PReD-Bench/PRed-Bench huggingface dataset:
The Fusion Core Complex of thePeste des Petits RuminantsVirus Is a Six-Helix Bundle Assembly†
Authors: Abdur Rahaman
N Srinivasan
N Shamala
M S Shaila
Journal: Biochemistry (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Peste des petits ruminants virus; fusion protein; heptad repeats; HR1; HR2
Affiliations: Department of Microbiology and Cell Biology, Molecular Biophysics Unit, and Department of Physics, Indian Institute of Science, Bangalore 560012, India.

Abstract:  We describe the properties of the two heptad repeats (HR1 and HR2) of the Peste des petits ruminants virus (PPRV) fusion protein (F) to obtain insights into the mechanism by which these repeats influence PPRV-mediated cell fusion. Both HR1 and HR2 inhibit PPRV-mediated syncytia formation in Vero cells in vitro. Of these, HR2 was found to be more effective than HR1. We studied the mechanism of fusion inhibition by these two repeats by using various biophysical and biochemical methods either separately or together. CD spectral analysis of these repeats revealed that the alpha-helical content of HR1 and HR2 when used together is higher than that of their simulated spectrum in the mixture, suggesting the formation of a highly structured complex by these repeats. Protease protection assays confirmed that such a complex is highly stable. Electrospray mass spectrometry of protease-digested products of the HR1-HR2 complex showed protection of fragments corresponding to both HR1 and HR2 sequences involved in complex formation. By employing size-exclusion chromatography and chemical cross-linking experiments, we show that three units each of HR1 and HR2 form a complex in which HR1 is a trimer and HR2 is a monomer. Homology-based three-dimensional modeling of this complex showed that HR1 and HR2 together form a six-helix and trimeric coiled-coil bundle. In this model, the HR1 trimer forms the core whereas HR2, while interacting with HR1 in an antiparallel orientation, forms a two-stranded coiled-coil structure and lies at the periphery of the structure. These results are discussed in the context of a common fusion mechanism among paramyxoviruses. 

Retracted: No

PubPeer comments:
 Fig. 3b iii and iv are basically the same and represent a case of image duplication. ![file] ,
Disruption of platelet-derived chemokine heteromers prevents neutrophil extravasation in acute lung injury
Authors: Jean-Eric Alard
Philipp Markart
Malgorzata Wygrecka
Wolfgang M Kuebler
Philipp von Hundelshausen
Sarawuth Wantha
Klaus T Preissner
Christian Weber
Tilman M Hackeng
Rory R Koenen
Oliver Soehnlein
Matthias Mörgelin
Jochen Grommes
Maik Drechsler
Michael Jacobs
Journal: American journal of respiratory and critical care medicine (2012)
Discipline: CLINICAL MEDICINE
Keywords: Acute lung injury; Gram-negative bacterial infections; Neutrophil recruitment; Platelets; P-selectin
Affiliations: Institute for Molecular Cardiovascular Research, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.

Abstract:  Rationale: Acute lung injury (ALI) causes high mortality, but its molecular mechanisms and therapeutic options remain ill-defined. Gram-negative bacterial infections are the main cause of ALI, leading to lung neutrophil infiltration, permeability increases, deterioration of gas exchange, and lung damage. Platelets are activated during ALI, but insights into their mechanistic contribution to neutrophil accumulation in the lung are elusive. Objectives: To determine mechanisms of platelet-mediated neutrophil recruitment in ALI. Methods: Interference with platelet-neutrophil interactions using antagonists to P-selectin and glycoprotein IIb/IIIa or a small peptide antagonist disrupting platelet chemokine heteromer formation in mouse models of ALI. Measurements and main results: In a murine model of LPS-induced ALI, we uncover important roles for neutrophils and platelets in permeability changes and subsequent lung damage. Furthermore, platelet depletion abrogated lung neutrophil infiltration, suggesting a sequential participation of platelets and neutrophils. Whereas antagonists to P-selectin and glycoprotein IIb/IIIa had no effects on LPS-mediated ALI, antibodies to the platelet-derived chemokines CCL5 and CXCL4 strongly diminished neutrophil eflux and permeability changes. The two chemokines were found to form heteromers in human and murine ALI samples, positively correlating with leukocyte influx into the lung. Disruption of CCL5-CXCL4 heteromers in LPS-, acid-, and sepsis-induced ALI abolished lung edema, neutrophil infiltration, and tissue damage, thereby revealing a causal contribution. Conclusions: Taken together, our data identify a novel function of platelet-derived chemokine heteromers during ALI and demonstrate means for therapeutic interference. 

Retracted: No

PubPeer comments:
 According to figure legend of Fig3A, the mice number is 7 in each group. But one rate points was 50% (red arrow), thus corresponding mice number should be 3.5. Could authors explain how to get this survivorship curve? ![file] , 
 The first author will reply about this figure. , 
 #1 I am Wei-Wei Luo, the first author of this paper. We are sorry for a writing error in the figure legend.  n=7 should be  n=6 . The conclusion is not affected. , 
 #1 The accurate description in the figure legend should be that the mice number of iRhom2- - group is 6, while the mice number of iRhom2+ + group is 8. The conclusion is not affected. ,
<p>Activation of GPR40 Suppresses AGE-Induced Reduction of Type II Collagen and Aggrecan in Human SW1353 Chondrocytes</p>
Authors: Xiawei Xue
Tao Xu
Hongsheng Lin
Tianliang Wang
Wenzhong Zhang
Hongjun Liu
Yiyuan Zhang
Jiaxiang Gu
Journal: Drug Design Development and Therapy (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ADAMTS; GPR40; GW9508; MMPs; NF-κB
Affiliations: Department of Orthopaedics, Subei People's Hospital Affiliated to Yangzhou University, Yangzhou 225000, People's Republic of China., Department of Orthopaedics, Xiangya Second Affiliated Hospital of Center South University, Changsha 410008, People's Republic of China.

