PReD-Bench/PRed-Bench huggingface dataset:
MiR-142-3p attenuates the migration of CD4⁺ T cells through regulating actin cytoskeleton via RAC1 and ROCK2 in arteriosclerosis obliterans
Authors: Shenming Wang
Chunxiang Zhang
Wenjian Wang
Jiawei Liu
Siwen Wang
Ruiming Liu
Wen Li
Jingsong Ou
Zilun Li
Yidan Wu
Journal: PloS one (2014)
Discipline: Multidisciplinary
Keywords: CD4+ T cells; migration; miR-142-3p; arteriosclerosis obliterans; CXCL12
Affiliations: Department of Vascular Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China., Laboratory of General Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China., Cardiovascular Research Center, Department of Pharmacology, Rush Medical College, Rush University, Chicago, Illinois, United States of America.

Abstract:  The migration of CD4+ T cells plays an important role in arteriosclerosis obliterans (ASO). However, the molecular mechanisms involved in CD4+ T cell migration are still unclear. The current study is aimed to determine the expression change of miR-142-3p in CD4+ T cells from patients with ASO and investigate its role in CD4+ T cell migration as well the potential mechanisms involved. We identified by qRT-PCR and in situ hybridization that the expression of miR-142-3p in CD4+ T cells was significantly down-regulated in patients with ASO. Chemokine (C-X-C motif) ligand 12 (CXCL12), a common inflammatory chemokine under the ASO condition, was able to down-regulate the expression of miR-142-3p in cultured CD4+ T cells. Up-regulation of miR-142-3p by lentivirus-mediated gene transfer had a strong inhibitory effect on CD4+ T cell migration both in cultured human cells in vitro and in mouse aortas and spleens in vivo. RAC1 and ROCK2 were identified to be the direct target genes in human CD4+ T cells, which are further confirmed by dual luciferase assay. MiR-142-3p had strong regulatory effects on actin cytoskeleton as shown by the actin staining in CD4+ T cells. The results suggest that the expression of miR-142-3p is down-regulated in CD4+ T cells from patients with ASO. The down-regulation of miR-142-3p could increase the migration of CD4+ T cells to the vascular walls by regulation of actin cytoskeleton via its target genes, RAC1 and ROCK2. 

Retracted: No

PubPeer comments:
 Figure 1B. * Red boxes: The control and ASO panels appear to look similar if one of them is rotated 180 degrees. Note that only the  Nuclear panels are marked below, but the similarity also holds for the other two columns. ![file] ,
Matrine inhibits cell proliferation and induces apoptosis of human rhabdomyosarcoma cells via downregulation of the extracellular signal-regulated kinase pathway
Authors: Penghui Yan
Zongqiang Huang
Junbo Zhu
Journal: Oncology Letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: ERK signaling; apoptosis; matrine; proliferation; rabdomyosarcoma.
Affiliations: Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.

Abstract:  Matrine, extracted from the Chinese traditional medicine Sophorae flavescentis, has been demonstrated to exhibit antitumor effects on numerous types of cancer in vivo and in vitro with low toxicity. However, its antitumor mechanism in rhabdomyosarcoma (RMS) cells remains unclear. In the present study, the antitumor effects of matrine and its underlying mechanisms in RMS were investigated in vitro. The results demonstrated that matrine inhibited cell proliferation, migration and invasion, and induced apoptosis of RMS cells in a dose-dependent manner. Furthermore, the expression levels of phosphorylated mitogen-activated protein kinase (p-MEK) and phosphorylated extracellular signal-regulated kinase (p-ERK) significantly decreased in RMS cells following matrine treatment. In addition, the apoptotic effects of matrine in RMS cells were partially inhibited upon MEK1 overexpression and enhanced upon combined treatment with an ERK inhibitor (U0126). In addition, the ratio of apoptosis regulator BCL-2/BAX significantly decreased following matrine treatment. In conclusion, these findings indicate that matrine inhibits cell proliferation and induces the apoptosis of RMS cells by suppressing the ERK signaling pathway, and may be a novel effective candidate for the treatment of patients with RMS. 

Retracted: No

PubPeer comments:
 Images are high degree of similarity (red box)uff0csome was modified (blue arrow). ![file] , 
 #1 The two panels from the upper left corner of Fig 5A... ![file] Here, I have black white reversed the 1.5 panel and superimposed it on the 1.0 panel, so that dots cancel out if present in both. Black dots are unique to 1.0 and white dots are unique to 1.5. ![file] , 
 #1 I agree that these two panels in Fig 5A also have more points in common than one would expect. ![file] ![file] ,
Roles and clinical implications of microRNAs in acute lymphoblastic leukemia
Authors: Simona Ultimo
Alberto M Martelli
George A Calin
Luca M Neri
Marco Vitale
Giorgio Zauli
Journal: Journal of Cellular Physiology (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: acute lymphoblastic leukemia; miRNAs; oncology; signaling pathways.
Affiliations: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy., Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Department of Medicine and Surgery, Sport and Exercise Medicine Centre (SEM), University of Parma, Parma, Italy., CoreLab, Hospital-University of Parma, Parma, Italy., Departments of Experimental Therapeutics and Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Abstract:  MicroRNAs (miRNAs) are a class of small noncoding RNAs which regulate the expression of target genes by binding to messenger RNAs. miRNAs play a role in various biological processes, including proliferation, apoptosis, and tumorigenesis. Dysregulation of miRNAs is implicated in invasion and metastasis in several human cancer types, and leukemia is not an exception. Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the proliferation of early lymphoid precursors that replace normal hematopoietic cells of the bone marrow. The expression profiling of miRNAs in ALL could be used for the classification of the disease establishing specific diagnoses and offering prognostic values in the near future. The correlation of miRNAs dysregulation and biology of ALL demonstrates that specific miRNA may be a potential therapeutic target. In this review we have focused our attention on the correlations between ALL and miRNAs, their link with signaling pathways and transcription factors in the disease and miRNA targeting therapeutic strategies with their advantages and potential use in clinical applications. 

