PReD-Bench/PRed-Bench huggingface dataset:
CCN5, a novel transcriptional repressor of the transforming growth factor Œ≤ signaling pathway
Authors: Nathalie Ferrand
C√©line Prunier
Nicolas Nazaret
Kathleen Lambein
Sylvie Dumont
Mich√®le Sabbah
G√©rard Redeuilh
Virginie Megalophonos
Jo√´l Lachuer
Olivier De Wever
Journal: Molecular and Cellular Biology (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CCN5; breast carcinogenesis; transcriptional repressor; histone deacetylase 1; epithelial-mesenchymal transition
Affiliations: INSERM U938, H√¥pital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75571 Paris cedex 12, France. 

Abstract:  CCN5 is a member of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that the CCN5 protein is localized mostly in the cytoplasm and in part in the nucleus of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor presumably through association with histone deacetylase 1 (HDAC1). Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the transforming growth factor Œ≤ (TGF-Œ≤) signaling pathway, prominent among them TGF-Œ≤RII receptor. We show that CCN5 is recruited to the TGF-Œ≤RII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-Œ≤RII gene. Consistent with this finding, CCN5, we found, functions to suppress TGF-Œ≤-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-Œ≤ signaling cascade that is known to promote EMT. 

Retracted: No

PubPeer comments:
 Figure 2D. * Red boxes: Lanes *150-250* and *1-94* look more similar than expected, albeit stretched differently  Figures 5B and 5D * Purple boxes: Two Actin lanes in Figure 5B look similar to two Actin lanes in Figure 5D.  Figure 6B * Orange boxes: Two of the right panels look very similar to each other * Green arrows: Some bands appear surrounded by rectangular areas  All concerns were shared with the journal in October 2016, but have not been addressed as of today. This paper was part of a structured search for image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long ,
Gouleako virus isolated from West African mosquitoes constitutes a proposed novel genus in the family Bunyaviridae
Authors: W Grasse
C Drosten
H Ellerbrok
A Lukashev
M Marklewitz
A Kurth
S Handrick
S Junglen
F H Leendertz
G Pauli
Journal: Journal of Virology (2011)
Discipline: MICROBIOLOGY
Keywords: Bunyaviridae; Goul√©ako virus; genome; mosquito species; novel bunyavirus
Affiliations: Institute of Virology, University of Bonn Medical Centre, Sigmund Freud Str. 25, 53127 Bonn, Germany.

Abstract:  The family Bunyaviridae is the most diversified family of RNA viruses. We describe a novel prototypic bunyavirus, tentatively named Goul√©ako virus, isolated from various mosquito species trapped in C√¥te d'Ivoire. The S segment comprised 1,087 nucleotides (nt), the M segment 3,188 nt, and the L segment 6,358 nt, constituting the shortest bunyavirus genome known so far. The virus had shorter genome termini than phleboviruses and showed no evidence of encoded NSs and NSm proteins. An uncharacterized 105-amino-acid (aa) putative open reading frame (ORF) was detected in the S segment. Genetic equidistance to other bunyaviruses (74 to 88% aa identity) and absence of serological cross-reactivity with phleboviruses suggested a proposed novel Bunyaviridae genus. 

Retracted: No

PubPeer comments:
 image duplication  ,
The protein tyrosine kinase p56lck is required for triggering NF-kappaB activation upon interaction of human immunodeficiency virus type 1 envelope glycoprotein gp120 with cell surface CD4
Authors: V Robert-Hebmann
M Marsh
A Pelchen-Matthews
C Devaux
C Acquaviva
L Briant
Journal: Journal of virology (1998)
Discipline: MICROBIOLOGY
Keywords: NF-kappaB; HIV-1; CD4; p56(lck); signal transduction
Affiliations: Laboratoire Infections R√©trovirales et Signalisation Cellulaire, CRBM-CNRS UPR 1086, Institut de Biologie, Montpellier, France., Laboratoire Infections ReÃÅtrovirales et Signalisation Cellulaire, CRBM-CNRS UPR 1086, Institut de Biologie, Montpellier, France,1 and, Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom2

Abstract:  We have previously shown that NF-kappaB nuclear translocation can be observed upon human immunodeficiency virus type 1 (HIV-1) binding to cells expressing the wild-type CD4 molecule, but not in cells expressing a truncated form of CD4 that lacks the cytoplasmic domain (M. Benkirane, K.-T. Jeang, and C. Devaux, EMBO J. 13:5559-5569, 1994). This result indicated that the signaling cascade which controls HIV-1-induced NF-kappaB activation requires the integrity of the CD4 cytoplasmic tail and suggested the involvement of a second protein that binds to this portion of the molecule. Here we investigate the putative role of p56(lck) as a possible cellular intermediate in this signal transduction pathway. Using human cervical carcinoma HeLa cells stably expressing CD4, p56(lck), or both molecules, we provide direct evidence that expression of CD4 and p56(lck) is required for HIV-1-induced NF-kappaB translocation. Moreover, the fact that HIV-1 stimulation did not induce nuclear translocation of NF-kappaB in cells expressing a mutant form of CD4 at position 420 (C420A) and the wild-type p56(lck) indicates the requirement for a functional CD4-p56(lck) complex. 