Abstract:  Introduction: Osteoarthritis (OA) is an age-related chronic degenerative disease. Accumulation of advanced glycation end products (AGEs) induces degradation of the articular extracellular matrix (ECM) and is considered a critical step toward the development and progression of OA. GPR40 is a well-known free fatty acid receptor, which possesses pleiotropic effects in different types of diseases. However, the biological function of GPR40 in OA is indistinct. The purpose of the present study was to determine the impact of the GPR40 agonist GW9508 on AGEs-treated chondrocytes. Materials and methods: Cultures of human SW1353 chondrocytes were stimulated with GW9508, followed by exposure to 100 µg/mL AGEs. Gene and protein expression of TNF-α, IL-6, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 were measured by real-time PCR and ELISA analysis. The levels of type II collagen, aggrecan, and nuclear NF-κB p65 were measured by Western blot analysis. A luciferase assay measured the transcriptional activity of NF-κB. Results: The results show that treatment with AGEs decreased the expression of GPR40 in human SW1353 chondrocytes. Treatment with GW9508 plays a beneficial role in protecting type II Collagen and aggrecan from degeneration by attenuating the expression of MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5. Additionally, GW9508 reduces the appearance of pro-inflammatory cytokines and suppresses NF-κB activation in AGEs-induced chondrocytes. Notably, co-treatment with GW1100, a specific antagonist of GPR40, abolishes the beneficial role of GW9508 against AGEs, implying that GPR40 mediates these effects of GW9508. Conclusion: Our results suggest that GPR40 is a novel therapeutic target for OA and that GPR40 agonists, including GW9508, may have therapeutic potential in preventing and slowing the progression of OA. 

Retracted: No

PubPeer comments:
 Some of the Western blots in this paper have unusual background noise, suggesting perhaps that they have been edited. In addition, the right and left ends of one of the bands in Figure 5 appear to be unexpectedly similar. Illustrated below by showing an original image juxtaposed with the same band flipped horizontally. *** ![file] ,
Comparative Analysis of Chromatin Binding by Sex Comb on Midleg (SCM) and Other Polycomb Group Repressors at a Drosophila Hox Gene
Authors: Ellen L Miller
Carrie S Ketel
Jeffrey A Simon
Liangjun Wang
Neal Jahren
Daniel R Mallin
Journal: Molecular and Cellular Biology (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Sex Comb on Midleg (SCM); Polycomb group (PcG); transcriptional repressor; Polycomb repressive complex 1 (PRC1); PRC2
Affiliations: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA., Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455

Abstract:  Sex Comb on Midleg (SCM) is a transcriptional repressor in the Polycomb group (PcG), but its molecular role in PcG silencing is not known. Although SCM can interact with Polycomb repressive complex 1 (PRC1) in vitro, biochemical studies have indicated that SCM is not a core constituent of PRC1 or PRC2. Nevertheless, SCM is just as critical for Drosophila Hox gene silencing as canonical subunits of these well-characterized PcG complexes. To address functional relationships between SCM and other PcG components, we have performed chromatin immunoprecipitation studies using cultured Drosophila Schneider line 2 (S2) cells and larval imaginal discs. We find that SCM associates with a Polycomb response element (PRE) upstream of the Ubx gene which also binds PRC1, PRC2, and the DNA-binding PcG protein Pleiohomeotic (PHO). However, SCM is retained at this Ubx PRE despite genetic disruption or knockdown of PHO, PRC1, or PRC2, suggesting that SCM chromatin targeting does not require prior association of these other PcG components. Chromatin immunoprecipitations (IPs) to test the consequences of SCM genetic disruption or knockdown revealed that PHO association is unaffected, but reduced levels of PRE-bound PRC2 and PRC1 were observed. We discuss these results in light of current models for recruitment of PcG complexes to chromatin targets. 

Retracted: No

PubPeer comments:
 July 2017 Correction, found here: https: mcb.asm.org content 37 15 e00148-17 It reads:  Fig. 5A: The Rp panel on the right is an inadvertent duplication of the Rp panel on the left. The corrected image should appear as shown below This change does not affect any of the conclusions of the study. Here is the original Figure 5A, with the duplication marked with red boxes. This was reported to the journal in September 2016. ![file] I thank the authors for correcting this error. This paper was part of a structured search for image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long ,
NIR triggered PLGA coated Au-TiO core loaded CPT-11 nanoparticles for human papillary thyroid carcinoma therapy
Authors: Tianyu Yu
Lingling Tong
Yunpeng Liu
Yu Ao
Genmao Zhang
Hejia Zhang
Journal: Drug Delivery (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Au@TiO2; CPT-11; anti-metastasis; thyroid cancer.
Affiliations: Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China., Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, China., Department of Pediatrics, The First Hospital of Jilin University, Changchun, China., Department of Ultrasonography, China-Japan Union Hospital of Jilin University, Changchun, China., Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, China.

