PReD-Bench/PRed-Bench huggingface dataset:
A tumour-derived mutant allele of XRCC2 preferentially suppresses homologous recombination at DNA replication forks
Authors: Thomas Helleday
Atul Mohindra
Emma Bolderson
Mark Meuth
Jason Stone
Michael Wells
Journal: Human Molecular Genetics (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Homologous recombination repair; DNA double strand breaks; XRCC2; 342delT; recombination reporter
Affiliations: Institute for Cancer Studies, University of Sheffield, School of Medicine, Sheffield, UK.

Abstract:  Homologous recombination repair (HRR) is required for both the repair of DNA double strand breaks (DSBs) and the maintenance of the integrity of DNA replication forks. To determine the effect of a mutant allele of the RAD51 paralog XRCC2 (342delT) found in an HRR-defective tumour cell line, 342delT was introduced into HRR proficient cells containing a recombination reporter substrate. In one set of transfectants, expression of 342delT conferred sensitivity to thymidine and mitomycin C and suppressed HRR induced at the recombination reporter by thymidine but not by DSBs. In a second set of transfectants, the expression of 342delT was accompanied by a decreased level of the full-length XRCC2. These cells were defective in the induction of HRR by either thymidine or DSBs. Thus 342delT suppresses recombination induced by thymidine in a dominant negative manner while recombination induced by DSBs appears to depend upon the level of XRCC2 as well as the expression of the mutant XRCC2 allele. These results suggest that HRR pathways responding to stalled replication forks or DSBs are genetically distinguishable. They further suggest a critical role for XRCC2 in HRR at replication forks, possibly in the loading of RAD51 onto gapped DNA. 

Retracted: No

PubPeer comments:
 Figure 1B. Much more similar after vertical stretch than expected.  , 
 Figure 2A much more similar to figures 1B and 1C than expected.  ,
IL-7 inhibits dexamethasone-induced apoptosis via Akt/PKB in mature, peripheral T cells
Authors: Apurva Sarin
Hadassah Sade
Journal: European Journal of Immunology (2003)
Discipline: IMMUNOLOGY
Keywords: IL-7; dexamethasone-induced apoptosis; T cells; caspase inhibitors; mitochondrial transmembrane potential
Affiliations: National Centre for Biological Sciences, UAS-GKVK Campus, Bangalore, India.

Abstract:  We have investigated the mechanism of IL-7-mediated inhibition of dexamethasone-induced apoptosis in T cells. Broad-spectrum caspase inhibitors block dexamethasone-triggered nuclear fragmentation, but not the loss of mitochondrial transmembrane potential or membrane integrity in CD3(+) mature T cells isolated from adult mouse spleens. IL-7 blocked dexamethasone-induced apoptosis and the processing of caspase-3 and caspase-7. IL-7 also blocked dexamethasone-triggered dephosphorylation of the serine-threonine kinase Akt/PKB and its target, the Ser(136) residue in Bad. The loss of anti-apoptotic proteins Bcl-x(L) and inhibitor of apoptosis protein-2 (IAP-2) was also blocked by IL-7. The protective effect was attenuated by pharmacological inhibitors of phosphatidylinositol-3 kinase (PI3K) with one exception: inhibition of PI3K did not abrogate Bcl-x(L) expression in the presence of IL-7. The anti-apoptotic role of Akt suggested by these experiments was tested by overexpression of constitutively active Akt, which blocked dexamethasone-induced apoptosis and elevated IAP-2 but not Bcl-x(L) levels in a mature T cell line. Thus, IL-7 regulates IAP-2 expression and inhibits dexamethasone-induced apoptosis by activating Akt via PI3K-dependent signaling, but regulates Bcl-x(L)expression via a PI3K-independent pathway in mature T cells. 

Retracted: No

PubPeer comments:
  ,
Long noncoding RNA ADAMTS9‚ÄêAS2 suppresses the progression of esophageal cancer by mediating CDH3 promoter methylation
Authors: Song Zhao
Donglei Liu
Chunyang Zhang
Yang Yang
Dengyan Zhu
Kai Wu
Journal: Molecular Carcinogenesis (2020)
Discipline: CLINICAL MEDICINE
Keywords: ADAMTS9-AS2; CDH3; esophageal cancer; invasion; methylation
Affiliations: Department of Thoracic Surgery The First Affiliated Hospital of Zhengzhou University  Zhengzhou China

Abstract:  Long noncoding RNAs (lncRNAs) have been implicated in the biology of esophageal cancer via mRNA degradation or translational inhibition. CDH3 is also aberrantly expressed in numerous cancers. This study was conducted with the hypothesis that ADAMTS9-AS2 or CDH3 methylation plays a role in esophageal cancer cell activity and in vivo development. Firstly, mRNA levels of ADAMTS9-AS2 and CDH3 in esophageal cancer tissues and cells were detected by reverse-transcription quantitative polymerase chain reaction. Afterward, esophageal cancer OE21 cells were treated with overexpression of ADAMTS9-AS2, siRNA against ADAMTS9-AS2, overexpression of CDH3 and demethylating agent 5-aza-dc. The biological functions of esophageal cancer OE21 cells were assayed to define the regulatory mechanisms of ADAMTS9-AS2 in esophageal cancer. The interactions among ADAMTS9-AS2, DNMT1/DNMT3 (A/B) and CDH3 were detected by MSP, RNA pull-down, RIP, and ChIP assays. The in vitro findings were reproduced in nude mice to explore the role of ADAMTS9-AS2 in the development of esophageal cancer in vivo. Esophageal cancers expressed low levels of ADAMTS9-AS2 and high levels of CDH3. Methylation of CDH3 promoter was induced by ADAMTS9-AS2 via DNMT1/DNMT3 (A/B). Furthermore, proliferation, invasion, and migration of esophageal cancer cells were inhibited by ADAMTS9-AS2 via downregulation of CDH3. Suppressed esophageal cancer development in vivo was also detected after ADAMTS9-AS2 overexpression. Overexpressed ADAMTS9-AS2 aids in the suppression of esophageal cancer development, which is achieved via inducing CDH3 promoter methylation. 

