PReD-Bench/PRed-Bench huggingface dataset:
STAT1-avtiviated LINC00961 regulates myocardial infarction by the PI3K/AKT/GSK3β signaling pathway
Authors: Jun Shi
Li He
Lulu Liu
Ying He
Hao Ma
Shengzhong Liu
Yingqiang Guo
Journal: Journal of cellular biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LINC00961; long noncoding RNA; myocardial infarction (MI); phosphoinositide 3-kinases (PI3K); signal transducer and activator of transcription 1 (STAT1).
Affiliations: Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Cardiac Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China., Psychosomatic Medicine Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.

Abstract:  Myocardial infarction (MI) remains a severe cardiac disease because of its high incidence and mortality worldwide. A growing body of recent investigations have confirmed that LINC00961 acts as a tumor suppressor in diverse malignancies. However, the biological significance of LINC00961 and its molecular mechanism in MI are still elusive. Hypoxia is the leading cause of MI and induces myocardial injury. In this study, we found the upregulated expression of LINC00961 in cardiomyocytes H9c2 after hypoxia treatment. Knockdown of LINC00961 ameliorated hypoxia-induced cell injury by facilitating cell viability while repressing cell apoptosis. The significant increase of signal transducer and activator of transcription 1 (STAT1) expression and phosphorylation levels was observed in hypoxia-induced cells and proved to exacerbate hypoxia injury. In addition, STAT1 transcriptionally activated LINC00961 by binding to LINC00961 promoter. Furthermore, our results validated that suppressing LINC00961 contributed to the remarkable diminution in the phosphorylation levels of phosphoinositide 3-kinases (PI3K), AKT, and glycogen synthase kinase-3β (GSK3β). Inhibition of PI3K/AKT signaling or GSK3β pathway rescued the effects of LINC00961 knockdown on the hypoxia-induced injury of cardiomyocytes. Namely, we concluded that STAT1-avtiviated LINC00961 accelerated MI via the PI3K/AKT/GSK3β pathway, which may provide clues for the treatment of patients with MI. 

Retracted: No

PubPeer comments:
 Two of the flow cytometry plots in Figure 4 have perfectly matching regions (highlighted) and regions that do not match. I am struggling to find an inoccuous explanation to how this could occur. Would the authors be able to explain? ![file] ,
Transcription enhancer factor 1 interacts with a basic helix-loop-helix zipper protein, Max, for positive regulation of cardiac alpha-myosin heavy-chain gene expression
Authors: N Hay
R Zak
C S Amin
M Gupta
M P Gupta
Journal: Molecular and Cellular Biology (1997)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: M-CAT binding factor; TEF-1; Max; cardiac gene regulation; protein-protein interaction
Affiliations: Department of Medicine, The University of Chicago, Illinois 60637, USA.

Abstract:  The M-CAT binding factor transcription enhancer factor 1 (TEF-1) has been implicated in the regulation of several cardiac and skeletal muscle genes. Previously, we identified an E-box-M-CAT hybrid (EM) motif that is responsible for the basal and cyclic AMP-inducible expression of the rat cardiac alpha-myosin heavy chain (alpha-MHC) gene in cardiac myocytes. In this study, we report that two factors, TEF-1 and a basic helix-loop-helix leucine zipper protein, Max, bind to the alpha-MHC EM motif. We also found that Max was a part of the cardiac troponin T M-CAT-TEF-1 complex even when the DNA template did not contain an apparent E-box binding site. In the protein-protein interaction assay, a stable association of Max with TEF-1 was observed when glutathione S-transferase (GST)-TEF-1 or GST-Max was used to pull down in vitro-translated Max or TEF-1, respectively. In addition, Max was coimmunoprecipitated with TEF-1, thus documenting an in vivo TEF-1-Max interaction. In the transient transcription assay, overexpression of either Max or TEF-1 resulted a mild activation of the alpha-MHC-chloramphenicol acetyltransferase (CAT) reporter gene at lower concentrations and repression of this gene at higher concentrations. However, when Max and TEF-1 expression plasmids were transfected together, the repression mediated by a single expression plasmid was alleviated and a three- to fourfold transactivation of the alpha-MHC-CAT reporter gene was observed. This effect was abolished once the EM motif in the promoter-reporter construct was mutated, thus suggesting that the synergistic transactivation function of the TEF-1-Max heterotypic complex is mediated through binding of the complex to the EM motif. These results demonstrate a novel association between Max and TEF-1 and indicate a positive cooperation between these two factors in alpha-MHC gene regulation. 

Retracted: No

PubPeer comments:
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 #2 Figure 7A. https: imgur.com ptVbQQW ,
Menopause-induced uterine epithelium atrophy results from arachidonic acid/prostaglandin E2 axis inhibition-mediated autophagic cell death
Authors: Shengtao Zhou
Linjie Zhao
Tao Yi
Xia Zhao
Yuquan Wei
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Menopause; Estrogen; Uterine endometrial atrophy; Autophagy; Endoplasmic reticulum stress
Affiliations: Department of Gynecology and Obstetrics, Key Laboratory of Obstetrics &Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, and The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China.