Retracted: No

PubPeer comments:
 The similarity between the FACS data for the controls (white part) in these 2 panels of Fig 1 is too high to be due to chance!  ,
Decorin inhibits glucose-induced lens epithelial cell apoptosis via suppressing p22phox-p38 MAPK signaling pathway
Authors: Jingzhi Shao
Dandan Xie
Fengyan Zhang
Shanshan Du
Journal: PLoS ONE (2020)
Discipline: Multidisciplinary
Keywords: Decorin; oxidative stress; apoptosis; HLE cells; high glucose
Affiliations: Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou, Henan Province, China., School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan Province, China.

Abstract:  Purpose: To determine the effect of decorin on oxidative stress and apoptosis of human lens epithelial (HLE) cells under high glucose condition. Methods: HLE cell line (HLEB3) was incubated in normal glucose (5.5 mM) or high glucose (60 mM) medium. Decorin (50 nM) was applied 2 hours before high glucose medium was added. Apoptosis detection was executed by flow cytometry and western blotting (analysis of bcl-2 and bax). Oxidative stress level was measured by the generation of reactive oxygen species (ROS), glutathione peroxidase (GSH) and superoxide dismutase (SOD). P38 mitogen-activated protein kinase (MAPK) phosphorylation, the expression of p22phox of HLE cells and human lens anterior capsules were detected by western blotting. Small interfering RNA transfection to p22phox and p38 MAPK was also carried out on HLEB3. Results: High glucose caused HLE cells oxidative stress and apoptosis exhibiting the increase of apoptotic cells and ROS production and decrease of bcl-2/bax ratio, GSH/GSSG ration and SOD activity. P22phox and phospho-p38 MAPK were upregulated in high glucose treated HLEB3 cells. Knocking down p22phox or p38 by siRNAs can reduce high glucose induced cell apoptosis and oxidative stress level. Silencing p22phox by siRNA can downregulate the phosphorylation of p38 MAPK. Decorin can inhibit the apoptosis, oxidative stress level and the induction of p22phox and phospho-p38 of HLEB3 induced by high glucose. Furthermore, the expression of p22phox and p38 were found significantly increased in lens anterior capsules of diabetic cataract patients compared to that of normal age-related cataract patients. Conclusions: Results showed that p22phox-p38 pathway may be participated in high glucose induced lens epithelial cell injury, decorin may inhibit the high glucose induced apoptosis and oxidative stress injury by suppressing this pathway in part. 

Retracted: No

PubPeer comments:
 In Figure 1, part of a micrographs has been duplicated and presented as something else.  ,
Attenuation of lipopolysaccharide-induced lung vascular stiffening by lipoxin reduces lung inflammation
Authors: Margaret L Gardel
Anna A Birukova
Michael J Allen
Angelo Meliton
Isa Mambetsariev
Fanyong Meng
Yvonne Beckham
Konstantin G Birukov
Yufeng Tian
Alan Leff
Journal: American Journal of Respiratory Cell and Molecular Biology (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: endothelium; lipoxin; lung inflammation; stiffness; vascular leak.
Affiliations: 1 Lung Injury Center, Section of Pulmonary and Critical Care Medicine, Department of Medicine, and.

Abstract:  Reversible changes in lung microstructure accompany lung inflammation, although alterations in tissue micromechanics and their impact on inflammation remain unknown. This study investigated changes in extracellular matrix (ECM) remodeling and tissue stiffness in a model of LPS-induced inflammation and examined the role of lipoxin analog 15-epi-lipoxin A4 (eLXA4) in the reduction of stiffness-dependent exacerbation of the inflammatory process. Atomic force microscopy measurements of live lung slices were used to directly measure local tissue stiffness changes induced by intratracheal injection of LPS. Effects of LPS on ECM properties and inflammatory response were evaluated in an animal model of LPS-induced lung injury, live lung tissue slices, and pulmonary endothelial cell (EC) culture. In vivo, LPS increased perivascular stiffness in lung slices monitored by atomic force microscopy and stimulated expression of ECM proteins fibronectin, collagen I, and ECM crosslinker enzyme, lysyl oxidase. Increased stiffness and ECM remodeling escalated LPS-induced VCAM1 and ICAM1 expression and IL-8 production by lung ECs. Stiffness-dependent exacerbation of inflammatory signaling was confirmed in pulmonary ECs grown on substrates with high and low stiffness. eLXA4 inhibited LPS-increased stiffness in lung cross sections, attenuated stiffness-dependent enhancement of EC inflammatory activation, and restored lung compliance in vivo. This study shows that increased local vascular stiffness exacerbates lung inflammation. Attenuation of local stiffening of lung vasculature represents a novel mechanism of lipoxin antiinflammatory action. 

Retracted: No

PubPeer comments:
 duplications in figure 7  , 
 #1 Erratum: In original Figure 7C depicting F-actin staining of EC plated on 1.5 kPa substrate after 6-hr LPS treatment and EC plated on 40 kPa substrate after 2-hr LPS treatment erroneously presented 2 serial images of same condition: EC on 1.5 kPa substrate treated with 6-hr LPS. The revised Figure 7C presents correct image of EC at 40 kPa substrate treated with 2-hr LPS. The authors apologize for this technical glitch. The corrected figure is below. Anna Birukova.  , 
 thank you for the update ,
TPX2 gene silencing inhibits cell proliferation and promotes apoptosis through negative regulation of AKT signaling pathway in ovarian cancer
Authors: Yan Wang
Lian-Lian Liu
Yang Li
Yuan Tian
Fu-Ju Wu
Dong-Mei Guo
Wen-Hui Zha
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AKT signaling pathway; apoptosis; ovarian cancer; proliferation; targeting protein for Xklp2.
Affiliations: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, P.R. China.