Retracted: No

PubPeer comments:
 I am concerned in how the authors proven that the species was found in Easter Island, since the note is not indicated methodology of it. Showing a picture of the species and a map showing the locations is not enough. Perhaps, methodology is missing and an erratum for such mistake is necessary. Moreover, it is necessary to include the context of the species found, is it alive or dead? How did you sampled to get it? If the species was dead, it is not a mandatory to call a new record species. ,
Inactivation of E2F3 results in centrosome amplification
Authors: Yukari Tokuyama
Baidehi Maiti
Harold I Saavedra
Gustavo Leone
Kenji Fukasawa
Cynthia Timmers
Rachel Altura
Journal: Cancer Cell (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: E2F3; cell cycle progression; centrosome duplication cycle; cyclin E-dependent kinase activity; nucleophosmin B

Abstract:  The E2F family of transcription factors is critical for the control of cell cycle progression. We now show that the specific inactivation of E2F3 in mouse embryo fibroblasts (MEFs) results in a disruption of the centrosome duplication cycle. Loss of E2F3, but not E2F1, E2F2, E2F4, or E2F5 results in unregulated cyclin E-dependent kinase activity, defects in nucleophosmin B association with centrosomes, and premature centriole separation and duplication. Consequently, this defect leads to centrosome amplification, mitotic spindle defects, and aneuploidy. Our findings implicate the E2F3 transcription factor as an important link that orchestrates DNA and centrosome duplication cycles, ensuring the faithful transmission of genetic material to daughter cells. 

Retracted: No

PubPeer comments:
 Figure 7B. https: imgur.com hR4qqPN ,
NADPH oxidase 2 plays a critical role in dysfunction and apoptosis of pancreatic β-cells induced by very low-density lipoprotein
Authors: Yong Man
Miao Li
Juan Jiao
Jian Li
Lin Dou
Yonggang Lu
Shu Wang
Han-Bang Guo
Journal: Molecular and Cellular Biochemistry (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: type 2 diabetes; pancreatic β-cells; insulin resistance; lipid metabolism; hypertriglyceridemia
Affiliations: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Abstract:  In type 2 diabetes, pancreatic β-cells cannot secret enough insulin compensate for insulin resistance, which are often accompanied by abnormality in lipid metabolism such as hypertriglyceridemia. It is reported that oxidative stress is involved in pancreatic β-cell dysfunction. However, molecular mechanisms linking between excessive generations of reactive oxygen species (ROS) and β-cell dysfunction and apoptosis induced by high levels of very low-density lipoprotein (VLDL) are poorly understood. In this study, we test the hypothesis that NADPH oxidase 2 (NOX2)-derived ROS may play a key role in dysfunction and apoptosis of pancreatic β-cell induced by VLDL. Our results show that the ApoCIII transgenic mice displayed increased serum TG levels, enhanced generation of ROS and impaired insulin content in pancreatic β-cells. In vitro, the treatment of pancreatic NIT-1 cells with 1 mg/ml VLDL for 12 h stimulated NOX2-derived ROS generation, decreased expression and secretion of insulin. Furthermore, we found that VLDL induced dysfunction and apoptosis of pancreatic β-cells through JNK and p53 pathways, which were rescued by siRNA-mediated NOX2 reduction. In conclusion, our data demonstrate a critical role of NOX2-derived ROS in dysfunction and apoptosis through JNK and p53 pathways in pancreatic β-cells induced by VLDL. 

Retracted: No

PubPeer comments:
 Figure 1C. * Blue boxes: The Control and ApoCIII panels look very similar, although shown at different exposures. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. ![file] , 
 Dear Elisabeth M Bik: Thank you for bringing to my attention the fact that two figures in figure.1C of my article entitled: NADPH oxidase 2 plays a critical role in dysfunction and apoptosis od pancreatic u03b2-cells induced by very low-density lipoprotein, Molecular and Cellular Biochemisty (2012), appear to be shown at different exposures. After checking the original data carefully, I found that we mistook the photos during the figure preparation. And the correct figures were showed as below. The figure showed that ROS in pancreatic islet was reduced in control group compared with apoCIII- - group. I sincerely apologize for this mistake and inconvenience this may have caused to the readers. I agree that this is a very serious matter. And I am deeply sorry for the mistake and take full responsibility for the outcome. I will contact the journal editor to correct this issue and provide updated version. Thank you again for your comment. ![file] ,
The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development
Authors: J D Alvarez
T Joh
H Niida
D H Yasui
T Kohwi-Shigematsu
D Y Loh
Journal: Genes & Development (2000)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: SATB1; transcriptional repressor; matrix attachment regions (MARs); chromatin organization; T-cell lineage
Affiliations: Nippon Roche Research Center, Kamakura 247, Japan.