Abstract:  Women experience menopause later in life. Menopause is characterized by dramatically decreased circulating estrogen level secondary to loss of ovarian function and atrophic state of genital organs. However, the molecular mechanisms for this process are not fully understood. In this study, we aimed to investigate the potential molecular mechanisms that underlie menopause-induced uterine endometrial atrophy. Our data showed that autophagy was activated in the uterine epithelial cells of both ovariectomized rats and peri-menopausal females. Endoplasmic reticulum (ER) stress occurred even prior to autophagy induction. Integrated bioinformatics analysis revealed that ER stress induced downstream decreased release of arachidonic acid (AA) and downregulation of AA/prostaglandin E2 (PGE2) axis, which led to Akt/mTOR signaling pathway inactivation. Consequently, autophagosomes were recruited and LC3-dependent autophagy was induced in uterine epithelial cells. Treatment with exogenous E2, PGE2, salubrinal or RNAi-mediated silencing of key autophagy genes could effectively counteract estrogen depletion-induced autophagy. Collectively, autophagy is a critical regulator of the uterine epithelium that accounts for endometrial atrophy after menopause. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A95 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
miR-15b reduces amyloid-β accumulation in SH-SY5Y cell line through targetting NF-κB signaling and BACE1
Authors: Juan Li
Haitao Wang
Journal: Bioscience Reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Alzheimer’s disease; Aβ; BACE1; NF-κB; miR-15b.
Affiliations: Department of Geriatrics, Zhejiang Integrated Chinese and Western Medicine Hospital, Hangzhou 310006, P.R. China ., Department of Neurology, Wuhan Union Hospital, Attending Physician, Wuhan 430022, P.R. China.

Abstract:  Alzheimer's disease (AD) is the multifactorial neurodegenerative disorder causing progressive memory loss and cognitive impairment. The aberrant accumulation of amyloid-β (Aβ) and neuroinflammation are two major events in AD. BACE1 is required for the cleavage of amyloid precursor protein (APP) to generate Aβ, which stimulates the nuclear transcription factor κB (NF-κB) signaling, leading to the secretion of inflammatory cytokines. And NF-κB can up-regulate the expression of BACE1. miRNAs are small non-coding RNAs that regulate gene transcription. miR-15b down-regulates BACE1 expression while it is unclear whether miR-15b can regulate Aβ in human neuronal cells, and if so, whether it is by targetting NF-κB. SH-SY5Y cell line was transfected with Swedish APP mutant (APPswe) as an in vitro AD model. Quantitative PCR (qPCR), WB, and ELISA were used to detected related gene expression intracellularly or in supernatant. Dual luciferase assay was used to validate miRNA and targets binding. miR-15b inhibits expression of BACE1and APP. Moreover, the reduced level of Aβ was observed in response to miR-15b mimics in SH-SH5Y/APPswe cells. miR-15b directly targetted the conserved Bace1 3'UTR to regulate its expression. In addition, the inhibition of APPswe-induced secretion of inflammatory cytokines and the suppression of NF-κB activation by miR-15b were validated. And miR-15b directly targetted the 3'UTRs of NF-κB1 and inhibitor of NF-κB (IκB) kinase α (IKK-α), encoding NF-κB1 and IKK-α, respectively. Our study suggests that miR-15b inhibits Aβ accumulation through targetting NF-κB signaling and BACE1 and serves as a potential molecular target for AD therapy. 

Retracted: No

PubPeer comments:
 I have some concerns about figure 5B. The smears in the first lane (green) have some common characteristics. Could the authors please provide original uncropped scans of the gel to reassure readers? I also tried to analyze the image using some photo tools (see 2nd and 3rd image below). I find unusual areas identified with cyan and magenta outlines. Iu2019m not sure if these are signs of editing, or artifacts, but the original scans should address these issues. *** Closeup ![file] *** Colors appear inverse B W photo, possibly indicating editing in Photoshop. ![file] *** Forensically ![file] *** Full figure ![file] , 
 April 9, 2021 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. ,
Curcumin ameliorates PRMT5-MEP50 arginine methyltransferase expression by decreasing the Sp1 and NF-YA transcription factors in the A549 and MCF-7 cells
Authors: Biji Chatterjee
Santosh R Kanade
Lavanya Suresh
Krishna Ghosh
Journal: Molecular and Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AKT; Curcumin; Epigenetics; MEP50/WDR77; NF-YA
Affiliations: Department of Biochemistry and Molecular Biology, School of Biological Sciences, Central University of Kerala, Kasargod, Kerala, 671316, India., Department of Biochemistry and Molecular Biology, School of Biological Sciences, Central University of Kerala, Kasargod, Kerala, 671316, India. ., Department of Plant Sciences, School of Life Sciences, University of Hyderabad, Prof. C R Rao Road, Gachibowli, Telangana, 500046, India. .

