PReD-Bench/PRed-Bench huggingface dataset:
IL-33 induced inflammation exacerbated the development of chronic obstructive pulmonary disease through oxidative stress
Authors: J Jiang
J Song
S-C Zou
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: IL-33; chronic obstructive pulmonary disease; inflammation; oxidative stress; mouse model
Affiliations: Department of Respiratory Medicine, Yantai Yuhuangding Hospital, Yantai, China. .

Abstract:  Objective: We aimed at exploring the role of IL-33 in mouse chronic obstructive pulmonary disease and its potential molecular mechanism. Materials and methods: The chronic obstructive pulmonary disease (COPD) mice model was established by cigarette smoking (CS). COPD mice were randomly assigned into PBS group and IL-33 antibody group. The peripheral blood and lung tissues of mice from two groups were collected for the following experiments. Pathological changes of the lung tissues in both groups were analyzed by hematoxylin and eosin (HE) staining. IL-33 positive cells in lung tissues were detected by immunohistochemistry. Then, the mRNA and protein levels of IL-33, sST2, ERK and TNF-Œ± in the mice peripheral blood of the two groups were accessed by Real-time polymerase chain reaction (RT-PCR) and Western blot. Finally, the indicators related to oxidative stress, including superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) in the mice serum of two groups were measured. Results: After successful construction of COPD mouse model by CS, HE staining illustrated that the structure of airway wall of lung tissue in mice from PBS group was irregular. The ciliated columnar epithelium presented significant degeneration, necrosis and shedding. A large amount of inflammation cell infiltration was observed in vascular tissues. The alveolar epithelial structure was severely damaged and alveolar septum was narrowed and ruptured. Adjacent alveoli were found to be fused into larger cysts. The above pathological changes were relatively better in mice from IL-33 antibody group. Immunohistochemical results demonstrated that IL-33 was remarkably deposited in the lung tissue of PBS group. The mRNA and protein levels of IL-33, sST2, ERK and TNF-Œ± in peripheral blood of PBS group were much higher than those of IL-33 antibody group. At the same time, SOD level in PBS group decreased, while MDA level and ROS production increased. Conclusions: IL-33 aggravates lung injury in COPD mice by increasing inflammation response and oxidative stress, which may serve as a target for predicting and treating COPD. 

Retracted: No

PubPeer comments:
 Figure 4C.  IL-33 aggravated oxidative stress in COPD mice. ... C, ROS number in the PBS group was remarkably larger . Panels overlap and are unlikely to represent different conditions.  Fig 2C, 3B.  , 
 *[above]* Fig 1A,B. Two panels were taken from *[below]* Fig 12 of  The anti-allergic activity of Cymbopogon citratus is mediated via inhibition of nuclear factor kappa B (Nf-u039ab) activation ([Santos Serafim Machado et al 2015] ), after a 180-deg flip to turn them into original work.  ,
The linker region in receptor guanylyl cyclases is a key regulatory module: mutational analysis of guanylyl cyclase C
Authors: Sandhya S Visweswariah
Kabir Hassan Biswas
Sayanti Saha
Chandana Kondapalli
Nishitha Isloor
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Receptor guanylyl cyclases; ligand binding; intracellular cGMP; kinase homology domain (KHD); linker region
Affiliations: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.

Abstract:  Receptor guanylyl cyclases are multidomain proteins, and ligand binding to the extracellular domain increases the levels of intracellular cGMP. The intracellular domain of these receptors is composed of a kinase homology domain (KHD), a linker of approximately 70 amino acids, followed by the C-terminal guanylyl cyclase domain. Mechanisms by which these receptors are allosterically regulated by ligand binding to the extracellular domain and ATP binding to the KHD are not completely understood. Here we examine the role of the linker region in receptor guanylyl cyclases by a series of point mutations in receptor guanylyl cyclase C. The linker region is predicted to adopt a coiled coil structure and aid in dimerization, but we find that the effects of mutations neither follow a pattern predicted for a coiled coil peptide nor abrogate dimerization. Importantly, this region is critical for repressing the guanylyl cyclase activity of the receptor in the absence of ligand and permitting ligand-mediated activation of the cyclase domain. Mutant receptors with high basal guanylyl cyclase activity show no further activation in the presence of non-ionic detergents, suggesting that hydrophobic interactions in the basal and inactive conformation of the guanylyl cyclase domain are disrupted by mutation. Equivalent mutations in the linker region of guanylyl cyclase A also elevated the basal activity and abolished ligand- and detergent-mediated activation. We, therefore, have defined a key regulatory role for the linker region of receptor guanylyl cyclases which serves as a transducer of information from the extracellular domain via the KHD to the catalytic domain. 

Retracted: No

PubPeer comments:
  ,
C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium
Authors: Sofia Colmenares Benedetto
Giovanni Camussi
Maria Felice Brizzi
Patrizia Dentelli
Antonina Balsamo
Luigi Pegoraro
Annarita Zeoli
Marco Pegoraro
Arturo Rosso
Journal: Blood (2007)
Discipline: CLINICAL MEDICINE
Keywords: c-Kit; membrane-bound ligand; endothelial progenitor cell; recruitment; microvascular endothelial cells
Affiliations: Department of Internal Medicine, University of Turin, Italy.

