PReD-Bench/PRed-Bench huggingface dataset:
S100A8/A9 promotes MMP-9 expression in the fibroblasts from cardiac rupture after myocardial infarction by inducing macrophages secreting TNFŒ±
Authors: S Shi
J-L Yi
Journal: European Review for Medical and Pharmacological Sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Inflammation; extracellular matrix degradation; cardiac rupture; myocardial infarction; S100A8/A9
Affiliations: Feature Inspection Section, Urumqi, Xin-Jiang Medical University, China. .

Abstract:  Objective: Inflammation and extracellular matrix degradation play a role in cardiac rupture (CR) after myocardial infarction (MI). It has been found that the expression of inflammatory cytokine S100A8/A9 was elevated in acute MI patients, whereas its impact in CR after infarction remains unclear. Patients and methods: Samples from cardiac tissue and peripheral blood of patients with CR after MI, MI, patients without CR, and healthy control (cardiotrauma) were collected to test the expressions of S100A8/A9, p-p65, and MMP-9. Co-culture system for HCF cells and macrophages were established to identify the impact of hypoxia-ischemia on the expressions of S100A8/A9 and TNFŒ±. S100A9 and/or TNFŒ± blocking agent were applied to examine the effect on macrophages migration, expressions of S100A8, S100A9, and TNFŒ±. Western blot was adopted to determine levels of p-p65 and MMP-9 protein after the inhibition of S100A9 and/or TNFŒ±. Results: Compared with healthy control and non-CR patients, serum S100A8/A9 and MMP-9 levels were elevated in cardiac tissues of CR patients, while S100A8/A9, p-p65, and MMP-9 were also overexpressed. Hypoxia-ischemia significantly caused the increasing levels of S100A8/A9 and TNFŒ± in macrophages (p &lt; 0.05). The blockade of S100A9 and/or TNFŒ± suppressed the activation and migration of macrophages. The inhibition of S100A9 expression also decreased the secretion of TNFŒ± in macrophages, while the suppression of TNFŒ± showed no significant impact on S100A8 and S100A9 levels. Downregulation of TNFŒ± or NF-Œ∫B markedly declined p-p65 and MMP-9 protein levels in HCF cells from co-culture system or single culture, whereas the blockade of S100A9 only reduced their expressions in co-cultured HCF cells. Conclusions: The level of S100A8/A9 was upregulated in MI patients with CR. S100A8/A9 induced the activation of NF-Œ∫B and expression of MMP-9 protein in HCF cells through facilitating secretion of TNFŒ± from macrophages, which may play a role in triggering extracellular matrix degradation and CR. 

Retracted: No

PubPeer comments:
 Fig 2C  Fig 2D.  I am not convinced that these flow-cytometry plots all came from separate conditions and sessions. Fig 3A.  I am not convinced that these Transwell images all came from separate conditions. Fig 4.  What conditions resulted in these stark sharp-edged blobs of black on a featureless grey background? ,
RAGE receptor targeted bioconjuguate lipid nanoparticles of diallyl disulfide for improved apoptotic activity in triple negative breast cancer: in vitro studies
Authors: Shashank Tummala
S Nandha Kumar
Pavan Kumar Chintamaneni
Sai Kiran S S Pindiprolu
Venkata Talluri Siddhartha
Journal: Artificial Cells Nanomedicine and Biotechnology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Diallyl disulfide; apoptosis; breast cancer; receptor for advanced glycation endproducts; solid lipid nanoparticles.
Affiliations: Department of Pharmaceutics, JSS College of Pharmacy, Udhagamandalam (Jagadguru Sri Shivarathreeshwara University), Tamil Nadu, India;, Department of Pharmacology, JSS College of Pharmacy, Udhagamandalam (Jagadguru Sri Shivarathreeshwara University), Tamil Nadu, India;, Department of Pharmaceutics, GIET School of Pharmacy, Rajahmundry, Andhra Pradesh, India

Abstract:  In the present study, we have demonstrated receptor for advanced glycation endproducts (RAGE) as a target for delivery of drugs specifically to triple negative breast cancer cells. We have prepared solid lipid nanoparticle formulation of cytotoxic agent di-allyl-disulfide (DADS) to overcome its bioavailability issues. Then, we have surface modified DADS-loaded solid lipid nanoparticles (DADS-SLN) with RAGE antibody to achieve site-specific delivery of DADS to TNBC cells. We found a significant cellular internalization of RAGE surface modified DADS-SLN (DADS-RAGE-SLN) when compared to DADS-SLN. The cytotoxic effect of DADS was also significantly improved with DADS-RAGE-SLN by downregulating anti-apoptotic proteins and upregulating pro-apoptotic proteins as observed by western blot analysis. RAGE-targeted delivery of cytotoxic agents can be, therefore, a promising approach for improving antitumour activity and reducing off-target effects. 

Retracted: No

PubPeer comments:
 Article retracted. http: retractionwatch.com 2019 10 08 materials-scientist-will-soon-be-up-to-30-retractions ,
ShRNA-mediated Ku80 gene silencing inhibits cell proliferation and sensitizes to gamma-radiation and mitomycin C-induced apoptosis in esophageal squamous cell carcinoma lines
Authors: Jin-Long Gu
Yong Wang
Fei-Yue Fan
Li-Li Qin
Li-Li Jia
Qing-Shan Yang
Li-Qing Du
Journal: Journal of Radiation Research (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ku80 depletion; cell growth; sensitization; gamma-radiation; MMC-induced apoptosis
Affiliations: Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. 