Abstract:  Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. Accumulated studies have revealed that targeting protein for Xklp2 (TPX2) was tightly associated with the development and progression of OC. The present study further determined a novel mechanism of TPX2 in OC via the AKT signaling pathway. The differentially expressed genes were screened in GEO database for gene expression microarray of OC. Bioinformatics was used to analyze the key differentially expressed genes in OC. We prepared CD133/1+ OC stem cells. Then cells were treated with TPX2-1 siRNA and perifcsine to explore the correlation of TPX2 and the AKT signaling pathway. We determined the expression of TPX2, AKT, Pl3 K, PTEN, caspase-3, Bax and Bcl-2 in OC cells. Cell proliferation, migration, invasion, and apoptosis rate were respectively measured using MTT and EdU assays, Transwell assay, Scratch test, and flow cytometry. Xenograft tumor in nude mice was used to determine the effect of TPX2 in OC cells in vitro. Initially, TPX2 overexpression was observed in OC, and TPX2 mediated the effect of the AKT signaling pathway in OC. TPX2 knockdown decreased expression of AKT, Pl3 K, and Bcl-2, and the extent of AKT phosphorylation, but increased expression of PTEN, Caspase-3, and Bax. Furthermore, TPX2 knockdown suppressed OC cell proliferation, migration and invasion, but promoted OC cell apoptosis. Taken together, TPX2 silencing negatively regulates the AKT signaling pathway by which OC cell proliferation was inhibited yet cell apoptosis was accelerated, suggesting a potential therapeutic approach to OC. 

Retracted: Yes

PubPeer comments:
 Fig 5C,  grey values of of TPX2, AKT, Pl3 K, Bcl, p-AKT, PTEN, Caspase-3, Bax, Bcl-2, and GAPDH .  The protein blobs seem to come from the same restricted gamut shown in this montage:  , 
 Retracted [19 July 2021] -------------------------------------- The above article, published online on 15 June 2018 in Wiley Online Library has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid.). ---------------------------------------------- ,
A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of theranostic agents. [Corrected]
Authors: Pranay Agarwal
Xiongbin Lu
Jianhua Yu
Hai Wang
Shuting Zhao
Xiaoming He
Journal: Nature Communications (2015)
Discipline: Multidisciplinary
Keywords: Nanoparticles; drug delivery; encapsulation efficiency; drug loading content; hybrid nanoplatform
Affiliations: Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, USA., Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA., Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, USA., Division of Hematology, The Ohio State University, Columbus, Ohio 43210, USA., Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract:  Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ‚à?7%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases. 

Retracted: No

PubPeer comments:
 Erratum January 7, 2016 The original version of this Article contained an error in the spelling of u2018theranosticu2019 in the title of the paper. This has now been corrected in both the PDF and HTML versions of the Article. , 
 The mice in images at time 0 and time 6 hours in Figure 4a appear unexpectedly similar except for fluorescence, given that they are not in the same position at other times. *** Closeup  *** 4a showing location and other times  , 
 Thank you very much for the comments! I ll talk to my co-authors and carefully address them ASAP. Best regards! , 
 https: forbetterscience.com 2021 04 19 xiongbin-lu-nanobombs-cancer-with-fluorescent-nude-mouse-recycling Indiana University Research Integrity Officer Shelley Bizila u201cMy office, IUu2019s Research Integrity Office, is responsible for receiving any allegations of possible falsification, fabrication or plagiarism and for administering IUu2019s policy. As such, our office has previously been made aware of the concerns you cite and has already started an inquiry process. We will proceed according to our policy to ensure any concerns of possible research misconduct are addressed. u201c ,
Chronic Inhibition of STAT3/STAT5 in Treatment-Resistant Human Breast Cancer Cell Subtypes: Convergence on the ROS/SUMO Pathway and Its Effects on xCT Expression and System xc- Activity
Authors: Sina Haftchenary
David A Rosa
Gurmit Singh
Patrick T Gunning
Katja Linher-Melville
Robert G Ungard
Mina G Nashed
Journal: PloS one (2016)
Discipline: Multidisciplinary
Keywords: STAT3; STAT5; cancer research; system xc-; glutaminolysis
Affiliations: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, L8S 4L8, Canada., Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, Ontario, L5L 1C6, Canada.

Abstract:  Pharmacologically targeting activated STAT3 and/or STAT5 has been an active area of cancer research. The cystine/glutamate antiporter, system xc-, contributes to redox balance and export of intracellularly produced glutamate in response to up-regulated glutaminolysis in cancer cells. We have previously shown that blocking STAT3/5 using the small molecule inhibitor, SH-4-54, which targets the SH2 domains of both proteins, increases xCT expression, thereby increasing system xc- activity in human breast cancer cells. The current investigation demonstrates that chronic SH-4-54 administration, followed by clonal selection of treatment-resistant MDA-MB-231 and T47D breast cancer cells, elicits distinct subtype-dependent effects. xCT mRNA and protein levels, glutamate release, and cystine uptake are decreased relative to untreated passage-matched controls in triple-negative MDA-MB-231 cells, with the inverse occurring in estrogen-responsive T47D cells. This "ying-yang" effect is linked with a shifted balance between the phosphorylation status of STAT3 and STAT5, intracellular ROS levels, and STAT5 SUMOylation/de-SUMOylation. STAT5 emerged as a definitive negative regulator of xCT at the transcriptional level, while STAT3 activation is coupled with increased system xc- activity. We propose that careful classification of a patient's breast cancer subtype is central to effectively targeting STAT3/5 as a therapeutic means of treating breast cancer, particularly given that xCT is emerging as an important biomarker of aggressive cancers. 