Abstract:  We investigated the role of c-Kit and the membrane-bound ligand (mbKitL) in endothelial progenitor cell (EPC) recruitment by microvascular endothelial cells (ECs). We demonstrated that inflammatory activation induced the expression of the mbKitL on ECs both in vitro and in vivo, and that recruitment of EPCs depended on c-Kit/mbKitL interaction. Depletion of endogenous c-Kit or inhibition of c-Kit enzymatic activity by imatinib mesylate prevented adhesion of EPCs to activated ECs both in vitro and in vivo, indicating that a functional c-Kit on EPCs is essential. We also demonstrate that Akt was the downstream molecule regulating cell adhesion. A potential role of the c-Kit/mbKitL interaction in pathological settings is sustained by the expression of the mbKitL on ECs lining intraplaque neovessels. Thus, our results provide new insights into the mechanisms underlying EPC recruitment and the bases for novel strategies to hinder pathological angiogenesis. 

Retracted: No

PubPeer comments:
null, 
null, 
 #1  ,
Heme oxygenase-1-derived carbon monoxide requires the activation of transcription factor NF-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis
Authors: Fritz H Bach
Mark P Seldon
Miguel P Soares
Sophie Brouard
Edda Tobiasch
Pascal O Berberat
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Carbon monoxide; heme oxygenase-1; endothelial cells; TNF-alpha; apoptosis
Affiliations: Immunobiology Research Center, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract:  We have shown that carbon monoxide (CO) generated by heme oxygenase-1 (HO-1) protects endothelial cells (EC) from tumor necrosis alpha (TNF-alpha)-mediated apoptosis. This effect relies on the activation of p38 MAPK. We now demonstrate that HO-1/CO requires the activation of the transcription factor NF-kappaB to exert this anti-apoptotic effect. Our data suggest that EC have basal levels of NF-kappaB activity that sustain the expression of NF-kappaB-dependent anti-apoptotic genes required to support the anti-apoptotic effect of HO-1/CO. Over-expression of the inhibitor of NF-kappaB alpha (IkappaBalpha) suppresses the anti-apoptotic action of HO-1/CO. Reconstitution of NF-kappaB activity, by co-expression of IkappaBalpha with different members of the NF-kappaB family, i.e. p65/RelA or p65/RelA plus c-Rel, restores the anti-apoptotic effect of HO-1/CO. Expression of the NF-kappaB family members p65/RelA or p65/RelA with p50 or c-Rel up-regulates the expression of the anti-apoptotic genes A1, A20, c-IAP2, and manganese superoxide dismutase (MnSOD). Inhibition of NF-kappaB activity by over-expression of IkappaBalpha suppresses the expression of some of these anti-apoptotic genes, i.e. c-IAP2. Under inhibition of NF-kappaB, co-expression of some of these anti-apoptotic genes, i.e. c-IAP2 and A1, restores the anti-apoptotic action of HO-1/CO, whereas expression of A20 or MnSOD cannot. The ability of c-IAP2 and/or A1 to restore the anti-apoptotic action of HO-1/CO is abolished when p38 MAPK activation is blocked by over-expression of a p38 MAPK dominant negative mutant. In conclusion, we demonstrate that HO-1/CO cooperates with NF-kappaB-dependent anti-apoptotic genes, i.e. c-IAP2 and A1, to protect EC from TNF-alpha-mediated apoptosis. This effect is dependent on the ability of HO-1/CO to activate the p38 MAPK signal transduction pathway. 

Retracted: No

PubPeer comments:
 Figures 4D and 7H appear to have a repeated image. Figures 4I and 7H appear to have an overlapping image. In both cases, they appear to have been resized and in one case, slightly recolored. ***  ***  , 
 Figure 5G and 8E appear to have a repeated image. These types of errors are sometimes seen in paper mill (or outsourced) papers. ***  , 
 Figure 7H and 8E appear to have a repeated image. ***  ,
Lipopolysaccharides attenuates growth of HS cells through the JNK pathway
Authors: Hao Peng
Jinle Fu
Journal: Cytotechnology (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: LPS; MAPK; Rheumatoid arthritis.
Affiliations: Department of Orthopedics, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, Hubei, China., Department of Orthopedics, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, Hubei, China. .

Abstract:  Rheumatoid arthritis is characterized by inflammation of the synovial membrane, which can result in joint destruction within the first few years after onset. Lipopolysaccharides (LPS) are glycolipids found in abundance on the outer membranes of all Gram-negative bacteria and incite a vigorous inflammatory response. We studied the potential involvement of mitogen-activated protein kinase serine/threonine kinases in LPS-induced growth of HS synovial cells. Various concentrations of LPS were applied to cultured HS cells and growth rate, as well as changes in the phosphorylation states of extracellular regulated kinase 1/2, Jun N-terminal kinase (JNK), and p38 were determined. As results, growth of LPS-treated HS cells was inhibited primarily by phosphorylated JNK and this phosphorylation was mediated by the LPS receptor. Our results suggest that LPS inhibits growth of HS cells primarily through the JNK pathway. 

Retracted: No

PubPeer comments:
 Figure 7A * Red arrows: In the p-ERK panel, all four lanes look unexpectedly similar.  ,
Retinoic acid reduces migration of human breast cancer cells: role of retinoic acid receptor beta
Authors: Gisel Valeria Gauna
Beatriz Silvina Nadin
Angel Matias Sanchez
Laura Maria Vargas-Roig
Mayra Lis Sottile
Marina Ines Flamini
Journal: Journal of Cellular and Molecular Medicine (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FAK; RARŒ≤; breast cancer cells; cell migration; moesin
Affiliations: Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, National Research Council of Argentina, Mendoza, Argentina., Tumor Biology Laboratory Institute of Medicine and Experimental Biology of Cuyo National Research Council of Argentina Mendoza Argentina, School of Medical Sciences National University of Cuyo Mendoza Argentina, Reproduction and Lactation Laboratory Institute of Medicine and Experimental Biology of Cuyo National Research Council of Argentina Mendoza Argentina

