealed the increased levels of phase I detoxification proteins (cytochrome P450 and b5) and decreased activities of phase II detoxification enzymes (glutathione-S-transferase and glutathione reductase) in hepatic and mammary tissues. The levels of enzymatic and non-enzymatic antioxidants (superoxidedismutase, catalase, glutathione peroxidase, and (GPx) and reduced glutathione) were decreased and lipid peroxidation by-products (thiobarbituric acid reactive substance and lipid hydroperoxide) got increased in plasma and mammary tissues. Oral administration of different doses of citronellol (25, 50, and 100 mg/kg body weight) to DMBA-treated rats for 16 weeks absolutely inhibited the tumor incidence and restored the biochemical parameters near to normal level in 50 and 100 mg doses whereas the histopathological studies also supported the biochemical findings. Hence, the result suggests that the citronellol of 50 mg/kg body weight exerted significant chemopreventive effects and can be considered as a minimum optimum dose in the prevention of mammary carcinogenesis. 

Retracted: No

PubPeer comments:
 Figure 3. Panels a (control rats) and f (citronellol alone rats) appear to show an area of overlap. Shown with blue boxes. ![file] , 
 Corrigendum, June 2020: https: onlinelibrary.wiley.com doi full 10.1002 ddr.21703  In the abovementioned manuscript, there were errors in part F of Figure 3. A corrected version of Figure 3 appears below. The authors regret this error. This corrigendum does not affect the Figure 3 legend. Here is the corrected Figure 3. Unfortunately, there is still an overlap between panels a) and f) - just at a slightly different position. Marked with dark green boxes. I have now lost confidence in the ability of the authors to select the correct images. ![file] ,
Elimination of mycoplasma from leukemia–lymphoma cell lines using antibiotics
Authors: C Meyer
C C Uphoff
H G Drexler
Journal: Leukemia (2002)
Discipline: CLINICAL MEDICINE
Keywords: Mycoplasma contamination; cell culture systems; antibiotics; mycoplasma eradication; leukemia-lymphoma cell lines
Affiliations: DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.

Abstract:  Mycoplasmal contamination of cell culture systems continues to present major problems for basic research and for manufacturing of bioproducts. Previous work suggested that certain antibiotics have strong anti-mycoplasma properties and raised the prospect that the technically rather simple antibiotic treatment may be an appropriate means for mycoplasma eradication. We have developed and validated an effective strategy to eliminate mycoplasma from chronically infected cell cultures using antibiotics which have shown strong activity against these contaminants. Here, we describe our experience with the treatment of 123 consecutive mycoplasma-positive leukemia-lymphoma cell lines, comparing five different antibiotic regimens (in total 433 treatments). We optimized the antibiotic dose schedules and the duration of treatments. The various antibiotic treatments which were employed in parallel had a high efficacy, as 71% to 86% of the infected cultures were cleansed. Treatment failure may result from the resistance of the mycoplasmas to antibiotic therapy and the inability of the eukaryotic cells to survive the cytotoxic effects of the antibiotics. Resistance to mycoplasma eradication was observed in 3% to 20% of the cultures. Loss of the cell culture caused by cytotoxicity was seen in 3% to 11% of the treatments. With regard to the overall outcome, 96% of the cell lines were rendered mycoplasma-free with at least one of the antibiotic treatments and were permanently cured. In conclusion, antibiotic treatment represents the most practical and efficient option to cleanse mycoplasma-positive cell lines. 

Retracted: No

PubPeer comments:
 What are we learning? ![file] , 
 How often do you need updates? https: www.ncbi.nlm.nih.gov pubmed ?term=drexler%20h%20mycoplasma ,
Silencing of APE1 enhances sensitivity of human hepatocellular carcinoma cells to radiotherapy in vitro and in a xenograft model
Authors: Yanping Cun
Chengyuan Qian
Jiangdong Sui
Nan Dai
Chengjie Xiong
Dong Wang
Zheng Li
Mengxia Li
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Radiotherapy resistance; Human hepatocellular carcinoma; APE1; DNA repair; Redox regulation
Affiliations: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.