Abstract:  SATB1 is expressed primarily in thymocytes and can act as a transcriptional repressor. SATB1 binds in vivo to the matrix attachment regions (MARs) of DNA, which are implicated in the loop domain organization of chromatin. The role of MAR-binding proteins in specific cell lineages is unknown. We generated SATB1-null mice to determine how SATB1 functions in the T-cell lineage. SATB1-null mice are small in size, have disproportionately small thymi and spleens, and die at 3 weeks of age. At the cellular level, multiple defects in T-cell development were observed. Immature CD3(-)CD4(-)CD8(-) triple negative (TN) thymocytes were greatly reduced in number, and thymocyte development was blocked mainly at the DP stage. The few peripheral CD4(+) single positive (SP) cells underwent apoptosis and failed to proliferate in response to activating stimuli. At the molecular level, among 589 genes examined, at least 2% of genes including a proto-oncogene, cytokine receptor genes, and apoptosis-related genes were derepressed at inappropriate stages of T-cell development in SATB1-null mice. For example, IL-2Ralpha and IL-7Ralpha genes were ectopically transcribed in CD4(+)CD8(+) double positive (DP) thymocytes. SATB1 appears to orchestrate the temporal and spatial expression of genes during T-cell development, thereby ensuring the proper development of this lineage. Our data provide the first evidence that MAR-binding proteins can act as global regulators of cell function in specific cell lineages. 

Retracted: No

PubPeer comments:
 Figure 8B. Much more similar than expected. ![file] ,
Chronic lymphocytic inflammation specifies the organ tropism of prions
Authors: Peter-Christian Klöhn
Charles Weissmann
Harald Seeger
Adriano Aguzzi
Nicolas Zeller
Mathias Heikenwalder
Nancy H Ruddle
Marco Prinz
Petra Schwarz
Journal: Science (2005)
Discipline: Multidisciplinary
Keywords: Prions; Inflammatory conditions; Lymphoid tissues; Proinflammatory cytokines; Immune cells

Abstract:  Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPC. By contrast, inflamed organs of mice lacking lymphotoxin-alpha or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission. 

Retracted: No

PubPeer comments:
 *[left]* Fig 6A from [Liu et al (2018)] .  Prucalopride promotes autophagy of ovarian cancer cell SKOV3. (A) Expression levels of LC3-II, Beclin1, and p62 were measured in the SKOV3 cells treated with prucalopride using Western blot analysis . *[right]* Figure 4A from [Zhang et al (2018)] .  ISL triggers autophagy in MKN28 cells. (A) LC3II, LC3I, Beclin 1 and p62 protein expression levels were determined by western blotting. ![file] A band seems to recur between papers. ,
The mechanism of blood concentrations of the Shenqi pill repairing injured epithelial cells of renal tubular in vitro
Authors: Wenfeng Ma
Fei Huang
Journal: Experimental and Therapeutic Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: Jag2/Notch2/hes1; Shenqi pill; injured hypoxia/reoxygenation model; renal tubular epithelial cells.
Affiliations: Department of Nephrology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China., Department of Pharmacy, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China.

Abstract:  In the present study, we investigated the best blood concentration of the mechanism of Shenqi pill repairing the injured epithelial cells of renal tubular in vitro. First, the injured hypoxia/reoxygenation model of rat proximal renal tubular epithelial cell strain (NRK-52E) was established. The animals were divided randomly into control, model, low concentration (5 µg/ml), moderate concentration (10 µg/ml) and high concentration (20 µg/ml) groups. The apoptotic rate was measured with flow cytometry and Jag2/Notch2/hes1 mRNA, and the protein expression was measured for 1, 3 and 7 days. It was found that in comparison to the control group, the growth of each group was prolonged with time, the levels of apoptosis, and the Jag2/Notch2/hes1 mRNA and protein expression decreased. Furthermore, the levels of the apoptotic rate, Jag2/Notch2/hes1 mRNA and protein expression of the moderate concentration and high concentration groups were significantly lower than those of the model and low-dose groups at each time-point (P&lt;0.05). In conclusion, the Shenqi Pill alleviates the damage of renal tubular epithelial cells by inhibiting the Jag2/Notch2/hes1 signaling pathway; suitable concentration such as 10-20 µg/ml can exert protective effect. 