Retracted: No

PubPeer comments:
 Could the authors please check Figure 2B? In the bottom two rows, the overlap merged images do not appear to correctly match the EDU images. I have marked the images that match with boxes of the same color.  , 
 Corrigendum, December 2021, found here: https: onlinelibrary.wiley.com doi 10.1002 mc.23387  Liu et al.1 have supplied the following correction to their article. In Figure 2, the position of u201csh-NCu201d and u201csh-ADAMTS9-AS2u201d groups in u201cOverlapu201d category in Figure 2B is incorrect (reversed). The corrected Figure 2 appears below. The authors wish to apologize for this mistake. I thank the authors and journal for correcting this error. ,
Clinical significance and effect of MTDH/AEG-1 in bladder urothelial cancer: a study based on immunohistochemistry, RNA-seq, and in vitro verification
Authors: Gang Chen
Yi-Wu Dang
Sheng-Hua Li
Li-Jie Zhang
Hai-Biao Yan
Yu Zhang
Journal: Cancer management and research (2018)
Discipline: CLINICAL MEDICINE
Keywords: AEG-1; MTDH; bladder urothelial cancer; meta-analysis.
Affiliations: Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China., Urology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China, , .

Abstract:  Background: Overexpression of metadherin/astrocyte elevated gene-1 (MTDH/AEG-1) has been implicated in various cancers. However, the clinical significance and the potential biological functions of MTDH/AEG-1 in bladder urothelial carcinoma (BUC) are not established. Methods: In this study, the expression of MTDH/AEG-1in BUC was measured using the Cancer Genome Atlas (TCGA) database and immunohistochemistry, together with a meta-analysis, to investigate the expression and diagnostic value of MTDH/AEG-1. The possible association between MTDH/AEG-1 expression and the viability, proliferation, and apoptosis in BUC cell lines (T24, HT1376, and RT4) was also assessed in vitro by viability, MTS, colony formation, and caspase-3/7 assays, as well as Hoechst 33342 and propidium iodide (PI) double staining. Results: MTDH/AEG-1 expression was significantly higher in BUC tissues than in normal bladder tissues, according to the TCGA and immunohistochemistry results, and these findings were verified by the meta-analysis. Functional knockdown of MTDH/AEG-1 suppressed BUC cell growth and induced apoptosis. Bioinformatics analyses indicated an involvement of MTDH/AEG-1 in several processes, including RNA binding, protein transport, intracellular transport, and the insulin signaling pathway. Conclusion: We hypothesize that MTDH/AEG-1 could play essential roles in BUC, especially in cell growth and apoptosis, via the insulin signaling pathway." 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: www.dovepress.com clinical-significance-and-effect-of-mtdhaeg-i-in-bladder-urothelial-ca-peer-reviewed-article-CMAR Zhang Y, Zhang L-J, Dang Y-W, Li S-H, Yan H-B, Chen G. Clinical significance and effect of MTDH AEG-I in bladder urothelial cancer: a study based on immunohistochemistry, RNA-seq, and in vitro verification. Cancer Manag Res. 2018;10:6921u2013 6936. At the request of the authors, the Editor-in-Chief and Publisher of Cancer Management and Research wish to retract the published article. Following a review of their experimental data the authors found they had inadvertently duplicated the Hoechst 33342 and propidium iodide (PI) images presented in Figure 11 of the published article, from Figure 11 of their liver cancer study: The essential role of MTDH in the progression of HCC: a study with immunohistochemistry, TCGA, meta-analysis and in vitro investigation. He R, Gao L, Ma J, et al. Am J Transl Res 2017;9(4):1561u2013 1579. http: www.ajtr.org files ajtr0043681.pdf. ,
Crucial role of calcium-sensing receptor activation in cardiac injury of diabetic rats
Authors: Ye Wang
Hongli Sun
Lijuan Liu
Zhong Ji
Yonggang Cao
Yang Liu
Hanping Qi
Lei Li
Wei Huang
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Cardiac injury; diabetes mellitus; calcium-sensing receptor (CaSR); diabetic model; streptozotocin (STZ)
Affiliations: Department of Pharmacology, Harbin Medical University-Daqing, Daqing, Heilongjiang, China.

Abstract:  Cardiac injury is a common pathological change frequently accompanied by diabetes mellitus. Recently, some evidence indicated that calcium-sensing receptor (CaSR) expressed in the cardiac tissue. However, the functional role of CaSR in diabetic cardiac injury remains unclear. The present study was designed to investigate the relationship between CaSR activation and diabetes-induced cardiac injury. Diabetic model was successfully established by administration of streptozotocin (STZ) in vivo, and cardiomyocyte injury was simulated by 25.5 mM glucose in vitro. Apoptotic rate, intracellular calcium concentration ([Ca¬≤‚Å∫](i)) and the expression of Bcl-2, Bax, extracellular signal-regulated protein kinase (ERK), c-Jun NH‚Ç?terminal protein kinase (JNK), and p38 were examined. We demonstrated a significant increase in left ventricular end-diastolic pressure (LVEDP) as well as decrease in maximum rate of left ventricular pressure rise and fall (¬±dp/dtmax), and left ventricular systolic pressure (LVSP), apoptosis of cardiomyocytes was also observed by TUNEL staining. In vitro, 25.5 mM glucose-induced apoptosis was detected by flow cytometry in neonatal rat cardiomyocytes. Further results showed that 25.5 mM glucose significantly increased [Ca¬≤‚Å∫](i), up-regulated the expression of Bax, P-ERK and P-JNK, and suppressed Bcl-2 expression. However, the above deleterious changes were further confirmed when co-treatment with CaSR agonist GdCl‚Ç?(300 ¬µM). But the effects of GdCl‚Ç?were attenuated by 10 ¬µM NPS-2390, a specific CaSR inhibitor. When CaSR was silence by siRNA transfection, the effects of high glucose were inhibited. These results suggest that CaSR activation could lead to the apoptosis of cardiomyocytes in diabetic cardiac injury through the induction of calcium overload, the activation of the mitochondrial, and mitogen-activated protein kinase pathway. 

