PReD-Bench/PRed-Bench huggingface dataset:
The modifier subunit of Drosophila glutamate-cysteine ligase regulates catalytic activity by covalent and noncovalent interactions and influences glutathione homeostasis in vivo
Authors: Pushpa Kansagra
Robert D C Saunders
Claire Kotecki
Jennifer A Fraser
Lesley I McLellan
Journal: Journal of Biological Chemistry (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Glutamate-cysteine ligase; Drosophila melanogaster; intersubunit disulfides; cysteine residues; catalytic efficiency
Affiliations: Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK.

Abstract:  Glutamate-cysteine ligase (GCL) has a key influence on glutathione homeostasis. It has been proposed that mammalian GCL is regulated by the redox environment, and we show here that cysteine residues in the Drosophila melanogaster GCL modifier subunit (DmGCLM) can form covalent interactions with the catalytic subunit (DmGCLC) and modify its activity. Candidate components of intersubunit disulfides (Cys213, Cys214, and Cys267) were identified using matrix-assisted laser desorption ionization time-of-flight spectroscopy of iodoacetamide-modified DmGCLM as well as examination of the evolutionary conservation of cysteines. Mutation of the 3 cysteine residues allowed DmGCLM to associate with DmGCLC, but inhibited the formation of intersubunit disulfides. This caused a 2-fold reduction in the catalytic efficiency of Drosophila GCL, although activity remained significantly higher than the catalytic subunit alone. The cysteine mutant was also more sensitive to inhibition by glutathione than the unmodified holoenzyme. Notably, human GCLM could substitute for DmGCLM in modification of DmGCLC activity. The role of DmGCLM in vivo was examined by analysis of a Drosophila mutant (l(3)L0580) containing a P-element insertion in Gclm. We found that the P-element is not responsible for the lethal phenotype and separated the recessive lethal mutation from the P-element by recombination. This yielded two fully viable and fertile recombinants bearing the P-element insertion, which Western and Northern blotting indicated is a severely hypomorphic allele of Gclm. Glutathione levels were approximately 2-fold lower in the GclmL0580 mutants than in control strains, demonstrating the importance of DmGCLM in the regulation of glutathione homeostasis in vivo. 

Retracted: No

PubPeer comments:
 ![file] undeclared gel slice site in Fig.1 ,
Decursin Isolated from Angelica gigas Nakai Rescues PC12 Cells from Amyloid β-Protein-Induced Neurotoxicity through Nrf2-Mediated Upregulation of Heme Oxygenase-1: Potential Roles of MAPK
Authors: Yong-Ho Kim
Tie Wu
Ji-Kun Du
Li-Yi Zou
Yong-Woo Lee
Li Li
Journal: Evidence-based Complementary and Alternative Medicine (2013)
Discipline: CLINICAL MEDICINE
Keywords: Decursin; neuroprotective; ROS; HO-1; Nrf2
Affiliations: Department of Pharmacology, Guangdong Medical College, Dongguan 523-808, China ; Department of Smart Food and Drugs, Graduate School, Inje University, Gimhae 621-749, Republic of Korea., Department of Clinical Laboratory, Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University, Shenzhen 518-104, China, Department of Pharmacology, Guangdong Medical College, Dongguan 523-808, China, Department of Smart Food and Drugs, Graduate School, Inje University, Gimhae 621-749, Republic of Korea

Abstract:  Decursin (D), purified from Angelica gigas Nakai, has been proven to exert neuroprotective property. Previous study revealed that D reduced A β 25 ‒ 35-induced cytotoxicity in PC12 cells. Our study explored the underlying mechanisms by which D mediates its therapeutic effects in vitro. Pretreatment of cells with D diminished intracellular generation of ROS in response to A β 25 ‒ 35. Western blot revealed that D significantly increased the expression and activity of HO-1, which was correlated with its protection against A β 25 ‒ 35-induced injury. Addition of ZnPP, an HO-1 competitive inhibitor, significantly attenuated its protective effect in A β 25 ‒ 35-treated cells, indicating the vital role of HO-1 resistance to oxidative injury. Moreover, D induced Nrf2 nuclear translocation, the upstream of HO-1 expression. While investigating the signaling pathways responsible for HO-1 induction, D activated ERK and dephosphorylated p38 in PC12 cells. Addition of U0126, a selective inhibitor of ERK, blocked D-induced Nrf2 activation and HO-1 induction and meanwhile reversed the protection of D against A β 25 ‒ 35-induced cell death. These findings suggest D augments cellular antioxidant defense capacity through both intrinsic free radical scavenging activity and activation of MAPK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction, thereby protecting the PC12 cells from A β 25 ‒ 35-induced oxidative cytotoxicity. 

Retracted: No

PubPeer comments:
  Figure 4. Migratory ability and invasiveness of melanoma cells determined by transwell assay . Migration and Invasion tests are supposed to be separate experiments, not overlapping to this extent. ![file] ,
MicroRNA-429 inhibits gastric cancer migration and invasion through the downregulation of specificity protein 1
Authors: Jingying Li
Shimao Jin
Jingbin Ni
Yisha Yang
Di Liu
Hui Sun
Journal: Oncology letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: gastric cancer; metastasis; microRNA-429; specificity protein 1.
Affiliations: Department of Gastroenterology, Wuxi No. 2 People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China.

Abstract:  microRNAs (miRs) have been reported to have an important role in tumorigenesis and tumor progression. Although miR-429 has been shown to be downregulated in gastric cancer (GC), the function of miR-429 in the metastasis of GC has yet to be investigated. In the present study, GC cells were transfected with miR-429, and reverse transcription-quantitative polymerase chain reaction, cell migration assays, cell invasion assays, western blot analysis and luciferase assays were conducted to investigate the role of miR-429 in GC cells. It was demonstrated that miR-429 expression was markedly increased following transfection of the cells with miR-429. Furthermore, miR-429 was shown to inhibit the migration and invasion of GC cell lines. In addition, this study provided evidence that miR-429 directly targets specificity protein 1 in GC cells. The results of the present study may enhance current knowledge regarding the molecular basis of cancer metastasis and provide a potential therapeutic strategy for GC. 