Retracted: No

PubPeer comments:
  Figure 2. - Detection of quantitative PCR method comparison of mRNA Jag2 Notch2 hes1 expression levels. Enhanced contrast reveals sharp-edged rectangular discontinuities *[below]*. ![file] Red box and red arrows indicate surprisingly similar blobs. , 
  Figure 3. - Jag2 Notch2 hes1 protein expression levels detected by western blot analysis. ![file] The 1st and 5th lanes in the loading-control band (duplicated below) are surprisingly similar. , 
  Figure 1. - Cell apoptotic rate by flow cytometry. (A) Control, (B) model, (C) low concentration, (D) moderate concentration and (E) high concentration groups. (D) and (E) are duplicates. (B) and (C) show partial duplications. Unexpectedly sharp transition between the lower-left and lower-right quadrants in (C). ![file] Close-up on 1B C. ![file] Suggested by a colleague on social media. ,
The bovine immunodeficiency virus: cloning of a tat/rev cDNA encoding a novel Tat protein with enhanced transactivation activity
Authors: M-C St-Louis
D Archambault
Y Abed
Journal: Archives of Virology (2005)
Discipline: MICROBIOLOGY
Keywords: BIV; Tat protein; transactivation; lentiviruses; sequence analysis
Affiliations: Department of Biological Sciences, University of Québec at Montréal, Montréal, Canada.

Abstract:  Previous studies have shown that BIV may encode two types of Tat proteins of 103 and 108 amino acids, respectively. Here, we report the characterization of a new BIV Tat protein (Tat236) derived from a tat/rev cDNA. The tat/rev cDNA was obtained by reverse transcription-PCR from RNA extracted from cells infected with BIV. BIV was rescued by cell co-cultivation from the spleen of rabbits exposed for 3 years to the R29 isolate of BIV. Sequence analysis indicated that BIV Tat236 contains the first 98 amino acids of Tat103 and the 3' end 138 amino acids of Rev. Reporter gene assays indicated that transactivation of BIV long terminal repeat (LTR) by Tat236 is higher than by the original BIV Tat proteins in several cell types. By using overlapping deletion mutants, evidence was given that the predicted basic domain of Rev within Tat236 plays a major role in the observed enhanced transactivation activity of the protein. However, the intact functional domain of the original BIV Tat is required for efficient transactivation. This is the first report of a hybrid Tat protein from BIV or any lentiviruses that shows higher transactivation than the original transactivator Tat proteins. 

Retracted: No

PubPeer comments:
 In Figure 3, lanes 4 and 5 are duplicates, while the legend indicates that they stand for different samples:  1 and 4: extracts from uninfected cells at 48 hrs after cell passage; 2 and 5: extracts from BIV-infected cells at 24 hrs after cell passage ![file] ,
Aspirin delimits platelet life span by proteasomal inhibition
Authors: Debabrata Dash
Nitesh Singh
Ayusman Dash
Manasa K Nayak
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Aspirin; platelets; cyclooxygenase; thrombogenesis; lifespan
Affiliations: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India., Indian Institute of Science Education and Research, Kolkata, India.

Abstract:  Aspirin is widely used in clinical settings as an anti-inflammatory and anti-platelet drug due its inhibitory effect on cyclooxygenase activity. Although the drug has long been considered to be an effective and safe therapeutic regime against inflammatory and cardiovascular disorders, consequences of its cyclooxygenase-independent attributes on platelets, the key players in thrombogenesis, beg serious investigation. In this report we explored the effect of aspirin on platelet lifespan in murine model and its possible cytotoxicity against human platelets in vitro. Aspirin administration in mice led to significant reduction in half-life of circulating platelets, indicative of enhanced rate of platelet clearance. Aspirin-treated human platelets were found to be phagocytosed more efficiently by macrophages, associated with attenuation in platelet proteasomal activity and upregulation of conformationally active Bax, which were consistent with enhanced platelet apoptosis. Although the dosage of aspirin administered in mice was higher than the therapeutic regimen against cardiovascular events, it is comparable with the recommended anti-inflammatory prescription. Thus, above observations provide cautionary framework to critically re-evaluate prophylactic and therapeutic dosage regime of aspirin in systemic inflammatory as well as cardiovascular ailments. 

Retracted: No

PubPeer comments:
null, 
null, 
 December 2014 correction, which reads:  The lower panel Western blot in Figure 2A is incorrect. The authors have provided a corrected Figure 2 here. https: journals.plos.org plosone article?id=10.1371 journal.pone.0115927 Note that this is a type 3 duplication which has been addressed with a correction. ,
Central Hemodynamics in Relation to Circulating Desphospho-Uncarboxylated Matrix Gla Protein: A Population Study
Authors: Tim S Nawrot
Harry A J Struijker-Boudier
Cai-Guo Yu
Cees Vermeer
Peter Verhamme
Fang-Fei Wei
Zhen-Yu Zhang
Lutgarde Thijs
Wen-Yi Yang
Tatiana Kuznetsova
Nicholas Cauwenberghs
Jan A Staessen
Journal: Journal of the American Heart Association (2019)
Discipline: CLINICAL MEDICINE
Keywords: aortic stiffness; calcification; hemodynamics; matrix proteins; pulse pressure.
Affiliations: 1 Studies Coordinating Centre Research Unit Hypertension and Cardiovascular Epidemiology Department of Cardiovascular Sciences University of Leuven Belgium., 2 Centre for Environmental Sciences Hasselt University Diepenbeek Belgium., Department of Pharmacology Maastricht University Maastricht the Netherlands, 4 Centre for Molecular and Vascular Biology Department of Cardiovascular Sciences University of Leuven Leuven Belgium., 5 Cardiovascular Research Institute Maastricht Maastricht University Maastricht the Netherlands.