Retracted: No

PubPeer comments:
 Figure 8 * Red boxes: The GAPDH panel in Figure 8B looks similar to the GAPDH panel in Figure 8C, although they represent different experiments.  , 
 Figure 9. * Green boxes: The T-ERK panel in Figure 9A looks similar to the T-JNK panel in Figure 9C. * Orange boxes: The P-ERK panel in Figure 9B looks similar to the P-JNK Panel in Figure 9D.  ,
Hepatitis C virus infection upregulates CD55 expression on the hepatocyte surface and promotes association with virus particles
Authors: Ratna B Ray
Keith Meyer
Adrian M Di Bisceglie
Sandip K Bose
Hangeun Kim
Michael S Diamond
John P Atkinson
Budhaditya Mazumdar
Ranjit Ray
Journal: Journal of Virology (2013)
Discipline: MICROBIOLOGY
Keywords: CD55; complement activation; hepatitis C virus; hepatocytes; core protein
Affiliations: Department of Internal Medicine, St. Louis University, St. Louis, Missouri, USA.

Abstract:  CD55 limits excessive complement activation on the host cell surface by accelerating the decay of C3 convertases. In this study, we observed that hepatitis C virus (HCV) infection of hepatocytes or HCV core protein expression in transfected hepatocytes upregulated CD55 expression at the mRNA and protein levels. Further analysis suggested that the HCV core protein or full-length (FL) genome enhanced CD55 promoter activity in a luciferase-based assay, which was further augmented in the presence of interleukin-6. Mutation of the CREB or SP-1 binding site on the CD55 promoter impaired HCV core protein-mediated upregulation of CD55. HCV-infected or core protein-transfected Huh7.5 cells displayed greater viability in the presence of CD81 and CD55 antibodies and complement. Biochemical analysis revealed that CD55 was associated with cell culture-grown HCV after purification by sucrose density gradient ultracentrifugation. Consistent with this, a polyclonal antibody to CD55 captured cell culture-grown HCV. Blocking antibodies against CD55 or virus envelope glycoproteins in the presence of normal human serum as a source of complement inhibited HCV infection. The inhibition was enhanced in the presence of both the antibodies and serum complement. Collectively, these results suggest that HCV induces and associates with a negative regulator of the complement pathway, a likely mechanism for immune evasion. 

Retracted: No

PubPeer comments:
   ,
c-Jun N-terminal kinase 1 defective CD4+CD25+FoxP3+ cells prolong islet allograft survival in diabetic mice
Authors: Padmaja Paidipally
Ramakrishna Vankayalapati
Rajesh Kumar Radhakrishnan
Amy R Tvinnereim
Ramya Sivangala Thandi
Deepak Tripathi
Satyanarayana S Cheekatla
Elwyn Welch
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: Tregs; JNK1; islet allograft survival; liver parenchyma; CDM
Affiliations: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, 75708, USA. ., Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, 75708, USA., Department of Biotechnology, Gandhi Institute of Technology and Management (GITAM) Institute of Science, GITAM University, Visakhapatnam, Andhra Pradesh, 530045, India.

Abstract:  CD4+CD25+FoxP3+ cells (Tregs) inhibit inflammatory immune responses to allografts. Here, we found that co-transplantation of allogeneic pancreatic islets with Tregs that are defective in c-Jun N-terminal kinase 1 (JNK1) signaling prolongs islet allograft survival in the liver parenchyma of chemically induced diabetic mice (CDM). Adoptively transferred JNK1-/- but not wild-type (WT) Tregs survive longer in the liver parenchyma of CDM. JNK1-/- Tregs are resistant to apoptosis and express anti-apoptotic molecules. JNK1-/- Tregs express higher levels of lymphocyte activation gene-3 molecule (LAG-3) on their surface and produce higher amounts of the anti-inflammatory cytokine interleukin (IL)-10 compared with WT Tregs. JNK1-/- Tregs inhibit liver alloimmune responses more efficiently than WT Tregs. JNK1-/- but not WT Tregs are able to inhibit IL-17 and IL-21 production through enhanced LAG-3 expression and IL-10 production. Our study identifies a novel role of JNK1 signaling in Tregs that enhances islet allograft survival in the liver parenchyma of CDM. 

Retracted: No

PubPeer comments:
  Figure 4D, histogram duplication ,
Mitochondria Restrict Growth of the Intracellular Parasite Toxoplasma gondii by Limiting Its Uptake of Fatty Acids
Authors: Luca Scorrano
Lena Pernas
Camilla Bean
John C Boothroyd
Journal: Cell metabolism (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Toxoplasma gondii; autophagy; fusion; lipid droplets; lipid metabolism
Affiliations: Department of Biology, University of Padova, 35121 Padova, Italy; Venetian Institute of Molecular Medicine, 35129 Padova, Italy., Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA., Department of Biology, University of Padova, 35121 Padova, Italy; Venetian Institute of Molecular Medicine, 35129 Padova, Italy. Electronic address: .