Abstract:  To investigate the effects of Ku80 depletion on cell growth and sensitization to gamma-radiation and MMC-induced apoptosis in esophageal squamous cell carcinoma lines. Six human carcinoma cell lines (LNcaP, K562, MDA-MB-231, MCF-7, EC9706, and K150) and normal HEK293 cell line were examined for basal levels of Ku80 protein by western blotting analysis. The suppression of Ku80 expression was performed using vector-based shRNA in EC9706 cells. Cell proliferation was determined with MTT assay and colony formation assay and tumorigenicity in a xenograft model in vitro and in vivo. Sensitivity of EC9706 cells treated with shRNA vector to gamma-radiation and MMC was determined with colony formation assay and MTT assay. The cell cycle distribution was determined by Flow cytometry. Apoptosis induced by gamma-radiation and MMC was analyzed using GENMED-TUNEL FACS kit. Ku80 showed higher basal levels in six carcinoma cell lines than in HEK293. The suppression of Ku80 expression decreased cellular proliferation, colony formation and inhibited tumorigenicity in a xenograft model. Furthermore, it sensitized apoptosis of the cancer cells induced by gamma-radiation and MMC. Ku80 plays an important role not only in tumorigenesis but also in radiation resistance and chemotherapy resistance in esophageal cancer cells. Hence Ku80 may serve as a promising therapeutic target, particularly for recurrent esophageal tumors. 

Retracted: No

PubPeer comments:
 Figure 6A. Much more similar than you would expect. https: imgur.com jbPa3rU ,
Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling
Authors: Shou-Sen Wang
Hong-Jie Chen
Jian-He Zhang
Kai-Chun Fan
Jian-Jun Gu
Journal: International Journal of Molecular Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: Glioblastoma; gene therapy; microRNA; miR-130b; PTEN
Affiliations: Stroke Center, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China., Department of Gastroenterology, Chinese PLA General Hospital, Beijing 100853, P.R. China., Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. China.

Abstract:  Glioblastoma is the most common malignant brain tumor in adults and is characterized by extensive proliferation and the diffused invasion of tumor cells. Due to the intricate signaling pathways involved in glioma progression, more effective targeted therapies and prognostic biomarkers in clinical practice are required. The suppression of proto-oncogene function or recovery of tumor suppressor gene function remains one of the primary approaches in gene therapy. The close association between the abnormal expression or mutation of microRNA (miRNA) and the tumorigenesis, progression and staging in glioma have been demonstrated previously. However, the expression pattern and specific role of microRNA‚Ä?30b (miR‚Ä?30b) in the tumor occurrence and progression of glioma are unclear. In the present study, quantitative polymerase chain reaction was performed to determine the expression level of miR-130b in 30 brain glioma patients and 3 glioma cell lines. An miR‚Ä?30b inhibitor was transfected into U87 cells to downregulate the expression of miR-130b, and assessments of cell proliferation, cell cycle, apoptosis, cell invasion and migration in vitro and nude mouse tumorigenicity in vivo were conducted. Western blotting and luciferase reporter gene technology were used to verify the downstream target gene of miR-130b, namely phosphatase and tensin homolog (PTEN). The results demonstrated that miR-130b expression was increased in glioma tissues and cell lines in comparison with non-glioma tissues or cells. The downregulated expression of miR-130b inhibited the proliferation and invasion of glioma cells, induced apoptosis of the cells in vitro and inhibited their tumorigenicity in vivo. Western blotting and luciferase reporter assays demonstrated that the PTEN gene is a direct target of miR‚Ä?30b. Western blotting revealed that the miR-130b inhibitor upregulated the expression of PTEN, inhibited AKT pathway activation, upregulated the tumor suppressor gene p27, and suppressed cyclin D1, matrix metalloproteinase 2 and 9 expression. These results suggest that the miR-130b inhibitor suppressed glioma cell proliferation and invasion via the PTEN/AKT pathway. Therefore, miR‚Ä?30b is suggested to be an effective therapeutic target for glioma. 

Retracted: No

PubPeer comments:
 Figure 5 appears to have many partially overlaps in images for different treatments.  ,
Antigen-activated dendritic cells ameliorate influenza A infections
Authors: Kobporn Boonnak
Marlene Orandle
Leatrice Vogel
Eyal Talor
Daniel Zimmerman
Kanta Subbarao
Journal: Journal of Clinical Investigation (2013)
Discipline: CLINICAL MEDICINE
Keywords: Influenza A viruses; alternative therapies; antiviral drugs; LEAPS technology; immune-based treatment
Affiliations: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892-3203, USA.

Abstract:  Influenza A viruses cause significant morbidity and mortality worldwide. There is a need for alternative or adjunct therapies, as resistance to currently used antiviral drugs is emerging rapidly. We tested ligand epitope antigen presentation system (LEAPS) technology as a new immune-based treatment for influenza virus infection in a mouse model. Influenza-J-LEAPS peptides were synthesized by conjugating the binding ligand derived from the Œ≤2-microglobulin chain of the human MHC class I molecule (J-LEAPS) with 15 to 30 amino acid-long peptides derived from influenza virus NP, M, or HA proteins. DCs were stimulated with influenza-J-LEAPS peptides (influenza-J-LEAPS) and injected intravenously into infected mice. Antigen-specific LEAPS-stimulated DCs were effective in reducing influenza virus replication in the lungs and enhancing survival of infected animals. Additionally, they augmented influenza-specific T cell responses in the lungs and reduced the severity of disease by limiting excessive cytokine responses, which are known to contribute to morbidity and mortality following influenza virus infection. Our data demonstrate that influenza-J-LEAPS-pulsed DCs reduce virus replication in the lungs, enhance survival, and modulate the protective immune responses that eliminate the virus while preventing excessive cytokines that could injure the host. This approach shows promise as an adjunct to antiviral treatment of influenza virus infections. 