Retracted: No

PubPeer comments:
 Fig. 1A vs Fig. 6D https: imgur.com a dxQLFq5 , 
 https: onties.com canada under-the-microscope-research-lab-promising-cancer-breakthrough-and-whistleblower-who-uncovered-false-data , 
 Any update, considering other McMaster investigations? https: retractionwatch.com 2020 02 10 those-unfortunate-events-second-retraction-for-stem-cell-scientist-in-canada-accused-of-misconduct #more-118882 ,
CSNK2A1 Promotes Gastric Cancer Invasion Through the PI3K-Akt-mTOR Signaling Pathway
Authors: Zhenghong Ma
Xigui Yang
Chao Jiang
Weibo Wang
Guoan Zhang
Qin Du
Journal: Cancer management and research (2019)
Discipline: CLINICAL MEDICINE
Keywords: CSNK2A1; function; gastric cancer; mechanism.
Affiliations: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China., Departments of Oncology, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong 250031, People's Republic of China., Forensic Science Center, Jining Medical University, Jining, Shandong 272067, People's Republic of China., Cancer Pathology Institute, Jining Medical University, Jining, Shandong 272000, People's Republic of China., Departments of Oncology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, People's Republic of China.

Abstract:  Objective: Casein kinase 2 a1 (CSNK2A1) has been shown to be involved in tumorigenesis by enhancing several oncogenic signaling pathways in various cancers. However, the function and mechanism of CSNK2A1 in gastric cancer remain unclear, and this study aimed to elucidate the role of CSNK2A1 in gastric cancer. Methods: CSNK2A1 expression was assessed by Western blot and qPCR in four gastric cancer (GC) cell lines and one normal gastric epithelial cell line. Stable cancer cell lines with CSNK2A1 gene overexpression or knockdown were established to investigate the function and mechanism of CSNK2A1 in GC cells. Results: CSNK2A1 expression was higher in GC cells than in normal gastric epithelial cells. Stable overexpression of CSNK2A1 in SNU216 cells significantly increased cellular proliferation, invasion, and migration. Silencing CSNK2A1 expression in SGC-790 cells effectively inhibited its oncogenic function. We further verified that epithelial-mesenchymal transition (EMT) was affected by CSNK2A1 and that CSNK2A1 promotes GC cell invasion through the PI3K-Akt-mTOR signaling pathway. Conclusion: Our findings suggested that CSNK2A1 plays important oncogenic roles in GC invasion via EMT and the PI3K-Akt-mTOR signaling pathway and that CSNK2A1 may serve as a novel prognostic and/or therapeutic target in GC. 

Retracted: No

PubPeer comments:
 In the section  Participants , the authors said they used snowball sampling, and obviously, there could be two questions: 1. Why a snowball sampling is used in the cross-sectional study on common young people aged 14u201335? I think the application of snowball sampling has reduced the level of randomization in this study , and seems no other benefits. 2. Whatu2019s WeChat circle of friends? Who could access the authorsu2019 and participantsu2019 u201cWeChat circle of friendsu201d? When a participant forwarded the questionnaire to their own WeChat circle of friends, were only young people with specific social determinants seeing and filling out the questionnaire? What make your sample different from a convenient sample? ,
Six-Month Freedom From Amputation Rates and Quality of Life Following Tibial and Pedal Endovascular Revascularization for Critical Limb Ischemia
Authors: Jisun J Lee
Sapan S Desai
Kara A Rothenberg
Rebecca Gologorsky
Anahita Dua
Journal: Vascular and endovascular surgery (2019)
Discipline: CLINICAL MEDICINE
Keywords: angioplasty; critical limb ischemia; limb salvage.
Affiliations: 1 Division of Vascular Surgery, Department of Surgery, Stanford Hospital and Clinics, Palo Alto, CA, USA., 2 Department of Surgery, University of California San Francisco-East Bay, Oakland, CA, USA., 3 Division of Vascular Surgery, Department of Surgery, Northwest Hospital, Arlington, IL, USA.

Abstract:  Objective:: Patients with critical limb ischemia (CLI) and gangrene have a 10% to 38% rate of major amputation at 6 months. The purpose of this study is to report short- and mid-term major and minor amputation rates for patients who underwent tibial and pedal revascularization in addition to quality-of-life (QoL) scores. Methods:: All patients who presented to a single institution with CLI (defined as rest pain or nonhealing wounds) and underwent antegrade or retrograde tibial access, atherectomy and angioplasty of the tibial circulation, and angioplasty of pedal circulation (antegrade or retrograde) from June 2016 to September 2017 were included. The Stark QoL questionnaire was used at each visit. Patients were scored at 1, 3, and 6 months postprocedure. Amputation rates were recorded. Results:: Forty-two patients with CLI and gangrene underwent 57 peripheral interventions for limb salvage between June 2016 and September 2017. Thirty-two limbs had dry gangrene along the dorsalis pedis angiosome, 14 limbs had dry gangrene along the posterior tibial angiogram, and 11 limbs had a combined disease pattern. Twelve limbs underwent angioplasty of the superficial femoral artery (SFA), 18 limbs underwent angioplasty and stenting of the SFA, and 14 limbs underwent atherectomy, angioplasty, and stenting of the SFA. All patients had 1 or 2 tibial vessel runoff and high-grade stenosis of the pedal circulation. Immediate technical success defined as 3-vessel outflow to the foot occurred in 49 limbs (86%) with zero 30-day complications (30-day readmission, major amputation, or sepsis). Major amputation rate at 1, 3, and 6 months was 0%, 2%, and 4%, respectively. Patient satisfaction in terms of QoL increased over the 6-month follow-up period. Conclusion:: Aggressive tibial and pedal revascularization may improve freedom from minor and major amputation at 6 months and may be associated with a short- and mid-term higher QoL. 