Abstract:  How intracellular pathogens acquire essential non-diffusible host metabolites and whether the host cell counteracts the siphoning of these nutrients by its invaders are open questions. Here we show that host mitochondria fuse during infection by the intracellular parasite Toxoplasma gondii to limit its uptake of fatty acids (FAs). A combination of genetics and imaging of FA trafficking indicates that Toxoplasma infection triggers lipophagy, the autophagy of host lipid droplets (LDs), to secure cellular FAs essential for its proliferation. Indeed, Toxoplasma FA siphoning and growth are reduced in host cells genetically deficient for autophagy or triglyceride depots. Conversely, Toxoplasma FA uptake and proliferation are increased in host cells lacking mitochondrial fusion, required for efficient mitochondrial FA oxidation, or where mitochondrial FA oxidation is pharmacologically inhibited. Thus, mitochondrial fusion can be regarded as a cellular defense mechanism against intracellular parasites, by limiting Toxoplasma access to host nutrients liberated by lipophagy. 

Retracted: No

PubPeer comments:
 Figure S4a: Image duplication  , 
 Thank you for pointing out this error. We will work with journal to make the correction. Sincerely, Lena Pernas, PhD , 
 Please see the corrected Figure S4. Sincerely, Lena Pernas , 
 From this new representative image provided by the authors, it looks like that the %RFP cells is higher in the pyrimethamine than the DMSO group at 6h time-point. Could authors please comment on that?  ,
Tetrahedral DNA nanostructures facilitate neural stem cell migration via activating RHOA/ROCK2 signalling pathway
Authors: Wenjuan Ma
Yuxi Zhan
Chenchen Mao
Dan Zhao
Qianshun Li
Xiaoru Shao
Mengting Liu
Xueping Xie
Yuxin Zhang
Yunfeng Lin
Journal: Cell Proliferation (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: TDNs; neuroectodermal stem cells; migration; mechanisms; self-assembled
Affiliations: State Key Laboratory of Oral Diseases; National Clinical Research Center for Oral Diseases; West China Hospital of Stomatology; Sichuan University; Chengdu China

Abstract:  Objectives: The main purpose of current study was to explore the effects of tetrahedral DNA nanostructures (TDNs) on neuroectodermal (NE-4C) stem cells migration and unveil the potential mechanisms. Materials and methods: The successfully self-assembled TDNs were also determined by dynamic light scattering (DLS). A bidirectional wound-healing assay and transwell chamber assay were employed to test the migrating behaviour of NE-4C stem cells cultured under different conditions. Results: Through an in vitro study, we found that stem cells could internalize TDNs quickly, and the cells' parallel and vertical migration was promoted effectively. Besides, the effects of TDNs were found being exerted by upregulating the gene and protein expression levels of RhoA, Rock2 and Vinculin, indicating that the RHOA/ROCK2 pathway was activated by the TDNs during the cell migration. Conclusions: In conclusion, TDNs could enter NSCs without the aid of other transfection reagents in large amounts, whereas only small amounts of ssDNA could enter the cells. TDNs taken up by NSCs activated the RHOA/ROCK2 signalling pathway, which had effects on the relevant genes and proteins expression, eventually promoting the migration of NE-4C stem cells. These findings suggested that TDNs have great potential in application for the repair and regeneration of neural tissue. 

Retracted: No

PubPeer comments:
  , 
 Sorry for the errors, we have send a correction to the journal and Erratum will be published soon. We apoligize for the errors. Thanks. ,
Notch4 Signaling Confers Susceptibility to TRAIL-Induced Apoptosis in Breast Cancer Cells
Authors: Apurva Sarin
Marion MacFarlane
Shambhavi Naik
Journal: Journal of Cellular Biochemistry (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: APOPTOSIS; BREAST CANCER; NOTCH4; SIGNALING; TRAIL.
Affiliations: National Centre for Biological Sciences; Tata Institute of Fundamental Research; Bangalore 560065 Karnataka India, MRC Toxicology Unit; Hodgkin Building; Leicester UK

Abstract:  Notch signaling has been established as a key regulator of cell fate in development, differentiation, and homeostasis. In breast cancers, increased Notch1 and Notch4 activity have been implicated in tumor progression and, accumulation of the intracellular domain of Notch4 (ICN4), reported in basal breast cancer cells. While, TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists have demonstrated selectively in targeting tumor cells, the majority of primary tumors are resistant to TRAIL. This necessitates the identification of factors that might regulate TRAIL sensitivity. Here we investigate TRAIL sensitivity in tumor cells following the modulation of Notch (1 and 4) activity using siRNA-mediated depletions or ectopic expression of GFP-tagged constructs of the intracellular domains of Notch1 (ICN1) or Notch4 (ICN4). Our findings suggest that Notch4, but not Notch1 signaling, sensitizes breast tumor cells to TRAIL-induced apoptosis. ICN4-induced sensitization to TRAIL is characterized by CBF1-dependence. Apoptosis was mediated via caspase-8 activation and regulated by the Bcl-2 family pro-apoptotic proteins Bak and Bid. Finally, we present evidence that endogenous Notch4 activity regulates susceptibility to TRAIL in basal-like breast cancer cells but not in cell lines of luminal origin. These experiments reveal a hitherto unexplored Notch4-TRAIL signaling axis in breast cancer cells. 

