PReD-Bench/PRed-Bench huggingface dataset:
The lignan glycosides lyoniside and saracoside poison the unusual type IB topoisomerase of Leishmania donovani and kill the parasite both in vitro and in vivo
Authors: Hemanta K Majumder
Sourav Saha
Somenath Roy Chowdhury
Parasuraman Jaisankar
Tulika Mukherjee
Sibabrata Mukhopadhyay
Amartya Mishra
Sayan Chowdhury
Journal: Biochemical pharmacology (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Antileishmanial agent; Apoptosis; DMSO; DNA topoisomerase IB poison; DTT
Affiliations: Molecular Parasitology Laboratory (S.S., S.C., A.M., S.R.C., H.K.M.), Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.

Abstract:  Lignans are diphenyl propanoids with vast range of biological activities. The present study provides an important insight into the anti-leishmanial activities of two lignan glycosides, viz. lyoniside and saracoside. These compounds inhibit catalytic activities of topoisomerase IB (LdTopIB) of Leishmania donovani in non-competitive manner and stabilize the LdTopIB mediated cleavage complex formation both in vitro and in Leishmania promastigotes and subsequently inhibit the religation of cleaved strand. These two compounds not only poison LdTopIB but also can interact with the free enzyme LdTopIB. We have also shown that lyoniside and saracoside are cytotoxic to promastigotes and intracellular amastigotes. The protein-DNA complex formation leads to double strand breaks in DNA which ultimately triggers apoptosis-like cell death in the parasite. Along with their cytotoxicity towards sodium antimony gluconate (SAG) sensitive AG83 strain, their ability to kill SAG resistant GE1 strain makes these two compounds potential anti-leishmanial candidates. Not only they effectively kill L. donovani amastigotes inside macrophages in vitro, lyoniside and saracoside demonstrated strong anti-leishmanial efficacies in BALB/c mice model of leishmaniasis. Treatment with these lignan glycosides produce nitric oxide and reactive oxygen species which result in almost complete clearance of the liver and splenic parasite burden. These compounds do not inhibit human topoisomerase IB upto 200ŒºM concentrations and had poor cytotoxic effect on uninfected cultured murine peritoneal macrophages upto 100ŒºM concentrations. Taken together it can be concluded that these compounds can be developed into excellent therapeutic agent against deadly disease leishmaniasis. 

Retracted: No

PubPeer comments:
  , 
 #1 Reader is requested to carefully check both the lanes. Lane 2 does not have any remaining DNA supercoil indicative of complete relaxation whereas Lane 6 clearly shows residual supercoil indicative of partial relaxation. ,
Adenoviral neutral endopeptidase gene delivery in combination with paclitaxel for the treatment of prostate cancer
Authors: Rong Zheng
Ruoqian Shen
Katsuyuki Iida
David M Nanus
Journal: International Journal of Oncology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Neutral endopeptidase; prostate cancer; adenovirus gene delivery; paclitaxel chemotherapy; Akt kinase
Affiliations: Genitourinary Oncology Research Laboratory, Department of Medicine, Weill Cornell Medical College and Weill Cornell Cancer Center, New York, NY, USA.

Abstract:  Neutral endopeptidase (NEP) is a cell-surface peptidase that inhibits prostate cancer cell growth partly via inhibition of Akt kinase. We investigated the antitumor effects of an adenovirus gene delivery system (AdNEP) to restore NEP expression in DU145 prostate cancer cells in combination with paclitaxel chemotherapy. DU145 cells were infected with adenovirus expressing NEP or LacZ, treated with paclitaxel, and assessed for cell viability, Akt activation and induction of apoptosis. Athymic mice with established DU145 xenografts were injected intratumorally with AdNEP or AdLacZ and intraperitoneally with paclitaxel and monitored for tumor growth over 28 days. Compared to AdLacZ plus paclitaxel, AdNEP plus paclitaxel significantly inhibited DU145 cell growth and increased apoptosis as determined by increased caspase-3 and PARP-1 proteolytic fragments. In a xenograft model, tumor volume was reduced in mice treated with AdNEP plus paclitaxel (122.85¬±89.5 mm3; P&lt;0.01) compared with mice treated with AdNEP plus saline (653.9¬±230.3 mm3), AdLacZ plus paclitaxel (575.9¬±176.6 mm3) or AdLacZ plus saline (920.2¬±238.2 mm3). In conclusion, these data suggest that NEP can augment taxane-induced apoptosis through inhibition of Akt/Bad signaling, and that the combination of NEP plus paclitaxel may be an effective strategy to inhibit castration-resistant prostate cancer growth. 

Retracted: No

PubPeer comments:
 image duplication  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. ,
PR-LncRNA signature regulates glioma cell activity through expression of SOX factors
Authors: Nicolas Sampr√≥n
Idoia Garcia
Sergio Torres-Bayona
Ander Saenz-Anto√±anzas
Marcos J Ara√∫zo-Bravo
Mariano Arrazola
Jorge Villan√∫a
Arrate Querejeta
Jaione Auzmendi-Iriarte
Ander Matheu
Enrique Urculo
Cristina Sarasqueta
Daniela Gerovska
Paula Aldaz
Maite Huarte
Jose Undabeitia
Irune Ruiz
Larraitz Ega√±a
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: Long non-coding RNAs; LncRNAs; tumor suppressor signature; PR-LncRNAs; gliomas
Affiliations: Donostia University Hospital, San Sebastian, Spain., Cellular Oncology group, Biodonostia Institute, San Sebastian, Spain., CIBERFES, Madrid, Spain., IKERBASQUE, Basque Foundation for Science, Bilbao, Spain., Biodonostia Institute, San Sebastian, REDISSEC, Madrid, Spain., Computational Biology and Systems Biomedicine group and Computational Biomedicine Data Analysis Platform, Biodonostia Institute, San Sebastian, Spain., Surgery and Radiology Department, School of Medicine, University of the Basque Country UPV/EHU, San Sebastian, Spain., Center for Applied Medical Research, University of Navarra, Pamplona, Spain., Cellular Oncology group, Biodonostia Institute, San Sebastian, Spain. ., IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. ., CIBERFES, Madrid, Spain. .

