PReD-Bench/PRed-Bench huggingface dataset:
The K-Ras 4A isoform promotes apoptosis but does not affect either lifespan or spontaneous tumor incidence in aging mice
Authors: Martin L Hooper
Paul S Devenney
Sarah J Plowman
Rachel L Berry
Ann-Marie Ritchie
David J Harrison
David G Brownstein
Feijun Luo
Charles E Patek
Lorraine Rose
Mark J Arends
Journal: Experimental Cell Research (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ras proteins; K-ras4A; K-ras4B; splice variants; cell function
Affiliations: Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.

Abstract:  Ras proteins function as molecular switches in signal transduction pathways, and, here, we examined the effects of the K-ras4A and 4B splice variants on cell function by comparing wild-type embryonic stem (ES) cells with K-ras(tmDelta4A/tmDelta4A) (exon 4A knock-out) ES cells which express K-ras4B only and K-ras(-/-) (exons 1-3 knock-out) ES cells which express neither splice variant, and intestinal epithelium from wild-type and K-ras(tmDelta4A/tmDelta4A) mice. RT-qPCR analysis found that K-ras4B expression was reduced in K-ras(tmDelta4A/tmDelta4A) ES cells but unaffected in small intestine. K-Ras deficiency did not affect ES cell growth, and K-Ras4A deficiency did not affect intestinal epithelial proliferation. K-ras(tmDelta4A/tmDelta4A) and K-ras(-/-) ES cells showed a reduced capacity for differentiation following LIF withdrawal, and K-ras(-/-) cells were least differentiated. K-Ras4A deficiency inhibited etoposide-induced apoptosis in ES cells and intestinal epithelial cells. However, K-ras(tmDelta4A/tmDelta4A) ES cells were more resistant to etoposide-induced apoptosis than K-ras(-/-) cells. The results indicate that (1) K-Ras4A promotes apoptosis while K-Ras4B inhibits it, and (2) K-Ras4B, and possibly K-Ras4A, promotes differentiation. The findings raise the possibility that alteration of the K-Ras4A/4B isoform ratio modulates tumorigenesis by differentially affecting stem cell survival and/or differentiation. However, K-Ras4A deficiency did not affect life expectancy or spontaneous overall tumor incidence in aging mice. 

Retracted: No

PubPeer comments:
 Figure 1B. Much more similar than expected. ![file] ,
ROCK1, a novel target of miR-145, promotes glioma cell invasion
Authors: Renjun Peng
Zigui Chen
Yiqiang Cao
Zhiming Ma
Xin Wan
Quan Cheng
Bing Jiang
Journal: Molecular Medicine Reports (2014)
Discipline: CLINICAL MEDICINE
Keywords: Malignant glioma; Rho-associated protein kinase (ROCK1); microRNA-145 (miRNA-145); actin cytoskeleton reorganization; cancer cell invasion
Affiliations: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Abstract:  Malignant glioma is the most common type of cancer in the central nervous system, with highly invasive characteristics. The Rho-associated protein kinase (ROCK1) has been found to act as key regulator of actin cytoskeleton reorganization, a process closely associated with cancer cell invasion. microRNA-145 (miRNA-145) has been recently shown to act as a suppressor in several types of tumor, including glioma. However, the exact regulatory mechanism by which miR-145 inhibits glioma still remains to be uncovered. In this study, we report that the miR-145 level was significantly reduced in glioma tissues and in the human glioma cell lines U87 and U251, as compared to matched adjacent and normal brain tissues. We then identified the ROCK1 gene as a novel target of miR-145. The expression of ROCK1 was markedly upregulated in glioma tissues, as well as in U87 and U251 cells. Moreover, miR-145 significantly inhibited ROCK1 protein expression in U87 cells. We further show that miR-145 transfection considerably reduced the invasive ability of U87 cells, and was accompanied by the downregulation of matrix metalloproteinase 2 and 9, an effect which could be attenuated by overexpression of ROCK1. In conclusion, the present study suggests that miR-145 can inhibit U87 glioma cell invasion, at least partially via downregulation of the RhoA/ROCK1 pathway. In conclusion, this is the first study to report that ROCK1, as a novel target of miR-145, acts as a positive regulator of glioma cell invasion. Therefore, ROCK1 may constitute a promising target for glioma treatment. 

Retracted: No

PubPeer comments:
 Fig 5A.  The apoptosis of GC cells detected by flow cytometry. (A) Groups of AGS cell lines: AGS, AGS-NC, AGS-miR-31 inhibitor, AGS-miR-31 inhibitor + RhoA siRNA, AGS-miR-31 inhibitor + ROCK siRNA. A large area of similarly-arranged points is shared between two panels (though displaced vertically). ![file] ,
The role of p53 in base excision repair following genotoxic stress
Authors: Yehudit Cohen
Irit Zurer
S Perwez Hussain
Curtis C Harris
Varda Rotter
Meng Xu-Welliver
Lorne J Hofseth
Journal: Carcinogenesis (2003)
Discipline: CLINICAL MEDICINE
Keywords: p53; base excision repair; 3-MeAde DNA glycosylase; genotoxic stress; gamma-irradiation
Affiliations: Department of Molecular Cell Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.

