PReD-Bench/PRed-Bench huggingface dataset:
Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer
Authors: Wei Guo
Shuai Zhang
Tingting Ren
Yifeng Sun
Zhiyuan Lou
Xinchang Lu
Qunshan Lu
Xianbo Peng
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Keywords: non-small cell lung cancer; skeletal metastasis; RANKL; RANK; OPG
Affiliations: Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.

Abstract:  Background: Human non-small cell lung cancer (NSCLC) patients exhibit a high propensity to develop skeletal metastasis, resulting in excessive osteolytic activity. The RANKL/RANK/OPG system, which plays a pivotal role in bone remodeling by regulating osteoclast formation and activity, is of potential interest in this context. Materials and methods: Reverse transcriptase polymerase chain reaction, western blotting, and immunohistochemical analysis were used to examine the expression of RANKL, RANK, and OPG in human NSCLC cell lines with different metastatic potentials, as well as in 52 primary NSCLC samples and 75 NSCLC bone metastasis samples. In primary NSCLC patients, the expression of these proteins was correlated with clinicopathological parameters. Recombinant human RANKL and transfected RANKL cDNA were added to the PAa cell line to evaluate the promoter action of RANKL during the process of metastasis in vitro and in vivo. Results: Up-regulated RANKL, RANK, and OPG expression and increased RANKL:OPG ratio were detected in NSCLC cell lines and in tumor tissues with bone metastasis, and were correlated with higher metastatic potential. The metastatic potential of NSCLC in vitro and in vivo, including migration and invasion ability, was significantly enhanced by recombinant human RANKL and the transfection of RANKL cDNA, and was impaired after OPG was added. The increased expression of RANKL and OPG correlated with tumor stage, lymph node metastasis, and distant metastasis. Conclusions: Differential expression of RANKL, RANK, and OPG is associated with the metastatic potential of human NSCLC to skeleton, raising the possibility that the RANKL/RANK/OPG system could be a therapeutic target for the treatment of metastatic NSCLC patients. 

Retracted: No

PubPeer comments:
 Figure 1C and 2A. * Red boxes: The MMP9 panel in Figure 1C looks similar to the OPG panel in Figure 2A, if one of the two is rotated 180 degrees and stretched differently. ![file] ,
Systematic prediction of health-relevant human-microbial co-metabolism through a computational framework
Authors: Ines Thiele
Almut Heinken
Journal: Gut microbes (2015)
Discipline: MICROBIOLOGY
Keywords: human gut microbiome; in silico; metabolic modeling; metabolome.
Affiliations: a Luxembourg Center for Systems Biomedicine ; University of Luxembourg ; Belval , Luxembourg.

Abstract:  The gut microbiota is well known to affect host metabolic phenotypes. The systemic effects of the gut microbiota on host metabolism are generally evaluated via the comparison of germfree and conventional mice, which is impossible to perform for humans. Hence, it remains difficult to determine the impact of the gut microbiota on human metabolic phenotypes. We demonstrate that a constraint-based modeling framework that simulates "germfree" and "ex-germfree" human individuals can partially fill this gap and allow for in silico predictions of systemic human-microbial co-metabolism. To this end, we constructed the first constraint-based host-microbial community model, comprising the most comprehensive model of human metabolism and 11 manually curated, validated metabolic models of commensals, probiotics, pathogens, and opportunistic pathogens. We used this host-microbiota model to predict potential metabolic host-microbe interactions under 4 in silico dietary regimes. Our model predicts that gut microbes secrete numerous health-relevant metabolites into the lumen, thereby modulating the molecular composition of the body fluid metabolome. Our key results include the following: 1. Replacing a commensal community with pathogens caused a loss of important host metabolic functions. 2. The gut microbiota can produce important precursors of host hormone synthesis and thus serves as an endocrine organ. 3. The synthesis of important neurotransmitters is elevated in the presence of the gut microbiota. 4. Gut microbes contribute essential precursors for glutathione, taurine, and leukotrienes. This computational modeling framework provides novel insight into complex metabolic host-microbiota interactions and can serve as a powerful tool with which to generate novel, non-obvious hypotheses regarding host-microbe co-metabolism. 

Retracted: No

PubPeer comments:
 The results presented in Table 4 are not consistent with those in Table 3 and the fault tree. For example, the value of M11 in Table 4 should be larger than X19 and X20 in Table 3 because it is an  OR relation. ![file] ![file] ![file] ![file] ,
A Gutsy Move for Cell-Based Regenerative Medicine in Parkinson’s Disease: Targeting the Gut Microbiome to Sequester Inflammation and Neurotoxicity
Authors: Brooke Bonsack
Jea-Young Lee
Sandra Acosta
Cesario V Borlongan
Sydney Corey
Julian P Tuazon
Paul R Sanberg
Jared Ehrhart
Journal: Stem Cell Reviews and Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Brain repair; Cord blood stem cells; Gastrointestinal mucosa; Neurodegeneration; Plasma.
Affiliations: Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd. MDC 78, Tampa, FL, 33612, USA., Saneron CCEL Therapeutics, Inc., Tampa, FL, 33618, USA., Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd. MDC 78, Tampa, FL, 33612, USA. .