Abstract:  MDR (multi-drug resistance) is one of the significant deterrents of effective chemotherapy for malignant growth. One of the powerful ways to deal with defeat of the MDR is to utilize inorganic nanoparticle-intervened tranquilize conveyance to build the medication aggregations in cancerous growth cells. In this work, we have developed the presentation that is accurately made of medication conveyance framework dependent on the TiO2 nanoparticles stacked CPT-11 to defeat the thyroid malignancy cells. The synthesized nanoparticles are characterized by spectroscopy methods (UV-vis, XPS, SEM, TEM, and DLS). The TEM results suggested that the shape of PLGA-Au-TiO2@CPT-11 of nanoparticles is ∼250 nm. After successful synthesis, we have evaluated the MTT of PLGA-Au-TiO2@CPT-11 nanoparticles with and without NIR radiations. Further, the morphological changes were observed using various biochemical stainings, such as acridine orange and ethidium bromide (AO-EB) and nuclear staining through Hoechst-33258. Also, migration and cell invasion were examined. The results show that these PLGA-Au-TiO2@CPT-11 and PLGA-Au-TiO2@CPT-11 + NIR nanoparticles exhibited promising antimetastatic property and reduced the cell invasion activity in B-CPAP and FTC-133 thyroid cancer cell lines. Based on the above findings, these PLGA-Au-TiO2@CPT-11 and PLGA-Au-TiO2@CPT-11 + NIR nanoparticles can be used as a promising candidate for the malignant thyroid cells. 

Retracted: No

PubPeer comments:
 Fig. 5.  Th17 is downregulated in the peripheral blood and spleen of rats undergoing CPB after u03b17nAchR activation. A: The peripheral blood and spleen were collected from the sham, CPB, and PHA groups. PBMCs were isolated. Flow cytometry was used to determine the percentage of CD4+ IL-17+ (Th17) cells. Different cell subsets were distinguished according to different cell labels. B: The percentage of CD4+ IL-17+ cells in rat spleen. C: The percentage of CD4+ IL-17+ cells in rat blood. Three panels of (A) and (B) differ mainly in their lower right quadrants, but are more similar than one would expect in the lower left quadrants. ![file] (C) contains more unexpected similarities. ![file] Fig 8(A): Unexpected similarities. ![file] 8(B): More similar than one might expect. ![file] ,
Pretreatment with 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside attenuates cerebral ischemia/reperfusion-induced injury in vitro and in vivo
Authors: Aiqing Deng
Fei Ding
Xia Chen
Tianqiu Zhou
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Salidroside; GlcNAc-Sal; neuroprotective effects; oxygen-glucose deprivation-reperfusion; global cerebral ischemia-reperfusion
Affiliations: Basic Medical Research Centre, Medical School, Nantong University, Nantong, China., Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, China., Department of ophtalmology, Affiliated Hospital of Nantong University, Nantong, China., Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.

Abstract:  Salidroside, extracted from the root of Rhodiola rosea L, is known for its pharmacological properties, in particular its neuroprotective effects. 2-(4-Methoxyphenyl) ethyl-2-acetamido-2-deoxy-β-D-pyranoside (GlcNAc-Sal), an analog of salidroside, was recently synthesized and shown to possess neuroprotective properties. The purpose of the current study was to investigate the neuroprotective effects of GlcNAc-Sal against oxygen-glucose deprivation-reperfusion (OGD-R)-induced neurotoxicity in vitro and global cerebral ischemia-reperfusion (GCI-R) injury in vivo. Cell viability tests and Hoechst 33342 staining confirmed that GlcNAc-Sal pretreatment markedly attenuated OGD-R induced apoptotic cell death in immortalized mouse hippocampal HT22 cells. Western blot, immunofluorescence and PCR analyses revealed that GlcNAc-Sal pretreatment restored the balance of pro- and anti-apoptotic proteins and inhibited the activation of caspase-3 and PARP induced by OGD-R treatment. Further analyses showed that GlcNAc-Sal pretreatment antagonized reactive oxygen species (ROS) generation, iNOS-derived NO production and NO-related apoptotic cell death during OGD-R stimulation. GCI-R was induced by bilateral common carotid artery occlusion (BCCAO) and reperfusion in mice in vivo. Western blot analysis showed that GlcNAc-Sal pretreatment decreased the expression of caspase-3 and increased the expression of Bcl-2 (B-cell lymphoma 2)/Bax (Bcl-2-associated X protein) induced by GCI-R treatment. Our findings suggest that GlcNAc-Sal pretreatment prevents brain ischemia reperfusion injury by the direct or indirect suppression of cell apoptosis and GlcNAc-Sal could be developed as a broad-spectrum agent for the prevention and/or treatment of cerebral ischemic injury. 