Retracted: No

PubPeer comments:
 Can the authors please indicate which institutional review board approved this study. It would also help interpret the study if the single institution was identified. ,
Systemic administration with tetrahydrocannabinol causes retinal damage in BALB/c mice
Authors: R Li
Z Zhang
H Lu
X Zhang
Journal: Human & experimental toxicology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: BALB/c mice; Tetrahydrocannabinol; inflammatory responses; oxidative stress; retinal damage.
Affiliations: Ophthalmology Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.

Abstract:  Recent years have seen substantial shifts in cultural attitudes towards cannabis for medical and recreational use. However, legalizing recreational marijuana may have adverse effects on individual and public health. As the most widely used illicit agent, cannabis is commonly reported to disrupt learning and memory. Unfortunately, the molecular mechanisms underlying behavioral impairment by cannabis abuse remain poorly understood. Tetrahydrocannabinol (THC), a major component in cannabis, causes short-term effects on the visual system, but little is known about persisting visual disturbances. This study was to investigate the effects of systemic administration with THC on retina and explore its underlying mechanisms. BALB/c mice were treated with 1 or 2 mg/kg THC intraperitoneally daily for 2 months, mice treated with vehicle as negative control. The retinal function was tested by electroretinography after THC treatment. Morphology and pathology changes of retina were detected by hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect the apoptosis in photoreceptor cells. Enzyme-linked immunosorbent assay was used to show the inflammatory responses and oxidative stress. mRNA and protein changes were measured by real-time polymerase chain reaction and Western blot to explore the underlying mechanisms. Results indicated that 2-month treatment with THC caused retinal damage, evidenced by its functional loss and increased apoptosis in photoreceptor cells through inducing inflammatory responses and oxidative stress. Our study demonstrated that systemic administration with THC caused toxic effects on retinas of BALB/c mice, suggesting the potential mechanisms for the retina damage caused by cannabis abuse. 

Retracted: No

PubPeer comments:
 The proposed method is deficient because the ranking method based on the score function is flawed.   , 
 We have given clear explanation for this issue, please see the following link: https: pubpeer.com publications 30814165353935C154DB0FBFFBB70A Thanks for your comments. ,
Association of atopic diseases and attention-deficit/hyperactivity disorder: A systematic review and meta-analyses
Authors: Rukiye √ái√ßek
Pieter J Hoekstra
Jurjen van der Schans
Eelko Hak
Tjalling W de Vries
Journal: Neuroscience and biobehavioral reviews (2017)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Allergy; Asthma; Atopy; Attention-Deficit/Hyperactivity Disorder; Eczema
Affiliations: Department of Pharmacy, Pharmacoepidemiology & Pharmacoeconomics, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. Electronic address: ., Department of Pharmacy, Pharmacoepidemiology & Pharmacoeconomics, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands., Pediatrics, Medical Centre Leeuwarden, Henri Dunantweg 2, 8934 AD Leeuwarden, The Netherlands., Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

Abstract:  Over the last decades, the hypothesis has been raised that an atopic response could lead to the development of attention-deficit/hyperactivity disorder (ADHD). This study systematically reviews the observational cross-sectional and longitudinal studies that assessed the association between atopic disorders including asthma, atopic eczema, allergic rhinitis, and ADHD in children and adolescents. For longitudinal studies, a weighted Mantel-Haenszel odds ratio of these associations was estimated. The majority of cross-sectional and longitudinal studies reported a statistically significant positive association. The meta-analysis of longitudinal studies revealed an overall weighted odds ratio for asthma of 1.34 (95% confidence interval [CI] 1.24-1.44), 1.32 (95% CI 1.20-1.45) for atopic eczema, and 1.52 (95% CI 1.43-1.63) for allergic rhinitis. Heterogeneity of study data was low (I2: 0%, p=0.46 and p=0.64, respectively) for both studies examining asthma and eczema but substantial for rhinitis studies (I2: 82%, p=0.004). This current systematic review provides strong evidence that ADHD is associated with atopic diseases and that individuals have a 30% to 50% greater chance of developing ADHD compared to controls. 

Retracted: No

PubPeer comments:
 Minor error in referencing: In a forest plot, an article is named as Mogenson. Everywhere else in the article is Mogensen ,
Key role of the endothelial TGF-Œ≤/ALK1/endoglin signaling pathway in humans and rodents pulmonary hypertension
Authors: Beno√Æt Gore
Gerald Simonneau
Saadia Eddahibi
Franck Lebrin
Laurence Dewachter
Marc Humbert
Mohamed Izikki
Robert Naeije
Elie Fadel
Philippe Dartevelle
Olaf Mercier
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: TGF-Œ≤; ALK1; ENG; PAH; pulmonary arterial hypertension
Affiliations: INSERM U999, Le Plessis-Robinson, France., Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France., Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Brussels, Belgium., INSERM U833, Coll√®ge de France, Paris, France., INSERM U999, Le Plessis-Robinson, France; Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.