Abstract:  The protein arginine methyltransferase 5 (PRMT5) and its catalytic partner methylosome protein MEP50 (WDR77) catalyse the mono- and symmetric di-methylation of selective arginines in various histones and non-histone target proteins. It has emerged as a crucial epigenetic regulator in cell proliferation and differentiation; which also reported to be overexpressed in many forms of cancers in humans. In this study, we aimed to assess the modulations in the expression of this enzyme upon exposure to the well-studied natural compound from the spice turmeric, curcumin. We exposed the lung and breast cancer cell lines (A549 and MCF-7) to curcumin (2 and 20 μM) and observed a highly significant inhibitory effect on the expression of both PRMT5 and MEP50. The level of symmetrical dimethylarginine (SDMA) in multiple proteins, and more specifically, the H4R3me2s mark (which predominates in GC-rich motifs in nucleosomal DNA) was also diminished significantly. We also found that curcumin significantly reduced the level and enrichment of the transcription factors Sp1 and NF-YA which shares their binding sites within the GC-rich region of the PRMT5 proximal promoter. Furthermore, the involvement of both PKC-p38-ERK-cFos and AKT-mTOR signalling was observed in reducing the Sp1 and NF-YA expression by curcumin. Therefore, we propose curcumin decreased the expression of PRMT5 in these cells by affecting at least these two transcription factors. Altogether, we report a new molecular target of curcumin and further elucidation of this proposed mechanism through which curcumin affects the PRMT5-MEP50 methyltransferase expression might be explored for its therapeutic application. 

Retracted: No

PubPeer comments:
 Below: Figure 5A.  The impact of miR-155 on Bcl-2 protein expression in osteosarcoma cells. A, Western blot detection of Bcl-2 protein expression . Above: Figure 6B from [Yang et al (2017)] .  MiR-33b regulation and MMP-9 expression in endometrial cells. ... (B) Western blot for MMP-9 protein expression in endometrial tissues . Same loading bands in completely different contexts from unrelated research groups. It is a mystery. ![file] ,
<p>Anti-Inflammatory Effects of Magnetically Targeted Mesenchymal Stem Cells on Laser-Induced Skin Injuries in Rats</p>
Authors: Huiying Lv
Jinlan Jiang
Bai Yang
Xiuying Li
Wei Zhang
Liya Wu
Mingji Zhu
Zhenhong Wei
Jing Li
Hao Zhang
Journal: International Journal of Nanomedicine (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Fe3O4 nanoparticle; anti-inflammatory effect; magnetic targeting; mesenchymal stem cells; skin injury.
Affiliations: Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China., Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China., State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, People's Republic of China., Dermatological Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China.

Abstract:  Introduction: Mesenchymal stem cells (MSCs) are a promising resource for tissue regeneration and repair. However, their clinical application is hindered by technical limitations related to MSC enrichment at the target sites. Methods: MSCs were labeled with magnetic Fe3O4 nanoparticles (NPs). We analyzed the effects of NP on cell proliferation, stem cell characteristics, and cytokine secretion. Furthermore, we induced NP-labeled MSC migration with an external magnetic field toward laser-induced skin wounds in rats and evaluated the associated anti-inflammatory effects. Results: Fe3O4 NP application did not adversely affect MSC characteristics. Moreover, Fe3O4 NP-labeled MSCs presented increased anti-inflammatory cytokine and chemokine production compared with unlabeled MSCs. Furthermore, MSCs accumulated at the injury site and magnetic targeting promoted NP-labeled MSC migration toward burn injury sites in vivo. On day 7 following MSC injection, reduced inflammation and promoted angiogenesis were observed in the magnetically targeted MSC group. In addition, anti-inflammatory factors were upregulated, whereas pro-inflammatory factors were downregulated within the magnetically targeted MSC group compared with those in the PBS group. Conclusion: This study demonstrates that magnetically targeted MSCs contribute to cell migration to the site of skin injury, improve anti-inflammatory effects and enhance angiogenesis compared with MSC injection alone. Therefore, magnetically targeted MSC therapy may be an effective treatment approach for epithelial tissue injuries. 

Retracted: No

PubPeer comments:
 Figure 8 of 10.2147 ijn.s258017 (Original August 2020) appears to include an image with **different description, rotation, dimensions, and coloring**, that seems to overlap with an image included as a correction to 10.2147 ijn.s184920 (Original Jan 2019), that was published as 10.2147 IJN.S275285 (Correction Aug 2020). All of this occurred in the same journal. As the dates are similar, I am posting to both PubPeer threads. *** ![file] , 
 #1 ![file] , 
 One of the images of the mice in Figure 5A seems to show a repeated region. *** ![file] ,
A Chinese Medicine Formula “Xian-Jia-Tang” for Treating Bladder Outlet Obstruction by Improving Urodynamics and Inhibiting Oxidative Stress through Potassium Channels
Authors: Wenjin An
Jie Sun
Shunan Qiu
Wei Shen
Qiufen Li
Shaobo Jiang
Journal: Evidence-based Complementary and Alternative Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: Chinese medicine; Xian-Jia-Tang; bladder outlet obstruction; rats; efficacy
Affiliations: Department of Urology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City 310006, China, Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou City 310006, China

Abstract:  The aim of this study is to investigate efficacy of a traditional Chinese medicine formula (named Xian-Jia-Tang, XJT) on bladder outlet obstruction (BOO) in rats and explore its mechanisms. Total 80 BOO model rats were established and randomly divided into 4 groups: physiological saline, XJT, Cesium Chloride (CC), and XJT and CC groups. Meanwhile, 12 rats were used as normal control. Bladder weight and urodynamics were measured. Oxidative stress level and mRNA expressions of potassium channels gene were detected in detrusor. The mRNA and protein levels of hypoxia inducible factor-α (HIF-α) in detrusor were detected by RT-PCR and Western blot. BOO model rats showed significantly higher bladder weight and abnormal urodynamics. XJT significantly improved the abnormal urodynamics and inhibited the oxidative stress and changes of mRNA levels of potassium channels genes in detrusor of BOO model rats. Moreover, KATP and SK2/3 mRNA were overexpressed in BOO model rats treated by XJT. Besides, the significantly increased levels of HIF-α mRNA and protein were also inhibited by XJT. However, these inhibition effects of XJT were weakened by CC. XJT could effectively improve the urodynamics and inhibit the oxidative stress caused by hypoxia through suppressing the role of potassium channels in BOO model rats. 