Abstract:  Background Stiffening and calcification of the large arteries are forerunners of cardiovascular complications. MGP (Matrix Gla protein), which requires vitamin K-dependent activation, is a potent locally acting inhibitor of arterial calcification. We hypothesized that the central hemodynamic properties might be associated with inactive desphospho-uncarboxylated MGP (dp-uc MGP ). Methods and Results In 835 randomly recruited Flemish individuals (mean age, 49.7 years; 45.6% women), we measured plasma dp-uc MGP , using an ELISA -based assay. We derived central pulse pressure and carotid-femoral pulse wave velocity (PWV) from applanation tonometry and calculated forward and backward pulse waves using an automated, pressure-based wave separation analysis algorithm. Aortic PWV (n=657), central pulse pressure, forward pulse wave, and backward pulse wave mean± SD values were 7.34±1.64 m/s, 45.2±15.3 mm Hg, 33.2±10.2 mm Hg, and 21.8±8.6 mm Hg, respectively. The geometric mean plasma concentration of dp-uc MGP was 4.09 μg/L. All hemodynamic indexes increased across tertiles of dp-uc MGP distribution. In multivariable-adjusted analyses, a doubling of dp-uc MGP was associated with higher PWV (0.15 m/s; 95% CI, 0.01-0.28 m/s), central pulse pressure (1.70 mm Hg; 95% CI, 0.49-2.91 mm Hg), forward pulse wave (0.93 mm Hg; 95% CI, 0.01-1.84 mm Hg), and backward pulse wave (0.71 mm Hg; 95% CI, 0.11-1.30 mm Hg). Categorization of aortic PWV by tertiles of its distribution highlighted a decreasing trend of PWV at low dp-uc MGP (&lt;3.35 μg/L) and an increasing trend at high dp-uc MGP (≥5.31 μg/L). Conclusions In people representative for the general population, higher inactive dp-uc MGP was associated with greater PWV , central pulse pressure, forward pulse wave, and backward pulse wave. These observations highlight new avenues for preserving vascular integrity and preventing cardiovascular complications (eg, by improving a person's vitamin K status). 

Retracted: No

PubPeer comments:
 In Figure 2, the SEM values are identical for all five measurement in A, B, C and D, which is surprising. ![file] ,
<p><em>Protocadherin 17</em> is a tumor suppressor and is frequently methylated in nasopharyngeal carcinoma</p>
Authors: Ya He
Zhihai Wang
Guohua Hu
Chuan Liu
Tao Lu
Yanshi Li
Zhitao Gong
Journal: Cancer Management and Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: PCDH17; epigenetic inactivation; methylation; nasopharyngeal carcinoma; tumor suppressor gene.
Affiliations: Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, ., Department of Otolaryngology Head and Neck Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Abstract:  Purpose: Several PCDH genes were shown to be downregulated or silenced in carcinomas and act as candidate tumor suppressor genes. However, the functions of PCDH17 in nasopharyngeal carcinoma (NPC) remain unclear. Here, we investigated the PCDH17 promoter methylation status and its impact on the expression and functions of PCDH17 in NPC. Patients and methods: To determine the mRNA levels and promoter methylation status of PCDH17 in NPC cell lines as well as 42 NPC patient specimens, we performed reverse transcription PCR, methylation-specific PCR, and bisulfite genome sequencing. The effects of ectopic PCDH17 expression in NPC cell lines were determined by colony formation, cell proliferation, wound healing, in vitro human umbilical vein endothelial cells tube formation, migration, invasion, cell cycle, and apoptosis assays and an in vivo subcutaneous tumor model. Results: PCDH17 expression was almost absent or significantly reduced in 100% of the NPC cell lines (5/5). However, 5-aza-2'-deoxycytidine and trichostatin A treatment restored PCDH17 expression. Promoter methylation was involved in PCDH17 silencing. Ectopic expression of PCDH17 in silenced NPC cells reduced colony formation, cell migration, angiogenesis, VEGF secretion, and tumorigenicity. Conclusion: PCDH17 plays a tumor suppressor role in NPC. PCDH17 methylation may be a tumor-specific event and can be used as an epigenetic biomarker for NPC. 

Retracted: Yes

PubPeer comments:
 Peer review seems to have been rather informal. Figure 1C and 1B. *** Closeup, enhanced contrast ![file] *** Original ![file] ,
Quercetin in hypoxia-induced oxidative stress: novel target for neuroprotection
Authors: Aruna Sharma
Anand Kumar Pandey
Ranjana Patnaik
Hari Shanker Sharma
Dafin F Muresanu
Journal: International review of neurobiology (2012)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Oxidative stress; Central nervous system; Neurodegeneration; Antioxidants; Alzheimer's disease
Affiliations: School of Biomedical Engineering, Institute of Technology, Banaras Hindu University, Varanasi, India.