Abstract:  Mutations affecting transforming growth factor-beta (TGF-Œ≤) superfamily receptors, activin receptor-like kinase (ALK)-1, and endoglin (ENG) occur in patients with pulmonary arterial hypertension (PAH). To determine whether the TGF-Œ≤/ALK1/ENG pathway was involved in PAH, we investigated pulmonary TGF-Œ≤, ALK1, ALK5, and ENG expressions in human lung tissue and cultured pulmonary-artery smooth-muscle-cells (PA-SMCs) and pulmonary endothelial cells (PECs) from 14 patients with idiopathic PAH (iPAH) and 15 controls. Seeing that ENG was highly expressed in PEC, we assessed the effects of TGF-Œ≤ on Smad1/5/8 and Smad2/3 activation and on growth factor production by the cells. Finally, we studied the consequence of ENG deficiency on the chronic hypoxic-PH development by measuring right ventricular (RV) systolic pressure (RVSP), RV hypertrophy, and pulmonary arteriolar remodeling in ENG-deficient (Eng+/-) and wild-type (Eng+/+) mice. We also evaluated the pulmonary blood vessel density, macrophage infiltration, and cytokine expression in the lungs of the animals. Compared to controls, iPAH patients had higher serum and pulmonary TGF-Œ≤ levels and increased ALK1 and ENG expressions in lung tissue, predominantly in PECs. Incubation of the cells with TGF-Œ≤ led to Smad1/5/8 phosphorylation and to a production of FGF2, PDGFb and endothelin-inducing PA-SMC growth. Endoglin deficiency protected mice from hypoxic PH. As compared to wild-type, Eng+/- mice had a lower pulmonary vessel density, and no change in macrophage infiltration after exposure to chronic hypoxia despite the higher pulmonary expressions of interleukin-6 and monocyte chemoattractant protein-1. The TGF-Œ≤/ALK1/ENG signaling pathway plays a key role in iPAH and experimental hypoxic PH via a direct effect on PECs leading to production of growth factors and inflammatory cytokines involved in the pathogenesis of PAH. 

Retracted: No

PubPeer comments:
 Figure 6A * Green boxes: IN the  Pure Drug row, the  Day 15 and  Day 21 photo appear to be taken from the same animal on the same day. Light reflection and hair position are remarkably similar.  ,
mTORC1 maintains the tumorigenicity of SSEA-4(+) high-grade osteosarcoma
Authors: Wu Zhang
Xiao-Yi Ding
Jian-Ru Qiu
Meng-Lei Ding
Yu-Hui Shen
Lian-Fu Deng
Jiang Zhu
Jia-Nian Zhang
Wei-Bin Zhang
Journal: Scientific Reports (2015)
Discipline: Multidisciplinary
Keywords: p53; Rb pathways; osteoblasts; cell-cycle exit; terminal differentiation
Affiliations: 1] State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology and Collaborative Innovation Center of Hematology, Rui-Jin Hospital affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, People's Republic of China [2] Collaborative Innovation Center of Systems Biomedicine, Shanghai 200025, People's Republic of China., State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology and Collaborative Innovation Center of Hematology, Rui-Jin Hospital affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, People's Republic of China., Shanghai Institute of Digestive Surgery, Shanghai 200025, People's Republic of China., Division of Orthopedics and Shanghai Institute of Traumatology and Orthopaedics, Shanghai 200025, People's Republic of China., Department of Radiology, Rui-Jin Hospital, Shanghai 200025, People's Republic of China.

Abstract:  Inactivation of p53 and/or Rb pathways restrains osteoblasts from cell-cycle exit and terminal differentiation, which underpins osteosarcoma formation coupled with dedifferentiation. Recently, the level of p-S6K was shown to independently predict the prognosis for osteosarcomas, while the reason behind this is not understood. Here we show that in certain high-grade osteosarcomas, immature SSEA-4(+) tumor cells represent a subset of tumor-initiating cells (TICs) whose pool size is maintained by mTORC1 activity. mTORC1 supports not only SSEA-4(+) cell self-renewal through S6K but also the regeneration of SSEA-4(+) TICs by SSEA-4(-) osteosarcoma cell dedifferentiation. Mechanistically, active mTORC1 is required to prevent a likely upregulation of the cell-cycle inhibitor p27 independently of p53 or Rb activation, which otherwise effectively drives the terminal differentiation of SSEA-4(-) osteosarcoma cells at the expense of dedifferentiation. Thus, mTORC1 is shown to critically regulate the retention of tumorigenicity versus differentiation in discrete differentiation phases in SSEA-4(+) TICs and their progeny. 