Retracted: No

PubPeer comments:
 This paper proposes an herbal remedy containing pangolin scales as a treatment for BPH  Chinese medicine is always considered to be milder and does not have as strong side effects as Western drugs. Xian-Jia-Tang (XJT) is a traditional Chinese medicine formula for invigorating kidney and promoting blood circulation (composition: root of Rehmannia glutinosa [shudi], leaves of Epimedium [yinyanghuo], fruit of barbary wolfberry [gouqizi], morinda root [bajitian], pangolin scales [chuanshanjia], root of Salvia miltiorrhiza [danshen], root of Rhizoma curcumae [eshu], and root of szechwan lovage rhizome [chuanxiong] at a rate of 2u2009:u20092u2009:u20093u2009:u20092u2009:u20091u2009:u20092u2009:u20091u2009:u20092 in dry weight, including 2.34u2009g dry medicine ml. XJT has been found to be able to suppress the proliferation of prostatic duct epithelium, reduce the deposition of collagen, and inhibit uncoordinated contraction of the bladder, thereby protecting the function of bladder in BPH rats This is quite ethically concering ,
Tongxinluo exerts protective effects via anti-apoptotic and pro-autophagic mechanisms by activating AMPK pathway in infarcted rat hearts
Authors: He-He Cui
Gui-Hao Chen
Yue-Jin Yang
Na Li
Chen Jin
Qing Li
Xia-Qiu Tian
Journal: Experimental physiology (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: AMPK; Tongxinluo; acute myocardial infarction; apoptosis; autophagy.
Affiliations: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China.

Abstract:  What is the central question of this study? In a rat model of acute myocardial infarction (AMI), we investigated the effect of Tongxinluo (TXL) treatment. Does TXL activate autophagy and attenuate apoptosis of cardiomyocytes through the AMPK pathway to facilitate survival of cardiomyocytes and improve cardiac function? What is the main finding and its importance? Major findings are as follows: (i) TXL treatment preserved cardiac function and reduced ventricular remodelling, infarct size and inflammation in rat hearts after AMI; (ii) TXL treatment dramatically increased autophagy and inhibited apoptosis in myocardium; and (iii) the AMPK signalling pathway played a crucial role in mediating the beneficial effects of TXL. Tongxinluo (TXL) has been demonstrated to have a protective role during ischaemia-reperfusion after acute myocardial infarction, but the long-term effects and underlying mechanisms are still unknown. The aim of this study was to investigate whether TXL could have an effect on apoptosis or autophagy of cardiomyocytes through the AMP-activated protein kinase (AMPK) pathway. Male Sprague-Dawley rats (n = 75) were randomly divided to sham, control, TXL (4 mg kg-1 day-1 orally), compound C (i.p. injection of 10 mg kg-1 day-1 ) and TXL + compound C groups. The extent of fibrosis, infarct size and angiogenesis were determined by pathological and histological studies. Four weeks after acute myocardial infarction, TXL treatment significantly increased ejection fraction, promoted angiogenesis in the peri-infarct region and substantially decreased fibrosis and the size of the infarcted area (P &lt; 0.05). Treatment with TXL also increased AMPK/mTOR phosphorylation, upregulated expression of the autophagic protein LC3 and downregulated expression of the apoptotic protein Bax in the infarcted myocardium (P &lt; 0.05). Addition of the AMPK inhibitor, compound C, counteracted these beneficial effects significantly (P &lt; 0.05). The cardioprotective benefits of TXL against myocardial infarction are related to the inhibition of apoptosis and promotion of autophagy in rat hearts after acute myocardial infarction. This effect may occur through the AMPK signalling pathway. 

Retracted: No

PubPeer comments:
 Fig 5,  A, representative images of autophagic cells detected by the immunofluorescence analysis of LC3. The scale bar represents 100 u03bcm. Is there any reason why the Sham, CC and TXL+CC columns contain overlapping versions of the same images? ![file] ,
Metabolic constraints drive self-organization of specialized cell groups
Authors: Sunil Laxman
Adhish Walvekar
Sandeep Krishna
Sriram Varahan
Vaibhhav Sinha
Journal: eLife (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: S. cerevisiae; cell biology; cell states; gluconeogenesis; pentose phosphate pathway
Affiliations: InStem - Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India., Simons Centre for the Study of Living Machines, National Centre for Biological Sciences-Tata Institute of Fundamental Research, Bangalore, India., Manipal Academy of Higher Education, Manipal, India.