Retracted: No

PubPeer comments:
 Figure 1. * The three flow cytometry panels representing T47D cells look similar to the three panels representing BT474 cells, albeit in a different order, with different gated percentages, and slight changes in the dots. Shown with boxes of the same color. Could the authors please provide the originals?  ,
Polyvalent oligonucleotide gold nanoparticle conjugates as delivery vehicles for platinum(IV) warheads
Authors: David A Giljohann
Stephen J Lippard
Weston L Daniel
Chad A Mirkin
Shanta Dhar
Journal: Journal of the American Chemical Society (2009)
Discipline: CHEMISTRY
Keywords: Amine-functionalized; polyvalent; oligonucleotide; gold nanoparticles; DNA-Au NPs
Affiliations: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Abstract:  Amine-functionalized polyvalent oligonucleotide gold nanoparticles (DNA-Au NPs) were derivatized with a cisplatin prodrug, and the resulting DNA-Au NP conjugates were used to internalize multiple platinum centers. A platinum(IV) complex, c,c,t-[Pt(NH(3))(2)Cl(2)(OH)(O(2)CCH(2)CH(2)CO(2)H)], was tethered to the surface of DNA-Au NPs through amide linkages. The platinum-tethered gold nanoparticles were taken into several cancer cells. The drop in intracellular pH facilitated reductive release of cisplatin from the prodrug, which then formed 1,2-d(GpG) intrastrand cross-links in the cell nuclei, as confirmed by an antibody specific for this adduct. The cytotoxicity of the platinum(IV) complex increases significantly in several cancer cell lines when the complex is attached to the surface of the DNA-Au NPs and in some instances exceeds that of cisplatin. 

Retracted: No

PubPeer comments:
 This is the first  spherical nucleic acid (not yet called this way) that mentions the word  endocytosis . A short discussion of the paper (and its predecessors) here: https: twitter.com raphavisses status 1262421017898766337 ,
Epigenetic high regulation of ATAD2 regulates the Hh pathway in human hepatocellular carcinoma
Authors: Yawei Wang
Yongfeng Liu
Kunming Zhen
Xiangyu Meng
Shuguan Xia
Xiaojun Lu
Gang Wu
Hui He
Journal: International journal of oncology (2014)
Discipline: CLINICAL MEDICINE
Keywords: ATAD2; cancer cells; HCC tissues; mir-372; Ptch1
Affiliations: Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Abstract:  ATAD2 is associated with many cellular progresses such as cell growth, differentiation and apoptosis. Some studies suggest ATAD2 is highly expressed in cancer cells. In our previous studies, we found that ATAD2 is highly expressed in HCC tissues, compared with adjacent normal tissues, and patients with high expression of ATAD2 had a poorer prognosis. Moreover, we found mir-372 can regulate the expression of ATAD2 in HCC cell lines. We also detected a relationship between the mRNA expression of ATAD2 and Ptch1 by gene microarray. Here, we completed the function studies of ATAD2 in vivo and in vitro, and tested whether ATAD2 could regulate the Hh pathway. ATAD2 and Hh pathway protein expressions in 80 HCC specimens were examined by immunohistochemistry (IHC). The mRNA expression of ATAD2 and Hh pathway members in paired-HCC tissues and cell lines were, respectively, analyzed using quantitative PCR. ATAD2‚ÄëRNAi was transduced into HCCLM3 and Huh7 cells, using a lentiviral vector. The effect of ATAD2 in HCC cell lines on cell cycle and apoptosis were evaluated by flow cytometry. Tumorigenicity experiments in nude mice were performed to test the function of ATAD2 in vivo. Pharmacological regulation of Hh signaling was performed to test the relation between the ATAD2 and Hh pathways and C-myc. We found that ATAD2 and Ptch1 were both highly expressed in HCC tissues, compared with paired normal hepatic tissues. In addition, we found that ATAD2 could affect the expression of the Hh pathway by PCR and western blot anaysis in HCC cell lines, by observing the outcome before and after transfection. We speculate that ATAD2 cooperates with the MYC gene to regulate the expression of SMO and Gli, activating the Hh pathway and inducing an active feedback of the Hh pathway. 

Retracted: No

PubPeer comments:
 Figure 2. * Red boxes: The insets in A (ATAD2) and B (Ptch1) appear to overlap * Blue boxes: The insets in B (SMO) and D (Gli 2) appear to look very similar  , 
 Figure 3C. * Pink boxes: Two lanes displaying different treatments and proteins appear to look similar.  , 
 Figure 4A. * The two panels look more similar than expected. I marked some of the similar groups of data points with boxes of the same color  ,
GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration
Authors: Alexander Koenig
Jin-San Zhang
Daniel D Billadeau
Charles Young
Journal: Molecular Biology of the Cell (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RhoU; EGFR; GRB2; endosomes; EGF stimulation
Affiliations: Division of Oncology Research and Schulze Center for Novel Therapeutics., Division of Oncology Research and Schulze Center for Novel Therapeutics, Urology Research, Mayo Clinic College of Medicine, Rochester, MN 55905

Abstract:  RhoU is an atypical Rho family member with high homology to CDC42 but containing unique N- and C-terminal extensions. The mechanisms regulating RhoU activation, as well as its downstream effectors, are not fully characterized. We show that after epidermal growth factor (EGF) stimulation RhoU colocalizes with EGF receptor (EGFR) on endosomes, which requires both its N- and C-terminal extension sequences. Moreover, RhoU physically associates with activated EGFR in a GRB2-dependent manner through specific proline-rich motifs within its N-terminus. Mutation of these proline-rich sequences or suppression of GRB2 by RNA interference abrogates the interaction of RhoU with activated EGFR, as well as EGF-stimulated RhoU GTP binding. In addition, RhoU is involved in EGFR-mediated signaling, leading to AP1 transcriptional activity and cell migration in pancreatic cancer cells, events that require its interaction with the Grb2-EGFR complex. Taken together, the data suggest a unique regulatory mechanism by which RhoU interaction with SH3 adaptor proteins might serve to integrate growth factor receptor signaling with RhoU activation. 

