PReD-Bench/PRed-Bench huggingface dataset:
Tumor necrosis factor alpha is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1
Authors: M Pandey
G S Hotamisligil
K T Uysal
D J Loskutoff
S M Wiesbrock
F Samad
Journal: Proceedings of the National Academy of Sciences of the United States of America (1999)
Discipline: Multidisciplinary
Keywords: Obesity; hypertension; insulin resistance; hyperinsulinemia; plasminogen activator inhibitor 1 (PAI-1)
Affiliations: The Scripps Research Institute, Department of Vascular Biology, 10550 North Torrey Pines Road, VB-3, La Jolla, CA 92037, USA.

Abstract:  Obesity is associated with a cluster of abnormalities, including hypertension, insulin resistance, hyperinsulinemia, and elevated levels of both plasminogen activator inhibitor 1 (PAI-1) and transforming growth factor beta (TGF-beta). Although these changes may increase the risk for accelerated atherosclerosis and fatal myocardial infarction, the underlying molecular mechanisms remain to be defined. Although tumor necrosis factor alpha (TNF-alpha) has been implicated in the insulin resistance associated with obesity, its role in other disorders of obesity is largely unknown. In this report, we show that in obese (ob/ob) mice, neutralization of TNF-alpha or deletion of both TNF receptors (TNFRs) results in significantly reduced levels of plasma PAI-1 antigen, plasma insulin, and adipose tissue PAI-1 and TGF-beta mRNAs. Studies in which exogenous TNF-alpha was infused into lean mice lacking individual TNFRs indicate that TNF-alpha signaling of PAI-1 in adipose tissue can be mediated by either the p55 or the p75 TNFR. However, TNF-alpha signaling of TGF-beta mRNA expression in adipose tissue is mediated exclusively via the p55 TNFR. Our results suggest that TNF-alpha is a common link between the insulin resistance and elevated PAI-1 and TGF-beta in obesity. The chronic elevation of TNF-alpha in obesity thus may directly promote the development of the complex cardiovascular risk profile associated with this condition. 

Retracted: No

PubPeer comments:
 TNF-a-treated wild-type (B) and p55 TNFR-deficient (D) are more similar than expected in Figure 4. Could authors check this please?  ,
MicroRNA-363-3p inhibits papillary thyroid carcinoma progression by targeting PIK3CA
Authors: Qun Li
Jia Liu
Su Dong
Peiyou Ren
Rui Li
Journal: American journal of cancer research (2017)
Discipline: CLINICAL MEDICINE
Keywords: PIK3CA; Papillary thyroid carcinoma; miR-363-3p; proliferation.
Affiliations: Department of Thyroid Surgery, The First Hospital of Jilin University 71# Xinmin Street, Chaoyang District, Changchun 130021, Jilin, P. R. China., Department of Anesthesia, The First Hospital of Jilin University 71# Xinmin Street, Chaoyang District, Changchun 130021, Jilin, P. R. China.

Abstract:  MicroRNA-363-3p (miR-363-3p) reportedly plays crucial roles in tumor development and progression in many types of cancers. However, its role in papillary thyroid carcinoma (PTC) remain largely unclear. We therefore investigated the function and underlying mechanism of miR-363-3p in PTC. Here, we found that miR-363-3p was significantly downregulated in human PTC tissue samples and cell lines, and that miR-363-3p levels are negatively correlated with advanced clinical stage and lymph node metastasis. In addition to suppressing tumor growth in vivo, restoration of miR-363-3p in TPC-1 cells significantly inhibits proliferation, migration, and invasion and induced apoptosis in vitro. Mechanistically, miR-363-3p was verified to directly bind to 3'UTR of the phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) mRNA, and reduce its expression at both mRNA and protein levels, which further inhibits phosphatidylinositol 3-kinase/Akt signaling pathway. PIK3CA expression was also found to be increased in human PTC tissues, and were inversely correlated with miR-363-3p. Furthermore, restoration of PIK3CA partially rescued the miR-363-3p-induced inhibition effect on TPC-1 cell proliferation, migration and invasion. Taken together, these findings indicated for the first time that miR-363-3p functions as a tumor suppressor in PTC, and its suppressive effect is mediated by repressing PIK3CA. 