Abstract:  Resistance to radiotherapy is a key limitation for the treatment of human hepatocellular carcinoma (HCC). To overcome this problem, we investigated the correlation between radioresistance and the human apurinic/apyrimidinic endonuclease (APE1), a bifunctional protein, which plays an important role in DNA repair and redox regulation activity of transcription factors. In the present study, we examined the radiosensitivity profiles of three human HCC cell lines, HepG2, Hep3B, and MHCC97L, using the adenoviral vector Ad5/F35-mediated APE1 siRNA (Ad5/F35-siAPE1). The p53 mutant cell lines MHCC97L showed radioresistance, compared with HepG2 and Hep3B cells. APE1 was strongly expressed in MHCC97L cells and was induced by irradiation in a dose-dependent manner, and Ad5/F35-siAPE1 effectively inhibited irradiation-induced APE1 and p53 expression. Moreover, silencing of APE1 significantly potentiated the growth inhibition and apoptosis induction by irradiation in all tested human HCC cell lines. In addition, Ad5/F35-siAPE1 significantly enhanced inhibition of tumor growth and potentiated cell apoptosis by irradiation both in HepG2 and MHCC97L xenografts. In conclusion, down regulation of APE1 could enhance sensitivity of human HCC cells to radiotherapy in vitro and in vivo. 

Retracted: No

PubPeer comments:
 Figure 8A. * Red boxes: Two panels appear to show an overlap. ![file] , 
 Figure 9A. * Pink boxes: Two panels appear to show an overlap. ![file] , 
 And, after a tip on social media, there appears to also be an overlap between Figure 8 (Ki67 immunohistochemistry) and Figure 9 (TUNEL staining) panels, as shown here with aqua boxes. ![file] ,
Regulation of Ca2+/calmodulin kinase II inhibitor alpha (CaMKIINalpha) in virus-infected mouse brain
Authors: Anand Ramanathan
Pundi N Rangarajan
Sougata Saha
Journal: Biochemical and Biophysical Research Communications (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CaMKIINalpha; CaMKII; CNS; regulation; function
Affiliations: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.

Abstract:  The alpha and beta isoforms of rat Ca(2+)/calmodulin kinase II inhibitor (CaMKIINalpha/beta) expressed in brain or brain and testis, respectively, are potent inhibitors of Ca(2+)/calmodulin kinase II (CaMKII) in vitro. However, the regulation or function of CaMKIINalpha/beta in the central nervous system (CNS) is not known. In this study, we demonstrate that mouse CaMKIINalpha gene encodes a 2.9kb brain-specific transcript whose expression is downregulated in mouse brain during Japanese encephalitis virus (JEV) and rabies virus infection. The downregulation is specific for CaMKIINalpha but not CaMKIINbeta mRNA. In addition to these changes in CaMKIINalpha mRNA, distinct changes are also observed in the phosphorylation as well as subcellular localization of CaMKIIalpha leading to an increase in cytosolic CaMKII activity in JEV-infected mouse brain. The differential regulation of CaMKIIalpha and CaMKIINalpha during JEV infection suggests a possible role for these proteins in viral infection and/or virus-induced neuropathogenesis in the CNS. 

Retracted: No

PubPeer comments:
 ![file] , 
 We are unable to trace the original data of Fig. 1A. This experiment was repeated and data from such an independent experiment has been uploaded. If we had forgotten to acknowledge splicing of lane 3 in the paper, it was not deliberate. [file] I (Pundi Rangarajan) am unable to register as an author at pubpeer as my email id (pnr@iisc.ac.in) was not accepted and hence replying anonymously. , 
 ![file] , 
 ![file] , 
 #4 I, P N Rangarajan, corresponding author wish to state that the Norther blot of Rabies G protein is a control blot to provide proof that rabies virus infected RNA was used in these experiments. The same control blot was used in Fig. 1C of BBRC paper and Fig. 4B J.Gen Virol paper and the blot was reprobed with several other mouse cDNAs such as clone 137 (in BBRC paper), cathepsin, OAS and GARG 49 in J Gen Virol paper. Therefore both the figures have the same rabies G protein RNA control blot. We forgot to mention this in the 2006 paper and we apologise for this oversight. , 
 To #5: We appreciate the comments! However, we are taught very early on that one cannot use the same data (RNA blot) in two different publications. This is not a simple use of the same data in 2 publications. But, the same blot has been used in two publications by u201ccompressingu201d it and using different probe names. For example, in one article (Biochemical and Biophysical Research Communications), the probe name is u201cRabies G Proteinu201d and in another article (Journal of General Virology), the probe name is u201cRabies Viral RNAu201d. , 
 I have already answered ,
Interpretation of BMP signaling in early Xenopus development
Authors: J B Gurdon
I Simeoni
Journal: Developmental Biology (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: extracellular binding; morphogen; nucleus; concentration-related; cells
Affiliations: Wellcome Trust/Cancer Research UK, Gurdon Institute of Cancer and Development Biology, CB2 1QN Cambridge, UK.