Abstract:  The p53 tumor suppressor protein is involved in apoptosis and cell cycle checkpoints. We have shown recently that p53 also facilitates base excision repair (BER). To further examine p53 involvement in the regulation of BER we chose to focus on 3-methyladenine DNA glycosylase (3-MeAde DNA glycosylase), the first enzyme acting in the BER pathway. 3-MeAde DNA glycosylase activity was found to be modulated by the p53 protein. This modulation was dependent on the type of genotoxic stress used. Gamma-irradiation damage resulted in activation of glycosylase, which was enhanced by p53. Doxorubicin and hydrogen peroxide (H2O2) treatment, although inducing p53 stabilization, did not cause the activation of glycosylase. Nitric oxide (NO) resulted in activation of 3-MeAde DNA glycosylase. Surprisingly this activation was down regulated by wild-type p53. The down regulation of 3-MeAde DNA glycosylase activity was due to trans repression of glycosylase mRNA by p53. Furthermore, we found that AP endonuclease (APE) activity was not altered by NO. Our study provides evidence for a possible antimutagenic role for p53 following exposure of cells to NO species. In the absence of p53, NO exposure results in elevation of 3-MeAde DNA glycosylase activity that results in elevation in the number of AP sites in DNA. At the same time, APE activity does not rise and removal of the AP sites is not further processed resulting in a mutator phenotype. When p53 is present, it down regulates the transcription of 3-MeAde DNA glycosylase. This provides a new model by which p53 prevents the creation of a mutator phenotype. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Ramelteon protects against human pulmonary microvascular endothelial cell injury induced by lipopolysaccharide (LPS) via activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway
Authors: Wenjun Yang
Keshi Yan
Dahao Lu
Weiwei Wang
Tianfeng Huang
Ju Gao
Yang Zhang
Journal: Bioengineered (2022)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ramelteon; acute lung injury; apoptosis; inflammation; lipopolysaccharide.
Affiliations: Department of Anesthesiology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou City, Jiangsu Province, China

Abstract:  Acute lung injury (ALI) is classified as a moderate or mild acute respiratory distress syndrome and is a prominent cause of morbidity and mortality among the critically ill population. Ramelteon is a melatonin receptor agonist with anti-inflammatory and antioxidant effects. The current study investigated the role of ramelteon in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMECs) and its potential regulatory mechanisms. A CCK-8 assay was used to examine the effect of ramelteon on the viability of LPS-induced HPMECs, HPMECs treated with ML385 [a Nrf2 inhibitor] and HPMECs treated with SnPP [a HO-1 inhibitor]. The Nrf2/HO-1 signaling pathway was additionally assessed by performing Western blotting. The levels of oxidative stress and inflammatory cytokines in HPMECs were detected using kits and reverse transcription-quantitative PCR. Cell apoptosis was evaluated via TUNEL staining. Furthermore, cell permeability was assessed using a FITC-dextran fluorescent probe, ZO-1 and occludin expression was determined via Western blotting. The results demonstrated that ramelteon elevated HPMEC viability after LPS stimulation. Additionally, ramelteon markedly reduced LPS-induced oxidative stress, inflammation and apoptosis. Moreover, cell permeability was notably decreased in ramelteon-treated groups and was accompanied by upregulated ZO-1 and occludin expression. Ramelteon treatment also activated the Nrf2/HO-1 signaling pathway in LPS-induced HPMECs. Furthermore, the addition of ML385 or SnPP reversed the protective effects of ramelteon on LPS-induced oxidative stress, inflammation, apoptosis and cell dysfunction in HPMECs. Collectively, the results suggested that ramelteon alleviated LPS-induced HPMEC damage by activating the Nrf2/HO-1 signaling pathway, making it an effective treatment for ALI. 

Retracted: No

PubPeer comments:
 In this study, critical information is lacking. Can the authors please provide details regarding: - Antibodies used in Western immunoblotting. - Instrument used for reading the ECL signals. - qRT-PCR primers (sequences). Without this information it s impossible to judge and trust the results and conclusions. It is surprising that the peer-reviewers, if any, let this pass. ,
LncRNA MT1JP acts as a tumor inhibitor via reciprocally regulating Wnt/β-Catenin pathway in retinoblastoma
Authors: L-L Bi
Y-Y Li
X-M Zhang
F Han
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MT1JP; β-catenin; retinoblastoma; Wnt/β-catenin signaling pathway; tumor suppressor
Affiliations: Department of Medical Engineering, The Second Affiliated Hospital, Mudanjiang College of Medicine, Mudanjiang, China. .

Abstract:  Objective: The aim of this study was to investigate the roles of MT1JP and β-catenin in retinoblastoma. Patients and methods: We performed quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) to quantify the expressions of MT1JP and β-catenin in 44 retinoblastoma tissues and matched non-tumor tissues. What's more, retinoblastoma cell lines were transfected with pcDNA3.1-MT1JP, after which proliferation, cell cycle, apoptosis, and expression of β-catenin as well as its downstream targets were assayed. We also conducted TOP-Flash reporter assay to explore the activity of Wnt/β-catenin signaling pathway. Results: The results revealed that MT1JP was down-regulated, while β-catenin was highly expressed in retinoblastoma cells. Meanwhile, the forced expression of MT1JP impaired the expression of the β-catenin protein and its downstream targets such as cyclin D1, c-myc. Conclusions: We demonstrated that MT1JP was a tumor suppressor by negatively modulating the activity of the Wnt/β-catenin signaling pathway in the development of retinoblastoma and might function as a prognostic biomarker and therapeutic target. 