Retracted: No

PubPeer comments:
 *[right]* Fig 6B.  Photographs of xenograft tumors from nude mice in each treatment group on day 35 after injection . *[left]* Fig 6B from [Li et al (2017)] .  The mice were sacrificed at 30 days after inoculation, and the tumor tissues were imaged . I have concerns.  , 
 *[right]* Fig 2C from **[Liu et al (2017)] **. Cell  cycle distribution ... determined in TPC-1 cells transfected with miR-363 mimic or miR-NC. *[left]* Fig 2C from [Yang et al (2018)] .  Flow cytometry analysis of cell cycle arrest in SKOV3 cells transfected with si-PVT1 or si-Ctrl . *[middle]* Fig 2D from [Xu et al (2016)] .  Cell cycle arrest was determined in MCF7 cells transfected with miR-154 mimic or miR-Ctrl by flow cytometer assay .  Could the authors of any of these papers comment on the appearance of the same flow-cytometry histograms in all three of them? UPDATE: Another sighting! Fic 2C from [Liu, Wang Liu (2019)] .  ,
RETRACTED ARTICLE: Resveratrol rescues hyperglycemia-induced endothelial dysfunction via activation of Akt
Authors: Rong-Hui Tu
Yan He
Bei-Bei Luo
Jin-Yi Li
Guo-Qiang Zhong
Wei-Qiang Huang
Journal: Acta Pharmacologica Sinica (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Resveratrol; endothelial dysfunction; hyperglycemia; signaling mechanisms; Akt phosphorylation
Affiliations: Department of Aging, the First Hospital Affiliated to Guangxi Medical University, Nanning 530021, China., Department of Cardiology, the First Hospital Affiliated to Guangxi Medical University, Nanning 530021, China.

Abstract:  Resveratrol (RSV), a phytoalexin, has shown to prevent endothelial dysfunction and reduce diabetic vascular complications and the risk of cardiovascular diseases. The aim of this study was to investigate the signaling mechanisms underlying the protecting effects of RSV against endothelial dysfunction during hyperglycemia in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were treated with RSV, and then exposed to high glucose (HG, 30 mmol/L). Akt-Ser473 phosphorylation, eNOS-Ser1177 phosphorylation, and PTEN protein levels in the cells were detected using Western blot. For in vivo studies, WT and Akt-/- mice were fed a normal diet containing RSV (400 mg¬∑kg-1¬∑d-1) for 2 weeks, then followed by injection of STZ to induce hyperglycemia (300 mg/dL). Endothelial function was evaluated using aortic rings by assessing ACh-induced vasorelaxation. RSV (5-20 Œºmol/L) dose-dependently increased Akt-Ser473 phosphorylation, accompanied by increased eNOS-Ser1177 phosphorylation in HUVECs; these effects were more prominent under HG stimulation. Transfection with Akt siRNA abolished RSV-enhanced eNOS phosphorylation and NO release. Furthermore, RSV (5-20 Œºmol/L) dose-dependently decreased the levels of PTEN, which was significantly increased under HG stimulation, and PTEN overexpression abolished RSV-stimulated Akt phosphorylation in HG-treated HUVECs. Moreover, RSV dramatically increased 26S proteasome activity, which induced degradation of PTEN. In in vivo studies, pretreatment with RSV significantly increased Akt and eNOS phosphorylation in aortic tissues and ACh-induced vasorelaxation, and improved diabetes-induced endothelial dysfunction in wild-type mice but not in Akt-/- mice. RSV attenuates endothelial function during hyperglycemia via activating proteasome-dependent degradation of PTEN, which increases Akt phosphorylation, and consequentially upregulation of eNOS-derived NO production. 

Retracted: Yes

PubPeer comments:
 Red boxes appear to indicate an area where two images overlap in Figure 1. However, the dimensions and coloring have been altered, suggesting that this is not simply a matter of selecting the wrong image during figure assembly. Why were the images edited? Note: the corresponding authoru2019s email address is an institutional address but the names donu2019t appear to be similar. ***  ,
High-resolution maps of magnetization transfer with inherent correction for RF inhomogeneity and T 1 relaxation obtained from 3D FLASH MRI
Authors: Peter Dechent
Gunther Helms
Kai Kallenberg
Henning Dathe
Journal: Magnetic Resonance in Medicine (2008)
Discipline: CLINICAL MEDICINE
Keywords: magnetization transfer; FLASH signal; semiquantitative parameter; percentage saturation; TR
Affiliations: MR-Forschung in der Neurologie und Psychiatrie, Universit√§tsmedizin G√∂ttingen, G√∂ttingen, Germany. 

Abstract:  An empirical equation for the magnetization transfer (MT) FLASH signal is derived by analogy to dual-excitation FLASH, introducing a novel semiquantitative parameter for MT, the percentage saturation imposed by one MT pulse during TR. This parameter is obtained by a linear transformation of the inverse signal, using two reference experiments of proton density and T(1) weighting. The influence of sequence parameters on the MT saturation was studied. An 8.5-min protocol for brain imaging at 3 T was based on nonselective sagittal 3D-FLASH at 1.25 mm isotropic resolution using partial acquisition techniques (TR/TE/alpha = 25ms/4.9ms/5 degrees or 11ms/4.9ms/15 degrees for the T(1) reference). A 12.8 ms Gaussian MT pulse was applied 2.2 kHz off-resonance with 540 degrees flip angle. The MT saturation maps showed an excellent contrast in the brain due to clearly separated distributions for white and gray matter and cerebrospinal fluid. Within the limits of the approximation (excitation &lt;15 degrees , TR/T(1) less sign 1) the MT term depends mainly on TR, the energy and offset of the MT pulse, but hardly on excitation and T(1) relaxation. It is inherently compensated for inhomogeneities of receive and transmit RF fields. The MT saturation appeared to be a sensitive parameter to depict MS lesions and alterations of normal-appearing white matter. 