Retracted: No

PubPeer comments:
 Figure 5C. * Red boxes: The left and right Ponceau panels might look more similar to each other than expected, if one of them is in mirror image. Could the authors please check? If the original blots are still available, that would be very helpful.  ,
Naringin protects endothelial cells from apoptosis and inflammation by regulating the Hippo-YAP Pathway
Authors: Hui Liu
Meirong Liu
Rong Suo
Chengzhi Lu
Hui Zhao
Journal: Bioscience Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Endothelial cells; Hippo-YAP Pathway; Naringin; apoptosis; inflammation.
Affiliations: Department of Cardiology, First Center Clinic College of Tianjin Medical University, Tianjin 300192, China., Department of Respiration, Tianjin Hospita, Tianjin 300211, China., Department of Cardiology, Tianjin Hospital, Tianjin 300211, China.

Abstract:  Atherosclerosis is the primary cause of several cardiovascular diseases. Oxidized low-density lipoprotein (ox-LDL)-induced apoptosis, endothelial-mesenchymal transition (EndMT), and inflammation are crucial for the progression of cardiovascular diseases, including atherosclerosis. Naringin, a major compound from tomatoes, grapefruits, and related citrus, reportedly exhibits potential protective effects during atherosclerosis development; however, its effect on ox-LDL-induced human umbilical vein endothelial cell (HUVEC) damage remains unknown. In the present study, we investigated the anti-apoptotic and anti-inflammatory activities of naringin against ox-LDL-induced endothelial cells, and the underlying mechanism. Naringin pretreatment significantly and concentration-dependently inhibited ox-LDL-induced cell injury and apoptosis. Additionally, naringin restored endothelial barrier integrity by preventing VE-cadherin disassembly and F-actin remodeling, and down-regulated pro-inflammatory factors like IL-1Œ≤, IL-6, and IL-18, in the HUVECs. We also demonstrated that naringin treatment restored ox-LDL-induced YAP (yes-associated protein) down-regulation, given the YAP-shRNA attenuated cytoprotective effect of naringin on ox-LDL-induced endothelial cell injury and apoptosis. Collectively, our data indicate that naringin reversed ox-LDL-triggered HUVEC apoptosis, EndMT, and inflammation by inhibiting the YAP pathway. Therefore, naringin may have a therapeutic effect on endothelial injury-related disorders. 

Retracted: No

PubPeer comments:
 A flow cytometry plot in Figure 2C appears to be repeated. ***  , 
  The original article u201cNaringin protects endothelial cells from apoptosis and inflammation by regulating the Hippo-YAP Pathwayu201d (Biosci Rep (2019) 40(3), DOI: 10.1042 BSR20193431) contained an image error and an incorrect description of the data presented. The authors state that they had placed a repeated plot in Figure 2C, and erroneously presented the data in the manuscript as meanu00b1SD, rather than the intended meanu00b1SEM. The corrected figure and its legend is presented below. The authors confirm that the correct equation was used in their analyses, and that this correction does not change their results.  ,
MiR-21 relieves rheumatoid arthritis in rats via targeting Wnt signaling pathway
Authors: Y Zhang
Y-C Mu
C-Y Li
X-G Liu
W-F Ju
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-21; rats; rheumatoid arthritis; Wnt signaling pathway; inflammatory factors
Affiliations: Department of Rheumatology, 970 Hospital of the Chinese People's Liberation Army, Weihai, China. .

Abstract:  Objective: To investigate the influence of micro ribonucleic acid (miR)-21 on rats with rheumatoid arthritis (RA) through the Wnt signaling pathway. Materials and methods: A total of 30 rats were divided into three groups: control group (healthy rats, n=10), model group (rat model of RA, n=10), and MiR group (rat model of RA injected with miR-21 lentivirus, n=10). The paw volume, arthritis indexes, and protein expression level in each group were analyzed by means of paw volume and arthritis index measurement, reverse transcription-polymerase chain reaction (RT-PCR) assay, and fluorescent Western blotting. Results: The expression levels of inflammatory factors declined in MiR group compared with those in model group, while they were higher in model group than those in control group and MiR group (p&lt;0.05). At 15 d after transfection with lentivirus, the paw volume in MiR group was smaller than that in model group, which was decreased markedly with the extended time of transfection (p&lt;0.05). On the 30th d, MiR group had a remarkably smaller paw volume than model group. In comparison with that in control group, the paw volume in model group was increased notably from the 7th d and displayed a significant difference in the 30th d (p&lt;0.05). The arthritis indexes in MiR group were lower than those in model group; however, there were no apparent inflammations at the joints at 15 d after drug administration. Moreover, the longer the time of drug administration was, the less apparent the inflammations at the joints will be. The inflammations at the joints were ameliorated evidently on the 30th d in MiR group (p&lt;0.05). Compared with those in control group, the inflammations in model group were increased significantly from the 7th d, with significant differences in the 30th d (p&lt;0.05). The messenger RNA (mRNA) expression levels of interleukin-6 (IL-6), IL-8, and Wnt in MiR group were higher than those in control group, but lower than those in model group (p&lt;0.05), while they were higher in model group than those in control group (p&lt;0.05). The expression level of Wnt protein was decreased in MiR group compared with that in model group (p&lt;0.05), and model group had a prominently elevated expression level of Wnt protein in comparison with control group (p&lt;0.05). Conclusions: MiR-21 overexpression can repress the expressions of IL-6 and IL-8 and relieve the symptoms of RA by down-regulating the Wnt signal. 

Retracted: No

PubPeer comments:
 Figure 3.  Relative expression of Wnt protein in synovial tissues in each group of rats . Control, Model and MiR all appear to be the same image with minor alterations.  ,
Lift mechanics of downhill skiing and snowboarding
Authors: Yiannis Andreopoulos
Sheldon Weinbaum
Yesim Igci
Qianhong Wu
Journal: Medicine and science in sports and exercise (2006)
Discipline: CLINICAL MEDICINE
Keywords: lift mechanics; downhill skiing; snowboarding; transiently trapped air; compressed solid phase
Affiliations: Department of Mechanical Engineering, Villanova University, Villanova, PA, USA.