Retracted: No

PubPeer comments:
 there are what appear to be unexpected similarities within and between Figures 2 A and 2 B.    , 
 Came here to post the same thing, so here we go, and I agree with all concerns raised in comment #1.  Figure 2 got corrected in August 2020: https: www.ncbi.nlm.nih.gov labs pmc articles PMC7410043 The correction states:  During the preparation of this manuscript, the middle panel of the bottom row in Figure 2A was inadvertently duplicated from the middle panel of the top row in Figure 2B. The correct figure is below. The correction only corrects the Type I simple duplication (marked by me with green boxes and marked in #1 by big red boxes), but does not address the much bigger concerns in some of the other panels, where similar constellations of data points can be observed across different panels. Of additional note, this paper is listed as one of the  Key Publications on the website of Cel-Sci Corporation. https: cel-sci.com key-publications-and-presentations (archived at https: archive.md gYwLO) ,
MSLN gene silencing has an anti-malignant effect on cell lines overexpressing mesothelin deriving from malignant pleural mesothelioma
Authors: Georgios Giamas
Alfonso Cristaudo
Roberto Barale
Elisa Bracci
Justin Stebbing
Luciano Mutti
Federica Gemignani
Norihisa Uehara
Alessandra Bonotti
Rudy Foddis
Stefano Landi
Ylenia Lombardo
Ombretta Melaiu
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Genes; Carcinogenetic mechanisms; Malignant pleural mesothelioma; Mesothelin; Membrane glycoprotein
Affiliations: Department of Biology, University of Pisa, Pisa, Italy., Department of Surgery and Cancer, Imperial College London, London, United Kingdom., Second Department of Pathology, Kansai Medical University, Moriguchi-Shi, Osaka, Japan., Department of Endocrinology and Metabolism, Orthopedics and Traumatology, Occupational Medicine, University of Pisa, Pisa, Italy., Laboratory of Clinical Oncology, Vercelli National Health Trust, Vercelli, Italy.

Abstract:  Genes involved in the carcinogenetic mechanisms underlying malignant pleural mesothelioma (MPM) are still poorly characterized. So far, mesothelin (MSLN) has aroused the most interest. It encodes for a membrane glycoprotein, frequently over-expressed in various malignancies such as MPM, and ovarian and pancreatic cancers. It has been proposed as a diagnostic and immunotherapeutic target with promising results. However, an alternative therapeutic approach seems to rise, whereby synthetic molecules, such as antisense oligonucleotides, could be used to inhibit MSLN activity. To date, such a gene-level inhibition has been attempted in two studies only, both on pancreatic and ovarian carcinoma cell lines, with the use of silencing RNA approaches. With regard to MPM, only one cell line (H2373) has been employed to study the effects of MSLN depletion. Indeed, the knowledge on the role of MSLN in MPM needs expanding. Accordingly, we investigated the expression of MSLN in a panel of three MPM cell lines, i.e., NCI-H28, Mero-14, and IstMes2; one non-MPM cell line was used as reference (Met5A). MSLN knock-down experiments on MSLN-overexpressing cells were also performed through silencing RNA (siRNA) to verify whether previous findings could be generalized to a different set of cell cultures. In agreement with previous studies, transient MSLN-silencing caused decreased proliferation rate and reduced invasive capacity and sphere formation in MSLN-overexpressing Mero-14 cells. Moreover, MSLN-siRNA combined with cisplatin, triggered a marked increase in apoptosis and a decrease in proliferation as compared to cells treated with each agent alone, thereby suggesting a sensitizing effect of siRNA towards cisplatin. In summary, our findings confirm that MSLN should be considered a key molecular target for novel gene-based targeted therapies of cancer. 

Retracted: No

PubPeer comments:
null, 
null, 
 Correction In Fig 4A, the incorrect image is used for siMSLN-1. Please see the correct Fig 4 here  Published: June 22, 2017 ,
RNAi-mediated targeting of noncoding and coding sequences in DNA repair gene messages efficiently radiosensitizes human tumor cells
Authors: Walter J Curran
Jeffrey J Olson
Wooi Loon Ng
Ya Wang
Chunhai Hao
Xiangming Zhang
Zhiming Zheng
Journal: Cancer Research (2012)
Discipline: CLINICAL MEDICINE
Keywords: tumor cell death; radiotherapy; ionizing radiation; DNA double-strand breaks; homologous recombination repair
Affiliations: Department of Neurosurgery, Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, China.

Abstract:  Human tumor cell death during radiotherapy is caused mainly by ionizing radiation (IR)-induced DNA double-strand breaks (DSB), which are repaired by either homologous recombination repair (HRR) or nonhomologous end-joining (NHEJ). Although siRNA-mediated knockdown of DNA DSB repair genes can sensitize tumor cells to IR, this approach is limited by inefficiencies of gene silencing. In this study, we show that combining an artificial miRNA (amiR) engineered to target 3'-untranslated regions of XRCC2 (an HRR factor) or XRCC4 (an NHEJ factor) along with an siRNA to target the gene coding region can improve silencing efficiencies to achieve more robust radiosensitization than a single approach alone. Mechanistically, the combinatorial knockdown decreased targeted gene expression through both a reduction in mRNA stability and a blockade to mRNA translation. Together, our findings establish a general method of gene silencing that is more efficient and particularly suited for suppressing genes that are difficult to downregulate by amiR- or siRNA-based methods alone. 