Retracted: No

PubPeer comments:
 The approximation from Eq.[3] to Eq.[4] is ambiguous. Eq. [3] $S_{1} cong A sin alpha_{1} frac{R_{1} mathrm{TR}-left(1-cos alpha_{2}right) R_{1} mathrm{TR}_{1}}{1-cos alpha_{1} cos alpha_{2}left(1-R_{1} mathrm{TR}right)}$ In the manuscript, the author says  The influence of the individual TR1 and TR2 can be neglected for small $alpha_{2}$ 1 (in radians). This yields with $cos alpha_{2} approx 1-alpha_{2}^2 2$  (actually, there is a typo about the cos() approximation $$in original manuscript, I fixed it here) Eq. [4] $S_{1} cong A sin alpha_{1} frac{R_{1} mathrm{TR}}{left(1-cos alpha_{1}right)+alpha_{2}^{2} 2+R_{1} mathrm{TR}}$ The approximation in the denominator just comes out of nowhere. ,
Regulation of PTEN stability and activity by Plk3
Authors: Xuejun Jiang
Wei Dai
Yixin Yao
Luo Lu
Dazhong Xu
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PLK3; PTEN; Akt1; GSK3Œ≤; phosphorylation
Affiliations: Department of Environmental Medicine and Pharmacology, New York University School of Medicine, Tuxedo, New York 10987, USA.

Abstract:  By studying primary isogenic murine embryonic fibroblasts (MEFs), we have shown that PLK3 null MEFs contain a reduced level of phosphatase and tensin homolog (PTEN) and increased Akt1 activation coupled with decreased GSK3Œ≤ activation under normoxia and hypoxia. Purified recombinant Plk3, but not a kinase-defective mutant, efficiently phosphorylates PTEN in vitro. Mass spectrometry identifies threonine 366 and serine 370 as two putative residues that are phosphorylated by Plk3. Immunoblotting using a phosphospecific antibody confirms these sites as Plk3 phosphorylation sites. Moreover, treatment of MEFs with LiCl, an inhibitor of GSK3Œ≤ and CK2, only partially suppresses the phosphorylation, suggesting Plk3 as an additional kinase that phosphorylates these sites in vivo. Plk3-targeting mutants of PTEN are expressed at a reduced level in comparison with the wild-type counterpart, which is associated with an enhanced activity of PDK1, an upstream activator of Akt1. Furthermore, the reduced level of PTEN in PLK3 null MEFs is stabilized by treatment with MG132, a proteosome inhibitor. Combined, our study identifies Plk3 as a new player in the regulation of the PI3K/PDK1/Akt signaling axis by phosphorylation and stabilization of PTEN. 

Retracted: No

PubPeer comments:
 Identified by another reader. Possible recycled control band. ***  ,
Identification of CD4+ T-cell-derived CD161+ CD39+ and CD39+CD73+ microparticles as new biomarkers for rheumatoid arthritis
Authors: Jinyan Guo
Jie Wu
Wenxiang Wang
Ling Ma
Wenqiang Fan
Journal: Biomarkers in Medicine (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CD4+ T; T helper 17 cells; Treg; biomarker; fibroblast-like synoviocytes
Affiliations: Department of Rheumatology, The Central Hospital of Xinxiang, Xinxiang, Henan, China., Department of Gynecology Oncology, The Central Hospital of Xinxiang, Xinxiang, Henan, China., Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Abstract:  Aim: This study aimed to identify CD4+ T-cell-derived microparticles (MPs) and investigate their roles in rheumatoid arthritis (RA). Methods: Synovial fluids from 34 RA, 33 osteoarthritis patients and 42 healthy individuals were analyzed by flow cytometry. Human fibroblast-like synoviocytes and peripheral blood mononuclear cells were cultured with or without isolated MPs, chemokines and cytokines were measured by ELISA. Results: CD4+CD161+CD39+ and CD4+CD39+CD73+ MPs were abundantly present in RA patients, which were positively or negatively correlated with RA features, respectively. Chemokines CCL20, CCL17 and CCL22, and cytokines IL-17 and IL-10 were influenced by these MPs in human fibroblast-like synoviocytes (HFLS) or PMBCs. Conclusion: CD4+ T-cell-derived CD161+CD39+ and CD39+CD73+ MPs could serve as new reciprocal biomarkers for RA evaluation. 

