PReD-Bench/PRed-Bench huggingface dataset:
Circular RNA hsa_circ_0000511 Improves Epithelial Mesenchymal Transition of Cervical Cancer by Regulating hsa-mir-296-5p/HMGA1
Authors: Wenli Fan
Ping Zhou
Qian Chen
Jia Xie
Journal: Journal of Immunology Research (2021)
Discipline: IMMUNOLOGY
Keywords: cervical cancer; circular RNA; hsa_circ_0000511; hsa-mir-296-5p; HMGA1
Affiliations: Department of Gynecology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China., Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

Abstract:  As the second largest gynecological cancer, cervical cancer has been widely reported in recent years in which circular RNA is involved in the disease process. We earlier found that the expression of hsa_circ_0000511 in cervical cancer cells increased significantly, but its role in the process of cervical cancer is not clear. The purpose of this study is to explore its possible mechanisms in cervical cancer. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), cell counting kit-8 assay, Transwell test, cell transfection, RNA pull-down assay and dual-luciferase reporter assay, and Western blot analysis were used to detect the expression and distribution of hsa_circ_0000511 in SiHa and HeLa cells, the ability of invasion and proliferation, and the modulated relationships between hsa_circ_0000511 and hsa-mir-296-5p, hsa-mir-296-5p, and HMGA1. hsa_circ_0000511 had the highest expression in SiHa and HeLa cells, and the expression in the cytoplasm was significantly higher than that in the nucleus, and its expression was not affected by RNase R. When hsa_circ_0000511 was silenced, its expression in SiHa and HeLa cells was significantly decreased; the proliferation, invasion, and migration abilities of the two kinds of cells were significantly enhanced; and the protein expression of E-cadherin was significantly upregulated, while the protein expression of N-cadherin was significantly downregulated. The expression of hsa-mir-296-5p was lower in SiHa and HeLa cells; however, its expression was increased when hsa_circ_0000511 was inhibited and decreased when hsa_circ_0000511 was overexpressed, so did the ability of proliferation, invasion, and migration and the protein expression of E-cadherin. Interestingly, the protein expression of HMGA1 also changed in these two cells when hsa-mir-296-5p was inhibited or overexpressed. Our results indicate that the upregulated hsa_circ_0000511 can inhibit the proliferation, invasion, and migration of SiHa and HeLa cells by regulating hsa-mir-296-5p/HMGA1, suggesting that the hsa_circ_0000511/hsa-mir-296-5p/HMGA1 pathway may be a potential target for the treatment of cervical cancer. 

Retracted: No

PubPeer comments:
 Figure 2D. * Yellow boxes: Two panels appear to show an overlap. https: imgur.com a jKzj3zA ,
STYXL1 promotes malignant progression of hepatocellular carcinoma via downregulating CELF2 through the PI3K/Akt pathway
Authors: J-Z Wu
N Jiang
X Liu
J-M Lin
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: STYXL1; hepatocellular carcinoma; CELF2; PI3K/Akt pathway; expression levels
Affiliations: Department of Infectious Disease, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China. .

Abstract:  Objective: This study was aimed to investigate the expression characteristics of STYXL1 in hepatocellular carcinoma (HCC), and to further analyze its regulatory role in promoting HCC development by targeting CELF2 to activate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Patients and methods: Expression levels of STYXL1 in 25 pairs of HCC tissue specimens and paracancerous normal ones collected from HCC patients were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, qRT-PCR was also performed to further verify the expression of STYXL1 in HCC cell lines. In addition, after STYXL1 knockdown model was constructed by lentivirus transfection in HCC cell lines Hep3B and Huh7, the Cell Counting Kit-8 (CCK-8), cell colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays were performed to analyze the influence of STYXL1 on HCC cell functions. Furthermore, an in-depth study of the relationship between STYXL1 and CELF2 was conducted to figure out the underlying mechanism. Results: The results of qRT-PCR revealed that the expression level of STYXL1 in HCC samples was remarkably higher than that in adjacent ones, and the difference was statistically significant. Compared with HCC patients with low expression of STYXL1, patients with high expression of STYXL1 had a higher overall survival rate. Similarly, the proliferation ability of HCC cells in sh-STYXL1 group remarkably decreased compared with controls, while the apoptosis ability was oppositely enhanced. In addition, Western Blotting results indicated that STYXL1 could elevate the expressions of PI3K/Akt pathway-related proteins. Meanwhile, a negative correlation between CELF2 and STYXL1 was identified in HCC tissues. Finally, the result of cell reverse experiments demonstrated that STYXL1 could affect the malignant progression of HCC via modulating CELF2 expression. Conclusions: STYXL1 expression was remarkably upregulated in HCC tissues, as well as in cell lines. Its level was closely related to the poor prognosis of HCC patients. In addition, STYXL1 might be able to accelerate HCC proliferation rate and inhibit cell apoptosis via downregulating CELF2 through the PI3K/Akt pathway. 