Abstract:  Very little is known about how the extracellular binding of a morphogen is transduced to the nucleus of a cell in a concentration-related way, enabling cells to interpret their position in a concentration gradient. Here, we have analyzed when and how Xenopus embryo cells perceive and interpret a BMP signal. Dissociated embryo cells are exposed for short times to different concentrations of BMP4. We find that cells are already competent to receive a BMP4 signal at the blastula stage. They phosphorylate Smad1 very rapidly and express downstream genes less than half an hour after exposure to BMP. However, Smad1 is present in the nucleus even in the absence of BMP. To quantitate intracellular signaling after BMP exposure, we have constructed a chimeric type I receptor that registers BMP signaling as the intranuclear migration of Smad2, and as the transcription of Smad2 downstream genes. The combination of the chimeric receptor and GFP-Smad2 makes it possible to follow the transduction of BMP signaling to the nucleus. From our results, we conclude that an extracellular BMP concentration is interpreted by the steady state nuclear concentration of phosphorylated Smad1. 

Retracted: No

PubPeer comments:
 Fig. 6A: More similar than expected. Could authors check please? ![file] ,
Insulin-like growth factor binding protein-3 is a new predictor of radiosensitivity on esophageal squamous cell carcinoma
Authors: Mian Xi
Ying-Xue Wang
Peng Zhang
Jing-Xian Shen
Li-Ru He
Meng-Zhong Liu
Qiao-Qiao Li
Xiao-Peng Tian
Li-Ling Luo
Shi-Liang Liu
Lei Zhao
Dan Xie
Journal: Scientific Reports (2015)
Discipline: Multidisciplinary
Keywords: IGFBP-3; radiosensitivity; ESCC; tumorigenicity; ionizing radiation
Affiliations: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China., State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China., Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China., Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Medical Imaging and Interventional Center, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Abstract:  Insulin-like growth factor binding protein-3 (IGFBP-3) plays an essential role in radiosensitivity of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism is not completely understood. Here, we observed that IGFBP-3 had favorable impact on the tumorigenicity of ESCC cells in nude mice by using an in vivo imaging system (IVIS) to monitor tumor growth treated with ionizing radiation (IR). Downregulation of IGFBP-3 expression enhanced tumor growth, inhibited anti-proliferative and apoptotic activity and result in IR resistance in vivo. Cell cycle antibody array suggested that silencing IGFBP-3 promoted transition from G0/G1 to S phase, perhaps though influencing Smad3 dephosphorylation and retinoblastoma protein (Rb) phosphorylation. Downregulation of P21 and P27, and upregulation of p-P27 (phospho-Thr187), cyclin-dependent kinase 2 (CDK2), and cyclin E1 might contribute to the G0/G1 to S phase transition promoted by IGFBP-3. Our results suggest that Smad3-P27/P21-cyclin E1/CDK2-phosphorylated retinoblastoma protein pathways might be involved in this IGFBP-3 mediated radiosensitivity transition in ESCC. 

Retracted: No

PubPeer comments:
 Images and Figures three AA and four AA appear to show the same animal twice, although they have slightly different dimensions. *** ![file] *** 3A ![file] *** 4A ![file] , 
 And figure 6A some images have been presented more than once. *** ![file] ,
A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas
Authors: Stephan Mathas
Cornelis F Calkhoven
Andreas Lietz
Bernd Dörken
Nina Raetzel
Christine Müller
Achim Leutz
Katharina Kley
Franziska Jundt
Journal: Blood (2005)
Discipline: CLINICAL MEDICINE
Keywords: rapamycin; everolimus; mTOR signaling pathway; antiproliferative activity; Hodgkin lymphoma
Affiliations: Charité, Campus Virchow-Klinikum, University Medicine Berlin, Augustenburger Platz 1, D-13 353 Berlin, Germany. , From the Department of Hematology and Oncology, Charité, Campus Virchow-Klinikum, University Medicine Berlin, and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.