Retracted: No

PubPeer comments:
 Image concerns in this paper were found during a systematic search of papers in Spandidos journals for possible duplicated images. Figure 2. * Blue ellipses: The miR-429 SGC-7901 invasion panel appears to show an overlap with the miR-429 AGS migration panel. * Red circles: The NC AGS migration panel appears to show an overlap with the NC AGS invasion panel. ![file] , 
 In addition to the possible overlapping areas between panels in Figure 2, there are interesting similarities to panels in Figure 4 of another paper from different authors and a different institute. That paper is: Wenyao Wang, Hongfei Zhang, Mao Tang, Longlong Liu, Zhengfang Zhou, Shaojun Zhang, Lichao Wangt MicroRNAu2010592 targets IGFu20101R to suppress cellular proliferation, migration and invasion in hepatocellular carcinomat ONCOLOGY LETTERS 13: 3522-3528, 2017tDOI: 10.3892 ol.2017.5902 https: pubpeer.com publications 8897790E850206F58AD08F1A54931E#2 ![file] , 
 #2 More fun with the cookie-cutter. ![file] ,
MicroRNA-365 inhibits ovarian cancer progression by targeting Wnt5a
Authors: Yanli Wang
Chunling Xu
Yun Wang
Xiaomeng Zhang
Journal: American journal of cancer research (2017)
Discipline: CLINICAL MEDICINE
Keywords: Wnt5a; miR-365; microRNAs; ovarian cancer.
Affiliations: Department of Gynecology, The First Hospital of Jilin UniversityChangchun 130021, China., Department of Ophthalmology, The Second Hospital of Jilin UniversityChangchun 130041, China., The Affiliated Hospital, Changchun University of Chinese Medicine1478# Gongnong Road, Chaoyang District, Changchun 130021, China.

Abstract:  MicroRNA-365 (miR-365) has been reported to play an important role in tumorigenesis in many types of cancers; however, the role of miR-365 in the carcinogenesis of ovarian cancer remains unknown. In this study, we focused on the roles and underlying mechanisms of miR-365 in ovarian cancer. Here, we found that miR-365 expression level was significantly decreased in ovarian cancer tissues and cell lines, and that low miR-365 expression was negatively significantly associated with advanced stages as defined by the International Federation of Gynecology and Obstetrics (FIGO), histological grading, and lymph node metastasis. Further functional assays showed that transfection with a miR-365 mimic significantly decreased ovarian cancer cell proliferation, colony formation, migration, and invasion. In addition, Wnt5a was identified as a target gene of miR-365 in ovarian cancer by bioinformatic analysis, luciferase reporter assay, qPCR, and western blot. Wnt5a expression levels were upregulated and inversely correlated with miR-365 expression in ovarian cancer tissues (r = -0.638, P &lt; 0.0001). Overexpression of Wnt5a could effectively reverse the miR-365 overexpression-induced suppression of proliferation and invasion in ovarian cancer cells. Additionally, in vivo studies utilizing a xenograft model demonstrated that overexpression of miR-365 could reduce tumor growth by repressing Wnt5a. Taken together, these findings suggest that miR-365 may be a promising candidate for therapeutic application in ovarian cancer treatment. 

Retracted: No

PubPeer comments:
 FIg 2. ![file] Flow-cytometry plots of a stylised nature, resembling the encounter of a meatball and a cigar; and stylised western blots , resembling playful sardines. These are the main characteristic features of the tadpole papermill . , 
 #1 We have found some issue about the paperu3002 In present stage, in order to avoid misleading the reader and other researchers, we want to withdrawal first. , 
 Retracted, [2 August 2021] .  This article has been retracted at the request of the corresponding author. The author stated that their recent experiments show that they cannot repeat the some of the previous results published in this article. The journal Editor in Chief agrees that unrepeatable work should not be published and supports the retraction. Totally **not** retracted on account of being the work of a papermill. ,
HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs
Authors: P Chaturvedi
H Wei
D M Gilkes
W A Mitzner
H Zhang
P T Winnard Jr
L Zhen
G L Semenza
V Raman
J Chen
S Sukumar
B Krishnamachary
C C L Wong
L Schito
P Korangath
Journal: Oncogene (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Breast cancer; vascular metastasis; endothelial cells; hypoxia-inducible factor; RNA interference
Affiliations: Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract:  Most cases of breast cancer (BrCa) mortality are due to vascular metastasis. BrCa cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor (HIF) activity in BrCa cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of BrCa cells to the lungs by blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC-EC interaction, whereas L1CAM increases the adherence of BrCa cells to ECs. Interference with HIF, ANGPTL4 or L1CAM expression inhibits vascular metastasis of BrCa cells to the lungs. 