Abstract:  Breast cancer is the most common malignancy in women and the appearance of distant metastases produces the death in 98% of cases. The retinoic acid receptor Œ≤ (RARŒ≤) is not expressed in 50% of invasive breast carcinoma compared with normal tissue and it has been associated with lymph node metastasis. Our hypothesis is that RARŒ≤ protein participates in the metastatic process. T47D and MCF7 breast cancer cell lines were used to perform viability assay, immunobloting, migration assays, RNA interference and immunofluorescence. Administration of retinoic acid (RA) in breast cancer cells induced RARŒ≤ gene expression that was greatest after 72 hrs with a concentration 1 ŒºM. High concentrations of RA increased the expression of RARŒ≤ causing an inhibition of the 60% in cell migration and significantly decreased the expression of migration-related proteins [moesin, c-Src and focal adhesion kinase (FAK)]. The treatment with RARŒ± and RARŒ≥ agonists did not affect the cell migration. On the contrary, the addition of the selective retinoid RARŒ≤-agonist (BMS453) significantly reduced cell migration comparable to RA inhibition. When RARŒ≤ gene silencing was performed, the RA failed to significantly inhibit migration and resulted ineffective to reduce moesin, c-Src and FAK expressions. RARŒ≤ is necessary to inhibit migration induced by RA in breast cancer cells modulating the expression of proteins involved in cell migration. 

Retracted: No

PubPeer comments:
 Two images in Figure 5A appears are unexpectedly similar, but not identical. ***  , 
 Thank you very much for reminding us of the repetition. I checked the original data and reports. Indeed, it is a mistake during figure preparation. In any case, these figures correspond to the moment of scratching of the wound in time zero when the treatments have not yet been added, so the initial wound at time zero should always be the same when performed with the same tip. Surely, I will ask the journal for the correction soon. Thank you very much for your efforts in making the scientific publication solid and clean. Sincerely, Marina ,
Hydrophobic motif phosphorylation is not required for activation loop phosphorylation of p70 ribosomal protein S6 kinase 1 (S6K1)
Authors: Susan S Taylor
Alexandra C Newton
Malik M Keshwani
Thomas K Harris
Sventja von Daake
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: p70 ribosomal protein S6 kinase 1; phosphorylation; AGC kinases; activation loop; turn motif
Affiliations: Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA.

Abstract:  p70 ribosomal protein S6 kinase 1 (S6K1) is regulated by multiple phosphorylation events. Three of these sites are highly conserved among AGC kinases (cAMP dependent Protein Kinase, cGMP dependent Protein Kinase, and Protein Kinase C subfamily): the activation loop in the kinase domain, and two C-terminal sites, the turn motif and the hydrophobic motif. The common dogma has been that phosphorylation of the hydrophobic motif primes S6K1 for the phosphorylation at the activation loop by phosphoinositide-dependent protein kinase 1 (PDK1). Here, we show that the turn motif is, in fact, phosphorylated first, the activation loop second, and the hydrophobic motif is third. Specifically, biochemical analyses of a construct of S6K1 lacking the C-terminal autoinhibitory domain as well as full-length S6K1, reveals that S6K1 is constitutively phosphorylated at the turn motif when expressed in insect cells and becomes phosphorylated in vitro by purified PDK1 at the activation loop. Only the species phosphorylated at the activation loop by PDK1 gets phosphorylated at the hydrophobic motif by mammalian target of rapamycin (mTOR) in vitro. These data are consistent with a previous model in which constitutive phosphorylation of the turn motif provides the key priming step in the phosphorylation of S6K1. The data provide evidence for regulation of S6K1, where hydrophobic motif phosphorylation is not required for PDK1 to phosphorylate S6K1 at the activation loop, but instead activation loop phosphorylation of S6K1 is required for mTOR to phosphorylate the hydrophobic motif of S6K1. 

Retracted: No

PubPeer comments:
 Figure 3B u2013 more similar than expected  ,
Effect of temperature on the oxidation of Cu nanowires and development of an easy to produce, oxidation-resistant transparent conducting electrode using a PEDOT:PSS coating
Authors: Harsojo Sabarman
Kyunghoon Kim
Yoonkyung Lee
Muhammad Q Mehmood
Niloufar Raeis-Hosseini
Dedi Mardiansyah
Trevon Badloe
Kuwat Triyana
Junsuk Rho
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: Oxidation; Cu nanowires; conductivity; transparent electrodes; temperature treatments

Abstract:  Oxidation can strongly influence the performance of Cu nanowires (CuNWs) by decreasing their conductivity. Here, we identify and investigate a way to prevent the oxidation process of CuNWs to maintain the high conducting performance of CuNWs as transparent electrodes. CuNWs were synthesised using an aqueous method. We prepared several temperature treatments (from 0-300 ¬∞C) to represent oxidation of CuNWs in different environments, to study the oxidation process and changes in morphology in detail. Depending on the temperature, smooth and uniform CuNWs exposed to oxidation produced rough Cu2O and CuO nanowires. We then suggest a method of protecting nanowires from oxidation, using the Mayer rod coating method to apply a layer of PEDOT:PSS to a transparent conducting film of CuNWs. The result indicates that this method of protection can protect the film, and maintain a stable, and constant resistance over of time, without effecting the excellent conductivity properties of pure CuNWs. 