Retracted: No

PubPeer comments:
 Concern about Figure 4A, reported to the journal in October 2015, but no action yet. * The GlcNAc-Sal (100 uM) and (200 uM) panels appear to show an overlap, as marked in the Bcl-2 and hoechst panels (also visible in the merge panels). Note a difference in signal strength in the Bcl-2 panels. Marked with yellow and green boxes. ![file] Concern about Figure 7, reported to the journal in October 2015, but no action yet. * The OGD-R and the 100 uM GlcNac-Sal + OGD-R panels appear to show an overlap. Marked with red boxes. ![file] ,
A family with Robertsonian translocation: a potential mechanism of speciation in humans
Authors: Xi Li
Lei Sun
Yanyi Yao
Shuqin Xu
Zhi Liu
Weipeng Wang
Han Rong
Jieping Song
Nian Liu
Bo Wang
Journal: Molecular cytogenetics (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Chromosome karyotype; Evolution; FISH; Robertsonian translocation homozygosity; aCGH.
Affiliations: Genetics Laboratory, Hubei Maternal and Child Health Hospital, Wuhan, Hubei People's Republic of China., Department of gastroenterology, Peking University Shenzhen Hospital, Shenzhen, Guangdong People's Republic of China., Laboratory of Medical Genetics, Qinzhou Maternal and Child Health Care Hospital, Guangxi, People's Republic of China., Shenzhen mental health center, Shenzhen Kangning Hospital, Shenzhen, Guangdong People's Republic of China.

Abstract:  Background: Robertsonian translocations occur in approximately one in every 1000 newborns. Although most Robertsonian translocation carriers are healthy and have a normal lifespan, they are at increased risk of spontaneous abortions and risk of producing unbalanced gametes and, therefore unbalanced offspring. Here we reported a previously undescribed Robertsonian translocation. Case presentation: We identified three Robertsonian translocation carriers in this family. Two were heterozygous translocation carriers of 45,XX or XY,der(14;15)(q10;q10) and their son was a homozygous translocation carrier of a 44,XY,der(14;15)(q10;q10), der(14;15)(q10;q10) karyotype. Chromosomal analysis of sperm showed 99.7 % of sperm from the homozygous translocation carrier were normal/balanced while only 79.9 % of sperm from the heterozygous translocation carrier were normal/balanced. There was a significantly higher frequency of aneuploidy for sex chromosome in the heterozygous translocation carrier. Conclusions: The reproductive fitness of Robertsonian translocation carriers is reduced. Robertsonian translocation homozygosity can be a potential speciation in humans with 44 chromosomes. 

Retracted: No

PubPeer comments:
 This paper uses a figure (Figure 1) from their previous paper (Figure 1, Wang et al., Biomedical Research 2013; 24 (1): 171-174) without proper acknowledgement or citation. Additionally, the proband is listed as a 25 year-old in both this paper as well as the 2013 paper. Though it is discouraged, it is not unethical to analyze a proband twice; however, proper citation of previous work (even if it is from the same authors) analyzing the same proband should be included, as well as an updated age of the proband (or improved transparency as to when the sample was originally taken). Figures from this 2016 were also used in a 2017 paper from the same authors (Wang et al., Balkan Journal of Medical Genetics 2017; 20 (1): 43-50), which is reported separately on PubPeer. ![file] ,
Pas1, a G1 cyclin, regulates amino acid uptake and rescues a delay in G1 arrest in Tsc1 and Tsc2 mutants in Schizosaccharomyces pombe
Authors: Aladdin Mustafa
Elizabeth Petri Henske
Marjon van Slegtenhorst
Journal: Human Molecular Genetics (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Tuberous sclerosis complex; TSC1; TSC2; Schizosaccharomyces pombe; G1 cyclin
Affiliations: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Abstract:  Tuberous sclerosis complex is a tumor suppressor syndrome caused by mutations in either the TSC1 or the TSC2 gene. Previous studies have shown that deletion of the TSC1 or TSC2 ortholog in Schizosaccharomyces pombe results in an amino acid uptake defect, with conditional lethality. We identified a G1 cyclin, pas1+, as a high-copy suppressor of this defect in Deltatsc1. Disruption of pas1+ causes defects in arginine and leucine uptake that are remarkably similar to Deltatsc1 and Deltatsc2, whereas Deltapas1Deltatsc1 and Deltapas1Deltatsc2 double mutants have more severe amino acid uptake defects. In a second screen, we identified a novel G63D/S165 N mutant of the small GTPase Rhb1, the target of the Tsc1/Tsc2 protein complex. The Rhb1 mutant suppresses amino acid uptake in Deltatsc1 yeast, but not in Deltapas1 yeast. Hence, Pas1 does not regulate amino acid uptake through Rhb1. To determine whether Pas1 links nutrient availability to cell cycle progression downstream of the Tsc1/Tsc2 complex, we examined the kinetics of G1 arrest in single and double mutant strains. After nitrogen starvation, Deltatsc1 and Deltatsc2 yeast had a delay in G1 arrest when compared with wild-type, which was rescued by deletion of pas1+. In summary, we identified the G1 cyclin, Pas1, as a novel regulator of amino acid uptake. Our data support a model in which Pas1 inhibits G1 arrest downstream of Tsc1 and Tsc2, linking nutrient uptake and cell cycle progression in yeast. 

Retracted: No

PubPeer comments:
 Figure 1A: More similar than expected. ![file] Figure 1A: Is very similar to a previous image published by the group (doi: 10.1074 jbc.M313874200) ![file] ,
Down-regulated long non-coding RNA RNAZFHX4-AS1 suppresses invasion and migration of breast cancer cells via FAT4-dependent Hippo signaling pathway
Authors: Shao-Jun Chen
Gui-Sen Li
Hong Wang
Guo-Feng Li
Bi-Chan Liang
Shao-Ying Li
Hui-Fang Mai
Journal: Cancer Gene Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: Breast cancer; lncRNAs; ZFHX4-AS1; Hippo signaling pathway; TAF4
Affiliations: Department of Thyroid and Breast Surgery, Baoan Maternal and Child Health Hospital, Jinan University, Sanming Project of Medicine in Shenzhen, 518000, Shenzhen, P.R. China. ., Department of Breast Surgery, Zhuhai Maternity and Child Health Hospital, 519001, Zhuhai, P.R. China., Department of Thyroid and Breast Surgery, Baoan Maternal and Child Health Hospital, Jinan University, Sanming Project of Medicine in Shenzhen, 518000, Shenzhen, P.R. China., Department of Thoracic Surgery, Shenzhen People's Hospital, 518000, Shenzhen, P.R. China., Department of Breast Surgery, Shenzhen Maternity and Child Health Hospital, 518000, Shenzhen, P.R. China.