Retracted: No

PubPeer comments:
 #1 Same beta-atin panels, yet treatments and L1CAM panels are different. , 
null, 
 Figure 1A. Much more similar than expected. ![file] , 
 Figure 1A. Much more similar than expected. ![file] , 
 2021 correction. https: www.nature.com articles s41388-020-01618-z Since publication of the article the authors noticed the following errors: (1) The actin immunoblot (loading control) from Fig. 6B was mistakenly included in Fig. 6G. The correct actin immunoblot is attached. It demonstrates that there was equal loading in all of the lanes. (2) The three panels in Fig. 1A (HIF-1alpha, HIF-2alpha, and actin immunoblots) are identical to three panels in Fig. 1B of Gilkes et al. (Cancer Res. 73:3285, 2013). These are validation immunoblots for knockdown subclones, which were generated through the combined effort of the first authors of the Oncogene and Cancer Research papers. We regret the two errors that were made. They do not alter any of the paperu2019s conclusions. , 
 #5 Correction does not address likely image duplication within figure 1A. Could the authors post full original blots here? , 
 Figure 3G. * Green boxes: Two mice from the  Saline group at day 10 look very similar to mice in the  Digoxin group at day 21. ![file] , 
 https: retractionwatch.com 2022 09 03 nobel-prize-winner-gregg-semenza-retracts-four-papers ,
Targeting the PI3K/mTOR axis, alone and in combination with autophagy blockade, for the treatment of malignant peripheral nerve sheath tumors
Authors: Eric D Young
Raphael E Pollock
Dina Lev
Keila E Torres
Aviad Hoffman
Kristelle Lusby
Roman Belousov
Gonzalo Lopez
Markus P Ghadimi
Jeffery Liu
Kari J Brewer
Alexander J Lazar
Journal: Molecular Cancer Therapeutics (2012)
Discipline: CLINICAL MEDICINE
Keywords: malignant peripheral nerve sheath tumors; PI3K/mTOR signaling; XL765; autophagy; apoptosis
Affiliations: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Abstract:  There is a critical need for efficacious therapeutic strategies to improve the outcome of patients afflicted by malignant peripheral nerve sheath tumors (MPNST). Multiple lines of evidence suggest a role for deregulated phosphoinositide 3-kinase (PI3K)/mTOR signaling in MPNST, making this axis an attractive target for therapeutic manipulation. On the basis of previous observations obtained from in vitro experimentation, here we aimed to assess the effects of PI3K/mTOR blockade on MPNST growth in vivo. The anti-MPNST impact of XL765, a dual PI3K/mTOR inhibitor currently being evaluated in human cancer clinical trials, was tested in two human MPNST xenograft models (STS26T and MPNST724) and an experimental model of pulmonary metastasis (STS26T). XL765 abrogated human MPNST local and metastatic growth in severe combined immunodeficient mice. Notably, this therapeutic approach failed to induce apoptosis in MPNST cells but rather resulted in marked productive autophagy. Importantly, genetic and pharmacologic autophagy blockade reversed apoptotic resistance and resulted in significant PI3K/mTOR inhibition-induced MPNST cell death. The addition of the autophagy inhibitor, chloroquine, to the therapeutic regimen of MPNST xenografts after pretreatment with XL765 resulted in superior antitumor effects as compared with either agent alone. Together, preclinical studies described here expand our previous findings and suggest that PI3K/mTOR inhibition alone and (most importantly) in combination with autophagy blockade may comprise a novel and efficacious therapy for patients harboring MPNST. 

Retracted: No

PubPeer comments:
 Fig 4B.  An invasion assay was performed to investigate the effects of microRNA-145 (miR-145) and ROCK1 on U87 cell invasion . ![file] The panels appear in other papers, representing different combinations of cell-line and treatment. For comparison: *[upper]* Figs 4 C D and 5C from [Yang et al (2016)] .  Transwell assays were conducted to examine the cell invasion capacities ofA549 cells transfected with (C) miR-133b mimics and (D) FSCN1 plasmids. Non-transfected A549 cells were used as control ....  Transwell assay were conducted to examine the cell migration and invasion in each group . *[lower]* Fig 5B from [Wang et al (2016)] .  Transwell assay to determine the invasive capacity of U2OS cells transfected with miRu2011101 mimics or cu2011FOS siRNA, or cou2011transfected with miRu2011101 mimics and cu2011FOS plasmid. Magnification, x100. Control: untransfected U2OS cells . ![file] ,
Kaempferol Regulates miR-15b/Bcl-2/TLR4 to Alleviate OGD-Induced Injury in H9c2 Cells
Authors: Linping Li
Hongjian Zheng
Yuanxia Shao
Heng Niu
Journal: International Heart Journal (2020)
Discipline: CLINICAL MEDICINE
Keywords: Cell apoptosis; Ischemic heart disease; Oxygen glucose deprivation; Wnt/β-catenin and PI3K/AKT pathways.
Affiliations: Department of Cardiology, Jining No.1 People's Hospital

Abstract:  Ischemic heart disease (IHD) is one of the world's leading causes of human death. Kaempferol (Kae) was proved to have anti-inflammatory, antioxidant, and anticancer effects. Such properties suggested that it might play protective roles in IHD. In this study, we have attempted to disclose the potential regulating mechanisms of Kae in primary cardiomyocytes and H9c2 cells.Cells were first stimulated by oxygen-glucose deprivation (OGD) and then exposed to Kae. CCK-8 assay and flow cytometry were used to examine cell characteristics. Quantitative reverse-transcription polymerase chain reaction was utilized to test the expression levels of miR-15b and TLR4. Afterward, cell transfection, dual-luciferase activity assay, and western blot were used to explore the potential mechanisms.OGD treatment suppressed cell viability, whereas it enhanced cell apoptosis. Besides, OGD treatment enhanced the expression of apoptosis-associated proteins. Kae exposure, however, attenuated the effects that OGD-induced. Further experiments showed that Kae exposure promoted down-regulation of miR-15b, Bcl-2 and TLR4 were a target of miR-15b. Moreover, Kae enhanced the expression of key factors involved in PI3K/AKT and Wnt/β-catenin pathways, whereas miR-15b mimic reversed the Kae-triggered effects.This investigation revealed that Kae diminished OGD-triggered cell damage through down-regulating miR-15b expression via activating PI3K/AKT and Wnt3a/β-catenin pathways. 