Retracted: Yes

PubPeer comments:
 Figure 1 E and G FACS dot plots have striking partial similarity...once you mirror G along the horizontal axis. However, staining was done for CD39 CD161 and CD39 CD73  , 
 **RETRACTED** https: www.futuremedicine.com doi 10.2217 bmm-2016-0261 ,
Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells
Authors: Christopher K Hui
Ian Adcock
Paul Kirkham
Kian Fan Chung
Matthew Whiteman
Mark E Wood
Charalambos Michaeloudes
Mark M Perry
Journal: American Journal of Respiratory Cell and Molecular Biology (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hydrogen sulfide; gasotransmitter; airway smooth muscle; proliferation; IL-8 release
Affiliations: Experimental Studies, National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Abstract:  Hydrogen sulfide (H(2)S) is synthesized intracellularly by the enzymes cystathionine-Œ≥-lyase and cystathionine-Œ≤-synthase (CBS), and is proposed to be a gasotransmitter with effects in modulating inflammation and cellular proliferation. We determined a role of H(2)S in airway smooth muscle (ASM) function. ASM were removed from resection or transplant donor lungs and were placed in culture. Proliferation of ASM was induced by FCS and the proinflammatory cytokine, IL-1Œ≤. Proliferation of ASM and IL-8 release were measured by bromodeoxyuridine incorporation and ELISA, respectively. Exposure of ASM to H(2)S "donors" inhibited this proliferation and IL-8 release. Methemoglobin, a scavenger of endogenous H(2)S, increased DNA synthesis induced by FCS and IL-1Œ≤. In addition, methemoglobin increased IL-8 release induced by FCS, but not by IL-1Œ≤, indicating a role for endogenous H(2)S in these systems. Inhibition of CBS, but not cystathionine-Œ≥-lyase, reversed the inhibitory effect of H(2)S on proliferation and IL-8 release, indicating that this is dependent on CBS. CBS mRNA and protein expression were inhibited by H(2)S donors, and were increased by methemoglobin, indicating that CBS is the main enzyme responsible for endogenous H(2)S production. Finally, we found that exogenous H(2)S inhibited the phosphorylation of extracellular signal-regulated kinase-1/2 and p38, which could represent a mechanism by which H(2)S inhibited cellular proliferation and IL-8 release. In summary, H(2)S production provides a novel mechanism for regulation of ASM proliferation and IL-8 release. Therefore, regulation of H(2)S may represent a novel approach to controlling ASM proliferation and cytokine release that is found in patients with asthma. 

Retracted: No

PubPeer comments:
 Figure 4B. The beta-actin blot, if flipped horizontally and compressed horizontally and vertically, is too similar to the beta-actin blot in Figure 6A.  , 
 #1 I have contacted the lead author asking for them to send me the original figures so that we can respond to the query. I will be in touch when I get a response. BW, Ian ,
Inhibition of BAMBI reduces the viability and motility of colon cancer via activating TGF-Œ≤/Smad pathway in vitro and in vivo
Authors: Wenzhen Yu
Hong Chai
Journal: Oncology Letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: BAMBI; TGF-Œ≤/Smad pathway; colon cancer; motility; viability.
Affiliations: Department of Gastroenterology, The People's Hospital of Wuhan University, Wuchang, Wuhan, Hubei 430060, P.R. China.

Abstract:  Colon cancer is a highly metastatic gastrointestinal cancer. BMP activin membrane-bound inhibitor (BAMBI), as a pseudo-receptor of the tumor growth factor (TGF)-Œ≤ signal transduction pathway, has previously been demonstrated to be involved in human cancers. The present study demonstrated that BAMBI-small interfering (si)RNA regulated the viability and motility of colon cancer by activating TGF-Œ≤ signaling. The expression level of BAMBI was suppressed by transfecting BAMBI-siRNA into the SW480 and HT-29 colon cancer cell lines. Decreased cell proliferation and increased cell apoptosis were detected in SW480 and HT-29 cells transfected with BAMBI-siRNA. Decreased expression of proliferation marker proteins Ki67 and proliferating cell nuclear antigen and elevated expression of apoptosis marker proteins (caspases-3, -8 and -9) further verified the role of BAMBI-siRNA in inhibiting cell viability. Silencing of BAMBI strongly reduced the closing rate and the number of invasive cells compared with control group. BAMBI-siRNA additionally resulted in decreased expression of migration marker proteins matrix metalloproteinase-9 (MMP-9), MMP-14 and vascular endothelial cell growth factor. In addition, the expression of TGF-Œ≤ and phosphorylated-mothers against decapentaplegic homolog (Smad) 2/3 was increased in W480 and HT-29 cells transfected with BAMBI-siRNA. Elevated expression of the downstream signaling molecule E2F transcription factor 4/5 and suppressed c-MYC were additionally detected in the BAMBI-siRNA group. Finally, the in vivo experiment in the CSC xenograft revealed that BAMBI-siRNA strongly reduced the tumor growth and tumor volume. BAMBI-siRNA inhibited hepatic metastases and the expression of metastasis-associated proteins. The upregulated expression of TGF-Œ≤ signaling proteins were detected in the BAMBI-siRNA group compared with control group in vivo. Overall, the results of the present study indicated that the inhibition of BAMBI reduces the viability and motility of colon cancer and may involve activation of the TGF-Œ≤/Smad pathway in vitro and in vivo. 