Retracted: No

PubPeer comments:
 The flow cytometry plots feature some heavy duplications. Can there be an inoccuous explanation? ![file] , 
 #1 https: en.wikipedia.org wiki Betteridge%27s_law_of_headlines , 
 Above: Fig 4C. Below: Fig 6B. ![file] , 
  Each patient was provided with written informed consents When research involves the enucleated eyeballs of young children (half of the patients younger than 2.5), readers need to know **who provided** the  written informed consents . ,
Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling
Authors: Guowei Zhang
Yang Wang
Bin Hu
Xiaolin Liu
Qing Li
Chunyuan Chen
Changqing Zhang
Jieyuan Zhang
Xin Niu
Journal: International journal of biological sciences (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Angiogenesis; Erk1/2.; Exosomes; Microarray; Wound healing.
Affiliations: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China;; Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China., Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China;; Graduate School of Nanchang University, 461 Bayi Road, Nanchang 330006, China., Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Abstract:  Chronic skin wounds represent one of the most common and disabling complications of diabetes. Endothelial progenitor cells (EPCs) are precursors of endothelial cells and can enhance diabetic wound repair by facilitating neovascularization. Recent studies indicate that the transplanted cells exert therapeutic effects primarily via a paracrine mechanism and exosomes are an important paracrine factor that can be directly used as therapeutic agents for regenerative medicine. However, application of exosomes in diabetic wound repair has been rarely reported. In this study, we demonstrated that the exosomes derived from human umbilical cord blood-derived EPCs (EPC-Exos) possessed robust pro-angiogenic and wound healing effects in streptozotocin-induced diabetic rats. By using a series of in vitro functional assays, we found that EPC-Exos could be incorporated into endothelial cells and significantly enhance endothelial cells' proliferation, migration, and angiogenic tubule formation. Moreover, microarray analyses indicated that exosomes treatment markedly altered the expression of a class of genes involved in Erk1/2 signaling pathway. It was further confirmed with functional study that this signaling process was the critical mediator during the exosomes-induced angiogenic responses of endothelial cells. Therefore, EPC-Exos are able to stimulate angiogenic activities of endothelial cells by activating Erk1/2 signaling, which finally facilitates cutaneous wound repair and regeneration. 

Retracted: No

PubPeer comments:
 Figure 5E and 7F appear to overlap. *** ![file] ,
Pro‐inflammatory role of high‐mobility group box‐1 on brain mast cells via the RAGE/NF‐κB pathway
Authors: Qing-Qing Qian
Jia-Wen Xu
Xiang Zhang
Bo Gui
Yi-Wei Wang
Hong-Quan Dong
Na-Na Li
Yan-Ning Qian
Journal: Journal of Neurochemistry (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: NF-κB; blood-brain barrier; high-mobility group box-1; mast cell; neuroinflammation
Affiliations: Department of Anesthesiology, 1st Affiliated Hospital, Nanjing Medical University, Nanjing, China., Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract:  High-mobility group box-1 (HMGB-1) acts as a pro-inflammatory cytokine contributing to the occurrence of many central inflammatory and infectious disorders. Brain mast cells (MCs) are the first responders to peripheral inflammatory stimulation because of their rapid response to external stimuli coupled with their release of preformed and newly synthesized reactive chemicals. Little is known about the involvement of brain MCs in the pro-inflammatory effects of HMGB-1 on the central nervous system (CNS). Thus, we investigated the activation process of MCs by HMGB-1 and explored whether this process is involved in the pro-inflammatory effects of HMGB-1 on the CNS. In this study, we used P815 cells to study the activating role of HMGB-1 on MCs and to explore its potential mechanism in vitro. In an in vivo study, adult male Sprague-Dawley rats received i.c.v. injection of sterile saline or cromoglycate (stabilizer of MCs) 30 min prior to i.p. injection of HMGB-1. Increased levels of tumor necrosis factor and IL-1β were observed in the P815 cells, as well as in the rats' brains, after HMGB-1 treatment. Pretreatment with the receptor of advanced glycation endproducts (RAGE)-siRNA inhibited the HMGB-1-induced inflammatory process in the P815 cells. Activation of the RAGE/nuclear factor-κB (NF-κB) pathway was observed in both the P815 cells and rats' brains. In addition, HMGB-1 induced the accumulation of brain MCs in the hippocampal CA1 region, and the blood-brain barrier was disrupted. Pretreatment with cromoglycate, a stabilizer of MCs, mitigated these HMGB-1-induced pro-inflammatory processes in rats. These findings indicate that brain MCs are involved in the pro-inflammatory effect of HMGB-1 on the CNS, probably via activating the RAGE/NF-κB pathway. 

Retracted: No

PubPeer comments:
 similar bands shown in two papers ![file] ,
Analysis of gene expression identifies candidate molecular markers in nasopharyngeal carcinoma using microdissection and cDNA microarray
Authors: Yanhong Zhou
Wenling Zhang
Minghua Wu
Ke Tang
Xiaoling Li
Guiyuan Li
Xiaomin Luo
Wei Xiong
Zhaoyang Zeng
Li Cao
Songqing Fan
Journal: Journal of Cancer Research and Clinical Oncology (2006)
Discipline: CLINICAL MEDICINE
Keywords: Microarray analysis; molecular mechanisms; gene expression; nasopharyngeal carcinoma; dysregulation
Affiliations: Cancer Research Institute, Central South University, Changsha, Hunan, 410078, People's Republic of China.