Abstract:  Oxidative stress in the central nervous system is one of the key players for neurodegeneration. Thus, antioxidants could play important roles in treating several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and aging-related brain disorders. This review is focused on the new developments in oxidative stress-induced neurodegeneration. Further, based on our own investigations, new roles of quercetin, an antioxidant compound in hypoxia and ischemia induced neuroprotection in relation to suppression of oxidative stress, improvement in behavioral function, reduction in infarct volume, brain swelling, and cellular injury in both in vivo and in vitro models are discussed. Our new findings clearly suggest that antioxidant compounds have potential role in therapeutic strategies to treat neurodegenerative diseases in clinical settings. 

Retracted: No

PubPeer comments:
 FIG. 10. Effect of quercetin (10 mg kg, i.p.) pre- and posttreatment on (A) cerebral infarct volume of rat following 1 24 h I R injury. (B) Representative TTC stained brain sections of sham, vehicle, quercetin, pre-, and posttreated rats (*P 0.05 vs. sham and **P 0.05 vs. vehicle). Authors could probably explain the similarity in images. The images are from two different publications and with different treatments.![file] , 
 Another instance of similar images of TTC staining from author research article in Neural Regeneration Research. Images background, dimensions and shade are altered. Different treatment but similar images?![file] ,
A systems biology-based investigation into the therapeutic effects of Gansui Banxia Tang on reversing the imbalanced network of hepatocellular carcinoma
Authors: Xiaodong Guo
Ying Xu
Danhua Wang
Ruisheng Li
Zhenli Liu
Zhiyan Li
Xiaojuan Li
Yanqiong Zhang
Ya Lin
Na Lin
Zhiqian Song
Journal: Scientific Reports (2014)
Discipline: Multidisciplinary
Keywords: tumorigenesis; hepatocellular carcinoma; Gansui Banxia Tang; imbalanced network; therapeutic effects
Affiliations: 1] Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China [2]., 1] 302 Hospital of PLA, Beijing 100039, China [2]., Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China., 302 Hospital of PLA, Beijing 100039, China., Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Abstract:  Several complex molecular events are involved in tumorigenesis of hepatocellular carcinoma (HCC). The interactions of these molecules may constitute the HCC imbalanced network. Gansui Banxia Tang (GSBXT), as a classic Chinese herbal formula, is a popular complementary and alternative medicine modality for treating HCC. In order to investigate the therapeutic effects and the pharmacological mechanisms of GSBXT on reversing HCC imbalanced network, we in the current study developed a comprehensive systems approach of integrating disease-specific and drug-specific networks, and successfully revealed the relationships of the ingredients in GSBXT with their putative targets, and with HCC significant molecules and HCC related pathway systems for the first time. Meanwhile, further experimental validation also demonstrated the preventive effects of GSBXT on tumor growth in mice and its regulatory effects on potential targets. 

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. , 
 #1 I agree and also note a similar issue with images in Figure S4. *** ![file] ,
Circ_0063517 acts as ceRNA, targeting the miR-31-5p-ETBR axis to regulate angiogenesis of vascular endothelial cells in preeclampsia
Authors: Su-Hua Chen
Jian-Li Wu
Lei Fan
Nan Yu
Wei Li
Journal: Life Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Angiogenesis; ETBR; Preeclampsia; circ_0063517; miR-31-5p.
Affiliations: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, PR China., Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, PR China. Electronic address: .

Abstract:  Aims: Accumulated evidence indicates that the dysregulation of circular RNAs (circRNAs) plays pivotal roles in many human diseases including preeclampsia (PE). Circ_0063517 has been verified to be down-regulated in PE. But the role of circ_0063517 in PE is still unclear. This research aims to probe into the effect of circ_0063517 on angiogenesis in PE development. Main methods: The expression of circ_0063517, endothelin receptor type B (ETBR) and miR-31-5p was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). MTT assay, colony formation assay, scratch assay, transwell assay, and tube formation assay were performed to detect proliferation, migration, and angiogenesis, respectively. Dual luciferase reporter system and RNA immunoprecipitation (RIP) assay were carried out to determine the interaction between miR-31-5p and circ_0063517(or ETBR). ETBR, VEGFRA, and VEGFR2 levels were detected by western blot analysis. The effect of circ_0063517 and ETBR on angiogenesis was evaluated in N-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced PE in vivo. Key findings: The levels of circ_0063517 and ETBR were down-regulated in the placenta tissue of PE patients. Conversely, the level of miR-31-5p was up-regulated in PE. Overexpression of circ_0063517 or knockdown of miR-31-5p facilitated growth, migration, and angiogenesis of vascular endothelial cells. Circ_0063517 knockdown-induced repression of the expression of ETBR, VEGFA, and VEGFR2 was partly counteracted by ETBR overexpression. Mechanistically, circ_0063517 sponged miR-31-5p to regulate ETBR expression. Finally, circ_0063517 promoted angiogenesis via enhancing ETBR expression in PE in vivo. Significance: Our findings suggest that circ_0063517-miR-31-5p-ETBR axis regulates angiogenesis during the pathological process of PE. 