Abstract:  Long non-coding RNAs (LncRNAs) have emerged as a relevant class of genome regulators involved in a broad range of biological processes and with important roles in tumor initiation and malignant progression. We have previously identified a p53-regulated tumor suppressor signature of LncRNAs (PR-LncRNAs) in colorectal cancer. Our aim was to identify the expression and function of this signature in gliomas. We found that the expression of the four PR-LncRNAs tested was high in human low-grade glioma samples and diminished with increasing grade of disease, being the lowest in glioblastoma samples. Functional assays demonstrated that PR-LncRNA silencing increased glioma cell proliferation and oncosphere formation. Mechanistically, we found an inverse correlation between PR-LncRNA expression and SOX1, SOX2 and SOX9 stem cell factors in human glioma biopsies and in glioma cells in vitro. Moreover, knock-down of SOX activity abolished the effect of PR-LncRNA silencing in glioma cell activity. In conclusion, our results demonstrate that the expression and function of PR-LncRNAs are significantly altered in gliomagenesis and that their activity is mediated by SOX factors. These results may provide important insights into the mechanisms responsible for glioblastoma pathogenesis. 

Retracted: No

PubPeer comments:
  Any comment on that image duplication?? thank you ,
Cell Damage in Light Chain Amyloidosis: FIBRIL INTERNALIZATION, TOXICITY AND CELL-MEDIATED SEEDING
Authors: Marta Marin-Argany
Laura R Elsbernd
Pinaki Misra
Angela Williams
Marina Ramirez-Alvarado
Megan McClure
Kyle G Howell
Yi Lin
Jonathan S Wall
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: amyloid; apoptosis; cardiomyocytes; cell internalization; endocytosis
Affiliations: From the Departments of Biochemistry and Molecular Biology and., the Division of Hematology, the Human Cell Therapy Lab, Division of Transfusion Medicine., the Departments of Medicine and Radiology, the University of Tennessee Graduate School of Medicine, Knoxville, Tennessee 37920., the Department of Microscopy and the Cell Analysis Core Facility, and., Immunology., the Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 and., From the Departments of Biochemistry and Molecular Biology and Immunology, .

Abstract:  Light chain (AL) amyloidosis is an incurable human disease characterized by the misfolding, aggregation, and systemic deposition of amyloid composed of immunoglobulin light chains (LC). This work describes our studies on potential mechanisms of AL cytotoxicity. We have studied the internalization of AL soluble proteins and amyloid fibrils into human AC16 cardiomyocytes by using real time live cell image analysis. Our results show how external amyloid aggregates rapidly surround the cells and act as a recruitment point for soluble protein, triggering the amyloid fibril elongation. Soluble protein and external aggregates are internalized into AC16 cells via macropinocytosis. AL amyloid fibrils are shown to be highly cytotoxic at low concentrations. Additionally, caspase assays revealed soluble protein induces apoptosis, demonstrating different cytotoxic mechanisms between soluble protein and amyloid aggregates. This study emphasizes the complex immunoglobulin light chain-cell interactions that result in fibril internalization, protein recruitment, and cytotoxicity that may occur in AL amyloidosis. 

Retracted: No

PubPeer comments:
 The cell morphology of different groups in blue boxes appear to look similar in Fig 1A and 1D.  , 
 Thanks for your comment. It is possible is the same experiment and same time point. Figure 1D is showing the disappearance of fluorescence as a function of time, suggesting that the protein is exocytosed. Figure 1A is showing the uptake with one wash before taking the picture. The figure was constructed by taking pictures of separate wells for the separate time points because we required to wash the well with media prior to taking the picture. IF we didn t wash the well, the fluorescence of the excess protein in the media affected the images. ,
IL‚Ä?3 enhances glioma cell migration and invasion by upregulation of MMP2 and MMP9 via the ST2-NF-Œ∫B pathway
Authors: Yu-Jin Yan
Jin-Jun Yu
Xin-Dong Wang
Yong Li
Jian-Fei Zhang
Peng Wang
Min-Wu Guan
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: IL-33; ST2 receptor; glioma; invasion; migration
Affiliations: Department of Neurosurgery, Affiliated Hospital of School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China., Department of Neurosurgery, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu 214002, P.R. China.