Abstract:  The immunosuppressive macrolide rapamycin and its derivative everolimus (SDZ RAD, RAD) inhibit the mammalian target of rapamycin (mTOR) signaling pathway. In this study, we provide evidence that RAD has profound antiproliferative activity in vitro and in NOD/SCID mice in vivo against Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) cells. Moreover, we identified 2 molecular mechanisms that showed how RAD exerts antiproliferative effects in HL and ALCL cells. RAD down-regulated the truncated isoform of the transcription factor CCAAT enhancer binding protein beta (C/EBPbeta), which is known to disrupt terminal differentiation and induce a transformed phenotype. Furthermore, RAD inhibited constitutive nuclear factor kappaB (NF-kappaB) activity, which is a critical survival factor of HL cells. Pharmacologic inhibition of the mTOR pathway by RAD therefore interferes with essential proliferation and survival pathways in HL and ALCL cells and might serve as a novel treatment option. 

Retracted: No

PubPeer comments:
 Fig 1B includes 2 WBs with unexpected similarities (ACC-032 and 17A11) marked in red. *** ![file] *** ![file] ,
Ambroxol modulates 6-Hydroxydopamine-induced temporal reduction in Glucocerebrosidase (GCase) enzymatic activity and Parkinson’s disease symptoms
Authors: Surendra Kumar Trigun
Lalit Pratap Chandravanshi
Sairam Krishnamurthy
Akanksha Mishra
Journal: Biochemical Pharmacology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 6-Hydroxydopamine; Ambroxol; Glucocerebrosidase; Mitochondrial dysfunction; Parkinson’s disease
Affiliations: Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India., Biochemistry Section, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, U.P., India., Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India. Electronic address: .

Abstract:  Reduced glucocerebrosidase (GCase) enzymatic activity is found in sporadic cases of Parkinson's disease making GCase a serious risk factor for PD. GCase gene mutations constitute a major risk factor in early-onset PD but only account for 5-10% cases. Having enough evidence for construct and face validity, 6-OHDA-induced hemiparkinson's model may be useful to assess the GCase-targeting drugs in order to have new leads for treatment of PD. Ambroxol (AMB) is reported to increase GCase activity in different brain-regions. Therefore, we investigated anti-PD like effects of AMB as well as GCase activity in striatal and nigral tissues of rats in hemiparkinson's model. AMB was given a dose of 400 mg/kg per oral twice daily and SEL used as positive control was given in the dose of 10 mg/kg per oral daily from D-4 to D-27 after 6-OHDA administration. 6-OHDA reduced GCase activity in striatal and in a progressive manner in nigral tissues. AMB and SEL attenuated 6-OHDA-induced motor impairments, dopamine (DA) depletion and GCase deficiency. AMB and SEL also ameliorated 6-OHDA-induced mitochondrial dysfunction in terms of MTT reduction, α-synuclein pathology, loss of nigral cells, and intrinsic pathway of apoptosis by modulating cytochrome-C, caspase-9, and caspase-3 expressions. The results suggest that AMB attenuated 6-OHDA-induced GCase deficiency and PD symptoms. Therefore, the regenerative effects of AMB in dopamine toxicity may be due to its effects on GCase activity and mitochondrial function. Results indicate that SEL also has regenerative effect in the 6-OHDA model. Thus, GCase enzymatic activity is likely to be involved in the development of PD symptoms, and 6-OHDA-induced hemiparkinson's model may be used to evaluate compounds targeting GCase activity for management of PD symptoms. 

Retracted: No

PubPeer comments:
 In Figure 2, a micrograph has been duplicated and presented as something else (A vs C). ![file] , 
 In Figure 2, a micrograph has been duplicated and presented as something else (A vs C). ![file] ,
Epstein-Barr Virus-Encoded LMP2A Induces an Epithelial–Mesenchymal Transition and Increases the Number of Side Population Stem-like Cancer Cells in Nasopharyngeal Carcinoma
Authors: Jing-Yan Cao
Li-Hua Xu
Hai-Qiang Mai
Chao-Nan Qian
Yi Liang
Xing Zhang
Bao-Hong Guo
Su Guan
Yi-Xin Zeng
Qing-Li Kong
Mu-Sheng Zeng
Li-Juan Hu
Dan Xiong
Jian-Yong Shao
Yun-Fei Xia
Man-Zhi Li
Qiu-Yan Chen
Li-Bing Song
Yi-Jun Huang
Journal: PLoS Pathogens (2010)
Discipline: MICROBIOLOGY
Keywords: Nasopharyngeal carcinoma; Stem-like cells; Epstein-Barr virus; LMP2A; Oncogenic processes
Affiliations: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.