Retracted: No

PubPeer comments:
 Evidently another product of the  Tadpole Papermill . ![file] [Sort-of-retracted in September 2020] , though the publishers did not progress any further than issuing an announcement, so the original paper remains on PubMed without any evidence of its problematic nature. ,
Blockade of IL-33R/ST2 Signaling Attenuates Toxoplasma gondii Ileitis Depending on IL-22 Expression
Authors: Isabelle Dimier-Poisson
Song Guo Zheng
François Erard
Feng Huang
Claire Mackowiak
Marbel Torres Arias
Julie Piotet
Bernhard Ryffel
Pauline Robinet
Corine Panek
Isabelle Couillin
Marc Le Bert
Journal: Frontiers in Immunology (2019)
Discipline: IMMUNOLOGY
Keywords: IL-22; IL-33/ST2 receptor; Toxoplasma gondii; innate immunity; neutralizing antibody
Affiliations: Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China., UMR 7355 Université-CNRS INEM, Orléans, France and IDM, University of Cape Town, Cape Town, South Africa., Immunology and Virology Laboratory, Nanoscience and Nanotechnology Center, Universidad de las Fuerzas Armadas, ESPE, Sangolquí, Ecuador., UMR 1282 Infectiologie Animale et Santé Publique, Université de Tours -INRA, Tours, France., Department of Internal Medicine, Ohio State College of Medicine, Columbus, OH, United States.

Abstract:  Oral T. gondii infection (30 cysts of 76K strain) induces acute lethal ileitis in sensitive C57BL/6 (B6) mice with increased expression of IL-33 and its receptor ST2 in the ileum. Here we show that IL-33 is involved in ileitis, since absence of IL-33R/ST2 attenuated neutrophilic inflammation and Th1 cytokines upon T. gondii infection with enhanced survival. Blockade of ST2 by neutralizing ST2 antibody in B6 mice conferred partial protection, while rmIL-33 aggravated ileitis. Since IL-22 expression further increased in absence of ST2, we blocked IL-22 by neutralizing antibody, which abrogated protection from acute ileitis in ST2 deficient mice. In conclusion, severe lethal ileitis induced by oral T. gondii infection is attenuated by blockade of ST2 signaling and may be mediated in part by endogenous IL-22. 

Retracted: No

PubPeer comments:
 Figure 4D (top) and 5D (bottom) appear to use the same image, although they are labeled differently. Apologies if I am misunderstanding something. *** ![file] , 
 See also these two images in Figure 5. *** ![file] , 
 It would be appreciated if the first author or other co-authors could reply, as it appears as if the last author may be focused elsewhere now: https: www.justice.gov opa pr researcher-charged-illegally-using-us-grant-funds-develop-scientific-expertise-china , 
 October 28, 2020 Corrigendum on Blockade of IL-33R ST2 Signaling Attenuates Toxoplasma gondii Ileitis Depending on IL-22 Expression by Ryffel, B., Huang, F., Robinet, P., Panek, C., Couillin, I., Erard, F., et al. (2019). Front. Immunol. 10:702. doi: 10.3389 fimmu.2019.00702 In the published article, there was an error in affiliation 2. Instead of u201cUMR 7355 Universitu00e9-CNRS INEM, Orlu00e9ans, France and IDM, University of Cape Town, South Africau201d, it should be u201cINEM UMR 7355 CNRS and University of Orleans, Orlu00e9ans, France.u201d In addition, the wrong microscopic plates were inserted into Figures 5E and F. The corrected Figure 5 appears below. ![file] ,
Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation
Authors: Toshiya Inaba
Hiroya Asou
Shunsuke Izumi
Tadashi Yamamoto
Akiko Nagamachi
Yoshihiro Takihara
Daisuke Aki
Yuko Ozaki
Miho Ohsugi
Hirotaka Matsui
Shin&#x27;ichiro Yasunaga
Hiroaki Honda
Journal: Molecular Cell (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: prometaphase; centrosomes; microtubule nucleation; spindles; chromosomes
Affiliations: Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.

Abstract:  During prometaphase, dense microtubule nucleation sites at centrosomes form robust spindles that align chromosomes promptly. Failure of centrosome maturation leaves chromosomes scattered, as seen routinely in cancer cells, including myelodysplastic syndrome (MDS). We previously reported that the Miki (LOC253012) gene is frequently deleted in MDS patients, and that low levels of Miki are associated with abnormal mitosis. Here we demonstrate that Miki localizes to the Golgi apparatus and is poly(ADP-ribosyl)ated by tankyrase-1 during late G2 and prophase. PARsylated Miki then translocates to mitotic centrosomes and anchors CG-NAP, a large scaffold protein of the γ-tubulin ring complex. Due to impairment of microtubule aster formation, cells in which tankyrase-1, Miki, or CG-NAP expression is downregulated all show prometaphase disturbances, including scattered and lagging chromosomes. Our data suggest that PARsylation of Miki by tankyrase-1 is a key initial event promoting prometaphase. 