Abstract:  Pharmaceuticals and cell-based regenerative medicine for Parkinson's disease (PD) offer palliative relief but do not arrest the disease progression. Cell therapy has emerged as an experimental treatment, but current cell sources such as human umbilical cord blood (hUCB) stem cells display only partial recapitulation of mature dopaminergic neuron phenotype and function. Nonetheless, stem cell grafts ameliorate PD-associated histological and behavioral deficits likely through stem cell graft-secreted therapeutic substances. We recently demonstrated the potential of hUCB-derived plasma in enhancing motor capabilities and gastrointestinal function, as well as preventing dopaminergic neuronal cell loss, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) rodent model of PD. Recognizing the translational need to test in another PD model, we now examined here the effects of an intravenously transplanted combination of hUCB and plasma into the 6-hydroxydopamine (6-OHDA) lesioned adult rats. Animals received three separate doses of 4 × 106 hUCB cells with plasma beginning at 7 days after stereotaxic 6-OHDA lesion, then behaviorally and immunohistochemically evaluated over 56 days post-lesion. Whereas vehicle-treated lesioned animals exhibited the typical 6-OHDA neurobehavioral symptoms, hUCB and plasma-treated lesioned animals showed significant attenuation of motor function, gut motility, and nigral dopaminergic neuronal survival, combined with diminished pro-inflammatory microbiomes not only in the nigra, but also in the gut. Altogether these data support a regenerative medicine approach for PD by sequestering inflammation and neurotoxicity through correction of gut dysbiosis. 

Retracted: No

PubPeer comments:
 Two images in Figure 5 appear to overlap, but are described differently. Could the authors please check and confirm that the quantification was not affected? *** ![file] *** Note: the last author appears to be a member of this journal s editorial board. ,
Krüppel-like factor 4 promotes differentiation by transforming growth factor-beta receptor-mediated Smad and p38 MAPK signaling in vascular smooth muscle cells
Authors: Mei Han
Hui-xuan Li
Jian-ran Fu
Shao-guang Sun
Michel Bernier
Bin Zheng
Jin-kun Wen
Rui Zhang
Ming Su
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: KLF4; TGF-beta; VSMC differentiation; Smad; p38 MAPK
Affiliations: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Ministry of Education, Hebei Medical University, No 361, Zhongshan East Road, Shijiazhuang 050017, China.

Abstract:  KLF4 (Krüppel-like factor 4) has been implicated in vascular smooth muscle cell (VSMC) differentiation induced by transforming growth factor beta (TGF-beta). However, the role of KLF4 and mechanism of KLF4 actions in regulating TGF-beta signaling in VSMCs remain unclear. In this study, we showed that TGF-beta1 inhibited cell cycle progression and induced differentiation in cultured rat VSMCs. This activity of TGF-beta1 was accompanied by up-regulation of KLF4, with concomitant increase in TbetaRI (TGF-beta type I receptor) expression. KLF4 was found to transduce TGF-beta1 signals via phosphorylation-mediated activation of Smad2, Smad3, and p38 MAPK. The activation of both pathways, in turn, increased the phosphorylation of KLF4, which enabled the formation of KLF4-Smad2 complex in response to TGF-beta1. Chromatin immunoprecipitation studies and oligonucleotide pull-down assays showed the direct binding of KLF4 to the KLF4-binding sites 2 and 3 of the TbetaRI promoter and the recruitment of Smad2 to the Smad-responsive region. Formation of a stable KLF4-Smad2 complex in the promoter's Smad-responsive region mediated cooperative TbetaRI promoter transcription in response to TGF-beta1. These results suggest that KLF4-dependent regulation of Smad and p38 MAPK signaling via TbetaRI requires prior phosphorylation of KLF4 through Smad and p38 MAPK pathways. This study demonstrates a novel mechanism by which TGF-beta1 regulates VSMC differentiation. 

Retracted: No

PubPeer comments:
 The jdifjlk jdiji kloj lulkj ;piueet , 
 Seven papers published by Wen Jinkun et al have data problemsuff0cincluding multi use of one image, cutting and splicing images, fictitious control blank data, and so on. All of them were journal papers with higher impact factors, such as Cell res (1), JBC (2), mol ther (1), CIRC res (1). The data of papers published in J Biol Chem (2010; 285(23): 17846-56) were most seriously modified by the Main author. Figure 6 B and Figure 7 C use the same picture, which is not consistent with the relative quantitative data shown in the corresponding histogram (right picture). This shows that it has been artificially modified. ![file] ,
approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel
Authors: Ravindra Donde
Gayatri Gouda
Ramakrishna Vadde
Lambodar Behera
Manoj Kumar Gupta
Sarojamma Vemula
Journal: Journal of biomolecular structure & dynamics (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Coronaviruses; docking; modeling; molecular dynamics; severe acute respiratory syndrome.
Affiliations: Department of Biotechnology & Bioinformatics, Yogi Vemana University, Kadapa, Andhra Pradesh, India., Department of Microbiology, Government Medical College, Anantapur, Andhra Pradesh, India., ICAR-National Rice Research Institute, Cuttack, Odisha, India.