Abstract:  As an important member of the interleukin (IL)-1 family, IL‚Ä?3 plays a significant role in tumor progression. To explore this, we previously analyzed the association between IL‚Ä?3 expression and the prognosis of patients with glioma. However, the function of the IL‚Ä?3/ST2 axis in glioma remained unclear. In the present study, immunofluorescent staining results revealed that the expression levels of IL‚Ä?3 and ST2 receptor in glioma tissues were higher than those in normal brain tissues. Invasion and migration assays demonstrated that IL‚Ä?3 significantly increased glioma cell invasion and migration in vitro. Furthermore, knockdown of ST2 by siRNA attenuated the IL‚Ä?3-induced increase in invasion and migration. In addition, ELISA results revealed that IL‚Ä?3 upregulated the expression of matrix metalloproteinase (MMP)2 and MMP9. Western blot analysis results indicated that IL‚Ä?3 stimulation increased the phosphorylation of nuclear factor-Œ∫B (NF-Œ∫B) in a time- and dose-dependent manner. Moreover, silencing of the NF-Œ∫B pathway by BAY 11‚Ä?082 resulted in the inhibition of IL‚Ä?3-induced invasion and migration, as well as the downregulation of MMP2 and MMP9 production. These findings indicate that IL‚Ä?3 may be involved in the process of glioma cell invasion and migration by upregulating MMP2 and MMP9 via the ST2-NF-Œ∫B signaling pathway. Thus, IL‚Ä?3 may be a novel therapeutic target for glioma. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have some images which overlap. The corresponding authoru2019s email address is numerical. Both of these issues are sometimes seen in papermill or outsourced papers. ***  ,
Cationic ligand appended nanoconstructs: a prospective strategy for brain targeting
Authors: Sanyog Jain
Himanshu Agrawal
Abhinav Agarwal
Govind P Agrawal
Shailja Tiwari
Journal: International journal of pharmaceutics (2011)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Solid lipid nanoparticles; Blood brain barrier; Doxorubicin; Cationic bovine serum albumin; Cellular uptake
Affiliations: Pharmaceutics Research Lab, Department of Pharmaceutical Sciences, Dr. H.S Gour University, Sagar 470003, MP, India.

Abstract:  The objective of present research was to evaluate the potential of engineered solid lipid nanoparticles (SLNs) as vectors to bypass the blood brain barrier. Anti-cancer agent, doxorubicin (DOX) loaded SLNs were prepared and conjugated with cationic bovine serum albumin (CBSA). The formation of CBSA tethered and plain SLNs were characterized by FTIR, NMR, and TEM analyses. Physicochemical parameters such as particle size/polydispersity index and zeta-potential were also determined. Cellular uptake studies on HNGC-1 cell lines depicted almost six times enhanced uptake of ligand conjugated SLNs as compared to plain DOX solution. Furthermore, CBSA conjugated formulation was more cytotoxic as compared to free drug or unconjugated SLNs. Transendothelial studies showed maximum transcytosis ability of CBSA conjugated SLNs across brain capillary endothelial cells. In vivo pharmacokinetic parameters and biodistribution pattern demonstrated efficiency of the system for spatial and temporal delivery of DOX to brain tissues. Lastly, hematological, nephrotoxic as well as hepatotoxic data suggested CBSA conjugated formulations to be less immunogenic compared to plain formulations. 

Retracted: No

PubPeer comments:
  Fig. 11. Fluorescent photomicrographs of DOX uptake in the HNGC 1 cells from Plain DOX, SLN-DOX, CBSA-SLN-DOX and CBSA+ CBSA-SLN-DOX. Could the authors comment on the 180-degree symmetry of the random pairs of cell in (C) and (D)?  Also unexpectedly similar to the cell clusters seen in Fig (13) of [Agarwal et al (2011)] ,  Fluorescent microscopy of qualitative uptake in the HNGC1 Tumor Cell Lines (A) Plain FITC; (B) FITC labeled plain SLNs and (C) FITC labeled CBSA conjugated SLNs.  , 
  Fig. 7. TEM photomicrographs of (a) SLN-DOX  My confidence in the veridicality of an image is not increased by repeated fragments. , 
 #2 Updated.  ,
Retraction Note to: Potential Start Codon Targeted (SCoT) and Interretrotransposon Amplified Polymorphism (IRAP) Markers for Evaluation of Genetic Diversity and Conservation of Wild Pistacia Species Population
Authors: Karim Sorkheh
Sezai Ercisli
Nazanin Amirbakhtiar
Journal: Biochemical Genetics (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Retracted; Publisher; Editor-in-Chief; Attribution; Acknowledged
Affiliations: Department of Agronomy and Plant Breeding, Faculty of Agriculture, Shahid Chamran University of Ahvaz, P.O.Box 61355/144, Ahvaz, Iran. ., Department of seed and Plant Improvement, Agricultural & Natural Resources Research and Education Center, P.O.Box 61333-3341, Ahvaz, Iran., Department of Horticulture, Agricultural Faculty, Ataturk University, 25240, Erzurum, Turkey.

Abstract:  "This article has been retracted by the Publisher in agreement with the Editor-in-Chief, because it contains portions of writings on the same topic already published and without sufficient attribution to these earlier works being given. The principal authors of the paper acknowledged that text from background sources was mistakenly used in this article without proper reference to the original source. Upon investigation carried out according to the Committee on Publication Ethics guidelines, it has been found that the authors have duplicated or rephrased parts from other articles of which the main sources. 

Retracted: No

PubPeer comments:
 Figure 4A: UBP69 day 0, 3 4 more similar than would be expected.u2029In addition, unusual splice line on Myogenin day 2 band  , 
  , 
 #1 I retired 5 years ago and no longer have original raw data. However, I do believe that the top panel of Fig. 4A was from the same blot and the lanes 1, 3 4 are different. For the Myogenin lane, I have no idea what  slice line meant for. #2 Photos typically represent the fields that were randomly chosen from culture plates. Unfortunately, however, two photos (top bottom) for UBPdeltaN appear to be taken from largely overlapping fields. I regret this careless mistake. However, please let me mention that this mistake was not intentional as there should have been so many available fields that we could choose even from a single plate. , 
 Fig. 4A, the lanes 0, 3 and 4 for UBP69 are strikingly similar to each other. Please see a black dot in the middle for instance. It appears that a same blot was exposed at three different exposures. , 
 I agree 4A lanes 0 and 3 are more likely the same than not, as even internal features appear to match; lane 4 appears similar but resized. *** False color  , 
 Figure 2A appears to have similar issues, internal features again appear to match. *** False color  *** Inverse  *** Original  ,
Receptor tyrosine kinase ErbB2 translocates into mitochondria and regulates cellular metabolism
Authors: Jianrong Lu
Ming Tan
Hong Yi
Zixing Liu
Glenn L Wilson
Susan P LeDoux
Shruti Desai
Oystein Fodstad
Windy Dean-Colomb
Hao Liu
Elizabeth R Wright
Yuhua Zhao
Lewis K Pannell
Laurie B Owen
Yan Ding
Journal: Nature Communications (2012)
Discipline: Multidisciplinary
Keywords: ErbB2; mitochondria; mtHSP70; respiratory functions; glycolysis
Affiliations: Mitchell Cancer Institute, University of South Alabama, MCI 3016, 1600 Spring Hill Avenue, Mobile, Alabama 36604, USA.