Retracted: No

PubPeer comments:
 2016 correction for figures 1 and 2. https: www.sciencedirect.com science article pii S2211124716314334?via=ihub The following errors have been identified in this article: (1) the Ferritin bands in Figure 1A are duplicated in Figure 1C as DMT1 bands, and (2) the C-Myc ER bands in Figure 2A are duplicated in Figure 2C as Ferritin bands. , 
 #1  (1) the Ferritin bands in Figure 1A are duplicated in Figure 1C as DMT1 bands and vertically flipped.  ,
MAEL expression links epithelial-mesenchymal transition and stem cell properties in colorectal cancer
Authors: Ye Xu
Yaqi Li
Qingguo Li
Dawei Li
Xinxiang Li
Ping Wei
Ben Huang
Sanjun Cai
Journal: International Journal of Cancer (2016)
Discipline: CLINICAL MEDICINE
Keywords: MAEL; colorectal cancer; epithelial-mesenchymal transition; stemness.
Affiliations: Department of Colorectal Surgery; Fudan University Shanghai Cancer Center; Shanghai 200032 China, Department of Oncology; Shanghai Medical College, Fudan University; Shanghai 200032 China

Abstract:  MAEL plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilisation, however, its role on cancers is unclear. In this study, MAEL expression was analysed in a tissue microarray containing 185 samples of primary colon cancer tumor samples and human colon cancer cell lines. The effect of MAEL on cell proliferation, tumorigenesis, metastasis and drug resistance was examined in vitro and in vivo. Immunoprecipitation assay, confocal immunofluorescent analysis and luciferase assay were used for mechanism study. As results, MAEL was significantly upregulated in colon cancer patient tissue samples, and elevated MAEL protein levels positively correlated with overall survival and disease free survival of colon cancer patients. Using in vitro and in vivo models, we demonstrated that MAEL expression was correlated with cell proliferation, invasion and drug resistance of colon cancer cells by inducing epithelial-mesenchymal transition and stemness characteristics. Mechanistically, our study demonstrated that MAEL interacts with Snail and inhibit E-cadherin promoter activity. Collectively, MAEL is an oncogene that plays an important role in the development and progression of colon cancer, which may be a novel potential therapeutic target for colon cancer. 

Retracted: No

PubPeer comments:
 This paper includes nearly 20 year old patient medical images with no mention of patient consent or IRB approval of the scanning procedures described. As it appears the first authoru2019s medical licenses were revoked following his felony conviction (background here: https: retractionwatch.com 2018 11 13 a-convicted-felon-writes-a-paper-on-hotly-debated-diets-what-could-go-wrong ), and his u201cinstituteu201d appears to be defunct (per IRS and state records), it isnu2019t clear which author or institution retained custody of these confidential patient records since 1999 and 2000. Could the authors clarify? ***  ,
Combined application of Embelin and tumor necrosis factor-related apoptosis-inducing ligand inhibits proliferation and invasion in osteosarcoma cells via caspase-induced apoptosis
Authors: Pengcheng Li
Yao Chen
Guangjian Jiang
Wei Zhang
Tao Huang
Shuo Cheng
Xiucheng Li
Tiemin Liu
Hao Qian
Journal: Oncology Letters (2018)
Discipline: CLINICAL MEDICINE
Keywords: Embelin; TRAIL; apoptosis; invasion; osteosarcoma.
Affiliations: Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

Abstract:  Embelin, as an inhibitor of the X-linked inhibitor of apoptosis protein (XIAP), may induce apoptosis in various types of cancer cells. The present study aimed to determine the effect of Embelin on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of osteosarcoma cells. Embelin and TRAIL were applied to U2OS and MG63 cells, respectively or in combination. MTT was initially used to detect the difference in survival rates between the group receiving combined application of 100 ng/ml TRAIL and 20 ¬µmol/l Embelin and the individual application groups. Light microscopic quantification was used to detect the morphology of the osteosarcoma cells in each group. Determination of cell apoptosis was subsequently performed using flow cytometry. The invasive ability of the cells was detected by a Transwell assay, prior to relative protein expression being determined by western blot analysis. Based on all the test data, it was revealed that the survival rates and the invasive ability were significantly lower following the combined application of 100 ng/ml TRAIL and 20 ¬µmol/l Embelin than following the individual application of either (P&lt;0.01). Additionally, upregulating expression of caspases, as well as death receptor 5, and downregulating expression of XIAP and matrix metalloproteinase 9 (MMP-9), had more significant effects in the combined group compared with the individual group and the control group. All these results suggested that Embelin may enhance TRAIL-induced apoptosis and inhibit the invasion of human osteosarcoma cells. 