Retracted: No

PubPeer comments:
 Figure 2A. https: imgur.com yItW0Sk ,
miRNA‐301b‐3p accelerates migration and invasion of high‐grade ovarian serous tumor via targeting CPEB3/EGFR axis
Authors: Guilian Zhang
Shiming Lv
Xinmian Wen
Peishu Liu
Fengying Liu
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cytoplasmic polyadenylation element binding protein 3; epidermal growth factor receptor; high-grade serous ovarian cancer; metastasis; miR-301b-3p.
Affiliations: Department of Gynecology and obstetrics, the Fourth Hospital of Jinan, Jinan, Shandong, China., Department of Laboratory Medicine, the Fourth Hospital of Jinan, Jinan, Shandong, China., Department of Gynecology and obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Abstract:  High-grade ovarian serous carcinoma (HGS-OvCa), a type of ovarian cancer with poor prognosis due to distant metastasis, is urgently in need of new therapeutic targets. microRNAs (miRNAs), a class of small noncoding RNAs, perform significant roles in tumor progression. Mounting evidence has revealed the aberrant expression of miRNA in various cancers, one of which is HGS-OvCa. Present study planned to investigate that miRNA-301b-3p accelerates migration and invasion of high-grade ovarian serous tumor via targeting CPEB3/EGFR axis. Upregulation of miR-301b-3p was uncovered in HGS-OvCa tissues and cell lines, and was identified to be associated with metastasis. The Kaplan-Meier analysis confirmed the association of miR-301b-3p with poor prognosis of HGS-OvCa patients. Transwell assay validated the oncogenic effect of miR-301b-3p on migration and invasion of HGS-OvCa cells. Cytoplasmic polyadenylation element binding protein 3 (CPEB3) was then identified as a target of miR-301b-3p. It was also discovered that CPEB3 was downregulated in HGS-OvCa tissues and cell lines. The Spearman correlation curve presented the negative correlation of CPEB3 expression with miR-301b-3p. Furthermore, rescue assays proved that miRNA-301b-3p regulated the invasion and migration through CPEB3. Western blot and qRT-PCR analysis showed that miRNA-301b-3p induced epidermal growth factor receptor and downstream metastasis-related proteins, p38, and extracellular signal-regulated kinase 1/2 (ERK1/2), through CPEB3. To be concluded, these results indicated that miRNA-301b-3p accelerated migration and invasion of high-grade ovarian serous tumor via targeting CPEB3/EGFR axis. 

Retracted: No

PubPeer comments:
 Figure 2B. * Red boxes: Two panels displaying different cell lines appear to show an overlap. However, the SKOV3 panel shows fewer cells than the HO8910 panel. * Blue boxes: Two panels displaying different inhibitors appear to show an overlap. However, the right panel shows fewer cells than the left panel. ![file] ,
Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin
Authors: Chuay-Yeng Koo
Douglas J Kelly
Ana R Gomes
Victoria A McGuire
David G Campbell
J Simon C Arthur
Kyle W Muir
Ursula B McGovern
Angel R Nebreda
Eric W-F Lam
Ka-Kei Ho
Lara J Monteiro
Natalia de Olano
Evie Maifoshie
Journal: Journal of Biological Chemistry (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: FOXO3a; p38; phosphorylation; doxorubicin; nuclear relocation
Affiliations: Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, United Kingdom.

Abstract:  FOXO3a is a forkhead transcription factor that regulates a multitude of important cellular processes, including proliferation, apoptosis, differentiation, and metabolism. Doxorubicin treatment of MCF-7 breast carcinoma cells results in FOXO3a nuclear relocation and the induction of the stress-activated kinase p38 MAPK. Here, we studied the potential regulation of FOXO3a by p38 in response to doxorubicin. Co-immunoprecipitation studies in MCF-7 cells demonstrated a direct interaction between p38 and FOXO3a. We also showed that p38 can bind and phosphorylate a recombinant FOXO3a directly in vitro. HPLC-coupled phosphopeptide mapping and mass spectrometric analyses identified serine 7 as a major site for p38 phosphorylation. Using a phosphorylated Ser-7 FOXO3a antibody, we demonstrated that FOXO3a is phosphorylated on Ser-7 in response to doxorubicin. Immunofluorescence staining studies showed that upon doxorubicin treatment, the wild-type FOXO3a relocalized to the nucleus, whereas the phosphorylation-defective FOXO3a (Ala-7) mutant remained largely in the cytoplasm. Treatment with SB202190 also inhibits the doxorubicin-induced FOXO3a Ser-7 phosphorylation and nuclear accumulation in MCF-7 cells. In addition, doxorubicin caused the nuclear translocation of FOXO3a in wild-type but not p38-depleted mouse fibroblasts. Together, our results suggest that p38 phosphorylation of FOXO3a on Ser-7 is essential for its nuclear relocalization in response to doxorubicin. 

Retracted: No

PubPeer comments:
 Figure 7B. Much more similar than expected. https: imgur.com ewRxikN ,
Chemoselective imaging of mouse brain tissue via multiplex CARS microscopy
Authors: Tiago Buckup
Christoph Pohling
Axel Pagenstecher
Marcus Motzkus
Journal: Biomedical Optics Express (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: (170.0170) Medical optics and biotechnology; (180.0180) Microscopy; (300.6230) Spectroscopy, coherent anti-Stokes Raman scattering.

Abstract:  The fast and reliable characterization of pathological tissue is a debated topic in the application of vibrational spectroscopy in medicine. In the present work we apply multiplex coherent anti-Stokes Raman scattering (MCARS) to the investigation of fresh mouse brain tissue. The combination of imaginary part extraction followed by principal component analysis led to color contrast between grey and white matter as well as layers of granule and Purkinje cells. Additional quantitative information was obtained by using a decomposition algorithm. The results perfectly agree with HE stained references slides prepared separately making multiplex CARS an ideal approach for chemoselective imaging. 

Retracted: No

PubPeer comments:
 Please have a look at the figure 3C carefully; between lane M2 and Lane 1, looks like gel images were constructed!! ![file] ,
Manumycin inhibits farnesyltransferase and induces apoptosis of drug-resistant interleukin 6-producing myeloma cells
Authors: Claudia Piccoli
Franco Dammacco
Maria Antonia Frassanito
Antonio Cusmai
Journal: British Journal of Haematology (2002)
Discipline: CLINICAL MEDICINE
Keywords: Interleukin 6; myeloma cells; Ras cascade; farnesylation; protein farnesyltransferase
Affiliations: Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.