Abstract:  How phenotypically distinct states in isogenic cell populations appear and stably co-exist remains unresolved. We find that within a mature, clonal yeast colony developing in low glucose, cells arrange into metabolically disparate cell groups. Using this system, we model and experimentally identify metabolic constraints sufficient to drive such self-assembly. Beginning in a uniformly gluconeogenic state, cells exhibiting a contrary, high pentose phosphate pathway activity state, spontaneously appear and proliferate, in a spatially constrained manner. Gluconeogenic cells in the colony produce and provide a resource, which we identify as trehalose. Above threshold concentrations of external trehalose, cells switch to the new metabolic state and proliferate. A self-organized system establishes, where cells in this new state are sustained by trehalose consumption, which thereby restrains other cells in the trehalose producing, gluconeogenic state. Our work suggests simple physico-chemical principles that determine how isogenic cells spontaneously self-organize into structured assemblies in complimentary, specialized states. 

Retracted: No

PubPeer comments:
 Figure 2F may have a repeated image; some readers on social media confirm and suggest that this should not be the case; others note some differences in the reflections. One of those readers prepared the illustration showing the rotation below. Could the authors comment? *** ![file] *** ![file] , 
 ![file] I am the first author SV ,
Chondroprotective Effects of Wogonin in Experimental Models of Osteoarthritis in vitro and in vivo
Authors: Dae Cheol Nam
Dong Yeong Lee
Jin Hoon Jeong
Sun-Chul Hwang
Choong Jae Lee
Jin Sung Park
Ho Seung Jo
Hyun Jae Lee
Dong Hee Kim
Journal: Biomolecules & therapeutics (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Chondrocyte; Metalloproteinase; Osteoarthritis; Wogonin.
Affiliations: Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University, Jinju 660-701, Republic of Korea., Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon 301-131, Republic of Korea.

Abstract:  We evaluated the chondroprotective effects of wogonin by investigating its effects on the gene expression and production of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as on production of MMP-3 in the rat knee. Rabbit articular chondrocytes were cultured in a monolayer, and RT-PCR was used to measure interleukin-1β (IL-1β)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and type II collagen. In rabbit articular chondrocytes, the effects of wogonin on IL-1β-induced production and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of wogonin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, wogonin inhibited the expression of MMP-3, MMP-1, MMP-13, and ADAMTS-4, but increased expression of type II collagen. Furthermore, wogonin inhibited the production and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that wogonin can regulate the gene expression and production of MMP-3, by directly acting on articular chondrocytes. 

Retracted: No

PubPeer comments:
 Could the authors comment on Figure 6? By readers on social media it is suggested that these two bands should not appear so similar, although some are unsure about the applicability of loading controls with casein zymography. *** ![file] ,
Image reconstruction in SNR units: a general method for SNR measurement
Authors: Elliot R McVeigh
Peter Kellman
Journal: Magnetic Resonance in Medicine (2005)
Discipline: CLINICAL MEDICINE
Keywords: Phased array; Image reconstruction; SNR units; Pixel basis; Root-sum-of-squares
Affiliations: Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, National Institutes of Health, DHHS, Bethesda, Maryland 20892-1061, USA. 

Abstract:  The method for phased array image reconstruction of uniform noise images may be used in conjunction with proper image scaling as a means of reconstructing images directly in SNR units. This facilitates accurate and precise SNR measurement on a per pixel basis. This method is applicable to root-sum-of-squares magnitude combining, B(1)-weighted combining, and parallel imaging such as SENSE. A procedure for image reconstruction and scaling is presented, and the method for SNR measurement is validated with phantom data. Alternative methods that rely on noise only regions are not appropriate for parallel imaging where the noise level is highly variable across the field-of-view. The purpose of this article is to provide a nuts and bolts procedure for calculating scale factors used for reconstructing images directly in SNR units. The procedure includes scaling for noise equivalent bandwidth of digital receivers, FFTs and associated window functions (raw data filters), and array combining. 

Retracted: No

PubPeer comments:
 Caption in Fig.6 is really misleading, or precisely speaking, is wrong. In caption of Fig.6, *(c) direct SNR estimate computed as ratio of (a) and (b)* , from this one would expect that Fig. 6c is Fig.6a divided by Fig.6 b. However, this it not the case. In the main body the authors says *The noise SD used in Fig. 6c SNR estimate is based on 256 samples (trials), whereas the noise SD used in Fig. 6a is based on 30 x 256 samples (pre-scan noise) and ...*. So Fig. 6c is the SNR calculated from direct SNR measurement, instead of Fig.6a divided by Fig.6 b. Similarly, caption of Fig. 7 is misleading, too. ,
Increased serum levels of the chemokine CXCL13 and up-regulation of its gene expression are distinctive features of HCV-related cryoglobulinemia and correlate with active cutaneous vasculitis
Authors: Michele Montrone
Domenico Sansonno
Franco Dammacco
Felicia Anna Tucci
Loredana Sansonno
Laura Troiani
Vincenza Conteduca
Gianfranco Lauletta
Journal: Blood (2008)
Discipline: CLINICAL MEDICINE
Keywords: Chemokine CXCL13; B-cell trafficking; Hepatitis C virus; B-cell dysfunction; Lymphoproliferative disorders
Affiliations: Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. , Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy

Abstract:  Chemokine CXCL13, also known as BCA-1 (B cell-attracting chemokine-1) or BLC (B-lymphocyte chemoattractant), is a major regulator of B-cell trafficking. Hepatitis C virus (HCV) infection may be associated with B-cell dysfunction and lymphoproliferative disorders, including mixed cryoglobulinemia (MC). This study evaluates circulating levels of CXCL13 protein and specific mRNA expression in chronically HCV-infected patients with and without MC. Compared with healthy controls and HCV-infected patients without MC, CXCL13 serum levels were significantly higher in MC patients. The highest CXCL13 levels strongly correlated with active cutaneous vasculitis. CXCL13 gene expression in portal tracts, isolated from liver biopsy tissues with laser capture microdissection, showed enhanced levels of specific mRNA in MC patients with active cutaneous vasculitis. Specific CXCL13 gene mRNA expression was also up-regulated in skin tissue of these patients. These findings paralleled specific deposits of CXCL13 protein both in the liver and in the skin. Our results indicate that up-regulation of CXCL13 gene expression is a distinctive feature of HCV-infected patients. Higher levels of this chemokine in the liver as well as in the skin of patients with active MC vasculitis suggest a possible interrelation between these biologic compartments. 

Retracted: No

PubPeer comments:
 Figure 1E. Much more similar than you would expect. https: imgur.com JvwfHOJ ,
Increased tau phosphorylation and impaired presynaptic function in hypertriglyceridemic ApoB-100 transgenic mice
Authors: Aniko Kasztner
Melinda E Tóth
Erika Bereczki
János Horváth
Miklós Sántha
Botond Penke
Viktor Szegedi
Nikolett Lénárt
Gábor Juhász
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: ApoB-100; hyperlipidemia; neurodegeneration; transgenic mice; serum
Affiliations: Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.

Abstract:  Aims: ApoB-100 is the major protein component of cholesterol- and triglyceride-rich LDL and VLDL lipoproteins in the serum. Previously, we generated and partially described transgenic mice overexpressing the human ApoB-100 protein. Here, we further characterize this transgenic strain in order to reveal a possible link between hypeprlipidemia and neurodegeneration. Methods and results: We analyzed the serum and cerebral lipid profiles, tau phosphorylation patterns, amyloid plaque-formation, neuronal apoptosis and synaptic plasticity of young (3 month old), adult (6 month old) and aging (10-11 month old) transgenic mice. We show that ApoB-100 transgenic animals present i) elevated serum and cerebral levels of triglycerides and ApoB-100, ii) increased cerebral tau phosphorylation at phosphosites Ser(199), Ser(199/202), Ser(396) and Ser(404). Furthermore, we demonstrate, that tau hyperphosphorylation is accompanied by impaired presynaptic function, long-term potentiation and widespread hippocampal neuronal apoptosis. Conclusions: The results presented here indicate that elevated ApoB-100 level and the consequent chronic hypertriglyceridemia may lead to impaired neuronal function and neurodegeneration, possibly via hyperphosphorylation of tau protein. On account of their specific phenotype, ApoB-100 transgenic mice may be considered a versatile model of hyperlipidemia-induced age-related neurodegeneration. 

Retracted: No

PubPeer comments:
 Figure 6A appears to have a repeated image. *** ![file] ,
What’s new in atopic eczema? An analysis of systematic reviews published in 2017. Part 2: epidemiology, aetiology and risk factors
Authors: E Davies
D J C Grindlay
K E Harman
G Hale
N K Rogers
Journal: Clinical and Experimental Dermatology (2019)
Discipline: CLINICAL MEDICINE
Keywords: Atopic eczema; Epidemiology; Aetiology; Risk factors; Sleep disturbance
Affiliations: Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK., Department of Dermatology, Countess of Chester Hospital, Chester, UK., Centre of Evidence Based Dermatology, University of Nottingham, King's Meadow Campus, Nottingham, UK.

Abstract:  This article forms part of a series of annual updates that summarizes the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2017, and focuses on the epidemiology, aetiology and risk factors of AE. AE is the largest single contributor to morbidity associated with skin disease worldwide, once mortality has been excluded. There is a high prevalence of sleep disturbance in individuals with AE and they take more sick leave than controls. While there is a lack of skin bacterial diversity in patients with AE, there is a relative abundance of Staphylococcus aureus and Staphylococcus epidermidis. Compared with controls, affected individuals more often show an IgE response to S. aureus antigens and have higher serum interleukin-31 levels. Early antibiotic exposure, environmental pollutants, maternal atopy and food allergy are associated with an increased risk of AE, and very preterm birth is associated with decreased risk. Patients with AE have a reduced risk of meningioma, but are more likely to develop attention-deficit hyperactivity disorder compared with controls. Patients with eosinophilic oesophagitis are significantly more likely than unaffected individuals to have AE. There is no significant overall association between AE and allergic contact dermatitis (ACD), and in children referred for patch testing, ACD was more common in those without AE. Hand eczema is more prevalent in patients with AE. There is no association between AE and Type 2 diabetes, hypertension, stroke or myocardial infarction. 