Retracted: No

PubPeer comments:
 Images in Figure 4 appear to overlap, with rotation in one case. This suggests that the error was more extensive than the selection of a wrong image. ***  ,
Synthesis of TiO2 nanofibers by electrospinning using water-soluble Ti-precursor
Authors: Otieno, Odhiambo Vincent
Cs√°ki, Edina
K√©ri, Orsolya
Simon, L√°szl√≥
Luk√°cs, Istv√°n Endre
Sz√©cs√©nyi, Katalin M√©sz√°ros
Szil√°gyi, Imre Mikl√≥s
Journal: Journal of Thermal Analysis and Calorimetry (2020)
Discipline: CHEMISTRY
Keywords: Electrospinning process; TiO2 nanofibers; Ti-precursor; Water-soluble; Anatase

Abstract: A new electrospinning process was developed for preparing TiO2 nanofibers using a water-soluble Ti-precursor, [bis(kappa1O-hydroxo)(bis(kappa2O,O‚Ä?lactato)titanium(IV)] commonly known as titanium(IV) bis (ammonium lactato) dihydroxide (TiBALDH). The importance of the study is justified by the fact that Ti-precursors used for electrospinning, sol‚Äìgel, hydrothermal and other fiber synthesis processes are mostly non-water soluble. Accordingly, anatase TiO2 nanofibers of diameter between 20 and 140&nbsp;nm were synthesized by electrospinning and annealing. Polyvinylpyrrolidone (PVP) and different concentrations of TiBALDH were dissolved in a mixture of water, ethyl alcohol and acetic acid to optimize the electrospinning conditions. The thermal decomposition and fragmentation of PVP, TiBALDH and the fibers with 50% mass fraction of TiBALDH were studied by TGA-MS measurements. The fibers were then annealed at 1&nbsp;¬∞C&nbsp;min\u22121 until 600&nbsp;¬∞C. The TiO2 fibers were characterized using SEM‚ÄìEDX, FTIR and XRD

Retracted: No

PubPeer comments:
 Detailed information is not available or the legend is not given for (a), (b), (c), and (d) in the images below! Different marker bars are seen! There is another inconsistency regarding the claimed VOLTAGES, one on the legend, another one in the text. Please clarify.!  ,
Up‚Äêregulated HMGB 1 in EAM directly led to collagen deposition by a PKC Œ≤/Erk1/2‚Äêdependent pathway: cardiac fibroblast/myofibroblast might be another source of HMGB 1
Authors: Ting Wang
Ping Ni
Dong Zheng
Zhaoliang Su
Huiling Shen
Jingping Yin
Huaxi Xu
Haitao Zhu
Yingkun Sun
Rui Ma
Wenlin Xu
Journal: Journal of Cellular and Molecular Medicine (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HMGB1; cardiac fibrosis; experimental autoimmune myocarditis.
Affiliations: The Central Laboratory The Fourth Affiliated Hospital of Jiangsu University Zhenjiang China, Department of Immunology &amp; Laboratory Immunology Jiangsu University Zhenjiang China

Abstract:  High mobility group box 1 (HMGB1), an important inflammatory mediator, is actively secreted by immune cells and some non-immune cells or passively released by necrotic cells. HMGB1 has been implicated in many inflammatory diseases. Our previous published data demonstrated that HMGB1 was up-regulated in heart tissue or serum in experimental autoimmune myocarditis (EAM); HMGB1 blockade could ameliorate cardiac fibrosis at the last stage of EAM. And yet, until now, no data directly showed that HMGB1 was associated with cardiac fibrosis. Therefore, the aims of the present work were to assess whether (1) up-regulated HMGB1 could directly lead to cardiac fibrosis in EAM; (2) cardiac fibroblast/myofibroblasts could secrete HMGB1 as another source of high-level HMGB1 in EAM; and (3) HMGB1 blockade could effectively prevent cardiac fibrosis at the last stage of EAM. Our results clearly demonstrated that HMGB1 could directly lead to cardiac collagen deposition, which was associated with PKCŒ≤/Erk1/2 signalling pathway; furthermore, cardiac fibroblast/myofibroblasts could actively secrete HMGB1 under external stress; and HMGB1 secreted by cardiac fibroblasts/myofibroblasts led to cardiac fibrosis via PKCŒ≤ activation by autocrine means; HMGB1 blockade could efficiently ameliorate cardiac fibrosis in EAM mice. 

Retracted: No

PubPeer comments:
 Where can the raw data for this article be found? ,
Preparation of icariin/TiO2 nanotube composite coating on pure titanium surface and analysis of early drug release
Authors: H-C Liu
F-F Wang
Y Li
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Preparation; icariin; TiO2 nanotube; composite coating; pure titanium surface
Affiliations: Medical College of Nankai University, Tianjin, P. R. China.

Abstract:  The article "Preparation of icariin/TiO2 nanotube composite coating on pure titanium surface and analysis of early drug release" by F.-F. Wang, Y. Li, H.-C. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23(5): 1864-1873 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,
Identification of peptide inhibitors of pre-mRNA splicing derived from the essential interaction domains of CDC5L and PLRG1
Authors: Paul Ajuh
Angus I Lamond
Journal: Nucleic Acids Research (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CDC5L; PLRG1; spliceosomal proteins; sub-spliceosomal protein complexes; pre-mRNA splicing
Affiliations: The University of Dundee, School of Life Sciences, Wellcome Trust Biocentre, Dow Street, Dundee DD1 5EH, UK.

Abstract:  CDC5L and PLRG1 are both spliceosomal proteins that are highly conserved across species. They have both been shown to be part of sub- spliceosomal protein complexes that are essential for pre-mRNA splicing in yeast and humans. CDC5L and PLRG1 interact directly in vitro. This interaction is mediated by WD40 regions in PLRG1 and the C-terminal domain of CDC5L. In order to determine whether this interaction is important for the splicing mechanism, we have designed peptides corresponding to highly conserved sequences in the interaction domains of both proteins. These peptides were used in in vitro splicing experiments as competitors to the cognate sequences in the endogenous proteins. Certain peptides derived from the binding domains of both proteins were found to inhibit in vitro splicing. This splicing inhibition could be prevented by preincubating the peptides with the corresponding partner protein that had been expressed in Escherichia coli. The results from this study indicate that the interaction between CDC5L and PLRG1 is essential for pre-mRNA splicing and further demonstrate that small peptides can be used as effective splicing inhibitors. 