Abstract:  It has been recently reported that a side population of cells in nasopharyngeal carcinoma (NPC) displayed characteristics of stem-like cancer cells. However, the molecular mechanisms underlying the modulation of such stem-like cell populations in NPC remain unclear. Epstein-Barr virus was the first identified human tumor virus to be associated with various malignancies, most notably NPC. LMP2A, the Epstein-Barr virus encoded latent protein, has been reported to play roles in oncogenic processes. We report by immunostaining in our current study that LMP2A is overexpressed in 57.6% of the nasopharyngeal carcinoma tumors sampled and is mainly localized at the tumor invasive front. We found also in NPC cells that the exogenous expression of LMP2A greatly increases their invasive/migratory ability, induces epithelial-mesenchymal transition (EMT)-like cellular marker alterations, and stimulates stem cell side populations and the expression of stem cell markers. In addition, LMP2A enhances the transforming ability of cancer cells in both colony formation and soft agar assays, as well as the self-renewal ability of stem-like cancer cells in a spherical culture assay. Additionally, LMP2A increases the number of cancer initiating cells in a xenograft tumor formation assay. More importantly, the endogenous expression of LMP2A positively correlates with the expression of ABCG2 in NPC samples. Finally, we demonstrate that Akt inhibitor (V) greatly decreases the size of the stem cell side populations in LMP2A-expressing cells. Taken together, our data indicate that LMP2A induces EMT and stem-like cell self-renewal in NPC, suggesting a novel mechanism by which Epstein-Barr virus induces the initiation, metastasis and recurrence of NPC. 

Retracted: No

PubPeer comments:
 Figure 2B. Two images appear to be duplicated, with brightness changed. ![file] , 
 Figure 7C contains two images which share multiple similar regions. ![file] ,
Long noncoding RNA RUSC1-AS1 promotes tumorigenesis in cervical cancer by acting as a competing endogenous RNA of microRNA-744 and consequently increasing Bcl-2 expression
Authors: Yanping Xu
Qin Zhang
Lianwei Lu
Qizhen Guo
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cervical cancer; RUSC1-AS1; malignancy; microRNA-744; therapeutic target.
Affiliations: Department of Gynaecology and Obstetrics, Gaomi People's Hospital, Gaomi, Shandong, P.R. China., Department of Neurosurgery, Gaomi People's Hospital, Gaomi, Shandong, P.R. China., Department of Radiology, Weifang People's Hospital, Weifang, Shandong, P.R. China., Department of General Surgery, Gaomi People's Hospital, Gaomi, Shandong, P.R. China.

Abstract:  The expression of a long noncoding RNA termed RUSC1-AS1 is dysregulated in breast cancer and laryngeal squamous cell carcinoma, and this dysregulation affects various tumor-associated biological processes. To our knowledge, the expression status and detailed roles of RUSC1-AS1 in cervical cancer as well as its regulatory mechanisms of action remain unknown. Therefore, the objectives of this study were to measure RUSC1-AS1 expression in cervical cancer, investigate the effects of RUSC1-AS1 on cervical cancer cells, and identify the mechanism underlying these effects. Herein, RUSC1-AS1 was found to be highly expressed in cervical cancer tissues and cell lines. High RUSC1-AS1 expression significantly correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and shorter overall survival among the patients with cervical cancer. Functional assays revealed that interference with RUSC1-AS1 expression suppressed cervical cancer cell proliferation, migration, and invasion in vitro; induced apoptosis in vitro; and impeded tumor growth in vivo. In addition, RUSC1-AS1 was demonstrated to act as a competing endogenous RNA of microRNA-744 (miR-744) and consequently increase B-cell lymphoma 2 (Bcl-2 or BCL2) expression levels in cervical cancer cells. Furthermore, either inhibition of miR-744 or restoration of Bcl-2 expression neutralized the effects of the RUSC1-AS1 silencing on the malignant characteristics of cervical cancer cells. Thus, RUSC1-AS1 promotes the aggressiveness of cervical cancer in vitro and in vivo by upregulating miR-744-Bcl-2 axis output. The RUSC1-AS1-miR-744-Bcl-2 pathway may be involved in cervical cancer pathogenesis and could serve as a novel target for anticancer therapies. 