Retracted: No

PubPeer comments:
 Re-use of ETBR band in western blot test in Figure 5D, ![file] ,
Formation of the Androgen Receptor Transcription Complex
Authors: Myles Brown
Yongfeng Shang
Molly Myers
Journal: Molecular Cell (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Androgen receptor; sexual differentiation; prostate cancer; cofactor proteins; gene regulatory elements

Abstract:  Androgen receptor (AR) is required for sexual differentiation and is implicated in the development of prostate cancer. Here we describe distinct functions for cofactor proteins and gene regulatory elements in the assembly of AR-mediated transcription complexes. The formation of an activation complex involves AR, coactivators, and RNA polymerase II recruitment to both the enhancer and promoter, whereas the formation of a repression complex involves factors bound only at the promoter and not the enhancer. These results suggest a model for the functional coordination between the promoter and enhancer in which communication between these elements is established through shared coactivators in the AR transcription complex. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. * Three  Input panels appear to overlap with each other. They all appear to show the same four lanes (marked in blue), with adjacent lanes on the left or right (marked in cyan, teal, and baby blue). * In Figure 6B, two panels appear to look very similar, marked with red boxes. ![file] ,
Phosphatidylethanolamine and monoglucosyldiacylglycerol are interchangeable in supporting topogenesis and function of the polytopic membrane protein lactose permease
Authors: Philip Heacock
Mikhail Bogdanov
William Dowhan
Jun Xie
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: lipids; membrane protein; topogenesis; Escherichia coli; lactose permease
Affiliations: Department of Biochemistry and Molecular Biology, University of Texas-Houston, Medical School, 77030, USA.

Abstract:  To determine the specific role lipids play in membrane protein topogenesis in vivo, the orientation with respect to the membrane bilayer of Escherichia coli lactose permease (LacY) transmembrane (TM) domains and their flanking extramembrane domains was compared after assembly in native membranes and membranes with genetically modified lipid content using the substituted cysteine accessibility method for determining TM domain mapping. LacY assembled in the absence of the major membrane lipid phosphatidylethanolamine (PE) does not carry out uphill transport of substrate and displays an inverted orientation for the N-terminal six-TM domain helical bundle (Bogdanov, M., Heacock, P. N., and Dowhan, W. (2002) EMBO J. 21, 2107-2116). Strikingly, the replacement of PE in vivo by the foreign lipid monoglucosyldiacylglycerol (MGlcDAG), synthesized by the Acholeplasma laidlawii MGlcDAG synthase, restored uphill transport and supported the wild type TM topology of the N-terminal helical bundle of LacY. An interchangeable role in defining membrane protein TM domain orientation and supporting function is played by the two most abundant lipids, PE and MGlcDAG, in gram-negative and gram-positive bacteria, respectively. Therefore, these structurally diverse lipids endow the membrane with similar properties necessary for the proper organization of protein domains in LacY that are highly sensitive to lipids as topological determinants. 

Retracted: No

PubPeer comments:
 ![file] There two bands in P5T 163C panel in Figgure 4B are duplicated from the bands in the P11 S375C panel in Figure 4C, marked in red boxes. Please check! ,
Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis
Authors: Aidin Tavakoli Tameh
Ritankar Majumdar
Carole A Parent
Journal: PLoS Biology (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Leukotriene B4; neutrophils; inflammation; exosomes; chemotactic activity
Affiliations: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Abstract:  Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments. 

Retracted: Yes

PubPeer comments:
 Figure 1 appears to include repeated images intended to represent different patients. I was assisted in confirming this by another reader on social media. *** Original showing matching images ![file] *** Superimposing one image over the other to confirm match. ![file] ,
2-Deoxyglucose induces Akt phosphorylation via a mechanism independent of LKB1/AMP-activated protein kinase signaling activation or glycolysis inhibition
Authors: Wei Zhou
Xiuju Liu
Katherine Schafer-Hales
Adam I Marcus
Diansheng Zhong
Shi-Yong Sun
Fadlo R Khuri
Journal: Molecular cancer therapeutics (2008)
Discipline: CLINICAL MEDICINE
Keywords: 2-deoxyglucose; chemotherapy; radiotherapy; Akt phosphorylation; glycolysis inhibition
Affiliations: The Winship Cancer Institute, Emory University School of Medicine, Building C, Room 4084, 1365 Clifton Road Northeast, Atlanta, GA 30322, USA.

Abstract:  The compound 2-deoxyglucose (2-DG) enhances chemotherapy/radiotherapy in cell lines and animal models, prompting two phase I clinical trials with this cancer therapeutic. Although its mechanism of action has not been fully elucidated, it is hypothesized that the molecular basis of 2-DG activity is related to glycolysis inhibition. Here, we report that 2-DG induced Akt phosphorylation at Thr(308) and Ser(473) as early as 15 min post-treatment. These phosphorylation events required phosphatidylinositol-3-kinase activity but were not related to LKB1/AMP-activated protein kinase signaling, the inhibition of glycolysis or epidermal growth factor receptor signaling. The 2-DG-mediated Akt phosphorylation also led to the phosphorylation of Akt downstream targets, such as Foxo3a, GSK3beta, and Chk1. Because the functional consequence of Akt activation includes chemotherapy/radiotherapy resistance, our data suggested that the combination of phosphatidylinositol-3-kinase/Akt inhibitory agents in 2-DG-based chemotherapy/radiotherapy may result in enhanced therapeutic efficacy. 