Abstract:  Recent outbreak of Coronavirus disease (COVID-19) pandemic around the world is associated with 'severe acute respiratory syndrome' (SARS-CoV2) in humans. SARS-CoV2 is an enveloped virus and E proteins present in them are reported to form ion channels, which is mainly associated with pathogenesis. Thus, there is always a quest to inhibit these ion channels, which in turn may help in controlling diseases caused by SARS-CoV2 in humans. Considering this, in the present study, authors employed computational approaches for studying the structure as well as function of the human 'SARS-CoV2 E' protein as well as its interaction with various phytochemicals. Result obtained revealed that α-helix and loops present in this protein experience random movement under optimal condition, which in turn modulate ion channel activity; thereby aiding the pathogenesis caused via SARS-CoV2 in human and other vertebrates. However, after binding with Belachinal, Macaflavanone E, and Vibsanol B, the random motion of the human 'SARS-CoV2 E' protein gets reduced, this, in turn, inhibits the function of the 'SARS-CoV2 E' protein. It is pertinent to note that two amino acids, namely VAL25 and PHE26, play a key role while interacting with these three phytochemicals. As these three phytochemicals, namely, Belachinal, Macaflavanone E &amp; Vibsanol B, have passed the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) property as well as 'Lipinski's Rule of 5s', they may be utilized as drugs in controlling disease caused via SARS-COV2, after further investigation.Communicated by Ramaswamy H. Sarma. 

Retracted: No

PubPeer comments:
 Figure 2b shows the C-alpha RMSF plot. How does the residue number become 10000? As the protein is a pentamer of a 75 residue monomeric subunit, the total number of C-alpha should be (75x5) = 375. How do the authors justify the RMSF calculation? ![file] , 
 In Figure 3, the authors represent cross-correlation analyses of C-alpha atoms. Again, how the number of C-alpha atom reaches more than 900? The pentameric structure of the protein contains 375 residues which correspond to 375 C-alpha atoms. ![file] ,
Suppression of TGF-beta signaling by phospholipase D
Authors: Evan Lee
David A Foster
Noga Gadir
Alfredo Toschi
Avalon Garcia
Journal: Cell Cycle (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MDA-MB-231; breast cancer cells; PLD; mTOR; MAP kinase
Affiliations: Department of Biological Sciences, Hunter College of the City University of New York, 695 Park Avenue, New York, New York 10021, USA.

Abstract:  MDA-MB-231 human breast cancer cells have a survival signal generated by phospholipase D (PLD) that involves the activation of mTOR and MAP kinase. TGF-beta signals that block cell cycle progression in G(1) are suppressed in MDA-MB-231 cells. We report here that the elevated PLD activity in MDA-MB-231 cells suppresses TGF-beta signaling. Suppression of PLD activity or PLD expression resulted in increased phosphorylation of Smad2 and Smad3 on Ser 465/467-sites on Smads that get phosphorylated by the TGF-beta receptor and positively regulate TGF-beta signaling. The effect of PLD suppression on Smad2/3 phosphorylation was dependent on the presence of TGF-beta. Suppression of PLD also suppressed phosphorylation of Smad2 on Ser 245/250/255-sites that are phosphorylated by MAP kinase and negatively regulate TGF-beta signaling. Suppression of PLD also led to increased expression of the cyclin-dependent kinase (CDK) inhibitors p21Cip1 and p27Kip1, the expression of which is stimulated in response to TGF-beta. Consistent with the elevated expression of CDK inhibitors, suppression of PLD also suppressed phosphorylation of the CDK substrate pRb. Similar effects were also seen in PANC-1 human pancreatic cancer cells. The data presented here indicate that the suppressed TGF-beta signaling in MDA-MB-231 and perhaps many other human cancer cells is due to elevated PLD activity and mediated by mTOR and MAP kinase. These results indicate that the survival signals generated by PLD involve the suppression TGF-beta signals that promote G(1) arrest. 

Retracted: No

PubPeer comments:
 Figures 1A and 1B. Much more similar than expected. ![file] , 
 Figures 1C and 1D much more similar than expected. ![file] , 
 #2 Figures 1C and 1D continued. Much more similar than expected after 180 degree rotation. ![file] ,
Infection by Streptococcus pyogenes Induces the Receptor Activator of NF-κB Ligand Expression in Mouse Osteoblastic Cells
Authors: Shigetada Kawabata
Taku Fujiwara
Shigeyuki Hamada
Nobuo Okahashi
Ichiro Nakagawa
Atsuo Amano
Atsuo Sakurai
Journal: Infection and Immunity (2003)
Discipline: IMMUNOLOGY
Keywords: Group A Streptococcus pyogenes; nongonococcal septic arthritis; osteoblasts; RANKL; interleukin-6
Affiliations: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Japan. , Departments of Oral and Molecular Microbiology, Pediatric Dentistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita-Osaka 565-0871, PRESTO, Japan Science and Technology Corporation, Kawaguchi-Saitama 332-0012, Japan, Oral Frontier Biology

Abstract:  Group A Streptococcus pyogenes is known to induce nongonococcal septic arthritis in addition to pharyngitis, scarlet fever, and poststreptococcal sequelae. However, little is known about the interaction between S. pyogenes and bone cells. We report here that S. pyogenes strain JRS4 (M6) attached to and invaded mouse primary osteoblasts. Reverse transcription-PCR demonstrated that S. pyogenes infection of osteoblasts stimulated expression of mRNA for the receptor activator of NF-kappaB ligand (RANKL). Western blot analysis followed by ligand precipitation with the receptor activator of NF-kappaB receptor showed that there was an increase in RANKL protein in infected osteoblasts. Production of interleukin-6 was also stimulated, but no production of interleukin-1beta or tumor necrosis factor alpha was observed. Stimulation of RANKL production was not observed in osteoblasts stimulated with heat-inactivated S. pyogenes, suggesting that an active interaction of S. pyogenes with osteoblasts is essential for this phenomenon. A Western blot analysis performed with antibodies specific for phosphorylated signal transduction proteins demonstrated that S. pyogenes infection induces phosphorylation of p38 mitogen-activated protein kinase. A specific inhibitor of this kinase, SB203580, inhibited RANKL production by infected osteoblasts. These results suggest that infection of osteoblasts by S. pyogenes stimulates RANKL production and may trigger bone destruction in infected bone tissue. 