Retracted: Yes

PubPeer comments:
 Figs 2B, 4D.  Pink box marks a panel which matches a panel in Figs 2C, 4C, 6C of [Li et al (2019)] . Maroon box marks a panel which matches one in Figs 2C, 4C, 5E of [Yan et al (2019)] - not an exact match but the vast majority of points are the same in both. Green box: matches a panel in Figs 2C, 5C, 6C of [Jiao, Liu Tian (2019)] .    Here in context:  -----------------------------------------  --------------------------------------  , 
 Another sighting of the green-boxed panel!  Figs 2E, 5E of [Guo Xue (2020)] .  ,
Rhubarb tannins extract inhibits the expression of aquaporins 2 and 3 in magnesium sulphate-induced diarrhoea model
Authors: Wen Xu
Na Lin
Yanfang Zheng
Chunfang Liu
Hui Wang
Journal: BioMed Research International (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Tannins; Chinese rhubarb; Aquaporins; Diarrhoea; Magnesium sulphate
Affiliations: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China., Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China ; Fujian University of Traditional Chinese Medicine, No. 1, Huatuo Road, Minhoushangjie, Fuzhou 350122, China.

Abstract:  Tannins, a group of major active components of Chinese rhubarb and widely distributed in nature, have a significant antidiarrhoeal activity. Aquaporins (AQPs) 2 and 3 play important roles in regulating water transfer during diarrhoea. The present study aims to determine the effect of the total tannins extract of rhubarb on aquaporins (AQPs) 2 and 3 in diarrhoea mice and HT-29 cells both induced by magnesium sulphate (MgSO4). Our results showed that rhubarb tannins extract (RTE) significantly decreased the faecal water content in colon and evaluation index of defecation of diarrhoea mice. Interestingly, RTE could markedly reduce the mRNA and protein expression levels of AQPs 2 and 3 in apical and lateral mucosal epithelial cells in the colons of diarrhoea mice and HT-29 cells both induced by MgSO4 in a dose-dependent manner. Furthermore, RTE suppressed the production of cyclic monophosphate- (cAMP-) dependent protein kinase A catalytic subunits Œ± (PKA C-Œ±) and phosphorylated cAMP response element-binding protein (p-CREB, Ser133) in MgSO4-induced HT-29 cells. Our data showed for the first time that RTE inhibit AQPs 2 and 3 expression in vivo and in vitro via downregulating PKA/p-CREB signal pathway, which accounts for the antidiarrhoeal effect of RTE. 

Retracted: No

PubPeer comments:
 Figure 4 and Figure 6. * Red pink boxes: Lanes 2-5 of the GAPDH panel in Figure 4A (RTE concentration series) look similar to lanes 1-4 of the GAPDH panel in Figure 6D (different RTE concentration series). * Blue boxes: The GAPDH panel in Figure 4B (RTE concentration series) looks similar to the GAPDH panel in Figure 6B (RTE time series).  , 
 The GAPDH panels marked in blue and red in comment #1 also look similar to GAPDH panels in Figures 4 and 6 of another paper by the same research group, i.e. Zeng YF et al. Fitoterapia 96 (2014) 25u201332, DOI: 10.1016 j.fitote.2014.04.002. See: https: pubpeer.com publications 030AEFF5F8D07925D79FFDCF5382E7 .  , 
 An additional finding, now including Figure 7 from this paper. * Green boxes: The GAPDH panel in Figurer 6A (RTE time series) looks similar to the GAPDH panel in Figure 7B (RTE concentration series).  ,
The BCL11A transcription factor directly activates RAG gene expression and V(D)J recombination
Authors: Baeck-seung Lee
Joseph D Dekker
Barry P Sleckman
Philip W Tucker
Arthur L Shaffer 3rd
Gregory C Ippolito
Bum-kyu Lee
Vishwanath R Iyer
Journal: Molecular and cellular biology (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RAG1; RAG2; BCL11A; B cell development; V(D)J recombination
Affiliations: Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, USA.

Abstract:  Recombination-activating gene 1 protein (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The transcription factor BCL11A is required for B cell development, but its molecular function(s) in B cell fate specification and commitment is unknown. We show here that the major B cell isoform, BCL11A-XL, binds the RAG1 promoter and Erag enhancer to activate RAG1 and RAG2 transcription in pre-B cells. We employed BCL11A overexpression with recombination substrates in a cultured pre-B cell line as well as Cre recombinase-mediated Bcl11a(lox/lox) deletion in explanted murine pre-B cells to demonstrate direct consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that BCL11A is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination. 

Retracted: Yes

PubPeer comments:
 2017 retraction notice. http: mcb.asm.org content 37 21 e00358-17.full , 
 #1 https: mcb.asm.org content 37 21 e00358-17.full Analysis of our data indicated duplicate bands in Fig. 6E and 7A. It is unclear whether the source of these errors was accidental or purposeful. However, these errors did not change the conclusions of the paper. Nonetheless, we thank the journal for recognizing these errors, and we hereby retract the paper. , 
 Here are the duplicated panels, as reported to the journal in October 2016.  ,
Cathepsin B and uPAR knockdown inhibits tumor-induced angiogenesis by modulating VEGF expression in glioma
Authors: K Alapati
C S Gondi
D H Dinh
R R Malla
S Gopinath
M Gujrati
J S Rao
Journal: Cancer Gene Therapy (2011)
Discipline: CLINICAL MEDICINE
Keywords: Angiogenesis; uPAR; cathepsin B; tumor progression; extracellular matrix
Affiliations: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA.