Abstract:  Interleukin 6 (IL-6) is an important survival and growth factor for myeloma cells and exerts its effects by activating several transduction pathways, including the Ras cascade. As farnesylation of the activated Ras oncogene product by protein farnesyltransferase (FTase) is a critical step for Ras functional activity, FTase has emerged as a potential target for the development of new anti-cancer agents. Based on our previous demonstration that IL-6-producing myeloma cells are refractory to drug-induced apoptosis, we have analysed the effect of manumycin, a natural FTase inhibitor, on IL-6-producing myeloma cells resistant to Fas-, dexamethasone- and doxorubicin-induced apoptosis. Treatment of myeloma cells with manumycin prevented cell proliferation and induced apoptosis. Western blotting experiments demonstrated that this effect was related to inhibition of the post-translational Ras processing.Further analysis showed that manumycin-induced apoptosis involved caspase-3. Activation of caspase-3, in fact, was observed in 6 h-treated myeloma cells expressing Apo 2.7 antigen, the marker of early apoptosis, whereas their treatment with cell-permeable DEVD-fmk, that irreversibly inhibits caspase-3 activity, prevented their apoptosis. Over-expression of caspase-3 was also demonstrated by reverse transcription-polymerase chain reaction. Finally, over-expression of Bcl-2 and its homologue Bcl-xL was observed in manumycin-treated cells as well as in control myeloma cells, implying that the Bcl-2 family is not involved. FTase inhibitors may thus be proposed as a potential pharmacological weapon, as they block the Ras pathway and induce the apoptosis of drug-resistant IL-6-producing myeloma cells. 

Retracted: No

PubPeer comments:
 Figure 2. Here is the full figure: ![file] In panel 2B, some features appear to be visible multiple times. Here is a close-up of that panel, with boxes of the same color highlighting areas that look more similar than expected. ![file] ,
The HIF-1–Inducible Lysyl Oxidase Activates HIF-1 via the Akt Pathway in a Positive Regulation Loop and Synergizes with HIF-1 in Promoting Tumor Cell Growth
Authors: Floriane Pez
Jacques Pouysségur
Pascal Sommer
Gabrielle S Le Provost
Philippe Clézardin
Caroline Reynaud
Frédéric Dayan
Jérome Durivault
Blandine Deux
Bastien Kaniewski
Géraldine Aimond
Journal: Cancer Research (2011)
Discipline: CLINICAL MEDICINE
Keywords: Hypoxia; Tumor progression; HIF-1; Lysyl oxidase; Colorectal cancer
Affiliations: CNRS (Centre National de la Recherche Scientifique), FRE3310-IFR128, IBCP, Lyon, France.

Abstract:  Adaptation to hypoxia is a driving force for tumor progression that leads to therapy resistance and poor clinical outcome. Hypoxic responses are mainly mediated by hypoxia-inducible transcription factor-1 (HIF-1). One critical HIF-1 target mediating tumor progression is lysyl oxidase (LOX), which catalyzes cross-linking of collagens and elastin in the extracellular matrix, thereby regulating tissue tensile strength. Paradoxically, LOX has been reported to be both upregulated and downregulated in cancer cells, especially in colorectal cancer. Thus, we hypothesized that LOX might regulate expression of HIF-1 to create a self-timing regulatory circuit. Using human colorectal carcinoma cell lines in which HIF-1 and LOX expression could be modulated, we showed that LOX induction enhanced HIF-1 expression, whereas LOX silencing reduced it. Mechanistic investigations revealed that LOX activated the PI3K (phosphoinositide 3-kinase)-Akt signaling pathway, thereby upregulating HIF-1α protein synthesis in a manner requiring LOX-mediated hydrogen peroxide production. Consistent with these results, cancer cell proliferation was stimulated by secreted and active LOX in an HIF-1α-dependent fashion. Furthermore, nude mice xenograft assays established that HIF-1 potentiated LOX action on tumor growth in vivo. Taken together, these findings provide compelling evidence that LOX and HIF-1 act in synergy to foster tumor formation, and they suggest that HIF-1/LOX mutual regulation is a pivotal mechanism in the adaptation of tumor cells to hypoxia. 

Retracted: No

PubPeer comments:
 Two images in figure 1A appear to overlap, although the magnification, coloring, and rotation appear to differ. Some similar features noted in red. *** ![file] *** Showing location and caption ![file] ,
Over-expression of COX-2 induces human ovarian cancer cells (CAOV-3) viability, migration and proliferation in association with PI3-k/Akt activation
Authors: Hui Gong
Yajuan Su
Lichen Teng
Youqun Cai
Juan Qi
Pingqing Gu
Shuyu Guo
Ye Xu
Journal: Cancer Investigation (2008)
Discipline: CLINICAL MEDICINE
Keywords: COX-2; ovarian cancer; CAOV-3; viability; migration
Affiliations: Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital, Nanjing, P.R. of China.

Abstract:  COX-2 is involved in several pathological processes. The action of COX-2 on human ovarian cancer cell line (CAOV-3) and relative signal pathway has not been demonstrated. We explored the effects of COX-2 on the CAOV-3 viability and migration, moreover the proliferation of CAOV-3, and then ascertained the roles of PI3-k/Akt in these processes. The results showed that COX-2 increased the cells viability, migration and augment the number of CAOV-3. LY294002 could reduce COX-2 induce cells viability, migration and proliferation. These data indicate that COX-2 induce cells viability and migration, moreover promote the proliferation of CAOV-3 via PI3-k/Akt signal pathway. 

Retracted: No

PubPeer comments:
 Figure 4B. Reported to the journal in 2015. * Red boxes: In the T-Stat panel, lanes 1 and 2 look similar to lanes 4 and 5. ![file] This paper was found during a systematic screen of biomedical papers for image duplications, as published in Bik et al., mBio (2016), doi: 10.1128 mBio.00809-16, https: journals.asm.org doi 10.1128 mBio.00809-16. This issue was reported to the journal in October 2015, but it has not yet been addressed by the journal, more than six years later. ,
Osteopontin regulates epithelial mesenchymal transition-associated growth of hepatocellular cancer in a mouse xenograft model
Authors: Lindsay J Talbot
Victoria M Kim
Zhiyong Mi
Syamal D Bhattacharya
Paul C Kuo
Hongtao Guo
Journal: Annals of Surgery (2012)
Discipline: CLINICAL MEDICINE
Keywords: Osteopontin; Hepatocellular cancer; Efficacy; Epithelial-mesenchymal transition; Adhesion
Affiliations: Department of Surgery, Duke University Medical Center, Durham, NC, USA.