Retracted: No

PubPeer comments:
 t20 looks like a reverted t0 image ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced apoptosis in alveolar macrophages from smokers
Authors: Gaetano Caramori
Ian M Adcock
Timothy Oates
Katsuyuki Tomita
Toyoyuki Hanazawa
Peter J Barnes
Irena Chiselita
K Fan Chung
Elen Jazrawi
Sam Lim
Kazuhiro Ito
Journal: American journal of respiratory and critical care medicine (2002)
Discipline: CLINICAL MEDICINE
Keywords: Alveolar macrophages; smokers; chronic obstructive pulmonary disease; apoptosis; p21(CIP1/WAF1)
Affiliations: Department of Thoracic Medicine, National Heart and Lung Institute at Imperial College School of Science, Technology and Medicine, London, United Kingdom.

Abstract:  Alveolar macrophages (AMs) are the predominant defense cells in the airway, and their numbers are increased in smokers and subjects with chronic obstructive pulmonary disease. This increase may result from increased recruitment, increased proliferation, or reduced cell death. Apoptosis regulates inflammatory cell survival, and p21(CIP1/WAF1) is an important inhibitory regulator of cycle progression after oxidative stress. We have investigated whether chronic smoke exposure influences the expression and localization of cell cycle and apoptotic proteins in AM and bronchial epithelial cells in vivo. The increased numbers of AMs seen in smokers were only partially due to enhanced proliferation. p21(CIP1/WAF1) protein expression was increased in AMs and biopsies isolated from smokers and was found predominantly within the cytoplasm. In addition, B cell lymphoma leukemia (Bcl)-x(L), an antiapoptotic regulator, was also highly expressed in macrophages from smokers compared with nonsmokers and subjects with asthma. Hydrogen peroxide, an oxidative stress, induced cytoplasmic expression of p21(CIP1/WAF1) and failed to induce apoptosis in an in vitro model. These results suggested that AM and bronchial epithelial cells from smokers, in contrast to those from normal subjects and subjects with asthma, have reduced cell death. Thus, oxidative stress induced by cigarette smoking may contribute to the chronicity of inflammation in the airway, through a reduction of apoptosis. 

Retracted: No

PubPeer comments:
 Figure 8A. Position of cell nuclei in Control and Ozone (300ppb) panels much more similar than expected. https: imgur.com QcBG44L , 
 I will try to find these files from 20 years ago but not sure whether I still have them. I will also contact Dr Tomita in Japan. BW, Ian ,
Differential chemokine expression in tubular cells in response to urinary proteins from patients with nephrotic syndrome
Authors: Xue-Qing Yu
Qiong Wen
Shu-Feng Zhou
Zhao Huang
Journal: Cytokine (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: urine proteins; idiopathic minimal change disease; focal segmental glomerulosclerosis; chemokine expression; tubular cells
Affiliations: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, PR China., Division of Chinese Medicine, School of Health Sciences, WHO Collaborating Centre for Traditional Medicine, RMIT University, Vic., Australia., Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, PR China. Electronic address: .

Abstract:  Background and aim: Comparison of urine proteins in idiopathic minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients has been previously conducted, but the relationship between the severity of tubular injury and the composition of urine proteins in various kidney diseases is unknown. This study aimed to investigate the chemokine expression in human tubular cells in response to urine proteins from patients with nephrotic syndrome. Methods: Urine proteins collected from patients with MCD or FSGS were extracted by ultrafiltration and coincubated with HK-2 cells. The expression of the RANTES and MIF genes and the activation of p38 and extracellular regulated kinase were determined. Results: The urine proteins from both MCD and FSGS patients contained a primary band of proteins with Mr of approximately 62 kDa. The major cytokines present in urine proteins from MCD and FSGS patients were IL-6 and IL-8, while IL-1beta, IL-10, IL-12p70 and TNF-alpha were only detectable. We observed time- and dose-dependent increases in RANTES and MIF expression with urine protein treatment in HK-2 cells. The urine proteins from FSGS patients induced a higher expression of these two chemokines in HK-2 cells compared to the urine proteins from MCD patients. ERK and p38 were activated by urine proteins from either MCD or FSGS patients. Pretreatment with SB203580 or PD98059 abolished the increase in RANTES and MIF expression induced by urine proteins from FSGS patients, while only SB203580 suppressed the high expression induced by urine proteins from MCD patients. Conclusion: These findings indicate that the urine proteins from MCD and FSGS patients induce a differential expression of RANTES and MIF in tubular cells through distinct activation of MAPK-related signaling pathways. 