Abstract:  Purpose: Microarray analysis was used to bring a comprehensive insight into underlying molecular mechanisms and obtain a whole assessment of aberrant gene expression in nasopharyngeal carcinoma (NPC). Methods: Combined with microdissection, gene expression profiles in 23 NPCs and 10 nontumor nasopharyngeal epithelial tissue samples were analyzed. Results: Gene expression patterns suggested the dysregulation of the GTP/GDP-bound Ras cycle and an abnormal hyperactivity of cell cycle in NPC. Alterations in the WNT pathway suggest that this pathway may be activated in NPC. A 6-feature weighted-voting model was chosen because it represented the main characteristics of NPCs and predicted NPCs most accurately from the nontumor tissues (33 of 34 correct calls; 97.1% accuracy, Fisher's exact test, P value = 8.389 x 10(-8)). Conclusions: The data generated in this study represent a comprehensive list of genes aberrantly regulated in NPC. The 6-feature weighted-voting model may provide an extensive list of potential molecular markers for early diagnosis. 

Retracted: No

PubPeer comments:
 There seems to be overlap between this paper and [another paper] with some common authors. Figure 1 and a portion of Table 1 are shown as examples. Could the authors please comment? *** ![file] *** ![file] ,
Raptor nest decorations are a reliable threat against conspecifics
Authors: J Blas
L López
F Sergio
J A Lemus
G Blanco
F Hiraldo
A Tanferna
Journal: Science (2011)
Discipline: Multidisciplinary
Keywords: Individual quality; phenotypic flags; extended phenotype signals; nest decoration; territorial raptor
Affiliations: Department of Conservation Biology, Estación Biológica de Doñana, Consejo Superior de Investigaciones Científicas (CSIC), C/ Americo Vespucio, 41092 Seville, Spain. 

Abstract:  Individual quality is often signaled by phenotypic flags, such as bright plumage patches in birds. Extended phenotype signals can similarly show quality, but in these cases the signals are external to the individual, often taking the form of objects scavenged from the environment. Through multiple manipulative experiments, we showed that objects used for nest decoration by a territorial raptor, the black kite (Milvus migrans), act as reliable threats to conspecifics, revealing the viability, territory quality, and conflict dominance of the signaler. Our results suggest that animal-built structures may serve as signaling devices much more frequently than currently recognized. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,
Suppressor of Cytokine Signaling (SOCS)1 Regulates Interleukin-4 (IL-4)-activated Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and Macrophages via the Proteasome
Authors: Sarah M McCormick
Nicola M Heller
Jessie X Fang
Nagaraj Gowda
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: allergy; asthma; insulin receptor substrate 2; interleukin-4; macrophage
Affiliations: From the Department of Anesthesiology and Critical Care Medicine and., From the Department of Anesthesiology and Critical Care Medicine and Division of Allergy and Clinical Immunology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 .

Abstract:  Allergic asthma is a chronic lung disease initiated and driven by Th2 cytokines IL-4/-13. In macrophages, IL-4/-13 bind IL-4 receptors, which signal through insulin receptor substrate (IRS)-2, inducing M2 macrophage differentiation. M2 macrophages correlate with disease severity and poor lung function, although the mechanisms that regulate M2 polarization are not understood. Following IL-4 exposure, suppressor of cytokine signaling (SOCS)1 is highly induced in human monocytes. We found that siRNA knockdown of SOCS1 prolonged IRS-2 tyrosine phosphorylation and enhanced M2 differentiation, although siRNA knockdown of SOCS3 did not affect either. By co-immunoprecipitation, we found that SOCS1 complexes with IRS-2 at baseline, and this association increased after IL-4 stimulation. Because SOCS1 is an E3 ubiquitin ligase, we examined the effect of proteasome inhibitors on IL-4-induced IRS-2 phosphorylation. Proteasomal inhibition prolonged IRS-2 tyrosine phosphorylation, increased ubiquitination of IRS-2, and enhanced M2 gene expression. siRNA knockdown of SOCS1 inhibited ubiquitin accumulation on IRS-2, although siRNA knockdown of SOCS3 had no effect on ubiquitination of IRS-2. Monocytes from healthy and allergic individuals revealed that SOCS1 is induced by IL-4 in healthy monocytes but not allergic cells, whereas SOCS3 is highly induced in allergic monocytes. Healthy monocytes displayed greater ubiquitination of IRS-2 and lower M2 polarization than allergic monocytes in response to IL-4 stimulation. Here, we identify SOCS1 as a key negative regulator of IL-4-induced IRS-2 signaling and M2 differentiation. Our findings provide novel insight into how dysregulated expression of SOCS increases IL-4 responses in allergic monocytes, and this may represent a new therapeutic avenue for managing allergic disease. 

Retracted: No

PubPeer comments:
 Red boxes :The immunoblot of different groups appear to look similar in Fig 2F. ![file] ,
Role of caveolin-1 in atrial fibrillation as an anti-fibrotic signaling molecule in human atrial fibroblasts
Authors: Jing-quan Zhong
Shao-lei Yi
Xiao-jun Liu
Yun Zhang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Atrial fibrillation; Caveolin-1; TGF-β1; fibrosis; structural remodeling
Affiliations: Key Laboratory of cardiovascular remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China ; School of Medicine, Shandong University, Jinan, Shandong Province, China., Key Laboratory of cardiovascular remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.