Abstract:  Objective: To determine the efficacy of osteopontin (OPN) targeting in hepatocellular cancer (HCC). SUMMARY/BACKGROUND: OPN is associated with HCC growth and metastasis and represents a unique therapeutic target. Methods: OPN and epithelial-mesenchymal transition (EMT) markers, α-smooth muscle actin (SMA), vimentin, and tenascin-c, were measured in archived human HCC tissues from metastatic (n = 4) and nonmetastatic (n = 4) settings. Additional studies utilized human Sk-Hep-1 (high OPN expression) and Hep3b (low OPN expression) HCC cells. An RNA aptamer (APT) that avidly binds (Kd = 18 nM; t1/2 = 7 hours) and ablates OPN binding was developed. Adhesion, migration/invasion, and EMT markers were determined with APT or a mutant control aptamer (Mu-APT). RFP-Luc-Sk-Hep-1 were implanted into NOD-scid mice livers and followed by using bioluminescence imaging. After verification of tumor growth, at week 3, APT (0.5 mg/kg; n = 4) or Mu-APT (0.5 mg/kg; n = 4) was injected q48h. When mice were killed at week 8, tumor cells were reisolated and assayed for EMT markers. Results: OPN and EMT markers were significantly increased in the metastatic cohort. APT inhibited Sk-Hep-1 adhesion and migration/invasion by 5- and 4-fold, respectively. APT significantly decreased EMT protein markers, SMA, vimentin, and tenascin-c. In contrast, APT did not alter Hep3B adhesion, or migration/invasion. EMT markers were slightly decreased. In the in vivo model, at weeks 6 to 8, APT inhibited HCC growth by more than 10-fold. SMA, vimentin, and tenascin-c mRNAs were decreased by 60%, 40%, and 49%, respectively, in RFP-positive Sk-Hep-1 recovered by fluorescence-activated cell sorting (P &lt; 0.04 vs Mu-APT for all). Conclusions: APT targeting of OPN significantly decreases EMT and tumor growth of HCC. 

Retracted: No

PubPeer comments:
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 #6 I attempted to equalize the contrast in this figure between the two bands with similarities. ![file] , 
 With respect to the journal editors, some of these concerns do not need an extensive investigation or input from the authors or institutions involved. For example, the editors should be able to review Figure 4B with their own eyes and see that two sets of images are essentially identical, but are used to represent two sets of animals. If the authors are not cooperating, an expression of concern seems a better solution than nothing. Readers deserve to know. *** ![file] ,
Adenovirus-mediated transfer of siRNA against MMP-2 mRNA results in impaired invasion and tumor-induced angiogenesis, induces apoptosis in vitro and inhibits tumor growth in vivo in glioblastoma
Authors: C S Gondi
J S Rao
O Kargiotis
S S Lakka
A J Tsung
C Chetty
D H Dinh
A P Kyritsis
M Gujrati
Journal: Oncogene (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Invasive tumors; gliomas; proteinases; extracellular matrix; diffusion
Affiliations: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA.

Abstract:  Invasive tumors, including gliomas, utilize proteinases to degrade extracellular matrix components and diffuse into the adjacent tissues or migrate toward distant ones. In addition, proteinase activity is required for the formation of new blood vessels within the tumor. Levels of the proteinase matrix metalloproteinase-2 (MMP-2) are highly increased in gliomas. In this study, we examined the effect of the downregulation of MMP-2 via adenovirus-mediated siRNA in gliomas. Here, we show that siRNA delivery significantly decreased levels of MMP-2 in the glioblastoma cell lines U-87 and U-251. U-87 and U-251 cells showed impaired invasion through matrigel as well as decreased migration from tumor spheroids transfected with adenoviral vector expressing siRNA against MMP-2. Additionally, tumor-induced angiogenesis was decreased in in vitro experiments in cultured human microvascular endothelial cells (HMECs) in serum-free conditioned medium of glioblastoma cells transfected with these constructs and co-cultures of glioma cells with HMECs. We also observed decreased angiogenesis in the in vivo dorsal skin-fold chamber model. Moreover, MMP-2 inhibition induced apoptotic cell death in vitro, and suppressed tumor growth of preestablished U-251 intracranial xenografts in nude mice. Thus, specific targeting of MMP-2 may provide a novel, efficient approach for the treatment of gliomas and improve the poor outcomes of patients with these brain tumors. 

Retracted: No

PubPeer comments:
 Figure 3B. An overlap appears to be visible between two panels representing different experiments. Contrast appears a bit different for each photo. ![file] , 
 Figure 3A. ![file] , 
 Three days ago I sent an expression of concern to the most affected journals and the University of Illinois to please clean up this awfull mess. Just for the record: the university started an investigation in 2013 and concluded that research misconduct did affect a large number of articles by Jasti S Rao. Six years later only two articles have been retracted. An overview of the affacted journals (based on Pubpeer posts): International Journal of Oncology: 14 articles Oncogene: 11 articles PlosOne: 8 articles Cancer Research: 5 articles (2 retractions) J Biol Chem: 4 articles Int. J Cancer: 2 articles Mol. Cancer Therapeutics: 2 articles Clinical Cancer Research: 2 articles Mol. Cancer Research: 2 articles Ceullar Signaling: 2 articles I will encourage you, friends of science, to contact the affected journals and the University of Illinois and ask them to act! ,
FGF23 promotes renal interstitial fibrosis by activating β-catenin
Authors: F-Q Li
D-K Zeng
Q Zhu
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: fibroblast growth factor 23; renal interstitial fibrosis; extracellular matrix; NRK-52E; TGFβ1
Affiliations: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. .