Retracted: No

PubPeer comments:
 Figure 6. Much more similar than expected.  , 
 15 July 2022 Editor s Note. https: academic.oup.com nar advance-article doi 10.1093 nar gkac623 6644944 Following allegations in 2021 of image manipulation, the authorsu2019 institution analysed the article and confirmed that lanes 7u20138 and 9u201310 in Figure 6 are duplicates. The institution notified the journal of this duplication in March 2022, and the authors have unreservedly apologised for this error. While the lanes show a negative result and the Editors believe the duplication to be a genuine mistake, they cannot confirm whether or not the results and conclusions presented in the article are affected because the original data are no longer available. The Editors, therefore, advise readers to examine the details of this study with care. Julian E. Sale and Barry L. Stoddard Senior Executive Editors ,
c-Myc down-regulation increases susceptibility to cisplatin through reactive oxygen species-mediated apoptosis in M14 human melanoma cells
Authors: D Del Bufalo
S Amodei
C Gabellini
B Benassi
G Zupi
A Biroccio
Journal: Molecular Pharmacology (2001)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: c-Myc; cisplatin sensitivity; melanoma cells; apoptosis; DNA repair
Affiliations: Experimental Chemotherapy Laboratory, Experimental Research Center, Regina Elena Cancer Institute, Rome, Italy.

Abstract:  Our aim in this work was to define the role of c-Myc in the susceptibility to cisplatin [cis-diamminedichloroplatinum(II) (CDDP)] in human melanoma cells. Two M14 melanoma cell clones obtained by transfection and expressing six to ten times lower c-Myc protein levels than the parental cells and the control clone were employed. Analysis of survival curves demonstrates an increase in CDDP sensitivity in c-Myc low-expressing clones if compared with the control clone and the parental line. The enhanced sensitivity is unrelated to the impairment in enzymatic DNA repair activity. Cell cycle analysis demonstrates that although the control clone is able to completely recover from the CDDP-induced S-G(2)/M block, this arrest is prolonged in c-Myc low-expressing clones and a fraction of cells undergoes apoptosis. Although no changes in P53, Bax, Bcl-2, and Bcl-x(L/S) protein levels are observed, apoptosis is associated with the formation of reactive oxygen species (ROS), activation of caspase-1, caspase-3 and cleavage of the specific caspase substrate poly-ADP-ribose polymerase. The use of the antioxidant N-acetyl cysteine and caspase inhibitors prevents CDDP-induced apoptosis in c-Myc low-expressing clones, demonstrating that ROS, caspase-1, and caspase-3 are required for apoptotic cell death. Moreover, ROS generation depends on caspase-1-like activation because the Ac-YVAD-cho inhibitor abrogates CDDP-induced ROS in the c-Myc low-expressing clones. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
null, 
 Figure 7. Much more similar than expected.  ,
Tumour necrosis factor-induced activation of c-Jun N-terminal kinase is sensitive to caspase-dependent modulation while activation of mitogen-activated protein kinase (MAPK) or p38 MAPK is not
Authors: Peter Vandenabeele
Helen M Anderson
Alison F Littlejohn
David J MacEwan
Ahmed A A Mohamed
Orla J Jupp
Journal: Biochemical Journal (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ERKs; TNF receptors; caspase sensitivity; TNFR subtype activation; CrmA
Affiliations: Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, U.K., Molecular Signalling and Cell Death Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, Ledeganckstraat 35, B-9000 Gent, Belgium

Abstract:  The activation of the extracellular signal-regulated kinases (ERKs) by tumour necrosis factor-alpha (TNF) receptors (TNFRs) is an integral part of the cytokine's pleiotropic cellular responses. Here we report differences in the caspase sensitivity and TNFR subtype activation of members of the ERK family. Inhibition in HeLa cells of caspase function by pharmacological inhibitors or the expression of CrmA (cytokine response modifier A), a viral modifier protein, blocks TNF-induced apoptosis or caspase-dependent protein kinase Cdelta and poly(ADP-ribose) polymerase protein degradation. TNFR1- or TNFR2-stimulated c-Jun N-terminal kinase (JNK) activity was attenuated in cells in which caspase activity was inhibited either by pharmacological blockers or CrmA expression. Both TNFR1- and TNFR2-stimulated JNK activity was caspase-sensitive; however, only TNFR1 was capable of stimulating p42/44 mitogen-activated protein kinase (MAPK) and p38 MAPK activities. TNFR1-stimulated p42/44 MAPK and p38 MAPK activities were insensitive to pharmacological caspase inhibition or CrmA. These findings were supported when measuring TNF-induced cytosolic phospholipase A(2) activation, which is a downstream target for MAPK and p38 MAPK. Profiling caspase enzymes activated by TNF in HeLa cells showed sequential caspase-8, -3, -7, -6 and -9 activation, with their inhibition characteristics suggesting a role for caspase-3 and/or caspase-6 in modulating JNK activity. Taken together these results show delineated ERK-activation pathways employed by TNFR subtypes. 