Abstract:  Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population; yet, the precise mechanisms resulting in AF are not fully understood. Caveolin-1 (Cav-1), the principal structural component of caveolae organelles in cardiac fibroblasts, is involved in several cardiovascular conditions; however, the study on its function in atrium, in particular, in AF, is still lacking. This report examines the hypothesis that Cav-1 confers an anti-AF effect by mediating atrial structural remodeling through its anti-fibrotic action. We evaluated the expression of Cav-1, transforming growth factor-β1 (TGF-β1), and fibrosis in atrial specimens of 13 patients with AF and 10 subjects with sinus rhythm, and found that the expression of Cav-1 was significantly downregulated, whereas TGF-β1 level, collagens I/III contents and atrial fibrosis were markedly increased, in AF. Western blot analysis demonstrated that treatment of human atrial fibroblasts (HAFs) with TGF-β1 resulted in a concentration- and time-dependent repression of Cav-1. Downregulation of Cav-1 with siRNA increased the TGF-β1-induced activation of Smad signal pathway and collagens production in HAFs. Furthermore, incubation of HAFs with the peptides derived from Cav-1 to achieve Cav-1 gain-of-function abolished the TGF-β1-induced production of collagens I/III and decreases of MMP-2/-9 expression. Therefore it was concluded that Cav-1 is an important anti-AF signaling mediator by conferring its anti-fibrotic effects in atrium. 

Retracted: No

PubPeer comments:
 October 2019 correction for an error in Figure 5, reported in May 2014. Correction found here: https: journals.plos.org plosone article?id=10.1371 journal.pone.0224190. Part of it reads: * There is an error in Fig 5, which incorrectly shows duplicate concentration series data in both panels 5A and 5B. The authors provide a revised Fig 5 which includes a corrected panel 5A showing time series data here. * Here is the original Figure 5. ![file] ,
RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells
Authors: Yanqin Hao
Delong Wang
Xingxing Li
Jin Zou
Xuan Ke
Yanhua Liu
Bingong Li
Yuqin Wang
Journal: International Journal of Molecular Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: Endothelial-mesenchymal transition; RUNX3; cardiovascular system; cardiovascular diseases; hypoxic conditions
Affiliations: Department of Cardiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, P.R. China., Department of Cardiology, Loudi Central Hospital, Loudi, Hunan 417000, P.R. China.

Abstract:  Endothelial-mesenchymal transition (EndMT) is an essential mechanism in the cardiovascular system, for both cardiovascular development and cardiovascular diseases (CVDs). Recent studies indicate that runt-related transcription factor 3 (RUNX3) contributes to EndMT and endothelial cell dysfunction. However, the underlying molecular mechanism remains unknown. The present study was designed to investigate the role of RUNX3 in EndMT and endothelial cell function, and to elucidate the underlying molecular mechanism. Human cardiac microvascular endothelial cells (HCMECs) were incubated in strictly controlled hypoxic conditions (1% O2). HCMECs were cultured under normoxic conditions (21% O2), and then moved to a strictly controlled hypoxic environment (1% O2). Under this hypoxic condition, the cells were transfected with the lentiviral vector containing RUNX3 or an empty lentiviral vector for 8 h. After the cells were cultured under hypoxic conditions for 4 days, CD31 and α-smooth muscle actin colocalization were assessed by immunofluorescence microscopy. Transwell migration and tube formation assays were used to examine the migration and angiogenesis ability. RT-qPCR and western blotting were used to determine the expression of molecules involved in EndMT. Hypoxia induced the transition of HCMECs to mesenchymal cells and markedly promoted tube formation and cell migration. Transforming growth factor-β (TGF-β) and Notch signaling were activated during the hypoxia-induced EndMT of HCMECs. RUNX3 knockdown attenuated EndMT of HCMECs, promoted angiogenic phenotype, and reduced endothelial cell migration. In conclusion, our results showed that RUNX3 knockdown attenuated hypoxia-induced EndMT and reversed endothelial cell functions. RUNX3 is a common downstream target of TGF-β and Notch signaling, and may be a novel therapeutic target for treating CVD mediated by EndMT. 

Retracted: No

PubPeer comments:
 In Figure 3O and Q, the Actin loading control has apparently been duplicated, manipulated and presented as something else (different cell type). ![file] ,
Long noncoding RNA HOXD-AS1 promotes non-small cell lung cancer migration and invasion through regulating miR-133b/MMP9 axis
Authors: Hongyu Jing
Xiaohong Lv
Yang Li
Huan Xia
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HOXD-AS1; Invasion; MMP-9; Non-small cell lung cancer; miR-133b.
Affiliations: Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130021, China. Electronic address: ., Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The corresponding author, Xiaohong Lv, submitted a corrigendum request to the journal, stating: “The authors regret the published figures were wrongly organized”. While assessing the request the journal identified an associated PubPeer post, in which Western blot images within Figure 5B+D appear to have been published in other articles, as detailed here: https://pubpeer.com/publications/B30052F80F25C0DA69B541B5000A67#2. The journal requested that the authors provide a more detailed explanation for their request, a response to the concerns raised on PubPeer, and the raw data associated with their article. The Authors did not respond to this request. The Editor-in-Chief assessed the case and decided to retract the article. 