Abstract:  Objective: To investigate the role and mechanism of fibroblast growth factor 23 (FGF23) in renal interstitial fibrosis. Materials and methods: Rat renal tubular epithelial cell line (NRK-52E) was selected for in vitro experiments. Effect of FGF23 on extracellular matrix was observed. High expression of FGF23 was induced by injecting the plasmid into the caudal vein. The model of unilateral ureteral obstruction (UUO) was established for in vivo experiments. Results: FGF23 increased the expression of extracellular matrix proteins FN, α-SMA and Type 1 collagen of NRK-52E induced by TGFβ1, while FGF23 increased the expression of p-β-catenin 675. In UUO model mice, fibrosis in the FGF23 high expression group increased significantly compared to that of the control group. Meanwhile, β-catenin signal was activated. Conclusions: FGF23 can promote the deposition of extracellular matrix of NRK-52E induced by TGFβ1 in vitro. It aggravated the degree of renal interstitial fibrosis in UUO model, which is related to the activation of β-catenin signaling pathway. 

Retracted: Yes

PubPeer comments:
 This January 2018 article has been withdrawn in September 2018. The retraction notice gives no further insight as to what has happened. The original paper PDF has been removed from the journal s website, but has been archived here: https: web.archive.org web 20180427172440 https: www.europeanreview.org wp wp-content uploads 174-183-FGF23-promotes-renal-interstitial-fibrosis-by-activating-%CE%B2-catenin.pdf ,
miR-376a inhibits the proliferation and invasion of osteosarcoma by targeting FBXO11
Authors: Wenjie Lu
Li Cheng
Jianyang Chen
Peinian Wang
Qiaolong Xu
Journal: Human Cell (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FBXO11; Osteosarcoma; Tumor suppressive miRNA; miR-376a.
Affiliations: Department of Orthopedic, The People's Hospital of Cixi, No. 999 East Nanerhuan Road, Hushan Street, Cixi, 315300, People's Republic of China., Department of Orthopedic, The People's Hospital of Cixi, No. 999 East Nanerhuan Road, Hushan Street, Cixi, 315300, People's Republic of China. .

Abstract:  Dysregulation of microRNAs (miRNAs) is frequently found in the tumorigenesis of osteosarcoma (OS). miR-376a was found to play tumor suppressive roles in human cancers. However, the role of miR-376a in OS remains unclear. The expression of miR-376a was analyzed by quantitative real-time PCR (qRT-PCR) in OS cell lines. Cell proliferation assay, cell invasion assay, and cell apoptosis assay were performed to detect the biological function of miR-376a after synthetic miRNA transfection. The target of miR-376a was predicted by TargetScan and miRDB, and further validated by luciferase activity reporter assay and western blot. miR-376a expression was revealed to be decreased in OS cell lines. In vitro experiments showed that overexpression of miR-376a inhibits OS cell proliferation and invasion but promotes apoptosis. Luciferase activity reporter assay and western blot assay showed F-box protein 11 (FBXO11) was a direct target of miR-376a. Furthermore, FBXO11 mediated the role of miR-376a on the proliferation, invasion, and apoptosis of OS cells. Collectively, these results revealed miR-376a functions as a tumor suppressor by targeting FBXO11 in OS. It may be developed as a therapeutic target for OS patients. 

Retracted: Yes

PubPeer comments:
 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 A101 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. 23 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 ,
Hyaluronic acid inhibits nitric oxide-induced apoptosis and dedifferentiation of articular chondrocytes in vitro
Authors: Bo Qiu
Jian-lin Zhou
Qiong-jie Hu
Hao Peng
Jiang-hua Ming
Shi-qing Liu
Journal: Inflammation Research (2010)
Discipline: IMMUNOLOGY
Keywords: Nitric oxide; Osteoarthritis; Apoptosis; Dedifferentiation; Articular chondrocytes
Affiliations: Department of Orthopedics, Renmin Hospital of Wuhan University, Hubei, People's Republic of China.

Abstract:  Objective: Nitric oxide is an important mediator in Osteoarthritis (OA), and causes apoptosis and dedifferentiation in articular chondrocytes. Protein kinase Calpha is involved in modulating apoptosis and dedifferentiation of articular chondrocytes induced by nitric oxide. Hyaluronic acid is widely used in the treatment of osteoarthritis and exerts significant chondroprotective effects. The exact mechanisms of its chondroprotective action are not yet fully elucidated. The present study was performed to investigate the effects and mechanisms of hyaluronic acid in NO-induced apoptosis and dedifferentiation of chondrocytes. Methods: The ratio of apoptotic cell and cell viability was surveyed by TUNEL, MTT assay and flow cytometry. The expression of aggrecan, type II collagen, and PKCalpha were determined by real-time PCR and Western blot. The expression changes of caspase-3 and bcl-2 was detected by Western blot. The mitochondrial membrane potential (DeltaPsim) was evaluated by Rhodamine-123 fluorescence. Results: HA reduces the TUNEL positive cell, nuclei fragment and the impairment of DeltaPsim. NO-induced chondrocyte dedifferentiation was blocked by HA, which restores expression of aggrecan and type II collagen of chondrocytes and cell viability. HA can block inhibition of PKC-alpha by NO. Conclusion: Our results show that HA blocks NO-induced apoptosis and dedifferentiation of articular chondrocytes by modulation of DeltaPsim and PKCalpha. 

Retracted: No

PubPeer comments:
 Figure 4 and 7: * Red boxes: The two marked Actin panels look very similar to each other if one of the two is rotated 180 degrees. ![file] ,