Abstract:  It is well known that ErbB2, a receptor tyrosine kinase, localizes to the plasma membrane. Here we describe a novel observation that ErbB2 also localizes in mitochondria of cancer cells and patient samples. We found that ErbB2 translocates into mitochondria through association with mtHSP70. Additionally, mitochondrial ErbB2 (mtErbB2) negatively regulates mitochondrial respiratory functions. Oxygen consumption and activities of complexes of the mitochondrial electron transport chain were decreased in mtErbB2-overexpressing cells. Mitochondrial membrane potential and cellular ATP levels were also decreased. In contrast, mtErbB2 enhanced cellular glycolysis. The translocation of ErbB2 and its impact on mitochondrial function are kinase dependent. Interestingly, cancer cells with higher levels of mtErbB2 were more resistant to the ErbB2-targeting antibody trastuzumab. Our study provides a novel perspective on the metabolic regulatory function of ErbB2 and reveals that mtErbB2 has an important role in the regulation of cellular metabolism and cancer cell resistance to therapeutics. 

Retracted: No

PubPeer comments:
 Figure 1 and 2. * Red boxes: Lanes 2-4 in the ErbB2 panel of Figure 1A look similar to one of the IB:mtHSP70 panels in Figure 2C. * Blue boxes: Lanes 6-8 in the ErbB2 panel of Figure 1A look similar to one of the IB:ErbB2 panels in Figure 2C, albeit rotated 180 degrees.  , 
 Figure 4A. Some panels appear to show an overlap.  , 
 Figure 6. * Orange boxes: Two of the a-Tubulin panels in Figure 6A representing different cells appear to look similar. * Green arrow: One of a-Tubulin lanes in Figure 6C appears to have a smoother background than the adjacent lanes.  ,
Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer
Authors: William Tong
Zvi Fuks
Luis Campodonico
H Rosie Xing
Carlos Cordon-Cardo
Richard Kolesnick
Xinzhu Deng
Journal: Nature Medicine (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: KSR1; antisense oligonucleotides; Ras-dependent malignancies; pancreatic cancer; xenografts
Affiliations: Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.

Abstract:  Inhibition of the kinase suppressor of ras-1 (KSR1) gene by continuous infusion of phosphorothioate antisense oligonucleotides (ODNs) prevented growth of K-Ras-dependent human PANC-1 pancreatic and A549 non-small-cell lung carcinoma xenografts in nude mice, effected regression of established PANC-1 tumors and inhibited A549 lung metastases, all without apparent toxicity. These studies suggest KSR1 antisense ODNs as a treatment for Ras-dependent human malignancies, in particular pancreatic cancer, which lacks effective curative therapy. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
null, 
null, 
null, 
null, 
null, 
 Identified by another reader. These were addressed by the corrigendum in which the authors published results in a repeated experiment. ***  , 
 https: retractionwatch.com 2013 11 27 cancer-researchers-retract-two-papers-in-the-jbc https: retractionwatch.com 2016 02 08 2014-ori-finding-results-in-retraction-of-cancer-paper-with-manipulated-images https: retractionwatch.com 2014 12 14 ori-sanctions-former-university-chicago-ucsf-scientists-faking-findings ,
Activated cofilin exacerbates tau pathology by impairing tau-mediated microtubule dynamics
Authors: Ksenia Yrigoin
Stephen B Liggett
Xinming Wang
Xingyu Zhao
Cenxiao C Fang
Teresa Kee
Courtney Penn
Jung-A A Woo
David E Kang
Patrick LePochat
Tian Liu
Sara Cazzaro
Journal: Communications Biology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Alzheimer's disease; neurodegenerative disorder; AŒ≤; tau; MAPT
Affiliations: 1USF Health Byrd Alzheimer's Institute, University of South Florida, Morsani College of Medicine, Tampa, FL 33613 USA.

Abstract:  Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. While the accumulation of AŒ≤ is pivotal to the etiology of AD, both the microtubule-associated protein tau (MAPT) and the F-actin severing protein cofilin are necessary for the deleterious effects of AŒ≤. However, the molecular link between tau and cofilin remains unclear. In this study, we found that cofilin competes with tau for direct microtubule binding in vitro, in cells, and in vivo, which inhibits tau-induced microtubule assembly. Genetic reduction of cofilin mitigates tauopathy and synaptic defects in Tau-P301S mice and movement deficits in tau transgenic C. elegans. The pathogenic effects of cofilin are selectively mediated by activated cofilin, as active but not inactive cofilin selectively interacts with tubulin, destabilizes microtubules, and promotes tauopathy. These results therefore indicate that activated cofilin plays an essential intermediary role in neurotoxic signaling that promotes tauopathy. 