Abstract:  Breast cancer is ranked as the second leading cause of cancer-related deaths among women. Accumulating evidences have revealed that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis owing to the regulation of essential pathways for tumor initiation and progression. Herein, the current study aimed to explore the regulatory mechanism of lncRNA ZFHX4-AS1 in breast cancer in relation to the Hippo signaling pathway. Initially, microarray analysis was conducted to screen out differentially expressed lncRNAs related to breast cancer. Next, the functional role of lncRNA ZFHX4-AS1 in breast cancer was determined using ectopic expression, knockdown, and reporter assay experiments. Subsequently, lncRNA ZFHX4-AS1, TAF4, TAZ, and YAP expressions were determined, followed by verification of the targeting relationship between lncRNA ZFHX4-AS1 and TAF4. Then cell proliferation, invasion, migration, cell cycle, and apoptosis were measured. Lastly, tumor growth and metastasis were detected by tumor xenograft in nude mice. LncRNA ZFHX4-AS1 was found to be highly expressed while FAT4 was poorly expressed in breast cancer tissues. FAT4 was the target gene of lncRNA ZFHX4-AS1, and lncRNA ZFHX4-AS1 silencing increased FAT4 expressions, while decreased YAP and TAZ expressions. In addition, knockdown of lncRNA ZFHX4-AS1 suppressed breast cancer cell proliferation, migration, and invasion as well as tumor growth, blocked cell cycle entry, while promoted cell apoptosis by inhibiting the Hippo signaling pathway. In conclusion, our findings reveal that lncRNA ZFHX4-AS1 silencing exerts an inhibitory effect on breast cancer development by suppressing the activation of the Hippo signaling pathway via FAT4. 

Retracted: No

PubPeer comments:
 The histology images in Figure 6C seem to be crops of one and the same larger image, despite ostensibly representing different experimental groups. I have highlighted the small slivers of overlap that allow the images to be puzzled together. ![file] , 
 Who did this to you, Figure 7a?! ![file] ,
Rapamycin inhibits human in stent restenosis vascular smooth muscle cells independently of pRB phosphorylation and p53
Authors: Nicola McCarthy
Dalya Rosner
Martin Bennett
Journal: Cardiovascular Research (2005)
Discipline: CLINICAL MEDICINE
Keywords: Drug-eluting stents; rapamycin; in-stent restenosis; vascular smooth muscle cells; cell proliferation
Affiliations: Unit of Cardiovascular Medicine, University of Cambridge Clinical School of Medicine, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, UK.

Abstract:  Objective: Drug-eluting stents containing the immunosuppressant rapamycin markedly inhibit in stent restenosis (ISR). However, the molecular mechanisms that underlie its effect on ISR-derived vascular smooth muscle cells (VSMCs), as opposed to normal VSMCs, are unknown. Specifically, as ISR-VSMCs have altered cell cycle regulation, rapamycin may arrest these cells via novel molecular pathways. Methods: We isolated human VSMCs from sites of ISR, and examined the effect of rapamycin on cell proliferation using MTT assay, time lapse videomicroscopy and flow cytometry. Regulation of G(1)-S transition was examined using Western blotting, and cell size and protein synthesis examined using flow cytometry and collagen assay, respectively. The requirement for pRB and p53 was examined using ISR VSMCs expressing E1A and a dominant negative p53, respectively. Results: ISR-VSMC proliferation was potently inhibited by rapamycin. Arrest was confined to G(1), as cell proliferation (but not cell size) of S/G(2)-arrested cells was unaffected by rapamycin. Moreover, ISR-VSMC lines generated with disrupted p53 or pRB function still arrested in the presence of rapamycin, suggesting that these genes are dispensable for rapamycin-induced arrest. Significantly, rapamycin completely inhibited the phosphorylation of p70(S6K), an mTOR-regulated kinase implicated in the control of proliferation, but had no effect on collagen or total protein synthesis. Conclusions: We demonstrate that rapamycin is a potent inhibitor of ISR VSMC proliferation during G(1). Rapamycin's action does not require p53 or pRB. We show that p70(S6K) is markedly inhibited in rapamycin-arrested ISR cells, suggesting that regulation of its upstream kinase, mTOR, is important for the control of proliferation in ISR cells. 