Retracted: No

PubPeer comments:
 This is probably some upload error, but Figures 4 and 5 are showing the same figure. Reported to the journal in October 2015, but no action was ever taken. ![file] ,
Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase
Authors: Laurence Florens
Yeon-Tae Jeong
Adam Antebi
Shanshan Duan
Anita Saraf
Moritz Horn
Michael P Washburn
Michele Pagano
Mario Rossi
Journal: Molecular Cell (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: F-box proteins; DCAF proteins; SCF; CRL4; ubiquitin ligase complexes
Affiliations: Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA. 

Abstract:  F-box proteins and DCAF proteins are the substrate binding subunits of the Skp1-Cul1-F-box protein (SCF) and Cul4-RING protein ligase (CRL4) ubiquitin ligase complexes, respectively. Using affinity purification and mass spectrometry, we determined that the F-box protein FBXO11 interacts with CDT2, a DCAF protein that controls cell-cycle progression, and recruits CDT2 to the SCF(FBXO11)complex to promote its proteasomal degradation. In contrast to most SCF substrates, which exhibit phosphodegron-dependent binding to F-box proteins, CDK-mediated phosphorylation of Thr464 present in the CDT2 degron inhibits recognition by FBXO11. Finally, our results show that the functional interaction between FBXO11 and CDT2 is evolutionary conserved from worms to humans and plays an important role in regulating the timing of cell-cycle exit. 

Retracted: No

PubPeer comments:
 Figure 3C u2013 it looks like that the same original image was used to represent long and short exposure in the right panel. ![file] , 
 #1 False color image suggests you are correct. *** ![file] ,
Fur-regulated iron uptake system of Edwardsiella ictaluri and its influence on pathogenesis and immunogenicity in the catfish host
Authors: Soo-Young Wanda
Javier Santander
Roy Curtiss 3rd
Greg Golden
Journal: Infection and Immunity (2012)
Discipline: IMMUNOLOGY
Keywords: bacterial pathogens; iron uptake; host high-affinity iron binding proteins; ferric uptake regulator (Fur); Edwardsiella ictaluri
Affiliations: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA. 

Abstract:  The ability of bacterial pathogens to take up iron from the host during infection is necessary for their multiplication within the host. However, host high-affinity iron binding proteins limit levels of free iron in fluids and tissues. To overcome this deficiency of iron during infection, bacterial pathogens have developed iron uptake systems that are upregulated in the absence of iron, typically tightly controlled by the ferric uptake regulator (Fur) protein. The iron uptake system of Edwardsiella ictaluri, a host-restricted pathogen of channel catfish (Ictalurus punctatus) and the main pathogen of this fish in aquaculture, is unknown. Here we describe the E. ictaluri Fur protein, the iron uptake machinery controlled by Fur, and the effects of fur gene deletion on virulence and immunogenicity in the fish host. Analysis of the E. ictaluri Fur protein shows that it lacks the N-terminal region found in the majority of pathogen-encoded Fur proteins. However, it is fully functional in regulated genes encoding iron uptake proteins. E. ictaluri grown under iron-limited conditions upregulates an outer membrane protein (HemR) that shows heme-hemoglobin transport activity and is tightly regulated by Fur. In vivo studies showed that an E. ictaluri Δfur mutant is attenuated and immune protective in zebrafish (Danio rerio) and catfish (Ictalurus punctatus), triggering systemic immunity. We conclude that an E. ictaluri Δfur mutant could be an effective component of an immersion-oral vaccine for the catfish industry. 

Retracted: No

PubPeer comments:
 November 2015 Correction found here: https: iai.asm.org content 83 12 4897 It reads:  Figure 8 should appear as shown below. Here is the original Figure 8G, as reported the journal in October 2014, with a duplication (90 degrees rotated) marked with red boxes. ![file] I thank the authors and journal staff for correcting this error. ,
Synthesis, Characterization, and Preclinical Evaluation of (99m)Tc-Labeled Macrobicyclic and Tricyclic Chelators as Single Photon Emission Computed Tomography Tracer
Authors: Krishna Chuttani
Anil K Mishra
Neelam Yadav
Bachcha Singh
Journal: Chemical Biology & Drug Design (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: 99mTechnetium; DFT; cancer; ligand; macrocyclic chelators
Affiliations: Department of Chemistry; Centre of Advanced Study; Faculty of Science; Banaras Hindu University; Varanasi 221005 India, Division of Cyclotron and Radiopharmaceutical Sciences; Institute of Nuclear Medicine and Allied Sciences; Defence Research and Development Organization; Brig. S. K. Mazumdar Road Timarpur Delhi 110054 India

Abstract:  The novel tetraaza macrobicyclic chelator 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-2,10-dione (TBPD) and pentaaza macrotricyclic chelator 9-oxa-3,6,12,15,21-pentaazatricyclo[15,3,2,1]trieicos-1(21),17,19-triene-2,7,11,16-tetradione (OPTT) were synthesized, characterized, and radiolabeled with (99m)Tc to produce (99m)Tc-TBPD and (99m)Tc-OPTT. These radiolabeled complexes were prepared with high radiolabeling yield, radiochemical purity, and good in vitro stability up to 24 h. The labeling efficiency of (99m)Tc-TBPD and (99m)Tc-OPTT was found 98% and 97%. In vitro serum stability of (99m)Tc-TBPD was found to be 95.2%, while that of (99m)Tc-OPTT 94.2% up to 24 h. Blood kinetics experiments of (99m)Tc-labeled complexes showed biphasic pattern of blood clearance. About 99.57 ± 0.89% activity of (99m)Tc-TBPD and 99.42 ± 0.88% activity of (9m)Tc-OPTT were cleared off blood stream at 24 h postadministration. The biological half-life of (99m) Tc-TBPD was observed: t1/2(F) 1 h 5 min and t1/2(S) 12 h and biological half-life of (99m)Tc-OPTT was observed: t1/2(F) 1 h 10 min and t1/2(S) 9 h 50 min, respectively. The biodistribution studies revealed that maximum uptake of (99m)Tc-TBPD was found in liver, concluded that excretory pathway is hepatobiliary, while that of (99m)Tc-OPTT was renal as well as hepatobiliary. The negligible activity observed in stomach confirming the stability of radiolabeled complex in biological milieu. In vitro cytotoxicity study of TBPD and OPTT did not show any considerable antiproliferative activity against cancer cells of human cervical SW756, HeLa, and glioblastoma U-87, U373 cell lines. 