Retracted: No

PubPeer comments:
 Examples of verbatim reproduction of contents by the same group of authors. ![file] ,
RGFP966, a histone deacetylase 3 inhibitor, promotes glioma stem cell differentiation by blocking TGF-β signaling via SMAD7
Authors: Hang Liang
Ding Wang
Baofeng Guo
Jiaxin Ren
Xuyang Chen
Ling Zhang
Qian Wang
Hua Lu
Dhan V Kalvakolanu
Hongwu Zheng
Naiyan Wen
Libo Xu
Journal: Biochemical Pharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Differentiation; Glioma stem cells; Growth arrest; HDAC3; SMAD7
Affiliations: Key Laboratory of Pathobiology, Ministry of Education, and Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China., Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA., Greenebaum NCI Comprehensive Cancer Center, Department of Microbiology and Immunology University of Maryland School Medicine, Baltimore, MD, USA., Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA., Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China. Electronic address: ., Key Laboratory of Pathobiology, Ministry of Education, and Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China. Electronic address: .

Abstract:  Glioma stem cells (GSC) play a major role in drug resistance and tumor recurrence. Using a genetic screen with a set of shRNAs that can target chromatin regulators in a GSC model, we have HDAC3 as a major negative regulator of GSC differentiation. Inhibition of HDAC3 using a pharmacological inhibitor or a siRNA led to the induction of GSC differentiation into astrocytes. Consequently, HDAC3-inhibition also caused a strong reduction of tumor-promoting and self-renewal capabilities of GSCs. These phenotypes were highly associated with an increased acetylation of SMAD7, which protected its ubiquitination. SMAD7 inhibits a TGF-β signaling axis that is required for maintaining stemness. These results demonstrate that HDAC3 appears to be a proper target in anti-glioma therapy. 

Retracted: No

PubPeer comments:
 2020 erratum. https: www.sciencedirect.com science article pii S0006295220304597?via%3Dihub The authors of this paper would like to point out some errors that are present in the published version. These errors are detailed below, along with their corrections: 1. In Fig. 5C, the labels of western blot were missing in published version. It should be RGFP966(u03bcM) 0 in left panel, 1.0 in middle panel and 2.5 in right panel. The error detail and correct figure are shown as follows. 2. In Fig. 9A, the third group and fourth group blotting in chase assay were in wrong order in published version. The error detail and correct figure are shown as follows. The authors apologise for these errors. ,
miRNA‑520c‑3p accelerates progression of nasopharyngeal carcinoma via targeting RAB22A
Authors: Wenrui Xu
Chuanshan Zang
Na Li
Xiaohan Sun
Journal: Oncology Letters (2019)
Discipline: CLINICAL MEDICINE
Keywords: RAB22A; cell cycle; miRNA-520c-3p; nasopharyngeal carcinoma; proliferation.
Affiliations: Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Abstract:  Biological function of microRNA-20c-3p (miRNA-520c-3p) in the progression of nasopharyngeal carcinoma (NPC) and the potential mechanism were investigated. Relative level of miRNA-520c-3p in NPC tissues and adjacent normal tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Particularly, miRNA-520c-3p level in NPC with different tumor stages and tumor sizes was examined. Subsequently, miRNA-520c-3p level in nasopharyngeal epithelial cells and NPC cells was detected. The potential influence of miRNA-520c-3p on the proliferative ability and cell cycle progression of NPC cells were evaluated through cell counting kit-8 (CCK-8) and flow cytometry. The target gene of miRNA-520c-3p was verified by dual-luciferase reporter gene assay. Regulatory role of miRNA-520c-3p/RAB22A in the malignant progression of NPC was identified. miRNA-520c-3p was downregulated in NPC tissues and cell lines. Its level was lower in NPC with worse tumor grade and larger tumor size. Overexpression of miRNA-520c-3p suppressed the proliferative ability and arrested cell cycle in G0/G1 phase. RAB22A was confirmed to be the downstream target of miRNA-520c-3p. In NPC tissues and cell lines, RAB22A remained in higher abundance relative to controls. Overexpression of RAB22A reversed the inhibitory effects of overexpressed miRNA-520c-3p on proliferative ability and cell cycle progression of NPC cells. miRNA-520c-3p is downregulated in NPC, which accelerates the malignant progression of NPC by targeting RAB22A. 