Retracted: No

PubPeer comments:
 There appears to be a repeated band in Figure 1g. ***  , 
 Could the authors review the similarities of the two images marked in red in Figure 4a? Would this be expected in different animal groups? ***  , 
 #1 I came across the original data provided in the supplemental files. I was able to extract the uncropped images from the PDF file and other than the brightness or exposure, these appear to be the same blots. ***  ,
MicroRNA-615-5p targets insulin-like growth factor 2 and exerts tumor-suppressing functions in human esophageal squamous cell carcinoma
Authors: Shang-Nong Wu
Jing-Fang Zhou
Cheng-Cheng Gao
Bingyin Yang
Rui Xie
Xiao-Zhong Yang
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: miR-615-5p; esophageal squamous cell carcinoma; expression pattern; clinical significance; functional roles
Affiliations: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China

Abstract:  To investigate the expression pattern, clinical significance and functional roles of microRNA (miR)-615-5p in human esophageal squamous cell carcinoma (ESCC), , quantitative real-time PCR was performed to detect expression levels of miR‚Ä?15‚Ä?p in ESCC tissues and cell lines. Associations between miR‚Ä?15‚Ä?p expression and various clinicopathological features of ESCC patients were also statistically evaluated. The candidate targets of miR‚Ä?15‚Ä?p were identified by integrating bioinformatics miRNA target prediction, western blot analysis and luciferase reporter assay. Moreover, the functions of miR‚Ä?15‚Ä?p in ESCC cell migration and invasion were determined using the transfection of miRNA mimics, or co-transfected with miRNA mimics and the expression vector of its target gene. As a result, miR‚Ä?15‚Ä?p expression in ESCC tissues and cells were markedly lower than those in non-cancerous esophageal mucosa and human normal esophageal cells, respectively (both P&lt;0.001). miR‚Ä?15‚Ä?p downregulation was significantly associated with advanced tumor-node-metastasis stage, positive lymph node metastasis and moderate-poor differentiation. Functionally, the re-expression of miR‚Ä?15‚Ä?p suppressed the invasion and migration of ESCC cells in vitro. Interestingly, insulin-like growth factor 2 (IGF2) was identified as a direct target gene of miR‚Ä?15‚Ä?p, and the inhibitory effects of miR‚Ä?15‚Ä?p in ESCC cell motility were reversed by the restoration of IGF2 expression. In conclusion, miR‚Ä?15‚Ä?p downregulation may be an underlying molecular mechanism of development and progression of ESCC, and may function as a potential therapeutic target of this malignancy. Also, we illustrate that the miR‚Ä?15‚Ä?p/IGF2 axis may bring important contributions to cell motility of human ESCC. 

Retracted: No

PubPeer comments:
 Figure 2B C. Some cells appear to be visible multiple times within the same photo, as marked here with boxes of the same color and shape.  , 
 Figure 5AB. Some cells appear to be visible multiple times within the same photo, as marked here with boxes of the same color and shape.  , 
 Figure 5CD. Some cells appear to be visible multiple times within the same photo, as marked here with boxes of the same color and shape.  ,
Beta-catenin levels influence rapid mechanical responses in osteoblasts
Authors: Janet Rubin
Natasha Case
Ted S Gross
Meiyun Ma
Buer Sen
Zhihui Xie
Journal: Journal of Biological Chemistry (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Mechanical loading; bone; anabolic; anticatabolic; Wnt/beta-catenin signaling
Affiliations: Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA. 

Abstract:  Mechanical loading of bone initiates an anabolic, anticatabolic pattern of response, yet the molecular events involved in mechanical signal transduction are not well understood. Wnt/beta-catenin signaling has been recognized in promoting bone anabolism, and application of strain has been shown to induce beta-catenin activation. In this work, we have used a preosteoblastic cell line to study the effects of dynamic mechanical strain on beta-catenin signaling. We found that mechanical strain caused a rapid, transient accumulation of active beta-catenin in the cytoplasm and its translocation to the nucleus. This was followed by up-regulation of the Wnt/beta-catenin target genes Wisp1 and Cox2, with peak responses at 4 and 1 h of strain, respectively. The increase of beta-catenin was temporally related to the activation of Akt and subsequent inactivation of GSK3beta, and caveolin-1 was not required for these molecular events. Application of Dkk-1, which disrupts canonical Wnt/LRP5 signaling, did not block strain-induced nuclear translocation of beta-catenin or up-regulation of Wisp1 and Cox2 expression. Conditions that increased basal beta-catenin levels, such as lithium chloride treatment or repression of caveolin-1 expression, were shown to enhance the effects of strain. In summary, mechanical strain activates Akt and inactivates GSK3beta to allow beta-catenin translocation, and Wnt signaling through LRP5 is not required for these strain-mediated responses. Thus, beta-catenin serves as both a modulator and effector of mechanical signals in bone cells. 

Retracted: No

PubPeer comments:
  ,
Injectable hydrogels of newly designed brush biopolymers as sustained drug-delivery vehicle for melanoma treatment
Authors: Akhand Pratap Singh
Aparna Shukla
Pralay Maiti
Journal: Signal Transduction and Targeted Therapy (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: biocompatible copolymers; drug release; polyurethane graft; hydrogel; controlled release
Affiliations: School of Materials Science and Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India., School of Materials Science and Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India. .

Abstract:  Novel biocompatible and brush copolymers have been developed for cancer treatment using its controlled drug-release potential. Polyurethane graft on linear dextrin has been synthesized to control the hydrophilic-hydrophobic balance for regulated drug delivery. The properties of the graft copolymers have been tuned through graft density. The prepared grafts are thermally stable and mechanically strong. An injectable hydrogel has been developed by embedding the drug-loaded brush copolymers in methyl cellulose to better control the release for a prolonged period, importantly by keeping the drug release at a constant rate. Cellular studies indicate the biocompatible nature of the brush copolymers whose controlled and slow release of drug exhibit significant cytotoxic effects on cancer cells. Endocytosis of drug tagged contrast agent indicates greater transport of biologically active material inside cell as observed through cellular uptake studies. In vivo studies on melanoma mice exhibit the real efficacy of the controlled drug release from the injectable hydrogel with significant melanoma suppression without any side effects as opposed to severe toxic effects observed in conventional chemotherapy. Special application method of drug-loaded hydrogel just beneath the tumor makes this system incredibly effective through confinement. Thus, brush copolymer injectable hydrogel is a promising vehicle for control release of drug for cancer treatment in future. 