Retracted: No

PubPeer comments:
 Fig. 6. of Chem Biol Drug Des **2016**; 87: 730u2013736 shows a strange similarity with Fig. 11a. of MedChemComm 6.8 (**2015**): 1452-1463 and Fig. 10 A .of CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS ; 25, 6, **2010** ![file] ,
Horizontal transfer of exosomal CXCR4 promotes murine hepatocarcinoma cell migration, invasion and lymphangiogenesis
Authors: Jingwen Wang
Lianhong Li
Yunchao Xu
Lu Wang
Yue Du
Jie Shen
Chenghong Zhang
Bo Song
Ying Lu
Jianwu Tang
Min Li
Bo Wang
Journal: Gene (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Exosomes; Lymphatic metastasis; SDF-1α/CXCR4.
Affiliations: Department of Pathology and Forensics, Dalian Medical University, Dalian 116044, China., Teaching Laboratory of Morphology, Dalian Medical University, Dalian 116044, China., Department of Pathology and Forensics, Dalian Medical University, Dalian 116044, China. Electronic address: .

Abstract:  Exosomes have been demonstrated as an important factor to influence cancer invasion and metastasis. Previous studies have shown that CXC chemokine recepter-4 (CXCR4) and stromal cell-derived factor-1α (SDF-1α) mediates matrix metalloproteinases (MMPs) secretions to facilitate lymph node metastasis of hepatocarcinoma cells. In this study, we demonstrated that exosomes containing elevated CXCR4 from high lymph node metastatic mouse hepatocarcinoma Hca-F cells were able to promote the migration and invasion of a paired syngeneic Hca-P cells that have low metastatic potential. Such impact on enhanced migratory and invasive capacities of Hca-P cells was triggered by the internalization of exosomes isolated from Hca-F cells. This was possibly due to the horizontal transferring of CXCR4 via exosomes. The lymphatic endothelial cells (LECs) increased the migration and invasion of Hca-F cells probably by expressing SDF-1α which bound with CXCR4 in the Hca-F cells and subsequently enhanced the secretions of MMP-9, MMP-2 and vascular endothelial growth factor C (VEGF-C). Exosomal CXCR4 from Hca-F cells promoted LECs proliferative rate and lymphatic tube formation ability. Our findings suggest that horizontal transfer of exosomal CXCR4 can promote murine hepatocarcinoma cell migration, invasion and lymphangiogenesis, and exosomal CXCR4 might be a novel therapeutic target against tumor lymphatic metastasis. 

Retracted: No

PubPeer comments:
 Figure 1C potential overlap between Invasion of Hca-P + F-Exo and Hca-F, indicated by green solid boxes. Interestingly, there are differences between the two green box marked images. Broken ovals are those missing from Hca-F invastion, while the solid ovals are features added to it, probably from sources on the same image. ![] , 
 Figure 3C potential overlap ![file] , 
 #2 ![file] , 
 #1 The middle top panel has problems as well. ![file] , 
 Fig 2D. ![file] Second row, second panel: ![file] , 
 Fig 4 D.  Exosomal CXCR4 increases lymphatic tube formation and LECs proliferation. ... (D) Tube-like formation and tube number were measured by analytical software Image J after incubating Hca-F cells derived exosomes with LECs alone (LEC+F-Exo), scramble siRNA transfected LECs (LEC-NC+F-Exo) and siCXCR4 transfected LECs (LEC-siCXCR4+F-Exo). ![file] ,
Long non-coding RNA SDPR-AS affects the development of non-small cell lung cancer by regulating SDPR through p38 MAPK/ERK signals
Authors: Junfei Zhu
Ruomin Liao
Lili Wang
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Non-small cell lung cancer; SDPR; long non-coding RNA SDPR-AS; p38 MAPK/ERK signaling pathway.
Affiliations: a Department of Respiratory Medicine, Taizhou Central Hospital , Taizhou , Zhejiang , China., b Department of ICU, The People's Hospital of Jiaozuo City , Jiaozuo , Hebei , China., c Department of Respiratory, Shanghai General Hospital, Shanghai Gongji Hospital , Shanghai , China.