Retracted: No

PubPeer comments:
 June 4 2021 Correction: It reads:  Following the publication of this article [1] concerns were raised regarding the u03b2-actin blot presented in Fig 6A. Horizontal discontinuities and repetitive elements were detected in the background directly below the bands representing u03b2-actin signal. The original u03b2-actin blot presented additional bands underneath the u03b2-actin results visible in lanes 1u20133, and 6u20139, which were removed from the panel to improve the clarity of the presented blot, and only the top bands were used for quantification. The removing of the bands beneath the u03b2-actin results contravenes PLOS ONEu2019s figure preparation guidelines, instead the lower bands should have been included in the published panel, and the text should have commented on the inconsistency. Here is the original marked Figure 6A as reported to the journal in October 2015. In the Beta actin panel, areas under the band appear to have been patched stamped.  ,
HCV infection selectively impairs type I but not type III IFN signaling
Authors: Partha K Chandra
Luis A Balart
Darren P Baker
Kyoungsub Song
Shuanghu Liu
Tong Wu
Fatma M Aboulnasr
William C Wimley
Nathan Shores
Lili Bao
Serge Y Fuchs
Srikanta Dash
Curt H Hagedorn
Journal: American Journal Of Pathology (2014)
Discipline: CLINICAL MEDICINE
Keywords: Hepatitis C virus (HCV); replication; interferon-Œ± (IFN-Œ±); IFN-Œª; ribavirin (RBV)
Affiliations: Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana., Biogen Idec, Inc., Cambridge, Massachusetts., Department of Gastroenterology and Hepatology, Tulane University School of Medicine, New Orleans, Louisiana., Department of Biochemistry, Tulane University School of Medicine, New Orleans, Louisiana., Department of Medicine and Pathology, University of Utah School of Medicine, Salt Lake City, Utah., Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania., Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana. Electronic address: .

Abstract:  A stable and persistent Hepatitis C virus (HCV) replication cell culture model was developed to examine clearance of viral replication during long-term treatment using interferon-Œ± (IFN-Œ±), IFN-Œª, and ribavirin (RBV). Persistently HCV-infected cell culture exhibited an impaired antiviral response to IFN-Œ±+RBV combination treatment, whereas IFN-Œª treatment produced a strong and sustained antiviral response that cleared HCV replication. HCV replication in persistently infected cells induced chronic endoplasmic reticulum (ER) stress and an autophagy response that selectively down-regulated the functional IFN-Œ± receptor-1 chain of type I, but not type II (IFN-Œ≥) or type III (IFN-Œª) IFN receptors. Down-regulation of IFN-Œ± receptor-1 resulted in defective JAK-STAT signaling, impaired STAT phosphorylation, and impaired nuclear translocation of STAT. Furthermore, HCV replication impaired RBV uptake, because of reduced expression of the nucleoside transporters ENT1 and CNT1. Silencing ER stress and the autophagy response using chemical inhibitors or siRNA additively inhibited HCV replication and induced viral clearance by the IFN-Œ±+RBV combination treatment. These results indicate that HCV induces ER stress and that the autophagy response selectively impairs type I (but not type III) IFN signaling, which explains why IFN-Œª (but not IFN-Œ±) produced a sustained antiviral response against HCV. The results also indicate that inhibition of ER stress and of the autophagy response overcomes IFN-Œ±+RBV resistance mechanisms associated with HCV infection. 

Retracted: No

PubPeer comments:
 Figure 2G. * Yellow boxes: Two panels appear to show an overlap  , 
 Some more similarities across panels in Figures 2E, 2G, and 9E, marked with boxes of the same color, as noted by ImageTwin. Although treatments (e.g. uninfected infected) labels suggest similar treatments, the number of days of infection and experimental set up might be different. Maybe the authors can clarify?   ,
Prion strain discrimination using luminescent conjugated polymers
Authors: Kurt W√ºthrich
Per Hammarstr√∂m
Simone Hornemann
Magdalini Polymenidou
Adriano Aguzzi
K Peter R Nilsson
Giuseppe Manco
Christina J Sigurdson
Mario Leclerc
Petra Schwarz
Journal: Nature Methods (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: prions; conformational variability; PrP(Sc); PrP(C); luminescent conjugated polymers (LCPs)
Affiliations: Universit√§tsSpital Z√ºrich, Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, CH-8091 Z√ºrich, Switzerland.

Abstract:  The occurrence of multiple strains of prions may reflect conformational variability of PrP(Sc), a disease-associated, aggregated variant of the cellular prion protein, PrP(C). Here we used luminescent conjugated polymers (LCPs), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. LCP reactivity and emission spectra of brain sections discriminated among four immunohistochemically indistinguishable, serially mouse-passaged prion strains derived from sheep scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and mouse-adapted Rocky Mountain Laboratory scrapie prions. Furthermore, using LCPs we differentiated between field isolates of BSE and bovine amyloidotic spongiform encephalopathy, and identified noncongophilic deposits in prion-infected deer and sheep. We found that fibrils with distinct morphologies generated from chemically identical recombinant PrP yielded unique LCP spectra, suggesting that spectral characteristic differences resulted from distinct supramolecular PrP structures. LCPs may help to detect structural differences among discrete protein aggregates and to link protein conformational features with disease phenotypes. 