Retracted: No

PubPeer comments:
 Figure 5B. Much more similar than expected. ![file] ,
Thalidomide ameliorate graft chronic rejection in an allogenic kidney transplant model
Authors: Dongdong Chen
Yan Zhang
Guanbao Tang
Tongyi Men
Yu Yang
Xianduo Li
Journal: International Immunopharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Chronic rejection; Kidney transplantation; T cell mediated rejection; Th17 cell; Thalidomide
Affiliations: Department of Urology, Qianfoshan Hospital Affiliated to Shandong University, China; Transplantation Center, The First Affiliate Hospital of Wenzhou Medical University, China., Department of Urology, Qianfoshan Hospital Affiliated to Shandong University, China; Department of Urology, The First Affiliate Hospital of Wenzhou Medical University, China., Department of Urology, Qianfoshan Hospital Affiliated to Shandong University, China., Department of Urology, Qianfoshan Hospital Affiliated to Shandong University, China. Electronic address: .

Abstract:  Chronic T cell mediated rejection (TCMR), which is characterized by infiltration of the interstitium by T cells and macrophages, still remains a major barrier to the long-term survival of kidney transplantation. Our recent report indicated that thalidomide can attenuate graft arteriosclerosis in an aortic transplant model. In this study, we investigated the effect of thalidomide on chronic TCMR in a rat model of kidney transplantation. Fischer or Lewis kidney allografts were transplanted into Lewis recipient rats. After kidney transplantation, recipient rats were divided into 3 groups: the isograft (Iso) group, allograft (Allo) group, and thalidomide (Tha) group. Rats were sacrificed at 8 weeks after kidney transplantation, and blood and kidney samples were collected. Serum concentrations of creatinine (SCr),interleukin (IL)-2, IL-6, IL-17, and TNF-α in recipients were determined, and flow cytometry was used to detect the percentages of CD4+CD25+, CD4+ Foxp3+and CD4+Th17+ cell subsets in the peripheral blood. Grafts were procured for histopathological examination, and the expressions of α-SMA, transforming growth-β1 (TGF-β1), and VEGF in kidney grafts were investigated using Western blot. Thalidomide treatment significantly ameliorated chronic rejection, reduced renal allograft tissue damage, and decreased serum creatinine levels. Attenuation of chronic TCMR was due to the prohibited production of inflammatory cytokines, altered distribution of the CD4+ CD25+ FoxP3+ regulatory T (Treg) and CD4+ Th17+ cells in the peripheral blood, and decreased expression of TGF-β1, α-SMA, and VEGF in the kidney graft. These results demonstrated that thalidomide could effectively ameliorate chronic TCMR in a rat kidney transplant model. 

Retracted: No

PubPeer comments:
 The background of Western-Blot is too clean. ![file] , 
 There is an image duplication from another paperuff0cbut the image was compressed. ![file] ![file] ![file] ![file] , 
 We found a paper for doctoral degree in https: www.cnki.net . An image in this paper is the same as that in the paper for doctoral degree, but the experiments were different. ![file] ![file] ![file] ![file] ,
The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining
Authors: X Wang
R S Weiss
Y Wang
B Hu
Journal: Oncogene (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hus1; genomic integrity; DNA damage; ionizing radiation; double strand breaks
Affiliations: Department of Radiation Oncology and Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.

Abstract:  Mammalian Hus1 plays an important role in maintaining genomic integrity. Cells lacking mouse Hus1 are hypersensitive to DNA damage inducers including UV and camptothecin (CPT). By using clonogenic assay, we show here that Hus1 deficient mouse cells are hypersensitive to ionizing radiation (IR) compared with their Hus1-positive counterparts. However, these cells show similar induction levels and similar rejoining rates of DNA double strand breaks (DSBs) following IR, indicating that the effect of Hus1 on cell radiosensitivity is independent of nonhomologous end-joining (NHEJ). By combining an I-SceI-induced-DNA DSBs system and a siRNA approach, we also show that knocking down Hus1 decreases the efficiency of homologous recombination repair (HRR), which is associated with the cellular sensitivity to IR-induced killing. Together, these results indicate that the role of Hus1 affecting the sensitivity of cells to IR-induced killing is independent of NHEJ but might be linked to HRR. 

Retracted: No

PubPeer comments:
 Figure 3a. Much more similar than you would expect. https: imgur.com pL2aHah , 
 Much more similar than you would expect even though the experiments are different. https: imgur.com GG619JU , 
 2008 corrigendum to figure 3a. Much more similar than you would expect. https: www.nature.com articles onc20081 figures 1 https: imgur.com SFocSxI ,
Trypanosome cyclic nucleotide phosphodiesterase 2B binds cAMP through its GAF-A domain
Authors: Ana Rascón
Joseph A Beavo
Sunil Laxman
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Trypanosoma brucei; cAMP-specific class I phosphodiesterases; GAF domains; ligands; TbPDE2B
Affiliations: Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA.

Abstract:  Trypanosoma brucei, the causative agent of sleeping sickness in humans and livestock, expresses at least three cAMP-specific class I phosphodiesterases (PDEs), all of which are essential for survival of the parasite. These PDEs have either one or two N-terminal GAF domains, which in other proteins function as signaling domains. However, neither the functional roles nor ligands for these domains in trypanosome PDEs are known. The present study shows that TbPDE2B, which contains two tandem GAF domains, binds cAMP with high affinity through its GAF-A domain. A purified recombinant N terminus + GAF-A domain binds cAMP with an affinity (Ki) of approximately 16 nM. It also binds cGMP but with a 15-fold lower affinity of approximately 275 nM. The TbPDE2B holoenzyme has a somewhat lower affinity (approximately 55 nM) for cAMP but a greatly lower affinity (approximately 10 microM) for cGMP. This suggests that both the selectivity and affinity for a ligand can be determined not only by the nature of the binding domain but also by the adjacent domains. Additionally, binding of cAMP to the holoenzyme showed positive cooperativity, with a Hill coefficient value of 1.75. However, binding of cGMP to the holoenzyme did not show any cooperativity, suggesting differences in the conformational changes caused by binding of these two cyclic nucleotides with the protein. Point mutation of a key predicted binding site residue (T317A) resulted in a complete loss of high affinity cAMP binding. This mutation increased the apparent Km of the mutant enzyme for substrate without altering the Vmax. A truncated catalytic domain construct of TbPDE2B also exhibited an increased Km, strongly suggesting that cAMP binding to the GAF-A domain can regulate TbPDE2B by allowing the full activity of the enzyme to be expressed. These properties of the GAF-A domain of TbPDE2B thus suggest that it could be a new target for anti-trypanosomal drugs. 