Abstract:  Purpose: This study is conducted to develop a simplified mathematical model to describe the lift mechanics of downhill skiing and snowboarding, where the lift contributions due to both the transiently trapped air and the compressed solid phase (snow crystals) are determined. To our knowledge, this is the first time that anyone has attempted to realistically estimate the relative contribution of the transiently trapped air to the total lift in skiing and snowboarding. Methods: The model uses Shimizu's empirical relation to predict the local variation in Darcy permeability due to the compression of the solid phase. The forces and moments on the skier or snowboarder are used to predict the angle of attack of the planing surface, the penetration depth at the leading edge, and the shift in the center of pressure for two typical snow types, fresh and wind-packed snow. We present numerical solutions for snowboarding and asymptotic analytic solutions for skiing for the case where there are no edging or turning maneuvers. The force and moment balance are then used to develop a theory for control and stability in response to changes in the center of mass as the individual shifts his/her weight. Results: Our model predicts that for fine-grained, windpacked snow that when the velocity (U) of the snowboarder or skier is 20 m.s, approximately 50% of the total lift force is generated by the trapped air for snowboarding and 40% for skiing. For highly permeable fresh powder snow, the lift contribution from the pore air pressure drops substantially. Conclusion: This paper develops a new theoretical framework for analyzing the lift mechanics and stability of skis and snowboards that could have important applications in future ski and snowboard design. 

Retracted: No

PubPeer comments:
  , 
 #1 I have replied before. one is a journal publication, the other is a conference presentation. the conference abstract was submitted when the journal paper was still under review. , 
 #2 FYI.  , 
 #2 FYI. **http: edmgr.ovid.com msse accounts ifauth.htm**  **https: www.pubpeer.com publications EC146BE496AB8CABE8729D28A1D8E9#null** , 
 #4 Thanks for checking. But the conference paper is way more brief and abstract. I respect your efforts but have doubt about your intention. , 
 Also, the conference paper came out much later than the journal publication. the conference one was submitted much later than the journal paper. , 
  , 
 **RETRACTED!** **The book chapter has been retracted by its publisher.**  **https: www.pubpeer.com publications EC146BE496AB8CABE8729D28A1D8E9** ,
ZZ domain is essentially required for the physiological binding of dystrophin and utrophin to beta-dystroglycan
Authors: Michiko Ishikawa-Sakurai
Kay E Davies
Michihiro Imamura
Eijiro Ozawa
Mikiharu Yoshida
Journal: Human molecular genetics (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: dystrophin; muscle fibers; Duchenne muscular dystrophy; binding site; C-terminal domain
Affiliations: Department of Cell Biology, National Institute of Neuroscience, Tokyo, Japan.

Abstract:  An intracellular protein, dystrophin, plays an important role in keeping muscle fibers intact by binding at its N-terminal end to the subsarcolemmal cytoskeletal actin network and via its C-terminal end to the transmembraneous protein beta-dystroglycan. Duchenne muscular dystrophy is caused by the loss of dystrophin, which can result from the loss of this binding. The N-terminal part of the latter binding site of dystrophin has been well documented using overlay assay and X-ray diffraction assays. However, the binding site at the C-terminal region of dystrophin has not been examined in detail. In the present work, we report a detailed analysis of the C-terminal binding domain as follows. (1). The full binding activity corresponding to the effective binding in vivo is expressed by the dystrophin fragment spanning amino acids 3026-3345 containing the ZZ domain at the C-terminus. Determination of this binding range is important not only for understanding of the mechanism of dystrophy, but also useful for the design of truncated dystrophin constructs for gene therapy. (2). The ZZ domain binds to EF1 domain in the dystrophin fragment to reinforce the binding activity. (3). The cysteine 3340 in the ZZ domain is essential for the binding of dystrophin to beta-dystroglycan. A reported case of DMD due to missense mutation C3340Y may be caused by inability to fix dystrophin beneath the cell membrane. (4). The binding mode of utrophin is different from that of dystrophin. The difference is conspicuous concerning the cysteine residues present in the ZZ domain. 

Retracted: No

PubPeer comments:
null, 
 #1  , 
  , 
 #3 I agree this looks unexpected. ,
Mulberry Fruit Extract Protects against Memory Impairment and Hippocampal Damage in Animal Model of Vascular Dementia
Authors: Sathaporn Wongcharoenwanakit
Pratchaya Kaewkaen
Terdthai Tong-Un
Wiroje Kaewrueng
Supaporn Muchimapura
Jintanaporn Wattanathorn
Journal: Evidence-based Complementary and Alternative Medicine (2012)
Discipline: CLINICAL MEDICINE
Keywords: vascular dementia; mulberry fruit extract; memory impairment; brain damage; animal model
Affiliations: Department of Physiology and Graduate School (Neuroscience Program), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand., Integrative Complementary Alternative Medicine Research Group, Khon Kaen University, Khon Kaen 40002, Thailand, Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand, The Queen Sirikit Department of Sericulture, Ministry of Agriculture and Cooperatives, Bangkok 10900, Thailand

Abstract:  Nowadays, the preventive strategy of vascular dementia, one of the challenge problems of elderly, has received attention due to the limitation of therapeutic efficacy. In this study, we aimed to determine the protective effect and possible mechanism of action of mulberry fruit extract on memory impairment and brain damage in animal model of vascular dementia. Male Wistar rats, weighing 300-350 g, were orally given mulberry extract at doses of 2, 10 and 50 mg/kg at a period of 7 days before and 21 days after the occlusion of right middle cerebral artery (Rt.MCAO). It was found that rats subjected to mulberry fruits plus Rt.MCAO showed the enhanced memory, the increased densities of neuron, cholinergic neuron, Bcl-2-immunopositive neuron together with the decreased oxidative stress in hippocampus. Taken all data together, the cognitive enhancing effect of mulberry fruit extract observed in this study might be partly associated with the increased cholinergic function and its neuroprotective effect in turn occurs partly via the decreased oxidative stress and apoptosis. Therefore, mulberry fruit is the potential natural cognitive enhancer and neuroprotectant. However, further researches are essential to elucidate the possible active ingredient. 