Retracted: Yes

PubPeer comments:
 October 2020 retraction: https: www.spandidos-publications.com 10.3892 ol.2020.12182 From the statement:  Following the publication of this article, the authors have contacted the Editor to request its retraction on account of having been unable to reproduce the same results on performing a further series of experiments. The Editor has agreed to the authors request, and therefore this article has been retracted from Oncology Letters. All the authors agree to this retraction. The authors apologize to the readership of the Journal for any inconvenience caused. ,
Differential activation of some transcription factors during rat liver ischemia, reperfusion, and heat shock
Authors: L Tacchini
A Bernelli-Zazzera
L Radice
Journal: Journal of Cellular Physiology (1999)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cells; gene expression; transcription factors; rat liver; ischemia
Affiliations: Istituto di Patologia Generale dell'Università degli Studi di Milano, Centro di Studio sulla Patologia Cellulare del CNR, Milan, Italy.

Abstract:  Cells respond to external stimuli by changes in gene expression that are largely dependent on transcription factors (TFs). We studied the behavior of some TFs in rat liver during ischemia, postischemic reperfusion, and heat shock. Knowledge of the conditions at the end of ischemia is essential to understand changes occurring at reperfusion. The TFs investigated are known to be typically responsive to heat shock (HSF), hypoxia (HIF-1), pro- and antioxidant conditions (AP-1), or to various environmental changes (HNF-1 and ATF/CREB family). The most relevant new information includes the following: 1) Liver ischemia activates extremely rapidly the DNA binding capacity of HSF, soon followed by analogous activation of HIF-1 and AP-1. 2) After a certain lag time from the activation of HIF-1, mRNAs accumulate for two glycolytic enzymes, in particular Aldolase A and Heme Oxygenase 1, which contain HIF-1 sequences in their promoters. 3) Reperfusion, which is known to further increase the binding of HSF and to induce NFkappaB binding, abrogates or decreases the binding of HIF-1 and AP-1, stimulated by ischemia, and activates the binding of ATF/CREB. Later on, a second peak of AP-1 binding is induced. 4) Heat shock activates both ischemia-responsive and reperfusion-responsive TFs. 5) Preliminary experiments of supergelshift reveal that the activation of AP-1 at reperfusion or upon heat shock may result from the different involvement of the component subunits. 