Retracted: No

PubPeer comments:
 Could the authors please examine figures 6b and 6c? It appears that the same set of mice appears twice (magenta boxes), 6c with added luminescence, although they seem to be described differently. ***  , 
 Author Correction Published: 27 October 2021 This Article contains an error in Figure 6, where the incorrect image was used for Figure 6c. The correct Figure 6 and its accompanying legend appear below.  ,
Nanoscale Metal‚ÄìOrganic Framework Co-delivers TLR-7 Agonists and Anti-CD47 Antibodies to Modulate Macrophages and Orchestrate Cancer Immunotherapy
Authors: Wenbin Lin
Xiaomin Jiang
Michael Kaufmann
Kaiyuan Ni
August Culbert
Taokun Luo
Journal: Journal of the American Chemical Society (2020)
Discipline: CHEMISTRY
Keywords: nMOFs; radiosensitizers; radiotherapy-radiodynamic therapy; surface modification; Hf-DBP

Abstract:  Nanoscale metal-organic frameworks (nMOFs) are excellent radiosensitizers for radiotherapy-radiodynamic therapy (RT-RDT). Herein, we report surface modification of a Hf-DBP nMOF for the co-delivery of a hydrophobic small-molecule toll-like receptor 7 agonist, imiquimod (IMD), and a hydrophilic macromolecule, anti-CD47 antibody (Œ±CD47), for macrophage modulation and reversal of immunosuppression in tumors. IMD repolarizes immunosuppressive M2 macrophages to immunostimulatory M1 macrophages, while Œ±CD47 blocks CD47 tumor cell surface marker to promote phagocytosis. Upon X-ray irradiation, IMD@Hf-DBP/Œ±CD47 effectively modulates the immunosuppressive tumor microenvironment and activates innate immunity to orchestrate adaptive immunity when synergized with an anti-PD-L1 immune checkpoint inhibitor, leading to complete eradication of both primary and distant tumors on a bilateral colorectal tumor model. nMOFs thus provide a unique platform to co-deliver multiple immunoadjuvants for macrophage therapy to induce systematic immune responses and superb antitumor efficacy. 

Retracted: No

PubPeer comments:
  Retraction of: Antitumor effects of helenalin in doxorubicin-resistant leukemia cells are mediated via mitochondrial mediated apoptosis, loss of mitochondrial membrane potential, inhibition of cell migration and invasion and downregulation of PI3-kinase AKT m-TOR signalling pathway , by Jingxin Liu, Yanan Zhao, Zhangzhen Shi, Yuansong Bai, JBUON 2019;24(5):2068-2074; PMID:31786877. Following the publication of the above article, readers drew to our attention that part of the data was unreliable. The authors were requested to provide the raw data to prove the originality, but were unable to do so. After an investigation, the Editors of JBUON decided to retract this article. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.  ,
Stress induces mitochondria-mediated apoptosis independent of SAPK/JNK activation in embryonic stem cells
Authors: Hiroyuki Kishimoto
Ryota Saito
Shuhei Tanemura
Gen Nishitai
Noriyuki Azuma
Hiroki Yoshida
Teiji Wada
Junko Kubota
Shinya Ohata
Nao Shimizu
Takahiro Negishi
Hiroshi Nishina
Tak W Mak
Daiju Kitagawa
Haruka Momose
Tomomi Watanabe
Josef M Penninger
Kentaro Nakagawa
Satoshi Asaka
Toshiaki Katada
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: SAPK/JNK; MAPK; apoptosis; embryonic development; immune responses
Affiliations: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Abstract:  SAPK/JNK, which belongs to the family of mitogen-activated protein kinase (MAPK), is activated by many types of cellular stresses or extracellular signals and is involved in embryonic development, immune responses, and cell survival or apoptosis. However, the physiological roles of SAPK/JNK in the signaling of stress-induced apoptosis are still controversial. To evaluate the precise function, SAPK/JNK-inactivated mouse embryonic stem (ES) cells were generated by disrupting genes of the MAPK activators, SEK1 and MKK7. Although SAPK/JNK activation by various stresses was completely abolished in sek1(-/-) mkk7(-/-) ES cells, apoptotic responses including DNA fragmentation and caspase 3 activation still occurred normally, which displays a sharp contrast to apaf1(-/-) ES cells exhibiting profound defects in the mitochondria-dependent apoptosis. These normal apoptotic responses without SAPK/JNK activation were also observed in fibroblasts derived from sek1(-/-) mkk7(-/-) ES cells. Instead, interleukin-1 beta (IL-1 beta)-induced IL-6 gene expression was greatly suppressed in sek1(-/-) mkk7(-/-) fibroblasts. These results clearly show that SAPK/JNK activation is responsible for the inflammatory cytokine-induced gene expression but not essentially required for the mitochondria-dependent apoptosis at least in ES or fibroblast-like cells, which are prototypes of all cell lineages. 

Retracted: No

PubPeer comments:
 Figure 2c. https: imgur.com 5erqAQc ,
Overexpression of insulin-like growth factor-1 attenuates the myocyte renin-angiotensin system in transgenic mice
Authors: P Anversa
A Malhotra
J Kajstura
A Leri
Y Liu
X Wang
L G Meggs
Journal: Circulation Research (1999)
Discipline: CLINICAL MEDICINE
Keywords: IGF-1; myocytes; apoptosis; hypertrophy; angiotensin II
Affiliations: Department of Medicine, New York Medical College, Valhalla, NY, USA., From the Department of Medicine, New York Medical College, Valhalla, NY.