Abstract:  Angiogenesis, which is the process of sprouting of new blood vessels from pre-existing vessels, is vital for tumor progression. Proteolytic remodeling of extracellular matrix is a key event in vessel sprouting during angiogenesis. Urokinase type plasminogen activator receptor (uPAR) and cathepsin B are both known to be overexpressed and implicated in tumor angiogenesis. In the present study, we observed that knockdown of uPAR and cathepsin B using puPAR (pU), pCathepsin B (pC), and a bicistronic construct of uPAR and cathepsin B (pCU) caused significant inhibition of angiogenesis by disrupting the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway-dependent expression of vascular endothelial growth factor (VEGF). Further, transcriptional suppression of uPAR and cathepsin B inhibited tumor-induced migration, proliferation of endothelial cells and decreased tumor-promoted expression of VEGF receptor-2, Rac1, gp91phox, cyclin D1, cyclin dependent kinase 4 and p-Rb in human dermal microvascular endothelial cell. Furthermore, U251 and SNB19 xenograft tissue sections from nude mice treated with pCU showed reduced expression of VEGF and CD31, which is a blood vessel visualization marker. Overall, results revealed that knockdown of uPAR and cathepsin B inhibited tumor-induced angiogenesis by disrupting the JAK/STAT pathway-dependent expression of VEGF. These data provide new insight in characterizing the pathways involved in the angiogenic cascade and for the identification of novel target proteins for use in therapeutic intervention for gliomas. 

Retracted: No

PubPeer comments:
 Figure 6C. * In red: a possible overlap in the Control panels representing two different cell lines.  , 
 Supplentary Figure 2A. Duplicated images for different experimental groups  , 
 Fig 6D  ,
Targeted deletion of the integrin beta4 signaling domain suppresses laminin-5-dependent nuclear entry of mitogen-activated protein kinases and NF-kappaB, causing defects in epidermal growth and migration
Authors: Carlo Tacchetti
Toshiaki Yoshioka
Wenjun Guo
Sotiris N Nikolopoulos
Pamela Blaikie
Filippo G Giancotti
Claudia Puri
Journal: Molecular and Cellular Biology (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: alpha6beta4 integrin; laminin-5 receptor; hemidesmosomes; Shc; phosphoinositide 3-kinase
Affiliations: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Box 216, 1275 York Avenue, New York, New York 10021, USA., Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, IFOM Center of Cell Oncology and Ultrastructure, Department of Experimental Medicine, University of Genova, Genoa, Italy

Abstract:  The alpha6beta4 integrin-a laminin-5 receptor-mediates assembly of hemidesmosomes and recruitment of Shc and phosphoinositide 3-kinase through the unique cytoplasmic extension of beta4. Mice carrying a targeted deletion of the signaling domain of beta4 develop normally and do not display signs of skin fragility. The epidermis of these mice contains well-structured hemidesmosomes and adheres stably to the basement membrane. However, it is hypoplastic due to reduced proliferation of basal keratinocytes and undergoes wound repair at a reduced rate. Keratinocytes from beta4 mutant mice undergo extensive spreading but fail to proliferate and migrate in response to epidermal growth factor (EGF) on laminin-5. EGF causes significant phosphorylation of extracellular signal-regulated kinase (ERK) and Jun N-terminal protein kinase (JNK) and phosphorylation and degradation of IkappaB in beta4 mutant cells adhering to laminin-5. Unexpectedly, however, ERK, JNK, and NF-kappaB remain in the cytoplasm in beta4 mutant cells on laminin-5, whereas they enter effectively into the nucleus in the same cells on fibronectin or in wild-type cells on both matrix proteins. Inhibitor studies indicate that alpha6beta4 promotes keratinocyte proliferation and migration through its effect on NF-kappaB and P-JNK. These findings provide evidence that beta4 signaling promotes epidermal growth and wound healing through a previously unrecognized effect on nuclear translocation of NF-kappaB and mitogen-activated protein kinases. 

Retracted: No

PubPeer comments:
 Figure 6A. Much more similar than expected.  ,
EFNB2 haploinsufficiency causes a syndromic neurodevelopmental disorder
Authors: N Teissier
C Dupont
N Marziliano
A Verloes
P Gressens
F Guimiot
J L√©vy
B Benzacken
E Pipiras
A-C Tabet
D Haye
G Casu
Journal: Clinical Genetics (2018)
Discipline: CLINICAL MEDICINE
Keywords: ARGLU1; EFNB2; 13q33; congenital heart defect; developmental delay
Affiliations: Genetics Department, AP-HP, Robert-Debr√© University Hospital, Paris, France., Sorbonne Paris-Cit√© University, Denis Diderot Medical School, Paris, France., INSERM UMR1141, Robert-Debr√© Hospital, Paris Diderot University, AP-HP, Paris, France., Unit√† Operatica Complessa di Cardiologia, ASSL3 Nuoro-ATS Sardegna, Italy., Department of Developmental Biology, AP-HP Robert-Debr√© University Hospital, Paris Diderot University, Sorbonne Paris-Cit√© University, Paris, France., Department of Cytogenetics, University Hospital Jean-Verdier, Embryology and Histology, Bondy, France., Neuroscience Department, Human Genetics et Cognitive Function Unit, Pasteur Institute, Paris, France.