Retracted: No

PubPeer comments:
 Blots more similar than you would expect. https: imgur.com fGinhLJ ,
EPHB6 controls catecholamine biosynthesis by up-regulating tyrosine hydroxylase transcription in adrenal gland chromaffin cells
Authors: Tomiyasu Murata
Nicolas Vitale
Jiangping Wu
Yujia Wang
Hongyu Luo
Norio Kaneda
Shijie Qi
Wei Shi
Junzheng Peng
Journal: Journal of Biological Chemistry (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: adrenal; c-JUN transcription factor; catecholamine; chromaffin cells; early growth response protein 1 (EGR1)
Affiliations: From the Research Centre and., the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China., the Institut des Neurosciences Cellulaires et Intégratives, UPR-3212, CNRS-Université de Strasbourg, 5 rue Blaise Pascal, 67000 Strasbourg, France, and., the Department of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Tempaku, Nagoya 4688503, Japan., From the Research Centre and ., Nephrology Department, Centre Hospitalier de l'Université de Montréal Montreal, Quebec, H2X 0A9, Canada.

Abstract:  EPHB6 is a member of the erythropoietin-producing hepatocellular kinase (EPH) family and a receptor tyrosine kinase with a dead kinase domain. It is involved in blood pressure regulation and adrenal gland catecholamine (CAT) secretion, but several facets of EPHB6-mediated CAT regulation are unclear. In this study, using biochemical, quantitative RT-PCR, immunoblotting, and gene microarray assays, we found that EPHB6 up-regulates CAT biosynthesis in adrenal gland chromaffin cells (AGCCs). We observed that epinephrine content is reduced in the AGCCs from male Ephb6-KO mice, caused by decreased expression of tyrosine hydroxylase, the rate-limiting enzyme in CAT biosynthesis. We demonstrate that the signaling pathway from EPHB6 to tyrosine hydroxylase expression in AGCCs involves Rac family small GTPase 1 (RAC1), MAP kinase kinase 7 (MKK7), c-Jun N-terminal kinase (JNK), proto-oncogene c-Jun, activator protein 1 (AP1), and early growth response 1 (EGR1). On the other hand, signaling via extracellular signal-regulated kinase (ERK1/2), p38 mitogen-activated protein kinase, and ELK1, ETS transcription factor (ELK1) was not affected by EPHB6 deletion. We further report that EPHB6's effect on AGCCs was via reverse signaling through ephrin B1 and that EPHB6 acted in concert with the nongenomic effect of testosterone to control CAT biosynthesis. Our findings elucidate the mechanisms by which EPHB6 modulates CAT biosynthesis and identify potential therapeutic targets for diseases, such as hypertension, caused by dysfunctional CAT biosynthesis. 

Retracted: No

PubPeer comments:
 2020 correction. https: www.jbc.org content 295 24 8349.short The wrong version of Fig. 1B was inadvertently used in the version of this article that was published on April 26, 2019. This error has now been corrected and does not affect the results or conclusions of this work. ,
Requirement for serum in medium supplemented with insulin-transferrin-selenium for hydrodynamic cultivation of engineered cartilage
Authors: Gilda A Barabino
Yueh-Hsun Yang
Journal: Tissue Engineering Part A (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: bioreactor systems; chondrocyte-seeded constructs; serum content; insulin-transferrin-selenium; culture media
Affiliations: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia.

Abstract:  Achievement of viable engineered tissues through in vitro cultivation in bioreactor systems requires a thorough understanding of the complex interplay between hydrodynamic forces and biochemical cues such as serum. To this end, chondrocyte-seeded constructs were cultured under continuous fluid-induced shear forces with reduced serum content (0%-2%, v/v), which was partially or completely replaced by a potential substitute, insulin-transferrin-selenium, to minimize deleterious effects associated with the use of culture media containing high levels of serum (10%-20%). Low-serum cultures yielded constructs with similar biochemical properties to those cultivated with high-serum supplements, whereas the serum-free constructs exhibited poor cell proliferation, insufficient extracellular matrix production, and rapid degradation of and/or shear-induced damage to polyglycolic acid scaffolds. A fibrous outer capsule typically observed in hydrodynamic cultures and characterized by increased cell density and decreased (virtually none) glycosaminoglycan deposition was eliminated when serum concentration was equal to or &lt;0.2% in the presence of hydrodynamic stimuli. Our findings suggest that serum is a requirement in insulin-transferrin-selenium-supplemented cultures in order for constructs to exhibit improved properties in response to hydrodynamic forces, and that mechanical and biochemical stimuli may synergistically modulate tissue properties and morphology through shear-responsive signals. 