Retracted: No

PubPeer comments:
 Much more similar than expected ![file] ,
LINC00707 contributes to hepatocellular carcinoma progression via sponging miR-206 to increase CDK14
Authors: Minjiang Chen
Zhongwei Zhao
Jiangmei Wang
Jianfei Tu
Jiansong Ji
Min Xu
Qiaoyou Weng
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CDK14; LINC00707; hepatocellular carcinoma; miR-206.
Affiliations: Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, Lishui, China., Department of Thoracic Surgery, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

Abstract:  Recently, increasing numbers of long noncoding RNAs (lncRNAs) have been found to be aberrantly expressed in various cancers. However, the roles of lncRNAs in hepatocellular carcinoma (HCC) progression is largely unknown. In our current study, we identified that long intergenic nonprotein-coding RNA 707 (LINC00707) was remarkably elevated in HCC cells, indicating that LINC00707 was involved in HCC development. Subsequently, LINC00707 was significantly decreased in HepG2 and Huh7 cells. The in vitro functional assays demonstrated that knockdown of LINC00707 significantly reduced HCC cell proliferation, induced cell apoptosis, and blocked the cell cycle progression. In addition, HCC cell migration and invasion was also greatly inhibited by downregulation of LINC00707. Increasing evidence has indicated that lncRNAs can act as molecular sponges of microRNAs. Currently, we observed that microRNA-206 (miR-206) was dramatically inhibited in HCC cells and LINC00707 can modulate HCC development through sponging miR-206. The binding correlation between LINC00707 and miR-206 was confirmed by dual-luciferase reporter assay, RNA pull down and RNA immunoprecipitation assay in our study. Moreover, cyclin-dependent kinase 14 (CDK14) was predicted as a target of miR-206 and we found that miR-206 suppressed CDK14 levels in HCC cells. Finally, in vivo assays were used and it was proved that silence of LINC00707 can restrain HCC development through modulating miR-206 to upregulate CDK14. In conclusion, it was implied that LINC00707 can lead to HCC progression through sponging miR-206 and modulating CDK14. 

Retracted: Yes

PubPeer comments:
 The tumors in Figure 7A of this paper look similar to tumors in Figure 7A of Li-Yun Yuan et al. (2019), doi: 10.1002 jcp.28538. Marked with red boxes. ![file] , 
 Retracted [16 March 2022] . ------------------ The above article, published online on 29 November 2018 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed after the authors asked for correction and following an investigation based on allegations raised by a third party. A detailed investigation revealed that image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid. ,
Higher cytolytic score correlates with an immunosuppressive tumor microenvironment and reduced survival in glioblastoma
Authors: Taemin Oh
Jia-Shu Chen
Rushikesh S Joshi
Alexander F Haddad
Manish K Aghi
Matheus P Pereira
Journal: Scientific Reports (2020)
Discipline: Multidisciplinary
Keywords: CYT; CD8+ T cell infiltration; granzyme; perforin; immune checkpoint gene score
Affiliations: School of Medicine, University of California San Francisco, 513 Parnassus Ave., San Francisco, CA, 94143-0410, USA. ., Department of Neurological Surgery, University of California San Francisco, San Francisco, USA., School of Medicine, University of California San Francisco, 513 Parnassus Ave., San Francisco, CA, 94143-0410, USA., School of Medicine, University of California San Diego, San Diego, USA.

Abstract:  Cytolytic score (CYT), calculated from mRNA expression levels of granzyme and perforin, positively correlates with CD8+ T cell infiltration/activity in a variety of cancers. Unlike other cancers, higher CYT has been associated with worse prognosis in glioblastoma (GBM). To address this discrepancy, we sought to investigate the relationship between CYT and immune checkpoint gene score (ICGscore), as well as their correlation with patient survival and tumor immune cell infiltration. Clinical and RNA-sequencing data for patients with newly diagnosed GBM were obtained from The Cancer Genome Atlas. Maximally-selected rank statistics was used to dichotomize subgroups. CIBERSORT was used to estimate abudence of immune cell-types. Spearman correlation was used to characterize the relationship between CYT and ICGscore. Kaplan-Meier curves were generated for survival analysis. Overall, 28/151 patients had high CYT. High CYT was associated with a mesenchymal subtype (p &lt; 0.001) and worse survival (7.45 vs. 12.2 months, p &lt; 0.001). There were no differences in patient demographics, IDH/MGMT mutation status, or treatment. On subgroup analysis, patients with high CYT/ICGscore had significantly increased CD8+ infiltration (p &lt; 0.001), as expected, and worse survival (HR 0.445, p &lt; 0.01). Furthermore, CYT strongly correlated with ICGscore (RS = 0.675, p &lt; 0.001). The high CYT/ICGscore subgroup was associated with greater infiltration of M2 macrophages (p = 0.011) and neutrophils (p = 0.055). Our study highlights a multidimensional immunosuppressive GBM microenvironment in patients with higher CYT and potentially identifies patients with high CYT/ICGscore as a subgroup that may particularly benefit from multi-faceted immunotherapies, given their already elevated tumor CD8+ T cell levels. 