Abstract:  Ephrin B2, one of the ligand of the EphB receptors, is involved in a complex signaling pathway regulating the development of the nervous system, neuronal migration, erythropoiesis and vasculogenesis. We report a patient with a de novo variant in EFNB2 and a family in which segregates a 610-kb deletion at chromosome 13q33 encompassing only ARGLU1 and EFNB2 genes. The de novo variant was observed in a patient with anal stenosis, hypoplastic left ventricle and mild developmental delay. The deletion was identified in 2 sibs with congenital heart defect and mild developmental delay. One of the affected sibs further had myoclonic epilepsy and bilateral sensorineural hearing loss. The carrier mother was apparently asymptomatic. Because EFNB2 is located in the subtelomeric region of 13q chromosome, we reviewed the previous reports of terminal 13q deletion. We suggest that haploinsufficiency of the EFNB2 could be at the origin of several clinical features reported in 13qter deletions, including intellectual disability, seizures, congenital heart defects, anorectal malformation and hearing loss. 

Retracted: No

PubPeer comments:
 Three cases presented as *EFNB2* haploinsufficiency - Case 1: A.IV.2. Developmental delay, pyramidal spasticity, myoclonic epilepsy, microcephaly. Brain MRI reported as normal. I am surprised to note that IQ was not assessed. EEG was not performed? I think that such examinations should be mandatory with this clinical pictures. - Case 2: A.IV.3. Microcephaly, developmental delay. Brain MRI: short corpus callosum. What are the standards used by the authors for assessing such a feature? Brain MRI is not illustrated. Who has read this MRI? There is no radiologist among the authors. - Case 3: B.II.1. Developmental delay but no cerebral MRI. Is it normal? ,
Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis
Authors: Andr√© A Pilon
Eric A Cohen
Andrew D Badley
Xiao-Jian Yao
Julian J Lum
Zhaoxia Chen
Timothy S Gomez
David Lynch
Michael Montpetit
Nanci Hawley
Joel G Weaver
Jaime Sanchez-Dardon
Oren J Cohen
Zilin Nie
John E Kim
Journal: Journal of Clinical Investigation (2003)
Discipline: CLINICAL MEDICINE
Keywords: LTNP; HIV; Vpr; apoptosis; T cell depletion
Affiliations: Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

Abstract:  The absence of immune defects that occurs in the syndrome of long-term nonprogressive (LTNP) HIV infection offers insights into the pathophysiology of HIV-induced immune disease. The (H[F/S]RIG)(2) domain of viral protein R (Vpr) induces apoptosis and may contribute to HIV-induced T cell depletion. We demonstrate a higher frequency of R77Q Vpr mutations in patients with LTNP than in patients with progressive disease. In addition, T cell infections using vesicular stomatitis virus G (VSV-G) pseudotyped HIV-1 Vpr R77Q result in less (P = 0.01) T cell death than infections using wild-type Vpr, despite similar levels of viral replication. Wild-type Vpr-associated events, including procaspase-8 and -3 cleavage, loss of mitochondrial transmembrane potential (deltapsi(m)), and DNA fragmentation factor activation are attenuated by R77Q Vpr. These data highlight the pathophysiologic role of Vpr in HIV-induced immune disease and suggest a novel mechanism of LTNP. 

Retracted: No

PubPeer comments:
 Figure 8a: More similar than expected. Could authors check this issue please?  ,
<p>The Long Noncoding RNA LINC00908 Facilitates Hepatocellular Carcinoma Progression Via Interaction With Sox-4</p>
Authors: Xinhua Hu
Qingxiang Li
Jinfeng Zhang
Journal: Cancer Management and Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: HCC; LINC00908; Sox-4; lncRNA.
Affiliations: Department of Laboratory Medicine, Juxian Hospital of Traditional Chinese Medicine, Rizhao 276500, Shandong, People's Republic of China.

Abstract:  Background: The hepatocellular carcinoma (HCC) is a highly aggressive and common malignancy worldwide. Accumulating evidence has demonstrated a pivotal role of long noncoding RNAs (lncRNAs) in various tumors. However, the function of intergenic lncRNA LINC00908 is still unknown in HCC. Methods: The RT-qPCR method was used to quantify the expression of LINC00908. Migration and viability assay were performed to evaluate the in vitro effect and xenograft tumor model was used to measure the in vivo effect. Immunoblot was used to identify the association of LINC00908 with Sox-4 and the stability of Sox-4. Results: We found a novel lncRNA related to HCC. LINC00908 is highly expressed in tumorous tissues and cell lines compared with normal ones. High LINC00908 expression correlated with advanced TNM stages, tumor size and metastasis. LINC00908 promoted the migration and viability of HCC cells. The in vivo xenograft tumor growth and proliferation were also enhanced by LINC00908 overexpression and inhibited by LINC00908 silence. LINC00908 physically interacted with Sox-4, and the association between LINC00908 and Sox-4 increased the stability of Sox-4 by reducing proteasomal degradation. Conclusion: Taken together, our current work has identified a novel lncRNA LINC00908 which is critically involved in HCC progression. The LINC00908-Sox-4 axis might provide a new and potential target for pharmaceutical therapies. 