Retracted: No

PubPeer comments:
 ![file] ,
Tumor-derived mutations in the TRAIL receptor DR5 inhibit TRAIL signaling through the DR4 receptor by competing for ligand binding
Authors: Lance R Thomas
Jacqueline Thorburn
Lianghua Bin
Andrew Thorburn
Robin Humphreys
Peter E Clark
Journal: Journal of Biological Chemistry (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: TRAIL; apoptosis; tumor cells; receptors; mutations
Affiliations: Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045, USA.

Abstract:  TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a cytokine that preferentially induces apoptosis in tumor cells compared with normal cells through two receptors (DR4 and DR5). Somatic mutations in these receptors have been found in different kinds of cancer; however, it is poorly understood how the mutations affect signaling. We found that point mutations (L334F, E326K, E338K, and K386N) that were identified in human tumors result in the DR5 receptor losing its ability to form a functional death-inducing signaling complex and induce apoptosis. The mutant receptors also have a "dominant negative" effect whereby they inhibit the ability of TRAIL to induce apoptosis through functional DR4 receptors. This dominant negative mechanism is achieved through competition for TRAIL binding as shown by experiments where the ability of the mutant DR5 receptor to bind with the ligand was abolished, thus restoring TRAIL signaling through DR4. The inhibitory effect on signaling through the wild-type DR4 protein can be overcome if the inhibitory mechanism is bypassed by using a DR4-agonistic antibody that is not subject to this competition. This study provides a molecular basis for the use of specific therapeutic agonists of TRAIL receptors in people whose tumors harbor somatic DR5 mutations. 

Retracted: No

PubPeer comments:
 ![file] ,
Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis
Authors: Anders S Byström
Anders Esberg
Bo Huang
Marcus J O Johansson
Journal: Molecular Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Saccharomyces cerevisiae; Elongator complex; transcriptional elongation; polarized exocytosis; modified wobble uridines
Affiliations: Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.

Abstract:  The Saccharomyces cerevisiae Elongator complex consisting of the six Elp1-Elp6 proteins has been proposed to participate in three distinct cellular processes: transcriptional elongation, polarized exocytosis, and formation of modified wobble uridines in tRNA. Therefore it was important to clarify whether Elongator has three distinct functions or whether it regulates one key process that leads to multiple downstream effects. Here, we show that the phenotypes of Elongator-deficient cells linking the complex to transcription and exocytosis are suppressed by increased expression of two tRNA species. Elongator is required for formation of the mcm(5) group of the modified wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U) in these tRNAs. Hence, in cells with normal levels of these tRNAs, presence of mcm(5)s(2)U is crucial for posttranscriptional expression of gene products important in transcription and exocytosis. Our results indicate that the physiologically relevant function of the evolutionary-conserved Elongator complex is in formation of modified nucleosides in tRNAs. 

Retracted: No

PubPeer comments:
 Figure 3C: More similar than expected. Could authors check please? ![file] Figure S1C: Same issue ![file] ,
Deletion of TGF-β1 Increases Bacterial Clearance by Cytotoxic T Cells in a Tuberculosis Granuloma Model
Authors: Jennifer J Linderman
Joshua T Mattila
Elsje Pienaar
Hayley C Warsinske
Denise E Kirschner
Journal: Frontiers in Immunology (2017)
Discipline: IMMUNOLOGY
Keywords: agent-based modeling; cells-T cells; cytotoxic; infections-bacterial; pulmonary
Affiliations: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, United States., Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, United States., Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, United States.