Retracted: No

PubPeer comments:
 Figure 2B. Much more simialr than you would expect. https: imgur.com bvUAmjq , 
 Figure 5. Much more similar than you would expect. https: imgur.com qe1gIHS ,
Widespread seasonal gene expression reveals annual differences in human immunity and physiology
Authors: Chris Wallace
Deborah J Smyth
Marina Evangelou
Andrew M Prentice
Nicholas Cooper
Ezio Bonifacio
Oliver S Burren
Anthony J Fulford
John A Todd
Anette-G Ziegler
Branwen J Hennig
Marcin L Pekalski
Xaquin Castro Dopico
Ricardo C Ferreira
Hui Guo
Journal: Nature Communications (2015)
Discipline: Multidisciplinary
Keywords: Seasonal variations; protein-coding mRNAs; white blood cells; adipose tissue; gene expression
Affiliations: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK., MRC International Nutrition Group at MRC Unit The Gambia &London School of Hygiene &Tropical Medicine, Keppel Street, London WC1E 7HT, UK., Institute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Ingolstaedter Landstr. 1, D 85764 Neuherberg, Germany., CRTD-DFG Research Center for Regenerative Therapies Dresden, Paul Langerhans Institute Dresden, Medical Faculty, Technische Universität Dresden, Fetscherstrasse, 01307 Dresden, Germany., MRC Biostatistics Unit, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.

Abstract:  Seasonal variations are rarely considered a contributing component to human tissue function or health, although many diseases and physiological process display annual periodicities. Here we find more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue to have seasonal expression profiles, with inverted patterns observed between Europe and Oceania. We also find the cellular composition of blood to vary by season, and these changes, which differ between the United Kingdom and The Gambia, could explain the gene expression periodicity. With regards to tissue function, the immune system has a profound pro-inflammatory transcriptomic profile during European winter, with increased levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for cardiovascular, psychiatric and autoimmune diseases that have peak incidences in winter. Circannual rhythms thus require further exploration as contributors to various aspects of human physiology and disease. 

Retracted: No

PubPeer comments:
 Could the authors please review the two sets of images marked in Figure 3A below? Should these appear so similar? Apologies if I m misunderstanding. *** ![file] ![file] , 
 There seem to be some concerning similarities in two bands shown in Figure 5 (magenta boxes). Do the authors still have access to the original data? *** ![file] *** ![file] ,
Overexpression of the VRK1 kinase, which is associated with breast cancer, induces a mesenchymal to epithelial transition in mammary epithelial cells
Authors: Aye M Mon
A Craig MacKinnon Jr
Paula Traktman
Journal: PLoS ONE (2018)
Discipline: Multidisciplinary
Keywords: VRK1; cell migration; invasion; colonization; epithelial properties
Affiliations: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, United States of America., Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, United States of America., Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, United States of America., The Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States of America.

Abstract:  Vaccinia-related kinase 1 (VRK1) is a pro-proliferative nuclear kinase. Mice engrafted with VRK1-depleted MDA-MB-231 breast cancer cells have been shown to develop fewer distal metastases than controls, suggesting VRK1 might play a role in cell migration, invasion, and/or colonization. In work described herein, we investigated the impact of VRK1 overexpression on human mammary epithelial cells. In 2D culture, VRK1 overexpression diminishes cell migration and invasion and impairs the migration-associated processes of cell spreading and cytoskeletal rearrangement. VRK1-overexpressing cells show reduced accumulation of the mesenchymal marker vimentin and increased accumulation of the epithelial markers E-cadherin and claudin-1. VRK1 overexpression also leads to reduced levels of the transcriptional repressors snail, slug, and twist1. Cumulatively, these data indicate that VRK1 overexpression augments the epithelial properties of both MCF10a and MDA-MB-231 cells. We further studied the impact of VRK1 on the epithelial properties of MCF10a cells in 3D matrigel culture, in which cells proliferate and form epithelial sheets that mature into hollow spherical acini. VRK1 overexpression significantly accelerates the initial stages of cell proliferation, leading to larger acini that nevertheless differentiate and mature. Our analysis of human tumor tissue microarrays (TMAs) revealed that VRK1 protein levels are higher in lymph node metastases than in patient-matched mammary tumors. Using public databases, we determined that VRK1 is among the top 10% of overexpressed transcripts in multiple subtypes of invasive breast cancer, and that high levels of VRK1 expression are correlated with decreased relapse-free survival. In sum, overexpression of VRK1, by regulating the transcription repressors snail, slug, and twist1, can promote a mesenchymal-to-epithelial transition (MET) in cell culture. VRK1-mediated MET might facilitate the colonization of distal sites by metastatic breast cancer cells, providing some insight into the frequent association of VRK1 overexpression with breast malignancies and the correlation between VRK1 overexpression and poor clinical outcome. 

Retracted: No

PubPeer comments:
 Figure 3A *** ![file] ,