Retracted: No

PubPeer comments:
 This Sigurdson work has completely changed the way we understand prion strains, by providing the first biophysical evidence that strains are encoded by specific conformations. They went beyond the state-of-the-art by even showing that polythiophenes can change colors when complexed to prions of different strains (as shown in Figure 2).  . ,
Use of liposomized tetracycline in elimination of Wolbachia endobacterium of human lymphatic filariid Brugia malayi in a rodent model
Authors: Prabh N Saxena
Preeti Bajpai
Mohammad Owais
Shailja Misra-Bhattacharya
Satish Vedi
Sharad K Sharma
Journal: Journal of drug targeting (2005)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Wolbachia bacteria; filarial parasite; symbiont; development; fecundity
Affiliations: Central Drug Research Institute, Divisions of Parasitology, Lucknow, India., Divisions of Parasitology Central Drug Research Institute, Biotechnology Unit Aligarh Muslim University, Department of Zoology Institute of Basic Sciences, B.R. Ambedkar University

Abstract:  Wolbachia bacteria, being filarial parasite symbiont have been implicated in a variety of roles, including development, fecundity and the pathogenesis of the filarial infections. Among various strategies used in the treatment of experimental filariasis, the elimination of symbiont Wolbachia seem to offer an efficient means of curing the disease. The antiwolbachial property of tetracycline has been well worked out; however, treatment needs to be continued for a prolonged period of time to achieve complete elimination of Wolbachia from the filarial parasites and their subsequent killing. This results in acute toxicity, thus limiting its practical utility for clinical implementation. In order to increase efficacy of the antibiotic with minimal toxic manifestations, we developed liposomized formulation of the tetracycline. The liposomized tetracycline was found to be significantly more effective when compared to the free form of the drug. In contrast to the 90/120 days oral administration of the drug, the treatment schedule using the liposomized form of the drug was reduced to 12 alternate days with better efficacy of the treatment. 

Retracted: No

PubPeer comments:
 Figure 3. Some lanes appear to be visible multiple times within the same photo or across panels A and B. Shown with boxes of the same color. Green arrows show sharp vertical background transitions. Could the authors please explain what happened here?  Here is Figure 3A, without markings, made a bit lighter to bring out the details.  And here is Figure 3B, without markings, made a bit lighter to bring out the details.  ,
Microbial culturomics: paradigm shift in the human gut microbiome study
Authors: P Hugon
M Million
J-C Lagier
B La Scola
G Gimenez
D Raoult
I Pagnier
C Robert
J-F Trape
M Maraninchi
E V Koonin
F Armougom
F Bittar
G Fournous
Journal: Clinical Microbiology and Infection (2012)
Discipline: IMMUNOLOGY
Keywords: microbial composition; gut microbiota; health; disease; metagenomic analysis
Affiliations: Aix Marseille Universit√©, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.

Abstract:  Comprehensive determination of the microbial composition of the gut microbiota and the relationships with health and disease are major challenges in the 21st century. Metagenomic analysis of the human gut microbiota detects mostly uncultured bacteria. We studied stools from two lean Africans and one obese European, using 212 different culture conditions (microbial culturomics), and tested the colonies by using mass spectrometry and 16S rRNA amplification and sequencing. In parallel, we analysed the same three samples by pyrosequencing 16S rRNA amplicons targeting the V6 region. The 32 500 colonies obtained by culturomics have yielded 340 species of bacteria from seven phyla and 117 genera, including two species from rare phyla (Deinococcus-Thermus and Synergistetes, five fungi, and a giant virus (Senegalvirus). The microbiome identified by culturomics included 174 species never described previously in the human gut, including 31 new species and genera for which the genomes were sequenced, generating c. 10 000 new unknown genes (ORFans), which will help in future molecular studies. Among these, the new species Microvirga massiliensis has the largest bacterial genome so far obtained from a human, and Senegalvirus is the largest virus reported in the human gut. Concurrent metagenomic analysis of the same samples produced 698 phylotypes, including 282 known species, 51 of which overlapped with the microbiome identified by culturomics. Thus, culturomics complements metagenomics by overcoming the depth bias inherent in metagenomic approaches. 

Retracted: No

PubPeer comments:
 In this paper, stool samples were obtained from two individuals in Senegal, and one subject in France. The Methods state that *Each patientu2019s consent was obtained, and the study was approved by the local ethics committee of IFR48 (agreement number 09-022; Marseille, France).* Could the authors please clarify if the study was also approved by an ethics board in Senegal? ,
Reduced immunomodulation potential of bone marrow-derived mesenchymal stem cells induced CCR4+CCR6+ Th/Treg cell subset imbalance in ankylosing spondylitis
Authors: Xinjun Liang
Mingliang Ren
Rui Yang
Yong Tang
Yanfeng Wu
Peng Wang
Lin Huang
Huiyong Shen
Keng Chen
Jichao Ye
Yuanchen Ma
Journal: Arthritis research & therapy (2011)
Discipline: CLINICAL MEDICINE
Keywords: Ankylosing spondylitis; BMSCs; Th17/Treg cells; immunomodulation; CCR4+CCR6+ Th/Treg cells
Affiliations: Department of Othopaedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yanjiangxi Road, Guangzhou 510120, PR China.