Abstract:  Mycobacterium tuberculosis is the pathogenic bacterium that causes tuberculosis (TB), one of the most lethal infectious diseases in the world. The only vaccine against TB is minimally protective, and multi-drug resistant TB necessitates new therapeutics to treat infection. Developing new therapies requires a better understanding of the complex host immune response to infection, including dissecting the processes leading to formation of granulomas, the dense cellular lesions associated with TB. In this work, we pair experimental and computational modeling studies to explore cytokine regulation in the context of TB. We use our next-generation hybrid multi-scale model of granuloma formation (GranSim) to capture molecular, cellular, and tissue scale dynamics of granuloma formation. We identify TGF-β1 as a major inhibitor of cytotoxic T-cell effector function in granulomas. Deletion of TGF-β1 from the system results in improved bacterial clearance and lesion sterilization. We also identify a novel dichotomous regulation of cytotoxic T cells and macrophages by TGF-β1 and IL-10, respectively. These findings suggest that increasing cytotoxic T-cell effector functions may increase bacterial clearance in granulomas and highlight potential new therapeutic targets for treating TB. 

Retracted: No

PubPeer comments:
 Pseudoreplication using individual cells as experimental units, violation of independence assumption and use of parametric tests on those pseudo-replicated samples. The authors do not discuss this. Also, if you re going to treat individual cells as experimental units, your inference is going to be made to that culture experiment only... ,
A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy
Authors: Maiko Takiguchi
Yuji Baba
Masaki Yasukawa
Yasuyuki Miyake
Tokuyuki Shinohara
Kazuhide Nakayama
Suguru Arima
Yutaka Yasui
Tetsuya Nakatsura
Akira Hayashi
Yuta Mishima
Shin Kaneko
Shoichi Iriguchi
Tatsuki Ueda
Mihoko Kunitomo
Yoshiaki Kassai
Atsutaka Minagawa
Yohei Kawai
Takayuki Sato
Nariaki Yanagawa
Journal: Nature Communications (2021)
Discipline: Multidisciplinary
Keywords: Chimeric antigen receptor; T-cell immunotherapy; off-the-shelf; pluripotent stem cells; differentiation efficiency
Affiliations: Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan., Takeda-CiRA Joint Program (T-CiRA), Fujisawa, Japan., T-CiRA Discovery, Takeda Pharmaceutical Company, Fujisawa, Japan., Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan., Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Japan., Ehime Prefectural University of Health Sciences, Tobe, Japan., Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan. ., Takeda-CiRA Joint Program (T-CiRA), Fujisawa, Japan. .

Abstract:  Clinical successes demonstrated by chimeric antigen receptor T-cell immunotherapy have facilitated further development of T-cell immunotherapy against wide variety of diseases. One approach is the development of "off-the-shelf" T-cell sources. Technologies to generate T-cells from pluripotent stem cells (PSCs) may offer platforms to produce "off-the-shelf" and synthetic allogeneic T-cells. However, low differentiation efficiency and poor scalability of current methods may compromise their utilities. Here we show improved differentiation efficiency of T-cells from induced PSCs (iPSCs) derived from an antigen-specific cytotoxic T-cell clone, or from T-cell receptor (TCR)-transduced iPSCs, as starting materials. We additionally describe feeder-free differentiation culture systems that span from iPSC maintenance to T-cell proliferation phases, enabling large-scale regenerated T-cell production. Moreover, simultaneous addition of SDF1α and a p38 inhibitor during T-cell differentiation enhances T-cell commitment. The regenerated T-cells show TCR-dependent functions in vitro and are capable of in vivo anti-tumor activity. This system provides a platform to generate a large number of regenerated T-cells for clinical application and investigate human T-cell differentiation and biology. 

Retracted: No

PubPeer comments:
 Figure 1F and 1L, loading controls appear as they are the same (red boxes). Could the authors please check? P.S. correction issued nine years ago was about authoru2019s contribution ![file] ,
In vitro and in vivo pharmacokinetics and toxicity evaluation of curcumin incorporated titanium dioxide nanoparticles for biomedical applications
Authors: Rukhmini Sudha Devi
Sainulabdeen Sherin
Sreedharan Balachandran
Annie Abraham
Sathyabhama Sheeja
Rema Sreenivasan Soumya
Journal: Chemico-Biological Interactions (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Bioavailability; Cellular uptake; Curcumin; Genotoxicity; Titaniumdioxide nanoparticles.
Affiliations: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, India., Department of Chemistry, M G College, Thiruvananthapuram, India., Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, India. Electronic address: .