Retracted: No

PubPeer comments:
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 This is a relatively recent paper. Surely the authors could post high resolution images of the full blots used to make figure 3A here? , 
 Cancelled, my mistake , 
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 #3 Figure 2C. Much more similar than you would expect. https: imgur.com xhX87r9 ,
Blocking CXCR1/2 contributes to amelioration of lipopolysaccharide‐induced sepsis by downregulating substance P
Authors: Ping Dong
Miaoshu Wang
Yukang Song
Danfeng Zhong
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: acute lung injury; necroptosis; reparixin; sepsis.
Affiliations: Department of Medical Intensive Care Unit, The First People's Hospital of Wenling, Taizhou, China.

Abstract:  Objectives: C-X-C chemokine receptor types 1/2 (CXCR1/2) is known to be activated in liver damage in acute-on-chronic liver failure; however, the role in lipopolysaccharide (LPS)-induced sepsis is unknown. The current study was designed to determine whether or not CXCR1/2 blockade with reparixin ameliorates acute lung injury (ALI) by affecting neuropeptides in a LPS-induced sepsis mouse model. Materials and methods: Male C57BL/6 mice (10 to 14-week old) were divided into sham, LPS, sham-R, and LPS-R groups. Bronchoalveolar lavage fluid (BALF) was collected and evaluated. The lung histopathology was assessed by immunocytochemistry staining. Western blot analysis was used to measure myeloperoxidase, substance P (SP), and vasoactive intestinal peptide. Results: LPS-induced animal models were ameliorated by cotreatment with a CXCR1/2 antagonist. Moreover, the protective effects of CXCR1/2 antagonists were attributed to the increased secretion of pro-opiomelanocortin and decreased the secretion of SP. Reparixin decreased the expression of necroptosis cell death markers induced by LPS. Conclusion: The results of this study indicate that blockade of CXCR1/2 may represent a promising therapeutic strategy for the treatment of sepsis-associated ALI through regulation of neuropeptides and necroptosis. 

Retracted: No

PubPeer comments:
 Figure 1B consists of four different panels representing lung tissue from four differently treated mice. Certain tissue parts appear to be visible multiple times within or between panels. Could the authors please check what happened here? ![file] , 
 Fig 4. There is little relationship between values of CXCR1 2 when they are correlated with SP, vs. VIP. In the SP correlation, for instance, there are 7 data points with values of CXCR1 2 greater than 0.8; in the VIP correlation, there are only 4. ![file] ,
Multielectrode array analysis of EEG biomarkers in a mouse model of Fragile X Syndrome
Authors: Devin K Binder
Iryna M Ethell
Carrie R Jonak
Khaleel A Razak
Jonathan W Lovelace
Journal: Neurobiology of Disease (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Auditory cortex; Autism; EEG; Fragile X syndrome; Gamma power
Affiliations: Division of Biomedical Sciences, School of Medicine, University of California, Riverside, United States of America., Department of Psychology, University of California, Riverside, United States of America., Division of Biomedical Sciences, School of Medicine, University of California, Riverside, United States of America; Neuroscience Graduate Program, University of California, Riverside, United States of America., Neuroscience Graduate Program, University of California, Riverside, United States of America; Department of Psychology, University of California, Riverside, United States of America., Division of Biomedical Sciences, School of Medicine, University of California, Riverside, United States of America; Neuroscience Graduate Program, University of California, Riverside, United States of America. Electronic address: .

Abstract:  Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety and social and sensory processing deficits. Recent EEG studies in humans with FXS have identified neural oscillation deficits that include increased resting state gamma power, increased amplitude of auditory evoked potentials, and reduced inter-trial phase coherence of sound-evoked gamma oscillations. Identification of comparable EEG biomarkers in mouse models of FXS could facilitate the pre-clinical to clinical therapeutic pipeline. However, while human EEG studies have involved 128-channel scalp EEG acquisition, no mouse studies have been performed with more than three EEG channels. In the current study, we employed a recently developed 30-channel mouse multielectrode array (MEA) system to record and analyze resting and stimulus-evoked EEG signals in WT vs. Fmr1 KO mice. Using this system, we now report robust MEA-derived phenotypes including higher resting EEG power, altered event-related potentials (ERPs) and reduced inter-trial phase coherence to auditory chirp stimuli in Fmr1 KO mice that are remarkably similar to those reported in humans with FXS. We propose that the MEA system can be used for: (i) derivation of higher-level EEG parameters; (ii) EEG biomarkers for drug testing; and (ii) mechanistic studies of FXS pathophysiology. 