Abstract:  Introduction: Ankylosing spondylitis (AS) is a chronic autoimmune disease, and the precise pathogenesis is largely unknown at present. Bone marrow-derived mesenchymal stem cells (BMSCs) with immunosuppressive and anti-inflammatory potential and Th17/Treg cells with a reciprocal relationship regulated by BMSCs have been reported to be involved in some autoimmune disorders. Here we studied the biological and immunological characteristics of BMSCs, the frequency and phenotype of CCR4+CCR6+ Th/Treg cells and their interaction in vitro in AS. Methods: The biological and immunomodulation characteristics of BMSCs were examined by induced multiple-differentiation and two-way mixed peripheral blood mononuclear cell (PBMC) reactions or after stimulation with phytohemagglutinin, respectively. The interactions of BMSCs and PBMCs were detected with a direct-contact co-culturing system. CCR4+CCR6+ Th/Treg cells and surface markers of BMSCs were assayed using flow cytometry. Results: The AS-BMSCs at active stage showed normal proliferation, cell viability, surface markers and multiple differentiation characteristics, but significantly reduced immunomodulation potential (decreased 68 ¬± 14%); the frequencies of Treg and Fox-P3+ cells in AS-PBMCs decreased, while CCR4+CCR6+ Th cells increased, compared with healthy donors. Moreover, the AS-BMSCs induced imbalance in the ratio of CCR4+CCR6+ Th/Treg cells by reducing Treg/PBMCs and increasing CCR4+CCR6+ Th/PBMCs, and also reduced Fox-P3+ cells when co-cultured with PBMCs. Correlation analysis showed that the immunomodulation potential of BMSCs has significant negative correlations with the ratio of CCR4+CCR6+ Th to Treg cells in peripheral blood. Conclusions: The immunomodulation potential of BMSCs is reduced and the ratio of CCR4+CCR6+ Th/Treg cells is imbalanced in AS. The BMSCs with reduced immunomodulation potential may play a novel role in AS pathogenesis by inducing CCR4+CCR6+ Th/Treg cell imbalance. 

Retracted: No

PubPeer comments:
 image duplication  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. ,
Bone morphogenetic protein signalling in heritable versus idiopathic pulmonary hypertension
Authors: P Dartevelle
E Fadel
E Marcos
G Simonneau
M Humbert
R Naeije
L Dewachter
S Adnot
S Eddahibi
L Tu
C Guignabert
Journal: European Respiratory Journal (2009)
Discipline: CLINICAL MEDICINE
Keywords: BMP receptor; pulmonary arterial hypertension; PASMCs; Smad signaling; p38 mitogen-activated protein kinase
Affiliations: INSERM U955, Institut Mondor de recherche biom√©dicale, Cr√©teil, France. 

Abstract:  Mutations in the gene encoding bone morphogenetic protein (BMP) receptor type 2 (BMPR-2) have been reported in pulmonary arterial hypertension (PAH), but their functional relevance remains incompletely understood. BMP receptor expression was evaluated in human lungs and in cultured pulmonary artery smooth muscle cells (PASMCs) isolated from 19 idiopathic PAH patients and nine heritable PAH patients with demonstrated BMPR-2 mutations. BMP4-treated PASMCs were assessed for Smad and p38 mitogen-activated protein kinase (MAPK) signalling associated with mitosis and apoptosis. Lung tissue and PASMCs from heritable PAH patients presented with decreased BMPR-2 expression and variable increases in BMPR-1A and BMPR-1B expression, while a less important decreased BMPR-2 expression was observed in PASMCs from idiopathic PAH patients. Heritable PAH PASMCs showed no increased phosphorylation of Smad1/5/8 in the presence of BMP4, which actually activated the p38MAPK pathway. Individual responses varied from one mutation to another. PASMCs from PAH patients presented with an in vitro proliferative pattern, which could be inhibited by BMP4 in idiopathic PAH but not in heritable PAH. PASMCs from idiopathic PAH and more so from heritable PAH presented an inhibition of BMP4-induced apoptosis. Most heterogeneous BMPR-2 mutations are associated with defective Smad signalling compensated for by an activation of p38MAPK signalling, accounting for PASMC proliferation and deficient apoptosis. 

Retracted: No

PubPeer comments:
 Western blots display several issues:  1. Western blots of BMPR1b and BMPR2 are duplicated 2. Loading controls are identical  1. Blots display a straight line, suggesting potential assembly ,
A New Ni(II)-Containing Coordination Complex Based on Carboxylate and Multinitrogen Co-Ligands: Crystal Structure and Protective Effect on Type 2 Diabetes by Down-Regulating PKC and MAPK Activation
Authors: Gong, X.
Wang, X.
Wang, S.
Guo, Y.
Tai, H.
Journal: Journal of Structural Chemistry (2020)
Discipline: CHEMISTRY
Keywords: Ni(II)-containing coordination complex; synthesis; characterization; nanosized complex; transmission electron microscopy

Abstract: In this study, a new Ni(II)-containing coordination complex [Ni2(H2O)2(Li)(L2)2] (1) is successfully prepared by the reaction of Ni(NO3)2¬∑6H2O, 5,5‚Ä?((1,4-phenylenebis(methylene))bis-(azanediyl))diisophthalic acid (H4L1), and 6,6‚Ä?bis(1H-benzo[d]imidazol-2-yl)-2,2‚Ä?bipyridine (L2) in a mixed solvent of DMF and water. Various characterization methods such as the elemental analysis and single crystal X-ray diffraction are used to probe the structural composition and the agreement of the as-prepared metal-coordination complex. Furthermore, nanosized complex 1 is prepared via the refluxing method, and the transmission electron microscopy images confirm the nanosize of the particles and their homogeneous distribution. To evaluate the treatment activity of nano-1 on the type 2 diabetes, the HepG2 liver cells are treated with the compound. The relative expression of PKC and MAPK in gene and the protein level are detected by RT-PCR and Western blot, respectively.