Abstract:  The present study deals with the preparation of stable Curcumin incorporated Titaniumdioxide Nanoparticles (CTNPs) by coprecipitation method for improving the bioavailability of curcumin and site specific drug delivery. The prepared nanoparticles were characterized by UV visible spectroscopy, FTIR, XRD, DLS, SEM and EDX. The characterization studies showed the interaction of curcumin to titanium dioxide nanoparticles. The average size of the prepared CTNPs was found to be ∼29 nm with zetapotential of-53.790 mV. In vivo and in vitro toxicological evaluations were carried out to determine the biological effect of CTNPs. In vitro parameters like cell viability, Lactate dehydrogenase (LDH) Assay, Neutral red uptake (NRU) assay and uptake of curcumin from CTNPs by the cells had been investigated. In vitro toxicity studies in THP1 and H9c2 cell lines showed that CTNPs are safe even at a dose of 200 ng. The in vivo part of the study was carried out with different doses of Curcumin (1 mg-20 mg/kg body weight), Titaniumdioxide Nanoparticles (TNPs) (1 mg-5 mg/kg Body weight) and CTNPs (5 mg-10 mg/kg Body weight) in Sprague dawley rat models to determine the pharmacokinetics and genotoxicity of the nanoparticle. This was done by analysing the parameters like SGPT, SGOT, LDH, hematological parameters and biodistribution of the nanomaterial at different organ sites. Genotoxicity of samples were done by comet assay on blood cells. No significant toxicity was observed in the parameters in samples treated group compared to controls. The overall results indicated that the CTNPs are nontoxic and is highly stable with improved site specific application compared to native curcumin and are suitable for biomedical applications. 

Retracted: No

PubPeer comments:
 Figure 3. * Red, cyan, and yellow boxes show possible overlaps between panels a, b, c, and d, suggesting four of the five panels are derived from the same sample. ![file] , 
 Figure 4. * Green boxes: Panels a and b appear to show an overlap * Orange boxes: Panels c and d appear to show an overlap ![file] ,
Solid-state dye-sensitized solar cells based on Zn1−xSnxO nanocomposite photoanodes
Authors: Mohamed F El-Shahat
Ayat Nasr El-Shazly
Elsayed Ali Abdel-Aal
Ahmed Esmail Shalan
Mohamed Mohamed Rashad
Ibrahim Ahmed Ibrahim
Journal: RSC Advances (2018)
Discipline: CHEMISTRY
Keywords: Solid-state dye-sensitized solar cells; Sn2+-substituted ZnO nanopowder; co-precipitation method; N719 ruthenium dye; spiro-OMeTAD
Affiliations: Central Metallurgical Research and Development Institute, Cairo, Egypt, Chemistry Department, Faculty of Science, Ain Shams University

Abstract:  Solid-state dye-sensitized solar cells (ss-DSSCs) comprising Sn2+-substituted ZnO nanopowder were purposefully tailored via a co-precipitation method. The solar cells assembled in this work were sensitized with N719 ruthenium dye and insinuated with spiro-OMeTAD as a solid hole transport layer (HTL). Evidently, significant enhancement in cell efficiency was accomplished with Sn2+ ions-substituted ZnO photoelectrodes by maintaining the weight ratio of SnO at 5%. The overall power conversion efficiency was improved from 3.0% for the cell with pure ZnO to 4.3% for the cell with 5% SnO substitution. The improvement in the cell efficiency with Sn2+-substituted ZnO photoelectrodes is attributed to the considerably large surface area of the nanopowders for dye adsorption, efficient charge separation and the suppression of charge recombination provided by SnO. Furthermore, the energy distinction between the conduction band edges of SnO and ZnO implied a type II band alignment. Moreover, the durability as well as the stability of 15 assembled cells were studied to show the outstanding long-term stability of the devices made of Sn2+ ion substituted ZnO, and the PCE of each cell remained stable and ∼96% of its primary value was retained for up to 100 h. Subsequently, the efficacy was drastically reduced to ∼35% after 250 h of storage. 