Retracted: No

PubPeer comments:
 This SSRN preprint appears to be computer-generated with [SCIgen] .  ---  ---  --- This comment was written by Guillaume Cabanac and Cyril Labbu00e9. Contact: [SeekAndBlastn-Operators@univ-grenoble-alpes.fr](mailto:SeekAndBlastn-Operators@univ-grenoble-alpes.fr). ,
Heat shock protein-90alpha (Hsp90Œ±) stabilizes hypoxia-inducible factor-1Œ± (HIF-1Œ±) in support of spermatogenesis and tumorigenesis
Authors: Mei Chen
Cheng Chang
Michelle Hao
David T Woodley
Axel H Sch√∂nthal
Xin Tang
Wei Li
Journal: Cancer Gene Therapy (2021)
Discipline: CLINICAL MEDICINE
Keywords: Hypoxia-inducible factor-1 (HIF-1); spermatogenesis; tumorigenesis; small molecule inhibitors; Hsp90Œ±
Affiliations: Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Center, Los Angeles, CA, USA., Department of Molecular Microbiology & Immunology, University of Southern California Keck Medical Center, Los Angeles, CA, USA., Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Center, Los Angeles, CA, USA. .

Abstract:  Hypoxia-inducible factor-1 (HIF-1), a master transcriptional factor for protecting cells from hypoxia, plays a critical role in spermatogenesis and tumorigenesis. For the past two decades, numerous small molecule inhibitors that block mRNA synthesis, protein translation, or DNA binding of HIF-1Œ± have entered clinical trials. To date, few have advanced to FDA approval for clinical applications due to limited efficacy at their toxicity-tolerable dosages. New windows for developing effective and safe therapeutics require better understanding of the specific mechanism of action. The finding that a chaperone-defective mutant heat shock protein-90-alpha (Hsp90Œ±) blocks spermatogenesis, a known hypoxia-driven process in mouse testis prompted us to focus on the role of Hsp90Œ± in HIF-1Œ±. Here we demonstrate that Hsp90Œ± gene knockout causes a dramatic reduction of the high steady-state level of HIF-1Œ± in the testis, blocking sperm production and causing infertility of the mice. In HIF-1Œ±-dependent tumor cells, we found that Hsp90Œ± forms protein complexes with hypoxia-elevated HIF-1Œ± and Hsp90Œ± knockout prevents hypoxia-induced HIF-1Œ± accumulation. In contrast, downregulation of Hsp90Œ≤ had little effect on hypoxia-induced accumulation of HIF-1Œ±. Instead, Hsp90Œ≤ protects signaling molecules responsible for cellular homeostasis from assault by 17-AAG (17-N-allylamino-17-demethoxygeldanamycin), a general ATPase inhibitor of both Hsp90Œ± and Hsp90Œ≤. Since targeting Hsp90Œ≤ gene is lethal in both cultured cells and in mice, our new finding explains the toxicity of the previous inhibitor trials and identifies the specific binding of Hsp90Œ± to HIF-1Œ± as a new therapeutic window for developing safer and more effective treatment of male infertility and cancer. 

Retracted: No

PubPeer comments:
 In Figure 4B, the Akt2 and Aktin Western immunoblots are based on the same blot. In Figure 6A,B, the p-Erk1 2 Western immunoblots have 7 lanes, the other blots have only 6.  , 
 This article was corrected on March 2021: https: www.nature.com articles s41417-021-00330-8 ,
CIPK11-Dependent Phosphorylation Modulates FIT Activity to Promote Arabidopsis Iron Acquisition in Response to Calcium Signaling
Authors: Regina Gratz
Petra Bauer
Ksenia Trofimov
Philipp K√∂ster
Sibylle Arendt
Hans-J√∂rg Mai
J√∂rg Kudla
Rumen Ivanov
Leonie Steinhorst
Prabha Manishankar
Uwe Karst
Tzvetina Brumbarova
Johannes Meiser
Inga Mohr
Michael Holtkamp
Maria Drerup
Journal: Developmental Cell (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CBL; CIPK11; FIT; bHLH039; iron deficiency
Affiliations: Institute of Botany, Heinrich-Heine University, D√ºsseldorf 40225, Germany., Institute of Plant Biology and Biotechnology, University of M√ºnster, M√ºnster 48149, Germany., Institute of Inorganic and Analytical Chemistry, University of M√ºnster, M√ºnster 48149, Germany., Institute of Botany, Heinrich-Heine University, D√ºsseldorf 40225, Germany; Cluster of Excellence on Plant Sciences, Heinrich-Heine University, D√ºsseldorf 40225, Germany. Electronic address: ., Institute of Botany, Heinrich-Heine University, D√ºsseldorf 40225, Germany. Electronic address: .