Retracted: No

PubPeer comments:
  The patients with type 1 diabetes rely on exogenous insulin for survival. Type 2 diabetes is combined with insulin resistance or abnormal insulin secretion [1, 2]. - [2]. D. Zhang, H. Q. Zhang, S. Zhao, Z. G. Li, and S. X. Hou. Int. J. Electrochem. Sci., 2019, 14, 4659. ** Electrochemical Impedance Spectroscopy Evaluation of Corrosion Protection of X65 Carbon Steel by Halloysite Nanotube-Filled Epoxy Composite Coatings in 3.5% NaCl Solution **  The blood glucose levels of patients with type 1 diabetes could usually be controlled by diet or oral hypoglycemic agents. A recent report showed that the type 2 diabetes accounts for over 90% diabetes cases of all cases worldwide [3]. - [3]. S. Guo, R. Chen, H. Li, T. Zhang, and Y. Liu. Int. J. Softw. Eng. Know., 2019, 29, 139 ** Identify Severity Bug Report with Distribution Imbalance by CR-SMOTE and ELM ** The dozens of other papers featuring this bizarre pair of references typically also include a cluster of X. Feng papers, which are relevant, but occur together more often than one might expect.  , 
 Fig. 4 in this article includes W-blots (left). By comparing with the blots found in [another article] already discussed on Pubpeer (right), it is found that the MAPK protein row (middle row on the left panel) is a copy of the caspase-3 row on the right panel.  The duplication is evidenced by comparing backgrounds. A zoom on the central lane is helpful:  , 
 #2  Another sighting! Fig 5 of [Zhou et al (2020)] .  ,
The transcription factor FOXO4 is down-regulated and inhibits tumor proliferation and metastasis in gastric cancer
Authors: Xiangqiang Liu
Yongquan Shi
Yongzhan Nie
Lifen Lv
Linna Su
Na Chai
Daiming Fan
Rui Wang
Xiaosa Li
Journal: BMC Cancer (2014)
Discipline: CLINICAL MEDICINE
Keywords: FOXO4; gastric cancer; expression profile; cell growth; metastasis

Abstract:  Background: FOXO4, a member of the FOXO family of transcription factors, is currently the focus of intense study. Its role and function in gastric cancer have not been fully elucidated. The present study was aimed to investigate the expression profile of FOXO4 in gastric cancer and the effect of FOXO4 on cancer cell growth and metastasis. Methods: Immunohistochemistry, Western blotting and qRT-PCR were performed to detect the FOXO4 expression in gastric cancer cells and tissues. Cell biological assays, subcutaneous tumorigenicity and tail vein metastatic assay in combination with lentivirus construction were performed to detect the impact of FOXO4 to gastric cancer in proliferation and metastasis in vitro and in vivo. Confocal and qRT-PCR were performed to explore the mechanisms. Results: We found that the expression of FOXO4 was decreased significantly in most gastric cancer tissues and in various human gastric cancer cell lines. Up-regulating FOXO4 inhibited the growth and metastasis of gastric cancer cell lines in vitro and led to dramatic attenuation of tumor growth, and liver and lung metastasis in vivo, whereas down-regulating FOXO4 with specific siRNAs promoted the growth and metastasis of gastric cancer cell lines. Furthermore, we found that up-regulating FOXO4 could induce significant G1 arrest and S phase reduction and down-regulation of the expression of vimentin. Conclusion: Our data suggest that loss of FOXO4 expression contributes to gastric cancer growth and metastasis, and it may serve as a potential therapeutic target for gastric cancer. 

Retracted: No

PubPeer comments:
 Figure 4B1. Image reuse.  , 
 Fig 3 A1,A2. Panels overlap and are unlikely to represent different experiments.  , 
 - *[left]* Fig 3B from  microRNA-526b servers as a prognostic factor and exhibits tumor suppressive property by targeting Sirtuin 7 in hepatocellular carcinoma ([Liu et al 2017] ). - *[right]* **Fig 4D**.  , 
  As we know, E-cadherin is an intercellular junction marker and is mainly located at the membrane. Vimentin is a cytoskeleton marker and is mainly located at the intracellular. However, the IF results showed both of them mainly located at the nucleus in Figure 5. ,
Combination therapy of VEGF-trap and gemcitabine results in improved anti-tumor efficacy in a mouse lung cancer model
Authors: Jianmin Fang
Huihong Tao
Yang Yang
Dong Li
Junli Zhang
Yaoqin Yang
Gening Jiang
Shuang Zhou
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Angiogenesis; Vascular endothelial growth factor (VEGF); Combination therapy; Gemcitabine; Lung tumor model
Affiliations: Department of Histology and Embryology, Tongji University School of Medicine, Shanghai, China.

Abstract:  Background: Angiogenesis is essential for the growth and metastasis of cancer. Although anti-angiogenic agents, particularly vascular endothelial growth factor (VEGF) inhibitors, have exhibited single-agent activity, there is considerable interest in combining these novel drugs with conventional chemotherapy reagents to achieve an optimal clinical efficacy. The objective of this study was to evaluate the benefits of the combination therapy of vascular endothelial growth factor trap (VEGF-Trap) with gemcitabine in a lung tumor model. Methods: A luciferase-expressing Lewis lung carcinoma (LLC) model was established in C57BL/6J mice and tumor-bearing mice were randomized into control, VEGF-Trap, gemcitabine and VEGF-Trap/gemcitabine combination groups. Tumor growth and animal survival were monitored. Tumor microvessel density and cell proliferation were evaluated by CD31 and Ki-67 immunohistochemical analysis. TUNEL assay was performed to detect apoptotic cells. The protein levels of Cyclin D1, Pro-Caspase-3, Bcl-2, MMP2 and MMP9 in tumor extracts were examined by western blot. Results: VEGF-Trap in combination with gemcitabine showed significantly enhanced inhibition of tumor growth and prolonged mouse survival compared to the VEGF-Trap or gemcitabine monotherapy. The VEGF-Trap/gemcitabine combination therapy not only potently inhibited tumor angiogenesis and cell proliferation, but also increased cellular apoptosis within tumor tissues. In addition, the combination treatment markedly down-regulated the expression of proliferation, anti-apoptosis and invasion related proteins. Conclusion: Combination therapy using VEGF-Trap and gemcitabine resulted in improved anti-tumor efficacy in a lung cancer model and VEGF-Trap/gemcitabine combination might represent a promising strategy in the treatment of human lung cancer. 