Retracted: No

PubPeer comments:
 Figure 5A. Much more similar than you would expect. https: imgur.com KgRPcyR ,
Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death
Authors: M Scott Vandiver
Jing Xu
Feng Rao
Solomon H Snyder
Bindu D Paul
Nilkantha Sen
Adele M Snowman
Risheng Xu
Journal: Science signaling (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p53; IPMK; transcription; acetylation; p300
Affiliations: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract:  The tumor suppressor protein p53 is a critical stress response transcription factor that induces the expression of genes leading to cell cycle arrest, apoptosis, and tumor suppression. We found that mammalian inositol polyphosphate multikinase (IPMK) stimulated p53-mediated transcription by binding to p53 and enhancing its acetylation by the acetyltransferase p300 independently of its inositol phosphate and lipid kinase activities. Genetic or RNA interference (RNAi)-mediated knockdown of IPMK resulted in decreased activation of p53, decreased recruitment of p53 and p300 to target gene promoters, abrogated transcription of p53 target genes, and enhanced cell viability. Additionally, blocking the IPMK-p53 interaction decreased the extent of p53-mediated transcription. These results suggest that IPMK acts as a transcriptional coactivator for p53 and that it is an integral part of the p53 transcriptional complex facilitating cell death. 

Retracted: No

PubPeer comments:
 Continued reading of this paper found more identical blots used as results from different experiments. Please clarify.   , 
 If one aligns the images side by side, it is rather obvious that they are not duplicates.      ,
Effect of galangin supplementation on oxidative damage and inflammatory changes in fructose-fed rat liver
Authors: Carani Venkatraman Anuradha
Allur Subramaniyan Sivakumar
Journal: Chemico-Biological Interactions (2011)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: galangin; oxidative stress; inflammatory cytokines; NF-Œ∫B activation; fructose-fed rats
Affiliations: Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India.

Abstract:  The study examined the effects of galangin (GA) on oxidative stress, inflammatory cytokine levels and nuclear factor-kappa B (NF-Œ∫B) activation in fructose-fed rat liver. Adult male albino Wistar rats were divided into 4 groups. Groups 1 and 4 received the control diet containing starch as the source of carbohydrate while groups 2 and 3 were fed a diet containing fructose. Groups 3 and 4 additionally received GA (100Œºg/kg, p.o) from the 15th day. At the end of 60 days, the levels of plasma glucose, insulin and triglycerides, insulin sensitivity indices and oxidative stress markers in the liver were determined. Cytokines of interest were assayed by ELISA and RT-PCR and NF-Œ∫B p65 nuclear translocation by Western blot and RT-PCR. Compared to control diet-fed animals, fructose-fed animals developed hyperglycemia, hyperinsulinemia, hypertriglyceridemia and insulin resistance (IR) (all p&lt;0.01). GA prevented the rise in plasma glucose, insulin and triglycerides and improved insulin sensitivity. Tumor necrosis factor-Œ± (TNF-Œ±) and interleukin-6 (IL-6) levels in plasma and the mRNA and protein levels of TNF-Œ± and transforming growth factor-Œ≤1(TGF-Œ≤(1)) in liver were significantly higher in fructose-fed rats than control rats. However, treatment with GA downregulated the expression of these cytokines. Translocation of NF-Œ∫B into the nucleus was also increased in fructose diet-fed animals, which was prevented by GA. These results suggest that GA prevents oxidative damage and has a downregulatory effect on the inflammatory pathway in liver of fructose-fed rats. 

Retracted: No

PubPeer comments:
  Fig. 1. RT-PCR analysis of TGF-b (A)... Lane 1-CON; lane 2-FRU; lane 3-FRU + GA; and lane 4- CON + GA and lane 5-base pairs marker. I have a concern about an unexpected similarity in lane 4. Shown below without color and with heightened contrast.  ,
MEF2D overexpression contributes to the progression of osteosarcoma
Authors: Jinhua Han
Yi Liu
Haichi Yu
Yunshen Bai
Honghui Sun
Guomin Liu
Nan Zhang
Journal: Gene (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cell cycle; MEF2D; Osteosarcoma; miR-144.

Abstract:  The underlying molecular pathogenesis of osteosarcoma remains poorly understood. The transcription factor MEF2D promotes the survival of various types of cells and functions as an oncogene in liver cancer. However, its potential contribution to osteosarcoma has not been explored. In this study, we investigated MEF2D expression and function in osteosarcoma, finding that MEF2D elevation in osteosarcoma clinical specimens was associated with patients' poor prognosis. MEF2D suppression was shown to decrease the proliferation of osteosarcoma cells, while forced expression of MEF2D was able to promote the proliferation of normal bone fibroblast. Notably, MEF2D silencing abolished osteosarcoma tumorigenicity in an animal model. Mechanistic investigations revealed that MEF2D silencing triggered G2-M arrest in osteosarcoma cells by suppressing RPRM and CDKN1A. miR-144 was found to suppress the expression of MEF2D in osteosarcoma cells. Collectively, our results demonstrated that MEF2D is a candidate oncogene for osteosarcoma and a potential molecular target for cancer therapy. 