Abstract:  Nutrient acquisition is entangled with growth and stress in sessile organisms. The bHLH transcription factor FIT is a key regulator of Arabidopsis iron (Fe) acquisition and post-translationally activated upon low Fe. We identified CBL-INTERACTING PROTEIN KINASE CIPK11 as a FIT interactor. Cytosolic Ca2+ concentration and CIPK11 expression are induced by Fe deficiency. cipk11 mutant plants display compromised root Fe mobilization and seed Fe content. Fe uptake is dependent on CBL1/CBL9. CIPK11 phosphorylates FIT at Ser272, and mutation of this target site modulates FIT nuclear accumulation, homo-dimerization, interaction with bHLH039, and transcriptional activity and affects the plant's Fe-uptake ability. We propose that Ca2+-triggered CBL1/9-mediated activation of CIPK11 and subsequent phosphorylation of FIT shifts inactive into active FIT, allowing regulatory protein interactions in the nucleus. This biochemical link between Fe deficiency and the cellular Ca2+ decoding machinery represents an environment-sensing mechanism to adjust nutrient uptake. 

Retracted: No

PubPeer comments:
 Figure 1A, much more similar than expected (yellow boxes). Red boxes are from original figure. Could the authors please check?  , 
 The panels for CIPK11 and CIPK13 (both positive growth controls) are indeed identical in the above figure. We are sorry that during the assembly for final figure preparation, there was an incorrect assembly. Please find here the corrected figure for CIPK13, is now exchanged with the correct data. , 
 #2 Thank you for your reply. Actually, I cannot find  here the corrected figure. Moreover, are you planning to contact the journal for a correction? , 
 The journal has been contacted and has received the corrected figure. If the figure does not display here, there was a problem with the upload. , 
  , 
 #4 #5 Thank you for taking care of correcting the article and keeping literature record correct. ,
C-reactive protein induces expression of matrix metalloproteinase-9: a possible link between inflammation and plaque rupture
Authors: Francesco Loffredo
Gianluca Petrillo
Giovanni Cimmino
Emanuela Falcinelli
Massimo Ragni
Paolo Gresele
Massimo Chiariello
Plinio Cirillo
Paolo Golino
Journal: International journal of cardiology (2013)
Discipline: CLINICAL MEDICINE
Keywords: Acute coronary syndromes; CRP; MMP-9.
Affiliations: Department of Cardiothoracic and Respiratory Sciences, Division of Cardiology, Second University of Naples, Naples, Italy.

Abstract:  Background: Matrix metalloproteases (MMPs) have been implicated in the pathogenesis of acute coronary syndromes (ACS). However, little is known about the mechanisms responsible for MMP expression in ACS. C-reactive protein (CRP) not only is an independent risk factor for cardiovascular events, but also may exert direct pro-atherosclerotic effects. Therefore, we aimed at determining whether CRP might induce MMP-9 in two different experimental conditions: 1) smooth muscle cells (SMCs) in vitro, and 2) patients with ACS. Methods and results: Effects of increasing concentrations of CRP on MMP-9 expression were evaluated in vitro in human SMCs. TIMP-1 protein expression, the selective inhibitor of MMP-9, was also evaluated. CRP dose-dependently induced MMP-9 expression in SMCs by promoting MMP-mRNA transcription, as well as MMP-9 secretion. In contrast, no differences were found for TIMP-1 protein expression. In vivo, MMP-9 and CRP levels were measured in blood samples obtained from the aorta (Ao) and the coronary sinus (Cs) of patients with normal coronary arteries (controls, n=21), stable angina (n=24), and ACS (n=30). Both MMP-9 and CRP plasma levels were significantly increased across the coronary circulation only in patients with ACS. Interestingly, a significant correlation between MMP-9 and CRP plasma levels was found. Conclusions: CRP induced MMP-9 expression and activity in human SMCs in culture; patients presenting with ACS have increased transcoronary plasma levels of MMP-9 and CRP with a significant correlation between these two markers. This may explain the heightened risk of coronary events in subjects with elevated levels of CRP. 

Retracted: No

PubPeer comments:
 Figure 5A and B. Several vertical splicings. Additionally could the authors check for images in the squares and provide the originals uncropped scans.  ,
Chronic alcohol ingestion increases mortality and organ injury in a murine model of septic peritonitis
Authors: Craig M Coopersmith
Christina J Ward
Elizabeth R Lusczek
Maylene E Wagener
Elise Breed
Zhe Liang
Mandy L Ford
Eileen M Burd
Alton B Farris
Benyam P Yoseph
Michael Koval
Christian E Overgaard
Daniel R Lexcen
Greg J Beilman
David M Guidot
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: alcohol use disorders; sepsis; mice; mortality; gut integrity
Affiliations: Department of Surgery and Emory Center for Critical Care, Emory University School of Medicine, Atlanta, Georgia, USA.

Abstract:  Background: Patients admitted to the intensive care unit with alcohol use disorders have increased morbidity and mortality. The purpose of this study was to determine how chronic alcohol ingestion alters the host response to sepsis in mice. Methods: Mice were randomized to receive either alcohol or water for 12 weeks and then subjected to cecal ligation and puncture. Mice were sacrificed 24 hours post-operatively or followed seven days for survival. Results: Septic alcohol-fed mice had a significantly higher mortality than septic water-fed mice (74% vs. 41%, p = 0.01). This was associated with worsened gut integrity in alcohol-fed mice with elevated intestinal epithelial apoptosis, decreased crypt proliferation and shortened villus length. Further, alcohol-fed mice had higher intestinal permeability with decreased ZO-1 and occludin protein expression in the intestinal tight junction. The frequency of splenic and bone marrow CD4+ T cells was similar between groups; however, splenic CD4+ T cells in septic alcohol-fed mice had a marked increase in both TNF and IFN-Œ≥ production following ex vivo stimulation. Neither the frequency nor function of CD8+ T cells differed between alcohol-fed and water-fed septic mice. NK cells were decreased in both the spleen and bone marrow of alcohol-fed septic mice. Pulmonary myeloperoxidase levels and BAL levels of G-CSF and TFG-Œ≤ were higher in alcohol-fed mice. Pancreatic metabolomics demonstrated increased acetate, adenosine, xanthine, acetoacetate, 3-hydroxybutyrate and betaine in alcohol-fed mice and decreased cytidine, uracil, fumarate, creatine phosphate, creatine, and choline. Serum and peritoneal cytokines were generally similar between alcohol-fed and water-fed mice, and there were no differences in bacteremia, lung wet to dry weight, or pulmonary, liver or splenic histology. Conclusions: When subjected to the same septic insult, mice with chronic alcohol ingestion have increased mortality. Alterations in intestinal integrity, the host immune response, and pancreatic metabolomics may help explain this differential response. 