Retracted: Yes

PubPeer comments:
 Fig 2A.  GP suppresses RANKL-induced bone resorption in vitro. ... Bone resorption was measured using an in vitro resorption pit assay . Some repeated areas, as marked.  , 
 Fig 1B.  BMMs at a density of 1 u00d7 104 cells well were cultured with 100 ng mL of RANKL and 30 ng mL of M-CSF in the absence or presence of increasing concentrations of GP (12.5, 25, and 50 u00b5M) for 4 days. Then, the cells were fixed with 4% formaldehyde and stained with the TRAP. C, TRAP-positive cells containing three or more nuclei were counted . The 12.5- and 25-u00b5M GP panels are remarkably similar, apart from circumscribed areas of difference. Shown enlarged below. At lower right, I have black white reversed the 25 GP image and superimposed it on the 12.5 GP image, to cancel out areas where they are the same and allow one to concentrate on the six small enclaves of difference.  ,
Is copper beneficial for COVID-19 patients?
Authors: Syamal Raha
Sanjay Basak
Asim K Duttaroy
Rahul Mallick
Journal: Medical Hypotheses (2020)
Discipline: CLINICAL MEDICINE
Keywords: Blood cells; COVID-19; Contact killing; Copper; Coronavirus
Affiliations: Inventis Solutions, Inc., Edmonton, Alberta, Canada., Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland., Molecular Biology Division, ICMR-National Institute of Nutrition, India., Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: .

Abstract:  Copper (Cu) is an essential micronutrient for both pathogens and the hosts during viral infection. Cu is involved in the functions of critical immune cells such as T helper cells, B cells, neutrophils natural killer (NK) cells, and macrophages. These blood cells are involved in the killing of infectious microbes, in cell-mediated immunity and the production of specific antibodies against the pathogens. Cu-deficient humans show an exceptional susceptibility to infections due to the decreased number and function of these blood cells. Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Moreover, Cu has the potent capacity of contact killing of several viruses, including SARS-CoV-2. Since the current outbreak of the COVID-19 continues to develop, and there is no vaccine or drugs are currently available, the critical option is now to make the immune system competent to fight against the SARS-CoV-2. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Moreover, owing to its potent antiviral activities, Cu may also act as a preventive and therapeutic regime against COVID-19. 

Retracted: No

PubPeer comments:
 This article is misleading and speculative. Please note that the central reference regarding antiviral effects of copper (reference 15; Sagripanti JL et al., 1993; Appl Envir Microbiol) described copper+peroxide used on surfaces, not in patients. It doesn t help that another reference in the same paragraph links to a predatory journal (reference 25; Ishida T, 2018; World Sci News).   ,
Differentiation-associated genes regulated by TPA-induced c-Jun expression via a PKC/JNK pathway in KYSE450 cells
Authors: Qimin Zhan
Min Wu
Zhihua Liu
Fang Ding
Aiping Luo
Changchun Zhou
Xinfeng Yu
Journal: Biochemical and Biophysical Research Communications (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: differentiation-associated genes; c-Jun/AP-1; mitogen-activated protein kinase signaling pathways; 12-o-tetradecanoylophorbol-13-acetate (TPA); pharmacological reagents
Affiliations: National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China.

Abstract:  A group of potential differentiation-associated genes had been identified by microarray analysis as c-Jun/AP-1 target genes essential for epithelial differentiation program. Our previous study showed that c-Jun/AP-1 could bind and activate these gene promoters in vivo using chromatin immunoprecipitation. To further understand how the mitogen-activated protein kinase signaling pathways regulate AP-1 activity and expression of c-Jun target genes, our strategy was based on the use of 12-o-tetradecanoylophorbol-13-acetate (TPA) and pharmacological reagents to induce or block c-Jun expression. The mRNA and protein expression of these genes increased in response to TPA-induced c-Jun/AP-1 expression. Inhibitors of JNK (SP600125) and PKC (GF109203X) mainly blocked expression and phosphorylation of c-Jun, while inhibition of MEK-ERK activity with PD98059 (an inhibitor of MEK) had little effect. Expression of involucrin and keratin 4 in response to TPA was attenuated by pretreatments with GF109203X and SP600125, but not PD98059, suggesting involvement of PKC and JNK in this response. Taken together, these results suggested that differentiation-associated genes were regulated by TPA-induced c-Jun/AP-1 mainly via a PKC/JNK pathway in esophageal cancer cell line KYSE450. 

Retracted: No

PubPeer comments:
 Figures 1A and 4A. Much more similar than expected. https: imgur.com PO4Ab2a ,