Retracted: No

PubPeer comments:
 The immunoblot for different groups appear to look similar in Fig. 5. ![file] ,
Relationship between DLK1 gene promoter region DNA methylation and non-small cell lung cancer biological behavior
Authors: Wei Guo
Zhaokui Zhong
Weicai Hu
Yongting Ye
Yi He
Journal: Oncology Letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: DLK1 gene; DNA methylation in promoter region; Notch; invasion ability; matrix metalloproteinase-9
Affiliations: Department of Thoracic Surgery, Central Hospital of Zhumadian, Zhumadian, Henan 463000, P.R. China., Department of Internal Medicine, The Fourth People's Hospital of Zhumadian, Zhumadian, Henan 463000, P.R. China., Department of Thoracic Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China.

Abstract:  We investigated the possible association between DLKI gene promoter region methylation and the increased invasion capacity of non-small cell lung cancer (NSCLC). Lung cancer cell line H1299, as well as the gene transfection and RNA interference technology were used to build DLK gene overexpression and knockdown cells. An in vitro invasion assay was performed to observe the changes in the invasion ability of lung cancer cells. Western blot analysis was used to verify Notchl and matrix metalloproteinase-9 (MMP-9) expression levels and a sulfurous acid sequencing technique was used to test the DNA methylation level in the promoter region. Our results showed that the invasion ability of cells in the overexpression group was significantly enhanced. This ability was considerably reduced in the knockdown group. The Notchl and MMP-9 expression level increased significantly in the overexpression group, while it was reduced considerably in the knockdown group. We detected significantly lower levels of DNA methylation in the promoter region in the overexpression group. It was concluded that methylation of the DLK1 gene promoter region increased the invasion ability of NSCLC. Furthermore, it is possible that this process is related to the Notch signaling pathway. 

Retracted: Yes

PubPeer comments:
 This article is compared with another article (doi:101371 journal.pone.0091509) and a doctoral dissertation in Chineses. Evidences of plagiarism is illustrated in the picture. ![1.png] ![2.png] , 
 Retracted [27 April 2020] . -------------------------------------------------- An interested reader drew to our attention that data featured in Figs. 3 and 5 of the above paper appeared to have been previously published in the journal PloS One [Li L, Tan J, Zhang Y, Han H, Di X, Xiao T, Cheng S, Gao Y and Liu Y: DLK1 promotes lung cancer cell invasion through upregulation of MMP9 expression depending on Notch signaling. PLoS One 9: e91509, 2014] and in a Chinese doctoral dissertation. Following an internal investigation, the Journal was able to confirm that this accusation of plagiarism was well-founded. On those grounds, the Editor of Oncology Letters has decided to retract this paper. Every effort was made to contact the authors in this regard, but without success. The Editor deeply regrets the inconvenience that this retraction has caused to the authors of the previously published articles, and to the readership of the Journal. ,
miR-183 inhibits TGF-beta1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells
Authors: Ruiyun Xing
Jie Zhu
Chengwang Xu
Zhixian Sun
Hanjiang Fu
Yide Qin
Xiaofei Zheng
Yi Tie
Jipeng Li
Journal: BMC Cancer (2010)
Discipline: CLINICAL MEDICINE
Keywords: miRNA; hepatocellular carcinoma; miR-183; qRT-PCR; target genes
Affiliations: Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, People's Republic of China.

Abstract:  Background: In recent years, some miRNAs have been reported to be connected closely with the development of human hepatocellular carcinoma. In our previous studies, a set of miRNAs were revealed to be dysregulated in HCC tissues. However, the functions of these miRNAs in HCC remain largely undefined. Methods: The expression profiles of miR-183 were compared between HCC tissues and adjacent normal liver tissues using qRT-PCR method. This method was used to screen the potential target genes of miR-183. A luciferase reporter assay was conducted to confirm target association. Finally, the functional effect of miR-183 in hepatoma cells was examined. Results: Among the 25 HCC samples analyzed, microRNA-183 was significantly up-regulated (twofold to 367-fold) in 17 samples compared with the matching nontumoral liver tissues. Programmed cell death 4 (PDCD4) was identified as the target gene of miR-183. Moreover, PDCD4 is a proapoptotic molecule involved in TGF-beta1-induced apoptosis in human HCC cells, we found that miR-183 transfectants were resistant to apoptosis induced by TGF-beta1. Conclusions: We conclude that miR-183 can inhibit apoptosis in human HCC cells by repressing the PDCD4 expression, and miR-183 may play an important role in HCC development. 