Abstract:  We aimed to determine the roles and possible mechanism of long non-coding RNA SDPR-AS in the processes of non-small cell lung cancer (NSCLC). The expressions of SDPR-AS and SDPR in different subtypes of lung cancer (AC, SCC, LCC and SCLC) tissues and cells were determined. Three NSCLC cells were infused with pcDNA-SDPR-AS, pcDNA3.1, sh-SDPR-AS, sh-NC, si-SDPR and si-NC. The effects of SDPR-AS dysregulation on cell behaviors (including cell viability, colony forming ability, migration, invasion and apoptosis) were assessed. Moreover, the combined effects of SDPR-AS overexpression and SDPR-AS knockdown on H522 cell behaviors and the levels of p-p38 and p-ERK were investigated. SDPR-AS was lowly expressed in NSCLC tissues and cells, but had no changes in SCLC tissues and cells. Down-regulation of SDPR-AS enhanced the proliferation, migration and invasion and inhibited apoptosis of NSCLC cells (H522, H661 and H520). Overexpression of SDPR-AS exhibited opposite effects. Moreover, SDPR was positively regulated by SDPR-AS and effects of SDPR-AS on the cell biological processes of NSCLC cells were through regulation of SDPR. Besides, the levels of p-p38 and p-ERK were significantly decreased after SDPR-AS overexpression, which were dramatically changeover by SDPR knockdownsimultaneously. Our findings indicate that SDPR-AS was lowly expressed in NSCLC cells and down-regulation of SDPR-AS may promote the malignant behaviors of NSCLC cells possible through regulating SDPR expression and involving in p38 MAPK/ERK signaling pathway. SDPR-AS may serve as a prospective target for NSCLC diagnosis and therapy. 

Retracted: No

PubPeer comments:
 The Figures are a combination of stylised WBs (resembling airbrushed dog-bones, or designer door-handles); colony plates which look as if someone has drawn the dots onto a blank disk with a felt pen; and equally stylised invasion-assay images. That is to say, the paper appears to be a product of the Tadpole Papermilll . ![file] ,
MicroRNA-1236-3p inhibits proliferation and invasion of breast cancer cells by targeting ZEB1
Authors: T-C Liang
W-G Fu
Y-S Zhong
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-1236-3p; breast cancer; ZEB1; proliferation; invasion
Affiliations: Department of Breast Surgery, Sichuan Luzhou TCM Hospital, Luzhou, China. .

Abstract:  Objective: This research aims to investigate the level of microRNA-1236-3p in breast cancer (BCa) tissues and to further investigate its possible mechanism in the progression of BCa. Patients and methods: The level of microRNA-1236-3p in BCa tissues and adjacent tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Regulatory effects of microRNA-1236-3p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) and transwell assay. The binding relationship between microRNA-1236-3p and zinc-finger E-box binding homeobox (ZEB1) was examined by the dual-luciferase reporter gene assay. Finally, rescue experiments were conducted to verify the potential role of microRNA-1236-3p/ ZEB1 axis in BCa. Results: MicroRNA-1236-3p was downregulated in BCa tissues relative to adjacent tissues, and the similar trend was shown in BCa cell lines. Overexpression of microRNA-1236-3p in MDA-MB-231 and MCF-7 cells inhibited proliferation and attenuated invasiveness, while knockdown of microRNA-1236-3p had an opposite effect. Dual-luciferase reporter gene assay and qRT-PCR results showed that microRNA-1236-3p could target ZEB1 to degrade it. Overexpression of ZEB1 in BCa cells can partially reverse the effect of overexpressed miR-1236-3p on cell proliferative and invasive abilities. Conclusions: MicroRNA-1236-3p could inhibit the growth and metastasis of BCa cells by inhibiting ZEB1 expression, suggesting that microRNA-1236-3p may be a potential therapeutic target for BCa. 

Retracted: No

PubPeer comments:
  Fresh BCa tissues and adjacent normal tissues were collected from 67 patients treated with surgery in Sichuan Luzhou TCM Hospital from **July 2015 to December 2017**. Fig 1D.  Analysis of the relationship between microRNA-1236-3p level and prognosis of BCa patients by Kaplan-Meier.  ![file] When this paper was published in 2019, the authors had followed their patients survival for six years, i.e. through to the date range **July 2021 to December 2023**. ,
Identification and optimization of piperlongumine analogues as potential antioxidant and anti-inflammatory agents via activation of Nrf2
Authors: Lailiang Qu
Huali Yang
Heng Luo
Shang Li
Cheng Wang
Limei Ji
Fucheng Yin
Dehua Lu
Xingchen Liu
Xiaobing Wang
Wan Peng
Lingyi Kong
Journal: European Journal of Medicinal Chemistry (2021)
Discipline: CHEMISTRY
Keywords: Keap1-Nrf2-ARE pathway; Neuroprotective effect; Oxidative stress; Piperlongumine analogues.
Affiliations: Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China., Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: .

Abstract:  Oxidative stress and inflammation are significant risk factors for neurodegenerative disease. The Keap1-Nrf2-ARE pathway is one of the most promising defensive systems against oxidative stress. Here, dozens of piperlongumine analogues were designed, synthesized, and tested on PC12 cells to examine neuroprotective effects against H2O2 and 6-OHDA induced damage. Among them, 6d was found to be able to alleviate the accumulation of ROS, inhibit the production of NO and downregulate the level of IL-6, which indicated its potential antioxidant and anti-inflammatory activity. Further studies proved that 6d could activate Nrf2 signaling pathway, induce the translocation of Nrf2 from cell cytosol to nucleus and upregulate the related phase II antioxidant enzymes including NQO1, HO-1, GCLC, GCLM and TrxR1. These results confirmed that 6d exerted antioxidant and anti-inflammatory activities by activating Nrf2 signaling pathway. Moreover, the parallel artificial membrane permeability assay indicated that 6d can cross the blood-brain barrier. In general, 6d is promising for further development as a therapeutic drug against oxidative stress and inflammation related neurodegenerative disorders. 