Retracted: No

PubPeer comments:
 Fig 5B.  ... protein levels were detected in A549 cells transfected with miR-133b mimics or miR-133b inhibitor . ![file] This is a versatile loading control, sometimes manifesting as beta-Actin, e.g. in *[right]* Fig 5F of [Zhang et al (2017)] . ![] The thread for [Pang et al (2015)] links to some other examples, e.g. *[lower right]* that paper s Fig 6D. ![] , 
 *[left]* Fig 5D.  The MMP-9 expression on ... protein levels were determined in A549 cells transfected with si-NC, si-HOXD-AS1, and si-HOXDAS1+miR-133b inhibitor . *[right]* Fig 6A from [Zhao et al (2018)] .  STAT3, CyclinD1, Bcl-2 and MMP-9 protein expression were determined by western blot in RA-FLS after the transfection of pCDNA3.1-GRIM19 and pCDNA3.1. ![file] UPDATE: Fig 3C, 5B from [Zhang et al (2018)] .  The .. protein expression levels were analyzed in mGCs transfected with miRu2010205 mimics or miRu2010NC by ... Western blot ;  CREB1, Bax, Bclu20102, and CYP19A1 protein expression was determined in mGCs transfected with miRu2010205 or the miRu2010NC plasmid, with or without the CREB1u2010overexpressing plasmid (without 3u2032u2010UTR) . ![file] Protein blobs are repeated, in different orders. ,
Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells
Authors: Wieslaw Cybulski
Maciej Kazmierski
Pawel Buszman
Krzysztof Milewski
Ewa Zuba-Surma
Mariusz Z Ratajczak
Michal Tendera
Eugeniusz Hrycek
Grzegorz Kaluza
Janina Ratajczak
David Wallace-Bradley
Piotr Wieczorek
Magda Kucia
Wojciech Wojakowski
Journal: International Journal of Oncology (2010)
Discipline: CLINICAL MEDICINE
Keywords: VSELs; pluripotent stem cells; cardiac regeneration; ex vivo expansion; cardiomyocytes
Affiliations: Third Division of Cardiology, Medical University of Silesia, Katowice, Poland.

Abstract:  VSELs are a population of rare Oct-4+CXCR4+ CD133+lin-CD45- cells that are deposited during early embryogenesis in developing organs/tissues as a reserve population of pluripotent stem cells for regeneration. We reported recently that they are mobilized into peripheral blood during acute myocardial infarction (AMI) in mice and humans. However, although freshly isolated VSELs in experimental AMI mouse models improve cardiac function, the number of these cells is limited and an ex vivo expansion strategy is needed to employ these cells more efficiently for cardiac regeneration. The aim of this study was to establish an efficient method to expand ex vivo BM-derived very small embryonic-like stem cells (VSELs) into cardiomyocytes. VSELs, highly purified by FACS from the bone marrow of GFP transgenic mice, were expanded over C2C12 cell line myoblasts and exposed to cardiac differentiating media. The changes in gene expression during cardiac differentiation of VSELs were evaluated by RTQ-PCR, immunostaining and gene array analysis. We developed an efficient, two-step, ex vivo expansion/differentiation model of BM-derived VSELs into cardiomyocytes. First, purified GFP+ VSELs are plated over C2C12 murine cell line myoblasts, where they expand and differentiate into characteristic spheres. Subsequently, cells from these spheres are expanded on cardiac differentiating media into cardiomyocytes. This study demonstrates that murine BM-derived VSELs can be efficiently expanded in vitro and differentiated into cardiomyocytes. 

Retracted: No

PubPeer comments:
 Concern about Figure 5. It appears that parts of this figure have been published before, in a 2008 paper by shared authors. That paper is: Ratajczak MZ et al., Exp Hematol 2008, DOI: 10.1016 j.exphem.2008.03.010. ![file] , 
 Concern about Figure 6: Two panels appear to look similar to panels in previously published papers: * Kucia et al. Cell Tissue Res (2008), DOI: 10.1007 s00441-007-0485-4 * Kucia et al. Expert Opin. Biol. Ther (2007), DOI: 10.1517 14712598.7.10.1499 ![file] ,
Neuropilin-1 promotes epithelial-to-mesenchymal transition by stimulating nuclear factor-kappa B and is associated with poor prognosis in human oral squamous cell carcinoma
Authors: Xiaomeng Song
Lu Ma
Mengying He
Xueming Yang
Zilu Wang
Weiming Chu
Yunong Wu
Jiang Zhu
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Epithelial-to-mesenchymal transition (EMT); Neuropilin-1 (NRP1); Nuclear factor-kappa B (NF-κB); Invasion; Metastasis
Affiliations: Institute of Stomatology, Nanjing Medical University, Nanjing, PR China; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China., Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China., Institute of Stomatology, Nanjing Medical University, Nanjing, PR China; Department of Basic Science of Stomatology, College of Stomatology, Nanjing Medical University, Nanjing, PR China., Institute of Stomatology, Nanjing Medical University, Nanjing, PR China.

Abstract:  Background: The epithelial-to-mesenchymal transition (EMT) is a key process in carcinogenesis, invasion, and metastasis of oral squamous cell carcinoma (OSCC). In our previous studies, we found that neuropilin-1 (NRP1) is overexpressed in tongue squamous cell carcinoma and that this overexpression is associated with cell migration and invasion. Nuclear factor-kappa B (NF-κB) plays an essential role both in the induction and the maintenance of EMT and tumor metastasis. Therefore, we hypothesized that NRP1 induces EMT, and that NRP1-induced migration and invasion may be an important mechanism for promoting invasion and metastasis of OSCC through NF-κB activation. Methods/results: The variations in gene and protein expression and the changes in the biological behavior of OSCC cell lines transfected with a vector encoding NRP1, or the corresponding vector control, were evaluated. NRP1 overexpression promoted EMT and was associated with enhanced invasive and metastatic properties. Furthermore, the induction of EMT promoted the acquisition of some cancer stem cell (CSC)-like characteristics in OSCC cells. We addressed whether selective inhibition of NF-κB suppresses the NRP1-mediated EMT by treating cells with pyrrolidinedithiocarbamate ammonium (PDTC), an inhibitor of NF-κB. Immunohistochemical analysis of NRP1 in OSCC tissue samples further supported a key mediator role for NRP1 in tumor progression, lymph node metastasis, and indicated that NRP1 is a predictor for poor prognosis in OSCC patients. Conclusion: Our results indicate that NRP1 may regulate the EMT process in OSCC cell lines through NF-κB activation, and that higher NRP1 expression levels are associated with lymph node metastasis and poor prognosis in OSCC patients. Further investigation of the role of NRP1 in tumorigenesis may help identify novel targets for the prevention and therapy of oral cancers. 