Retracted: No

PubPeer comments:
 image duplication, rotated  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. ,
Resveratrol causes WAF-1/p21-mediated G(1)-phase arrest of cell cycle and induction of apoptosis in human epidermoid carcinoma A431 cells
Authors: H Mukhtar
V M Adhami
F Afaq
N Ahmad
D K Feyes
Journal: Clinical Cancer Research (2001)
Discipline: CLINICAL MEDICINE
Keywords: Resveratrol; cancer chemopreventive effects; cell cycle; apoptosis; cyclin-dependent kinase
Affiliations: Department of Dermatology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA. 

Abstract:  Resveratrol (trans-3,4',5,-trihydroxystilbene), a phytoalexin found in grapes, nuts, fruits, and red wine, is a potent antioxidant with cancer-preventive properties. The mechanism by which resveratrol imparts cancer chemopreventive effects is not clearly defined. Here, we demonstrate that resveratrol, via modulations in cyclin-dependent kinase (cdk) inhibitor-cyclin-cdk machinery, results in a G(1)-phase arrest of the cell cycle followed by apoptosis of human epidermoid carcinoma (A431) cells. Resveratrol treatment (1-50 microM for 24 h) of A431 cells resulted in a dose-dependent (a) inhibition of cell growth as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, (b) G(1)-phase arrest of the cell cycle as shown by DNA cell cycle analysis, and (c) induction of apoptosis as assessed by ELISA. The immunoblot analysis revealed that resveratrol treatment causes a dose- and time-dependent (a) induction of WAF1/p21; (b) decrease in the protein expressions of cyclin D1, cyclin D2, and cyclin E; and (c) decrease in the protein expressions of cdk2, cdk4, and cdk6. Resveratrol treatment was also found to result in a dose- and time-dependent decrease in kinase activities associated with all of the cdks examined. Taken together, our study suggests that resveratrol treatment of the cells causes an induction of WAF1/p21 that inhibits cyclin D1/D2-cdk6, cyclin D1/D2-cdk4, and cyclin E-cdk2 complexes, thereby imposing an artificial checkpoint at the G(1)--&gt;S transition of the cell cycle. This series of events results in a G(1)-phase arrest of the cell cycle, which is an irreversible process that ultimately results in the apoptotic death of cancer cells. To our knowledge, this is the first systematic study showing the involvement of each component of cdk inhibitor-cyclin-cdk machinery during cell cycle arrest and apoptosis of cancer cells by resveratrol. 

Retracted: No

PubPeer comments:
 Figure 3A. Much more similar than expected. https: imgur.com esGMs4k Figure 4B. Much more similar than expected. https: imgur.com VSVlI4n ,
Ets1 is an effector of the transforming growth factor beta (TGF-beta ) signaling pathway and an antagonist of the profibrotic effects of TGF-beta
Authors: Dennis K Watson
Maria Trojanowska
Joanna Czuwara-Ladykowska
Victor I Sementchenko
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Extracellular matrix; Ets factors; metalloproteinases; TGF-beta; collagen type I
Affiliations: Department of Medicine, Division of Rheumatology and Immunology and the Hollings Cancer Center, Laboratory of Cancer Genomics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

Abstract:  Extracellular matrix (ECM) production and turnover are tightly controlled under normal physiological conditions. Ets factors regulate matrix turnover by activating transcription of several metalloproteinases (MMPs) and are frequently overexpressed in aggressive tumors and arthritis. Because of the prominent role of transforming growth factor beta (TGF-beta) in ECM synthesis, this study was undertaken to determine the possible interactions between Ets1 and the TGF-beta pathway. Experiments using adenoviral delivery of Ets1 in human fibroblasts have established that Ets1 strongly suppresses TGF-beta induction of collagen type I and other matrix-related genes and reverses TGF-beta-dependent inhibition of MMP-1. Subsequent experiments utilizing COL1A2 promoter demonstrated that Ets1 in the presence of TGF-beta signaling interferes with the stimulatory role of p300. To gain further insight into the mechanism of Ets1 inhibition of the TGF-beta signaling, the protein levels and post-translational modifications of Ets1 after TGF-beta treatment were analyzed. The level of total Ets1 protein was not affected after 24 h of TGF-beta stimulation. Moreover, TGF-beta did not affect either serine or threonine phosphorylation levels of Ets1. However, TGF-beta induced rapid and prolonged lysine acetylation of Ets1. In addition, analyses of endogenous p300.Ets1 complexes revealed that acetylated Ets1 is preferentially associated with the p300/CBP complexes. TGF-beta treatment leads to dissociation of Ets1 from the CBP/p300 complexes. Together, these findings suggest that elevated expression of Ets1 in fibroblasts fundamentally alters their responses to TGF-beta in favor of matrix degradation and away from matrix deposition as exemplified by arthritis and cancer. 

Retracted: No

PubPeer comments:
 **The bands of Smad2 3 (red boxes) in Figure 4D were reused in Figure 5B.**  ,