Retracted: No

PubPeer comments:
 Fig. 10C contain two WB bands which appear more similar than expected, with the adjustment of the background. ![file] , 
 Could the authors please provide the update about the comment processinguff1f , 
 #1 Thank you for pointing out the error in the figure. At the first time we received the comments, we checked our original records, and found that the WB band of GCLM is right and the WB band of HO-1 is misplaced. The figure should be corrected as following, and the corresponding corrigendum had been sent to the chief editor of the journal recently. ![file] Yours Sincerely, Xiaobing Wang ,
Pericyte loss influences Alzheimer-like neurodegeneration in mice
Authors: Robert D Bell
Qingyi Ma
Ethan A Winkler
Abhay P Sagare
Berislav V Zlokovic
Anita Ramanathan
Zhen Zhao
Journal: Nature Communications (2013)
Discipline: Multidisciplinary
Keywords: Pericytes; Alzheimer's disease; neurodegeneration; amyloid β-peptide; tau pathology
Affiliations: 1] Department of Physiology and Biophysics, Keck School of Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90033, USA [2]., 1] Center of Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Rochester, New York 14642, USA [2]., Department of Physiology and Biophysics, Keck School of Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90033, USA., Center of Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Rochester, New York 14642, USA.

Abstract:  Pericytes are cells in the blood-brain barrier that degenerate in Alzheimer's disease (AD), a neurological disorder associated with neurovascular dysfunction, abnormal elevation of amyloid β-peptide (Aβ), tau pathology and neuronal loss. Whether pericyte degeneration can influence AD-like neurodegeneration and contribute to disease pathogenesis remains, however, unknown. Here we show that in mice overexpressing Aβ-precursor protein, pericyte loss elevates brain Aβ40 and Aβ42 levels and accelerates amyloid angiopathy and cerebral β-amyloidosis by diminishing clearance of soluble Aβ40 and Aβ42 from brain interstitial fluid prior to Aβ deposition. We further show that pericyte deficiency leads to the development of tau pathology and an early neuronal loss that is normally absent in Aβ-precursor protein transgenic mice, resulting in cognitive decline. Our data suggest that pericytes control multiple steps of AD-like neurodegeneration pathogenic cascade in Aβ-precursor protein-overexpressing mice. Therefore, pericytes may represent a novel therapeutic target to modify disease progression in AD. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 Figure 6 appears to include two images which overlap (red boxes). *** ![file] , 
 #1 I have annotated Figure 7 again, noting some additional possible overlaps, also including Supplemental Figure S3. *** Figure 7 ![file] *** Supplemental Figure S3. ![file] ,
MicroRNA-135b regulates metastasis suppressor 1 expression and promotes migration and invasion in colorectal cancer
Authors: Jingfang Yang
Yu Zhou
Guoli Wei
Yuanhong Chen
Zhuang Wang
Shicai Ye
Pengchun Yang
Weiyun Wu
Hao Wang
Jian Liang
Journal: Molecular and Cellular Biochemistry (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MicroRNAs; miR-135b; colorectal cancer; metastasis suppressor-1 (MTSS1); gene expression
Affiliations: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, South Peoples Avenue No. 57, Xiashan District, Zhanjiang, Guangdong, China, .

Abstract:  MicroRNAs (miRNAs, miRs) play important roles in pathogenesis and development of human diseases, including malignancy. Some may affect tumor progression through targeting tumor suppressor genes. MiR-135b has been shown to be upregulated in CRC. In this study, we evaluated the role of miR-135b in colorectal cancer (CRC) and its regulatory role for metastasis suppressor-1 (MTSS1) and its mechanisms. The levels of miR-135b and MTSS1 gene expression in 35 CRC and corresponding cancer-adjacent tissues, 27 colorectal adenoma, and 16 normal tissue samples were quantified using qRT-PCR and western blot analysis. The effect of miR-135b on MTSS1 expression was assessed by miR-135b mimics or inhibitor transfection to deregulate miR-135b expression. The direct interaction between them was verified by 3'-UTR dual-luciferase reporter assay. Furthermore, the roles of miR-135b in regulating CRC cells migration and invasion properties were analyzed with miR-135b mimics or inhibitor-transfected cells and silenced expression of MTSS1 in miR-135b inhibitor transfected cells. CRC tissues showed significantly upregulated miR-135b expression and reduced MTSS1 expression. High miR-135b levels were significantly associated with lymph node and distant metastasis. The miR-135b inhibitor decreased miR-135b expression and caused MTSS1 upregulation at the post-transcriptional level. However, overexpression of miR-135b caused MTSS1 protein downregulation. The 3'-UTR of MTSS1 harbored a binding site for miR-135b. Finally, miR-135b inhibitor-transfected cells exhibited markedly reduced cell migration and invasive abilities, and this effect could be reversed by MTSS1-siRNA. Our results demonstrated that miR-135b downregulated MTSS1 expression and contributed to CRC cell invasion, indicating its involvement in CRC progression. 

Retracted: No

PubPeer comments:
 Figure 5 appears to have an overlapping image ![file] ,