Retracted: No

PubPeer comments:
 *[left]* Fig 2D,E.  MEF2D was investigated for their expression levels by immunoblot analysis in U2OS, and hFOB1.19 cells treated with (D) mimics and (E) inhibitors of miR-144 respectively . *[right]* Figs 3B, 4B from [Hong et al (2015)] .  Western blot assay was conducted to confirm the above results .  , 
 Thanks for your comment. We have carefully re-checked our raw data, the Fig 5D,E.  MEF2D was investigated for their expression levels by immunoblot analysis in U2OS, and hFOB1.19 cells treated with (D) mimics and (E) inhibitors of miR-144 respectively . in our work were detected using Western Blot in our laboratory. We would provide the original Western Blot image if need. Whatu2019s more, our work was finished at 6th Nov. 2014, and accepted by Gene at 10th Mar. 2015, which was available online at 23th Mar. 2015. But, Hong et.alu2019s work was finished at 23th May. 2015, and accepted by Tumor Biology at 30th Jun. 2015. We have no idea how Hong et.alu2019s work obtained these images. ,
Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-Œ∫B/IKK pathway-induced apoptosis
Authors: Yu Mei Li
Peng Xu
Jian Guo Shi
Jin Qing Li
Jian Lin Yuan
Yong Hua Lei
Xiao Ping Gao
Jing Yu Gao
Yong Wang
Chen Shao
Wei Zhang
Wei Xue
Yun Tao Zhang
He Wang
Chang Hong Shi
Qiang Fu
Juan Ying Wang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Bladder cancer; Hydroxycamptothecin; Genistein; Sensitization; Apoptosis
Affiliations: Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.

Abstract:  Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-Œ∫B pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-Œ∫B pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy. 

Retracted: No

PubPeer comments:
  Figure 5 C,D,F appear to contain the same WT and WT+GABA data, although the experiments are said to be done at different time points. , 
  In Figure 6 G and H, WT latency to platform and swim distance data appear identical, even though the data are supposed to from two experiments in which WT received different treatments. ,
Porf-2 Inhibits Neural Stem Cell Proliferation Through Wnt/Œ≤-Catenin Pathway by Its GAP Domain
Authors: Guo-Hui Huang
Xin-Cai Li
Liang Zhu
Sheng-Yi Zhang
Kui Chen
Jin Xing
Hong-Jiang Li
Dong-Fu Feng
Lin Guo
Xi-Tao Yang
Journal: Frontiers in Cellular Neuroscience (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: GAP; cell proliferation; neural stem cell; porf-2; wnt/Œ≤-catenin signaling.
Affiliations: Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China., Neuroscience Division, Department of Anatomy, Histology, and Embryology, Shanghai Jiao Tong University School of Medicine Shanghai, China., Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghai, China; Institute of Traumatic Medicine, Shanghai Jiao Tong University School of MedicineShanghai, China.

Abstract:  Neural stem cell (NSC) proliferation and differentiation play a pivotal role in the development of brain, the plasticity of the brain network, and the repair for brain function in CNS diseases. The mechanisms regulating NSC behavior are not well elucidated. Previous studies showed porf-2 functions as a modulator in central nerve system development. We here show that porf-2, a conserved family of RhoGAPs, is highly and specifically expressed in NSCs. We also demonstrate that porf-2 inhibits the proliferation of NSCs in vivo and in vitro, but has no effect on NSC differentiation. We investigated which domain is required for the role of porf-2 on NSC proliferation. By using neurosphere formation and Edu assay we confirmed the GAP domain is necessary for its function. In addition, we surveyed a few classical pathways on NSC proliferation and found that porf-2 inhibits NSC proliferation by suppressing the Œ≤-catenin nuclear translocation. Taken together, we show for the first time that porf-2 inhibits NSC proliferation through Wnt/Œ≤-catenin pathway by its GAP domain. 

Retracted: No

PubPeer comments:
 Same image used in figures 3 and 4, however in Fig.3B it is porf-2 overexpressing and in Fig.4B it is a control  ,
Loss of GABAergic cortical neurons underlies the neuropathology of Lafora disease
Authors: Carlos Spuch
Saida Ortolano
Irene Vieitez
Roberto Carlos Agis-Balboa
Journal: Molecular Brain (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Lafora disease; EPM2A; EPM2B; myoclonic epilepsy; neurodegeneration
Affiliations: Group of Neurodegenerative Diseases and Psychiatric Disorders, Institute of Biomedical Research of Vigo (IBIV), Xerencia de Xestion Integrada de Vigo, SERGAS, Psychiatric Hospital Rebull√≥n, Puxeiros s/n, Pontevedra 36415 Mos, Spain. .

Abstract:  Background: Lafora disease is an autosomal recessive form of progressive myoclonic epilepsy caused by defects in the EPM2A and EPM2B genes. Primary symptoms of the pathology include seizures, ataxia, myoclonus, and progressive development of severe dementia. Lafora disease can be caused by defects in the EPM2A gene, which encodes the laforin protein phosphatase, or in the NHLRC1 gene (also called EPM2B) codifying the malin E3 ubiquitin ligase. Studies on cellular models showed that laforin and malin interact and operate as a functional complex apparently regulating cellular functions such as glycogen metabolism, cellular stress response, and the proteolytic processes. However, the pathogenesis and the molecular mechanism of the disease, which imply either laforin or malin are poorly understood. Thus, the aim of our study is to elucidate the molecular mechanism of the pathology by characterizing cerebral cortex neurodegeneration in the well accepted murine model of Lafora disease EPM2A-/- mouse. Results: In this article, we want to asses the primary cause of the neurodegeneration in Lafora disease by studying GABAergic neurons in the cerebral cortex. We showed that the majority of Lafora bodies are specifically located in GABAergic neurons of the cerebral cortex of 3 months-old EPM2A-/- mice. Moreover, GABAergic neurons in the cerebral cortex of younger mice (1 month-old) are decreased in number and present altered neurotrophins and p75NTR signalling. Conclusions: Here, we concluded that there is impairment in GABAergic neurons neurodevelopment in the cerebral cortex, which occurs prior to the formation of Lafora bodies in the cytoplasm. The dysregulation of cerebral cortex development may contribute to Lafora disease pathogenesis. 

Retracted: No

PubPeer comments:
 unexpected 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. ,