Retracted: No

PubPeer comments:
 same image of Fig 4A appears twice in Fig 4C ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants
Authors: Tom D Bunney
Hugh F Paterson
Matilda Katan
Peter H Sugden
Sonia Caroline Sorli
Journal: Oncogene (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Phospholipase Cepsilon; splice variants; Ras GTP-ases; signaling pathways; tyrosine kinase
Affiliations: Cancer Research UK Centre for Cell and Molecular Biology, Chester Beatty Laboratories, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.

Abstract:  Phospholipase Cepsilon (PLCepsilon) is a novel member of phosphoinositide-specific phospholipase C enzymes with a unique regulatory link to Ras GTP-ases. In the present studies, we establish existence of two splice variants (PLCepsilon1a and PLCepsilon1b) derived from human PLCepsilon1 gene. When expressed in COS or HEK293 cells, PLCepsilon1a and PLCepsilon1b have similar potential to be stimulated by diverse signaling pathways via tyrosine kinase and G-protein coupled receptors and share the ability to function as an effector of Ras. The expression pattern shows broader mRNA expression of PLCepsilon1a in normal tissues; furthermore, in most cell lines expressing PLCepsilon, PLCepsilon1a is the only splice variant present. Analysis of normal/tumor matched pairs derived from colon and rectum demonstrates greatly reduced expression levels in tumor tissues. Further studies in a colorectal tumor cell line lacking PLCepsilon show restoration of transcription of PLCepsilon1a and PLCepsilon1b by demethylating agent 5-aza-2'-deoxycytidine, suggesting epigenetic silencing through hypermethylation. In addition, expression of exogenous PLCepsilon in this cell line demonstrates inhibitory effects of PLCepsilon on cell viability and proliferation. Taken together, our findings suggest that regulatory mechanisms controlling expression of PLCepsilon, broadened by diversity introduced by splice variants, could play important role in PLCepsilon regulation in normal and tumor cells. 

Retracted: No

PubPeer comments:
 Figure 1c. Much more similar than expected. ![file] ,
Astragaloside IV inhibits breast cancer cell invasion by suppressing Vav3 mediated Rac1/MAPK signaling
Authors: Weili Chen
Ke Jiang
Xiaohong Xue
Qiong Li
Yajie Ji
Qing Lu
Journal: International Immunopharmacology (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Astragaloside IV; Breast cancer cells; Rac1/MAPK signaling; Vav3.
Affiliations: Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, China., Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, China. Electronic address: .

Abstract:  Background: Astragaloside IV (AS-IV), the major active triterpenoid in Radix Astragali, has shown anti-tumorigenic properties in certain cancers; however, its role in breast cancer remains unclear. The present study investigated the effects of AS-IV on breast cancer in vitro and in vivo and examined the underlying mechanisms. Methods: The effects of AS-IV on MDA-MB-231 cell proliferation, migration, invasion and metastasis were investigated by MTT and Transwell assays, and western blotting. In addition, an orthotopic mouse tumor model was established for in vivo experiments. Results: AS-IV inhibited the viability and invasive potential of MDA-MB-231 breast cancer cells, suppressed the activation of the mitogen activated protein kinase (MAPK) family members ERK1/2 and JNK, and downregulated matrix metalloproteases (MMP)-2 and -9. The effects of AS-IV were mediated by the downregulation of Vav3, a guanine nucleotide exchange factor, leading to decreased levels of activated Rac1, a Rho family GTPase. Vav3 overexpression promoted cell proliferation and invasion in vitro, whereas Vav3 silencing had the opposite effects. AS-IV suppressed orthotopic breast tumor growth and metastasis to the lungs, whereas ectopic expression of Vav3 reversed the inhibitory effect of AS-IV on cell viability, invasiveness, MAPK signaling and MMP expression. Conclusion: The present results provide a mechanistic explanation for the antitumor effects of AS-IV and suggest its potential in the treatment of metastatic breast cancer. 

Retracted: No

PubPeer comments:
 Figure 3: ![file] ,
Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia
Authors: Hagop M Kantarjian
Guillermo Garcia-Manero
Jean-Pierre J Issa
Jerry Daniel
Sima Jeha
Maher Albitar
Jason Williamson
Journal: Cancer (2003)
Discipline: CLINICAL MEDICINE
Keywords: methylation; pediatric patients; adult patients; acute lymphocytic leukemia; CpG islands
Affiliations: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. 