Retracted: No

PubPeer comments:
 A concern about Figure 6B was reported to the journal in October 2015, but no action yet. * Red boxes: The CAL27-P and CAL27-P-PDTC panels appear to show an overlap. ![file] ,
Dexamethasone-induced apoptotic mechanisms in myeloma cells investigated by analysis of mutant glucocorticoid receptors
Authors: Sanjai Sharma
Alan Lichtenstein
Journal: Blood (2008)
Discipline: CLINICAL MEDICINE
Keywords: Glucocorticoid; Dexamethasone; Apoptosis; Multiple myeloma; GR mutants
Affiliations: Department of Hematology Oncology, Division of Hematology Oncology, UCLA West Los Angeles, VA Medical Center, Los Angeles, CA 90073, USA. 

Abstract:  The mechanism by which the glucocorticoid (GC) dexamethasone induces apoptosis in multiple myeloma (MM) cells is unknown, although previous work suggests that either transactivation through the glucocorticoid response element (GRE), transrepression of NF-kappaB, phosphorylation of RAFTK (Pyk2), or induction of Bim is important. We studied this question by ectopically expressing mutant glucocorticoid receptors (GRs) in the dexamethasone-resistant MM1R cell line, which has lost its GR. Lentiviral-mediated reexpression of wild-type GR restored GRE transactivation, NF-kappaB transrepression, RAFTK phosphorylation, Bim induction, and dexamethasone-induced apoptosis. We then reexpressed 4 GR mutants, each possessing various molecular effects, into MM1R cells. A perfect correlation was present between induction of GRE transactivation and induction of apoptosis. In contrast, NF-kappaB transrepression and RAFTK phosphorylation were not required for apoptosis. Although not required for dexamethasone-mediated apoptosis, NF-kappaB inhibition achieved by gene transfer suggested that NF-kappaB transrepression could contribute to apoptosis in dexamethasone-treated cells. Dexamethasone treatment of MM1R cells expressing a mutant incapable of inducing apoptosis successfully resulted in RAFTK (Pyk2) phosphorylation and Bim induction indicating the latter GR-mediated events were not sufficient to induce apoptosis. MM1R cells expressing mutant GRs will be helpful in defining the molecular mechanisms of dexamethasone-induced apoptosis of myeloma cells. 

Retracted: No

PubPeer comments:
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Critical role of diacylglycerol- and phospholipid-regulated protein kinase C epsilon in induction of low-density lipoprotein receptor transcription in response to depletion of cholesterol
Authors: Bhuvanesh Dave
Gurpreet S Kapoor
Anna Radominska-Pandya
Kamal D Mehta
Brett A Atkins
Journal: Molecular and Cellular Biology (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LDL receptor; transcription; protein kinase C; PKC epsilon; sterol depletion
Affiliations: Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA. , Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, Columbus, Ohio 43210

Abstract:  Induction of low-density lipoprotein (LDL) receptor transcription in response to depletion of cellular sterols in animal cells is well established. The intracellular signal or signals involved in regulating this process, however, remain unknown. Using a specific inhibitor of protein kinase C (PKC), calphostin C, we show the requirement of this kinase in the induction process in human hepatoma HepG2 cells. Overexpression of PKC epsilon, but not PKC alpha, -gamma, -delta, or -zeta was found to dramatically induce (approximately 18-fold) LDL receptor promoter activity. Interestingly, PKC epsilon-mediated induction was found to be sterol resistant. To further establish that PKC epsilon is involved in the sterol regulation of LDL receptor gene transcription, endogenous PKC epsilon was specifically inhibited by transfection with antisense PKC epsilon phosphorothionate oligonucleotides. Antisense treatment decreased endogenous PKC epsilon protein levels and completely blocked induction of LDL receptor transcription following sterol depletion. PKC epsilon-induced LDL receptor transcription is independent of the extracellular signal-regulated kinase 1 and 2 (p42/44(MAPK)) cascade, because the MEK-1/2 inhibitor, PD98059 did not inhibit, even though it blocked p42/44(MAPK) activation. Finally, photoaffinity labeling studies showed an isoform-specific interaction between PKC epsilon and sterols, suggesting that sterols may directly modulate its function by hampering binding of activators. This was confirmed by PKC activity assays. Altogether, these results define a novel signaling pathway leading to induction of LDL receptor transcription following sterol depletion, and a model is proposed to account for a new function for PKC epsilon as part of a sterol-sensitive signal transduction pathway in hepatic cells. 