Retracted: No

PubPeer comments:
 Figure 1. * Red ellipses: The photos of the D14 and D21 mice look very similar in several spots. The fur is much more similar than expected. Figure 2. * Red boxes: The first three mice in the  Control panel look very similar to the first three mice in the  Gemcitabine panel. Reported to the journal in October 2015, but nothing has happened since.  ,
Different apoptotic effects of wogonin via induction of H(2)O(2) generation and Ca(2+) overload in malignant hepatoma and normal hepatic cells
Authors: Qinsheng Dai
Yan Chen
Zhiyu Li
Jingjing Rong
Qidong You
Libin Wei
Qinglong Guo
Na Lu
Journal: Journal of cellular biochemistry (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Wogonin; Anticancer activities; Apoptotic effects; HepG2 cells; L02 cells
Affiliations: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, The People's Republic of China.

Abstract:  Wogonin, a major active constituent of Scutellaria baicalensis, possesses potent anticancer activities both in vivo and in vitro. This paper describes the different apoptotic effects of wogonin in HepG2 and L02 cells and the possible mechanism for the differences. Through DAPI staining, Annexin-V/PI double-staining assay, JC-1 detection and the expressions of the key apoptotic proteins, we find that wogonin prefers to induce apoptosis in HepG2 cells through the mitochondrial pathway, while has much less effects on L02 cells. Moreover, overexpression of Bcl-2 can block wogonin-induced apoptosis in HepG2 cells. To illustrate the specific selective mechanism of wogonin in apoptosis induction, H(2)O(2), (¬∑)O(2)(-) and Ca(2+) are measured by 2',7'-dichlorfluorescein-diacetate, dihydroethidium and Flou-3 AM assay, respectively. The results show that the different apoptotic effects of wogonin in HepG2 and L02 cells are due to the different regulations to the redox balance of reactive oxygen species and the Ca(2+) release from endoplasmic reticulum. IP(3)R-sensitive Ca(2+) channels are the key targets of the wogonin-increased H(2)O(2). Besides, the activation of PLCŒ≥1 plays as a bridge between H(2)O(2) signal molecules and Ca(2+) release. Taken together, wogonin preferentially kills hepatoma cells by H(2)O(2)-dependent apoptosis triggered by Ca(2+) overload. The results reveal that wogonin is a competitive anticancer drug candidate for the malignant hepatoma therapy. 

Retracted: No

PubPeer comments:
 In Figure 7, two cases of data duplication were detected. Part of a PLCg-blot (two lanes) has been duplicated (Figure 7A vs 7C). An actin blot (four lanes) has been duplicated (Figure 7A vs 7C).  , 
 Corrected [14 October 2019] :  In the original publication, the protein band quality in Figure 7C is poor and overexposed. The unclear protein band pictures caused some confusions. Therefore, we would like to update the protein bands in Figure 7C with the repeated data.  Original Figure 7C:   Revised Figure 7C   We apologize for this error and we declare that this correction does not affect the description, interpretation, or the original conclusions of the manuscript. ,
Suppression of AP1 transcription factor function in keratinocyte suppresses differentiation
Authors: Wen Xu
Yap Ching Chew
Richard L Eckert
Ellen A Rorke
Gautam Adhikary
Bingshe Han
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: AP1 transcription factor; TAM67; keratinocyte differentiation; nucleus; homodimers
Affiliations: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

Abstract:  Our previous study shows that inhibiting activator protein one (AP1) transcription factor function in murine epidermis, using dominant-negative c-jun (TAM67), increases cell proliferation and delays differentiation. To understand the mechanism of action, we compare TAM67 impact in mouse epidermis and in cultured normal human keratinocytes. We show that TAM67 localizes in the nucleus where it forms TAM67 homodimers that competitively interact with AP1 transcription factor DNA binding sites to reduce endogenous jun and fos factor binding. Involucrin is a marker of keratinocyte differentiation that is expressed in the suprabasal epidermis and this expression requires AP1 factor interaction at the AP1-5 site in the promoter. TAM67 interacts competitively at this site to reduce involucrin expression. TAM67 also reduces endogenous c-jun, junB and junD mRNA and protein level. Studies with c-jun promoter suggest that this is due to reduced transcription of the c-jun gene. We propose that TAM67 suppresses keratinocyte differentiation by interfering with endogenous AP1 factor binding to regulator elements in differentiation-associated target genes, and by reducing endogenous c-jun factor expression. 

Retracted: Yes

PubPeer comments:
 Fig 1D.  Kaplan Meier survival curve of patients with oral squamous cell carcinoma based on LACAT1 expression was shown; the prognosis of patients with high expression was significantly worse than that of low expression group .  Another manifestation of Hoya s Law for J.BUOn and ERMPS...  When 40 or 50 cases of any given cancer are dichotomised into half-groups of high- or low-expression of any given nc-RNA, survival rate for one half-group or both will drop to 0% at 75 months. , 
 *[right]* Fig 2D from [Wang et al (2019)] .  Flow cytometry was used to detect the effect of silencing LACAT1 on cell apoptosis of CAL-27 and Tca8113 cells. *[left]* Fig 2F from [Zhang et al (2019)] .  Apoptotic rate of HCC cells transfected with si-TRIM66 or si-NC .  , 
 Came here to post the same finding as in #2, with an additional similarity in Figure 4D of Wang et al.  ,