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. ,
Functional Characterization of PknI-Rv2159c Interaction in Redox Homeostasis of Mycobacterium tuberculosis
Authors: Sujatha Narayanan
Divakar Sharma
Arunkumar Venkatesan
Kannan Palaniyandi
Deepa Bisht
Journal: Frontiers in Microbiology (2016)
Discipline: MICROBIOLOGY
Keywords: 2D gel electrophoresis; PknI; Rv2159c; alkylhydroperoxidase; antisense knockdown
Affiliations: Department of Immunology, National Institute for Research in Tuberculosis Chennai, India., Department of Biochemistry, National JALMA Institute for Leprosy and other Mycobacterial Diseases Agra, India.

Abstract:  Mycobacterium tuberculosis adapts to stress conditions by responding to the signals from its external environment. M. tuberculosis genome encodes 11 eukaryotic like serine/threonine protein kinases (STPK) and their importance in regulating the physiology and virulence of the bacteria are being explored. Previous study from our lab identified the M. tuberculosis STPK, PknI interacts with two peroxidase proteins such as Rv2159c and Rv0148. In this study, we have characterized the biological function behind the PknI-Rv2159c interaction in M. tuberculosis. Point mutation of Ala-Gly-Trp motif identified that only Ala49 and Gly50 amino acids of Rv2159c are responsible for interaction and there is no phosphorylation involved in the PknI-Rv2159c interaction. Rv2159c is a member from the carboxymuconolactone decarboxylase family with peroxidase activity. Enzymatic assays with catalytic site point mutants showed that Cys84 of Rv2159c was responsible for its alkylhydroperoxidase activity. Interestingly, interaction with PknI increased its peroxidase activity by several folds. Gene knockdown of Rv2159c in M. tuberculosis showed increased sensitivity to peroxides such as cumene hydroperoxide and hydrogen peroxide. Proteomic analysis of differentially expressing Rv2159c strains by 2D gel electrophoresis and mass spectrometry revealed the differential abundance of 21 proteins. The total absence of oxidoreductase, GuaB1 suggests the essential role of Rv2159c in redox maintenance. Our findings provide new insights on signaling mechanisms of PknI in maintaining the redox homeostasis during oxidative stresses. 

Retracted: No

PubPeer comments:
 Figure 1B appears to have some repeated background features. Could the authors please provide a high-resolution image of the original scan? ***  ***  ,
PEG-PLA-PEG block copolymeric nanoparticles for oral immunization against hepatitis B
Authors: Amit K Goyal
Neeraj Mishra
Suresh P Vyas
Bhuvaneshwar Vaidya
Arvind K Jain
Sharad Mangal
Journal: International journal of pharmaceutics (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: PLA/PLGA nanoparticles; vaccine delivery systems; oral vaccine delivery; copolymerizing; PEG
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H.S. Gour Vishwavidyalaya Sagar (M.P.) 470003, India.

Abstract:  PLA/PLGA nanoparticles are well known as efficient vaccine delivery systems, but they have got limitation in oral vaccine delivery because of their sensitivity to harsh gastric environment. The aim of present study was to improve the stability of PLA nanoparticles in such environment by copolymerizing PLA with PEG. Nanoparticles were formulated using different block copolymers AB, ABA and BAB (where 'A' is PLA and 'B' is PEG) encapsulating hepatitis B surface antigen (HBsAg) to evaluate their efficacy as oral vaccine delivery system. The results of in vitro studies engrave the efficiency of copolymeric nanoparticles to retain encapsulated antigen and average particle size even after 2 h incubation in simulated gastric fluid and simulated intestinal fluid. Fluorescence microscopic studies indicated efficient uptake of copolymeric nanoparticles by gut mucosa of immunized mice model as compared to control. Finally copolymeric and PLA nanoparticles, encapsulating HBsAg, were evaluated for their adjuvancity in generating immune response after oral administration. PLA nanoparticles could not generate an effective immune response due to stability issues. On the other hand, oral administration of copolymeric nanoparticles exhibited effective levels of humoral immunity along with the mucosal (sIgA) and cellular immune response (T(H)1). The results of in vitro and in vivo studies demonstrate that BAB nanoparticles depict enhanced mucosal uptake leading to effective immune response as compared to other copolymeric nanoparticles. Present study indicates the efficacy of BAB nanoparticles as a promising carrier for oral immunization. 

Retracted: No

PubPeer comments:
 At top here:  Fig. 5. Fluorescent microscopy images showing the uptake of FITCu2013BSA loaded different nanoparticles by gut mucosa after oral administration. (A) Soluble FITCu2013BSA (control); (B) AB nanoparticles; (C) ABA nanoparticles; (D) BAB nanoparticles . Two concerns here. First is the overlap between (B) and (C), after a vertical stretch. Shown with purple boxes.  Second is the overlap between (D) and Fig 5(B) of [Tiwari et al (2009)] , after a 90-deg rotation:  Fig:5-Fluorescent microscopy images showing the uptake of FITC-BSA loaded different liposomal formulations by nasal mucosal surface after intranasal administration. ... (B) CL . Shown below. Were the cells treated with BAB nanoparticles or a CL liposome formulation? Also, were they gut or nasal mucosal cells? This information would assist anyone wanting to replicate this research. ,