Abstract:  Background: Aberrant methylation of promoter-associated cystosine-guanine (CpG) islands is an epigenetic modification of DNA frequently observed in adult patients with acute lymphocytic leukemia (ALL). This epigenetic modification has been associated with gene silencing, malignant transformation, and aging. It is not known whether there are epigenetic differences between pediatric patients and adult patients with ALL. Methods: To investigate the methylation characteristics of pediatric patients with ALL and to determine whether DNA methylation can explain prognostic or biologic differences between pediatric and adult patients, the authors analyzed the methylation status of 7 promoter-associated CpG islands in 16 pediatric patients with ALL and compared them with the methylation characteristics of a cohort of adult patients with ALL. The genes analyzed included the estrogen receptor gene (ER), multidrug resistance gene 1 (MDR1), p15, C-ABL, CD10, p16, and p73. Results: The mean methylation densities of ER, MDR1, CD10, p15, and C-ABL were 25.4%, 16.4%, 5.23%, 4.24%, and 4%, respectively. P16 was methylated in 11.7% of patients, and p73 was methylated in 17.6% of patients. One patient (6.2%) had methylation of 0 genes, 15 patients (93.7%) had methylation of &gt;/= 1 gene, and 4 patients (25%) had methylation of 3-4 genes. Methylation of all these genes was &lt; 2% (or methylation specific polymerase chain reaction negative) in nonneoplastic tissues. A significant inverse correlation was observed between methylation of CD10 and CD10 expression. No differences were observed between the methylation characteristics of pediatric patients and adult patients. Conclusions: The results indicate that DNA methylation is common in pediatric patients with ALL and that methylation of the genes studied does not account for prognostic differences between pediatric patients and adult patients with ALL. 

Retracted: No

PubPeer comments:
 Garcia-Manero has almost 700 articles published since 2002. Here is one from his early career, and one of the few which shows some raw data. Figure 1 presents old data in a new way, both in terms of patient studied and by changing the original methylation analysis. In this article the patients studied are pediatric, in the original article (Garacia-Manero G et al., 2002; Clinical Cancer Research) they are adults. ![file] ,
Bufalin Suppresses Migration and Invasion of Hepatocellular Carcinoma Cells Elicited by Poly (I:C) Therapy
Authors: Yinglu Feng
Qun Liu
Qingxin Cao
Chen Wang
Changquan Ling
Yongan Chen
Yongbin Meng
Journal: Oncoimmunology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bufalin; HCC; TBK1; TLR3; metastasis
Affiliations: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China., Department of Traditional Chinese Medicine, 401 Hospital of the Chinese People's Liberation Army, Qingdao, Shandong, China.

Abstract:  The Toll-like receptor 3 (TLR3) agonists as polyriboinosinic-polyribocytidylic acid (poly (I:C)) have been implicated as potential immunotherapy adjuvant for cancer whereas the exact roles of TLR3 agonists in hepatocellular carcinoma (HCC) treatment have not been clearly evaluated. In consistent with previous reports, we found that poly (I:C) triggering of TLR3 inhibited cell proliferation and induced apoptosis in HCC cells. However, poly (I:C), when used at lower concentration that cannot remarkably inhibit proliferation and induce apoptosis in HCC cells, enhanced the migration and invasion in vitro and the metastasis in vivo. More importantly, we found that bufalin, a prominent component of toad venom, could suppress poly (I:C)-inspired migration, invasion and metastasis of HCC cells despite that bufalin could not potentiate poly (I:C)-induced inhibition of proliferation and induction of apoptosis. In MHCC97 H cells, bufalin impaired poly (I:C)-induced activation of Tank-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) pathway and NF-κB pathway. Inhibitor for TBK1 but not NF-κB suppressed poly (I:C)-inspired migration and invasion, which was further supported by using TBK1 deficient (Tbk1-/- ) cells. In another model using poly (I:C) transfection, bufalin could also suppress the migration and invasion of HCC cells, which was not observed in Tbk1-/- MHCC97 H cells. Our data suggest that bufalin can suppress the metastasis of HCC cells in poly (I:C) therapy by impairing TBK1 activation, indicating that bufalin may be used in combination with poly (I:C) therapy in HCC treatment for the sake of reversing poly (I:C)-triggered metastasis of HCC cells. 

Retracted: No

PubPeer comments:
null, 
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A99 2. Account Res 2020; 28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 17 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,