Retracted: No

PubPeer comments:
 Figure 1. Much more similar and different than expected. https: imgur.com OqyCozd ,
Preclinical evaluation of the nonsteroidal anti-inflammatory agent celecoxib on malignant mesothelioma chemoprevention
Authors: Alfonso Catalano
Laura Graciotti
Giorgia Raffaelli
Walter Gianni
Salvatore Amoroso
Antonio Procopio
Piergiacomo Betta
Sabrina Rodilossi
Luciana Rinaldi
Journal: International Journal of Cancer (2004)
Discipline: CLINICAL MEDICINE
Keywords: Malignant mesothelioma; NSAIDs; COX-2 inhibitor; celecoxib; MM cells
Affiliations: Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona, Italy. 

Abstract:  Malignant mesothelioma (MM) remains the most lethal pleural, peritoneal and pericardial cancer. Here, we characterize the effects of nonsteroidal anti-inflammatory agents (NSAIDs) on in vitro and in vivo experimental MM models. Unlike primary normal mesothelial cells, the selective cyclooxygenase (COX)-2 inhibitor celecoxib reduced the in vitro proliferation of several MM cells derived from previously untreated MM patients. Moreover, celecoxib significantly inhibited MM cell colony formation in soft agarose (63-78% at 5 x 10(-5) M; p &lt; or = 0.05) and it elicited remarkable antitumor activity, leading to long-term survival in &gt;37% of nude mice bearing intraperitoneal MM. Celecoxib was more efficient in inhibiting MM cell growth than acetylsalicylic acid (10(-6) M-10(-2) M), indometacin (10(-6) M-10(-2) M) and the COX-2 inhibitor NS-398 (10(-6) M-10(-4) M). Efficacy of these different compounds was not related to the amount of COX-2 protein levels present on MM cells. Celecoxib, in a dose- and time-dependent manner, induced MM cell apoptosis, which involved decreased Akt phosphorylation, loss of Bcl-2 and Survivin protein expression and caspase-3 activation. Furthermore, vascular endothelial growth factor (VEGF), an MM autocrine growth factor and Akt inducer, rescued celecoxib-induced apoptosis and Akt dephosphorylation. When the VEGF receptor (KDR/Flk-1) inhibitor, SU-1498, was used in combination with celecoxib, IC50 of celecoxib in vitro was reduced up to 65%. These data demonstrate that celecoxib may have antitumor properties in MM and provide a rationale for the therapeutic use of celecoxib in combination with a selective VEGF inhibitor. 

Retracted: No

PubPeer comments:
null, 
 There appears to be an image duplication, wind flipped vertically, in figure 2A. Many similar issues previously identified, and most unaddressed, in papers by common author: https: pubpeer.com search?q=Antonio+Procopio *** ![file] , 
 #1 I see what the original commenter is saying about Figure 5B. Those bands do appear clearly different. *** 5B Enhanced contrast ![file] ,
Peroxisome proliferator activated receptor-gamma ligands induced cell growth inhibition and its influence on matrix metalloproteinase activity in human myeloid leukemia cells
Authors: Ming Hou
Yuqin Song
Renwei Huang
Jing Zheng
Dongjun Lin
Xinyao Wu
Feng Chen
Xiangyuan Wu
Huiling Lu
Jiajun Liu
Qu Lin
Maohong Zhang
Xianglin Pan
Jun Peng
Journal: Cancer Chemotherapy and Pharmacology (2005)
Discipline: CLINICAL MEDICINE
Keywords: PPAR-gamma; ligands; cell growth inhibition; matrix metalloproteinase; leukemia cells
Affiliations: Department of Haematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Guangzhou, 510630, P.R. China, .

Abstract:  Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is one of the best characterized nuclear hormone receptors (NHRs) in the superfamily of ligand-activated transcriptional factors. PPAR-gamma ligands have recently been demonstrated to affect proliferation, differentiation and apoptosis of different cell types. The present study was undertaken to investigate PPAR-gamma ligands induced cell growth inhibition and its influence on matrix metalloproteinase MMP-9 and MMP-2 activities on leukemia K562 and HL-60 cells in vitro. The results revealed that PPAR-gamma expression was detectable in the two kinds of leukemia cells; Both 15-deoxy-delta(12,14)-prostaglandin J2(15d-PGJ2) and troglitazone (TGZ) have significant growth inhibition effects on these two kinds of leukemia cells. These two PPAR-gamma ligands could inhibit the leukemic cell adhesion to the extracellular matrix (ECM) proteins and the invasion through matrigel matrix. The expressions of MMP-9 and MMP-2 as well as their gelatinolytic activities in both HL-60 and K562 cells were inhibited by 15d-PGJ2 and TGZ significantly. We therefore conclude that PPAR-gamma ligands 15d-PGJ2 and TGZ have significant growth inhibition effects on myeloid leukemia cells in vitro, and that PPAR-gamma ligands can inhibit K562 and HL-60 cell adhesion to and invasion through ECM as well as downregulate MMP-9 and MMP-2 expressions. The data suggest that PPAR-gamma ligands may serve as potential anti-leukemia reagents. 

Retracted: No

PubPeer comments:
 Figures 4 and 5. * Colored boxes point to panels or parts of panels in Figure 4 that appear to look repetitive. * Yellow boxes point to two lanes in Figure 5 that look more similar than expected. Similarities are noted between other lanes as well. Part of a set of 29 papers reported to the journal in the summer of 2015 with a friendly reminder in April 2017, but no answer. With the exception of one paper, the journal did not correct or retract a single paper from this set. ![file] ,