Retracted: No

PubPeer comments:
 The authors used tyrosinase enzyme doped 3D bio-printed formulation for wound healing. While reading through the article, I found some similarities on time dependant live-dead analysis. for the same sample, day 4 and day 7 live dead analysis images has some same pattern which is for me concerning. I am adding the matching areas I found. ![file] ,
Rosmarinic acid reverses non‐small cell lung cancer cisplatin resistance by activating the MAPK signaling pathway
Authors: Xiao-Zhong Liao
Han-Rui Chen
Ying Gao
Wen-Hui Chen
Zhuang-Zhong Chen
Li-Zhu Lin
Ling-Ling Sun
Ling Yu
Jia-Hui Liu
Journal: Phytotherapy Research (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MAPK; cisplatin; multidrug resistance; non-small cell lung cancer; rosmarinic acid.
Affiliations: Department of Oncology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China., Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China.

Abstract:  Cisplatin (DDP) is one of the first-line chemotherapeutic agents for non-small cell lung cancer (NSCLC). However, repeated use of cisplatin in clinical practice often induces chemoresistance. The aims of this study were to investigate whether rosmarinic acid (RA) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms. Our data demonstrated that RA significantly inhibited NSCLC cell proliferation and cell colony formation in a dose-dependent manner, induced G1 phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to DDP. Mechanistically, RA inhibited NSCLC cell growth, arrested cell cycle, and induced apoptosis by activating MAPK and inhibiting the expression of P-gp and MDR1, which correspondingly enhanced p21 and p53 expression. We observed that the growth of xenograft tumors derived from NSCLC cell lines in nude mice was significantly inhibited by combination therapy. We demonstrate that RA is a potentially effective MDR reversal agent for NSCLC, based on downregulation of MDR1 mRNA expression and P-gp. Together, these results emphasize the putative role of RA as a resistance reversal agent in NSCLC. 

Retracted: No

PubPeer comments:
 The flow cytometry plots in Figure 3A appear to have multiple areas which overlap, or are unexpectedly similar as below). Could the authors please comment? *** ![file] , 
 This paper is one of a small collection of papers which appears to include a typographical error in the spelling of an manufacturer. The company name is ACEA Biosciences headquartered in San Diego. In this paper and the others, the name is spelled ACEC. This suggests that the paper was written from a common template, although the author groups are mostly different. *** ![file] ,
Linkage between severe atopy and chromosome 11q13 in Japanese families
Authors: T Shirakawa
T Takeshita
K Morimoto
T Hashimoto
J Furuyama
Journal: Clinical Genetics (2008)
Discipline: CLINICAL MEDICINE
Keywords: Atopy; allergic asthma; rhinitis; IgE responses; aeroallergens
Affiliations: Department of Hygiene and Preventive Medicine, School of Medicine, Osaka University, Suita, Japan.

Abstract:  Atopy, characterised by allergic asthma and rhinitis, is due to increased IgE responses to common aeroallergens. An Oxford group has described maternal inheritance of atopy, where there is significant linkage between IgE responsiveness and a VNTR marker D11S97 and a CA microsatellite within a candidate gene, the high affinity IgE receptor beta subunit (Fc epsilon RI beta), on chromosome 11q. Attempts at independent replication have produced conflicting results. We therefore recruited 270 atopic asthmatic probands in a Japanese community population for genetic linkage analysis. Four families, each with more than 15 meioses and a clear phenotype for atopy, were selected for genetic analysis. Atopy was defined as presence of all of raised total IgE, positive RAST and skin tests to three or more aeroallergens; non-atopy, as absence of all these criteria. Linkage analysis showed a maximum two-point lod score of 9.35 for D11S97 and Fc epsilon RI beta under the assumption of unequal rates of maternal and paternal recombination. Two families showed close genetic linkage with Fc epsilon RI beta with a pattern of maternal inheritance. These results from a Japanese population provide further evidence for genetic linkage between severe atopy and chromosome 11q13 and the likelihood of genomic imprinting at the locus. 

Retracted: No

PubPeer comments:
 Linkage on chr 11q as described in this paper is a modern myth. Could that already be known in 1993? The huge selection bias could have been noticed, screening 270 families but reporting only 4 families that showed the desired effect. But why has nobody noticed that the number of meioses in table 1 is wrong for two familes? Several column sums are also wrong and there is a discrepancy with the numbers in the text. The reported lod scores can not be replicated without knowing the  penetrance function and the rates of maternal and paternal recombination ultimately used for table 1. Does it make sense to list variable thetas (where LODs can not be compared)? Were the LODs at different thetas really added as looks for at FceR1b? There are misinterpretations and errors in the printed pedigrees for example individual #1 II 2:1 has an impossible genotype. Familie #4 does not show a  perfect pattern of maternal inheritance as #4 III 4:3 is transmitted paternally. In addition there are 23 text number omission errors in the references including a fake reference.. ![file] ![file] ![file] ,