Abstract:  Constitutive overexpression of insulin-like growth factor-1 (IGF-1) in myocytes protects them from apoptosis and interferes with myocyte hypertrophy in the normal and pathological heart. Conversely, angiotensin II (Ang II) triggers cell death and promotes myocyte hypertrophy. Moreover, activation of p53 upregulates the cellular renin-angiotensin system (RAS). Therefore, IGF-1 overexpression in FVB.Igf+/- mice may downregulate the local RAS through the attenuation of p53 and p53-inducible genes. On this basis, p53 DNA binding activity to angiotensinogen (Aogen), bax, and the AT1 receptor was determined in left ventricular myocytes from FVB.Igf-/- and FVB.Igf+/- mice. The quantity of Bax, Bcl-2, Aogen, and AT1 receptor in these cells was evaluated. The presence of Mdm2-p53 complexes was also established. Finally, Ang II levels in myocytes were measured. Upregulation of IGF-1 in myocytes was associated with a protein-to-protein interaction between Mdm2 and p53, which attenuated p53 transcriptional activity for bax, Aogen, and AT1 receptor. Similarly, the amount of Bax, Aogen, and AT1 receptor proteins in these cells decreased. In contrast, the expression of Bcl-2 remained constant. The downregulation of Aogen in myocytes from FVB.Igf+/- mice was characterized by a reduction in Ang II. In conclusion, IGF-1 negatively influences the myocyte RAS through the upregulation of Mdm2 and its binding to p53. This may represent the molecular mechanism responsible for the effects of IGF-1 on cell viability and myocyte hypertrophy in the nonpathological and pathological heart in vivo. 

Retracted: No

PubPeer comments:
null, 
null, 
 Still nothing on this paper? https: retractionwatch.com 2018 12 13 anversa-cardiac-stem-cell-lab-earns-13-retractions ,
Dynamic telomerase gene suppression via network effects of GSK3 inhibition
Authors: Tim Hammonds
Katrina Stevenson
Jon Roffey
Stacey Hoare
Jane Plumb
W Nicol Keith
Alan E Bilsland
Kyle Lafferty-Whyte
Natividad Gomez-Roman
Claire Cairney
Sharon Burns
Journal: PloS one (2009)
Discipline: Multidisciplinary
Keywords: Telomerase; hTERT; GSK3 inhibitors; Cancer cells; Telomere length
Affiliations: Centre for Oncology and Applied Pharmacology, University of Glasgow, Cancer Research UK Beatson Laboratories, Garscube Estate, Bearsden, Glasgow, United Kingdom.

Abstract:  Background: Telomerase controls telomere homeostasis and cell immortality and is a promising anti-cancer target, but few small molecule telomerase inhibitors have been developed. Reactivated transcription of the catalytic subunit hTERT in cancer cells controls telomerase expression. Better understanding of upstream pathways is critical for effective anti-telomerase therapeutics and may reveal new targets to inhibit hTERT expression. Methodology/principal findings: In a focused promoter screen, several GSK3 inhibitors suppressed hTERT reporter activity. GSK3 inhibition using 6-bromoindirubin-3'-oxime suppressed hTERT expression, telomerase activity and telomere length in several cancer cell lines and growth and hTERT expression in ovarian cancer xenografts. Microarray analysis, network modelling and oligonucleotide binding assays suggested that multiple transcription factors were affected. Extensive remodelling involving Sp1, STAT3, c-Myc, NFkappaB, and p53 occurred at the endogenous hTERT promoter. RNAi screening of the hTERT promoter revealed multiple kinase genes which affect the hTERT promoter, potentially acting through these factors. Prolonged inhibitor treatments caused dynamic expression both of hTERT and of c-Jun, p53, STAT3, AR and c-Myc. Conclusions/significance: Our results indicate that GSK3 activates hTERT expression in cancer cells and contributes to telomere length homeostasis. GSK3 inhibition is a clinical strategy for several chronic diseases. These results imply that it may also be useful in cancer therapy. However, the complex network effects we show here have implications for either setting. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than expected.  ,
Facile one-pot multicomponent synthesis and molecular docking studies of steroidal oxazole/thiazole derivatives with effective antimicrobial, antibiofilm and hemolytic properties
Authors: Mohd Asif
Mohammad Owais
Abad Ali
Anam Ansari
Mohd Ahmar Rauf
Shamsuzzaman
Journal: Steroids (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Antibiofilm; Antimicrobial; Docking; Hemolysis; Heterocycle

Abstract:  A series of steroidal oxazole and thiazole derivatives have been synthesized employing thiosemicarbazide/semicarbazide hydrochloride and ethyl 2-chloroacetoacetate with a simple and facile one-pot multicomponent reaction pathway. The antimicrobial activity of newly synthesized compounds were evaluated against four bacterial strains namely Gram-negative (Escherichia coliand Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) in addition to pathogenic fungi (Candida albicans and Cryptococcus neoformans). Bioactivity assay manifested that most of the compounds exhibited good antimicrobial activity. To provide additional insight into antimicrobial activity, the compounds were also tested for their antibiofilm activity against S. aureus biofilm. Moreover, molecular docking study shows binding of compounds with amino acid residues of DNA gyrase and glucosamine-6-phosphate synthase (promising antimicrobial target) through hydrogen bonding interactions. Hemolytic activity have been also investigated to ascertain the effect of compounds over RBC lysis and results indicate good prospects for biocompatibility. The expedient synthesis of steroidal heterocycles, effective antibacterial and antifungal behavior against various clinically relevant human pathogens, promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents. 

Retracted: No

PubPeer comments:
 Figure 1. * Yellow boxes. Panels 12 and 13 appear to show an overlap, albeit with different zoom factors. Image made lighter to bring out more details.  ,