Retracted: No

PubPeer comments:
 Concern about Figure 2B: The Nrf2 panel looks very similar to bands in a Rap1B blot in Figure 4B of a slightly older paper by the same authors., i.e. doi: 10.1016 j.febslet.2012.08.007, published in FEBS Letters. ![file] , 
 Overlap was detected in Fig. 4D ![file] ,
Genetic ablation of Cyclin D1 abrogates genesis of rhabdoid tumors resulting from Ini1 loss
Authors: Ganjam V Kalpana
Winfried Edelman
Mary Tsikitis
Zhikai Zhang
David Zagzag
Journal: Proceedings of the National Academy of Sciences of the United States of America (2005)
Discipline: Multidisciplinary
Keywords: Rhabdoid tumors; INI1; Cyclin D1; tumor suppressor gene; histone deacetylase 1 complex
Affiliations: Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Abstract:  Rhabdoid tumors are aggressive pediatric malignancies for which, currently, there are no effective or standard treatment strategies. Rhabdoid tumors arise because of the loss of the tumor suppressor gene INI1. We have previously demonstrated that INI1 represses Cyclin D1 transcription in rhabdoid cells by directly recruiting histone deacetylase 1 complex to its promoter, leading to G(0)-G(1) arrest. Expression of Cyclin D1 overcomes cell cycle arrest mediated by INI1 and Cyclin D1 overexpression in human rhabdoid tumors is a common phenomenon. However, it is not clear whether Cyclin D1 is a critical downstream target of INI1 in vivo and whether the derepression of this gene is essential for rhabdoid tumorigenesis. To determine the requirement of Cyclin D1 for genesis of rhabdoid tumors in vivo, we developed Ini1 heterozygous mice by targeted disruption. We found that the tumors developed in these Ini1+/- mice are rhabdoid, defective for Ini1 protein, and like the human tumors, express Cyclin D1. We crossed Ini1+/- mice to Cyclin D1-/- mice and found that Ini1+/- mice with Cyclin D1 deficiency did not develop any spontaneous tumors, in contrast to the parental Ini1+/- mice. These results strongly support the hypothesis that Cyclin D1 is a key mediator in the genesis of rhabdoid tumors. Our results provide an in vivo proof of concept that drugs that target Cyclin D1 expression or activity could be potentially effective as novel therapeutic agents for rhabdoid tumors. 

Retracted: No

PubPeer comments:
 Figure 1a. Much more similar than expected. ![file] ,
CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells
Authors: M Synowitz
S Chen
N Mohr
K Volk
S Kleber
J Sykora
W Mueller
B Cirovic
J Tüttenberg
A Martin-Villalba
C R Wirtz
A Mateos
C Gieffers
M Drachsler
Journal: Cell death & disease (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Glioblastoma; Stemness; Epithelial-to-mesenchymal transition; CD95; Prognostic biomarker
Affiliations: Department of Molecular Neurobiology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany., Department of Cell Differentiation and Tumorigenesis, Max Delbrück Center, Berlin 13125, Germany., Department of Neurosurgery, Clinical Center Idar-Oberstein, Idar-Oberstein 55743, Germany., Apogenix GmbH, Heidelberg 69120, Germany., Department of Neurosurgery, University Hospital Ulm, Günzburg 89312, Germany., Department of Neuropathology, University Hospital Leipzig, Leipzig 04103, Germany., Department of Neurosurgery, Charité, University Medicine Berlin, Berlin 13353, Germany., Department of Neurosurgery, Campus Kiel, Kiel 24105, Germany.

Abstract:  Glioblastoma (GBM) is one of the most aggressive types of cancer with limited therapeutic options and unfavorable prognosis. Stemness and non-classical epithelial-to-mesenchymal transition (ncEMT) features underlie the switch from normal to neoplastic states as well as resistance of tumor clones to current therapies. Therefore, identification of ligand/receptor systems maintaining this privileged state is needed to devise efficient cancer therapies. In this study, we show that the expression of CD95 associates with stemness and EMT features in GBM tumors and cells and serves as a prognostic biomarker. CD95 expression increases in tumors and with tumor relapse as compared with non-tumor tissue. Recruitment of the activating PI3K subunit, p85, to CD95 death domain is required for maintenance of EMT-related transcripts. A combination of the current GBM therapy, temozolomide, with a CD95 inhibitor dramatically abrogates tumor sphere formation. This study molecularly dissects the role of CD95 in GBM cells and contributes the rational for CD95 inhibition as a GBM therapy. 

Retracted: No

PubPeer comments:
 Figure 6C (IPCD95) and D (IP p-tyrosine): CD95 and p-tyr blots look identical. ,
Detection of prions in blood
Authors: Claudio Soto
Paula Saá
Joaquín Castilla
Journal: Nature Medicine (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Prion diseases; prion protein; PMCA technology; sensitivity; detection methods
Affiliations: Department of Neurology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555-0646, USA.

Abstract:  Prion diseases are caused by an unconventional infectious agent termed prion, composed mainly of the misfolded prion protein (PrP(Sc)). The development of highly sensitive assays for biochemical detection of PrP(Sc) in blood is a top priority for minimizing the spread of the disease. Here we show that the protein misfolding cyclic amplification (PMCA) technology can be automated and optimized for high-efficiency amplification of PrP(Sc). We show that 140 PMCA cycles leads to a 6,600-fold increase in sensitivity over standard detection methods. Two successive rounds of PMCA cycles resulted in a 10 million-fold increase in sensitivity and a capability to detect as little as 8,000 equivalent molecules of PrP(Sc). Notably, serial PMCA enables detection of PrP(Sc) in blood samples of scrapie-afflicted hamsters with 89% sensitivity and 100% specificity. These findings represent the first time that PrP(Sc) has been detected biochemically in blood, offering promise for developing a noninvasive method for early diagnosis of prion diseases. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] , 
 In the online version this figure appears different. It seems it was corrected in January 2013. I do not see any problems with the new figure. , 
 #2 You are correct. Apologies for the oversight.  11 January 2013 In the version of this article initially published, there was a mistake in Figure 2. Several bands depicted in the second round of protein misfolding cyclic amplification were inadvertently duplicated in the third round. The error has been corrected in the HTML and PDF versions of the article. ,