Retracted: No

PubPeer comments:
 Fig 6A, B.  (A) Protein bands and protein level of VEGF in corneal tissues after alkali burn; (B) protein bands and protein level of HIF-1u03b1 in corneal tissues after alkali burn. ![file] It appears that a single GAPDH loading band (where the lanes are different treatments) has been used to control three different VEGF bands, corresponding to corneas harvested at different dates of recovery from injury. Another GAPDH loading control has been used to control for three different HIF-1u03b1 bands. How does this work? ,
SNX8 modulates innate immune response to DNA virus by mediating trafficking and activation of MITA
Authors: Yun-Da Chen
Wei Guo
Li Zhong
Xia-Nan Zhang
Wei-Wei Luo
Ru Zang
Shu Li
Ming-Ming Hu
Huan Lian
Qing Yang
Jin Wei
Hong-Bing Shu
Journal: PLoS Pathogens (2018)
Discipline: MICROBIOLOGY
Keywords: MITA; STING; innate immune response; cytosolic DNA; cellular trafficking
Affiliations: Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China., College of Life Sciences, Wuhan University, Wuhan, China., Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

Abstract:  MITA (also called STING) is a central adaptor protein in innate immune response to cytosolic DNA. Cellular trafficking of MITA from the ER to perinuclear microsomes after DNA virus infection is critical for MITA activation and onset of innate antiviral response. Here we found that SNX8 is a component of DNA-triggered induction of downstream effector genes and innate immune response. Snx8-/- mice infected with the DNA virus HSV-1 exhibited lower serum cytokine levels and higher viral titers in the brains, resulting in higher lethality. Mechanistically, SNX8 recruited the class III phosphatylinositol 3-kinase VPS34 to MITA, which is required for trafficking of MITA from the ER to perinuclear microsomes. Our findings suggest that SNX8 is a critical component in innate immune response to cytosolic DNA and DNA virus. 

Retracted: No

PubPeer comments:
 According to figure legend of Fig.3A, the mice number is 10 in each group. But some survival rate are not multiple of 10% (blue and red arrow). Could authors explain how to get this survivorship curve? ![file] , 
 #1 We are sorry for a writing error in the figure legend.  n=10 should be  n=9 . The conclusion is not affected. Jin Wei, Shu Li, Hong-Bing Shu , 
 According to In-Silico PCR result, primers for GAPDH showed no amplification. Also, primers for IFNB1 amplification is on the revers complement of IFNB1. Those primers were used in other 2 studies by the same team (pmid: 30321235, 32415261). Could authors give an explanation? ![file] , 
 There is a typo in GAPDH reverse primer, the correct sequence should be  GAGTCAACGGATTTGGTCGT . The primers provided in this paper were blasted in NCBI. The primers work fine and have been frequently used by us and others. ,
Proprotein convertase 1/3 (PC1/3) in the rat alveolar macrophage cell line NR8383: localization, trafficking and effects on cytokine secretion
Authors: Michel Salzet
Sandra Gagnon
Robert Day
Roxane Desjardins
Hugo Gagnon
Sarah Refaie
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: PC1/3; post-translational processing enzyme; Toll-like receptor; innate immune response; macrophages
Affiliations: Institut de pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada.

Abstract:  The proprotein convertase 1/3 (PC1/3) is an important post-translational processing enzyme for the activation of precursor proteins within the regulated secretory pathway. Well characterized for its role in the neural and endocrine systems, we recently reported an unconventional role of PC1/3 as a modulator of the Toll-like receptor innate immune response. There are only a few reports that have studied PC1/3 expression in macrophages, and more investigation is needed to better characterize its function. These studies would greatly benefit from model cell lines. Our study aims to identify and characterize PC1/3 in a relevant model macrophage cell line and to determine the links between PC1/3 and innate immune cellular responses. We describe the rat alveolar cell line, NR8383, as expressing PC1/3 and the most common Toll-like receptors. In NR8383 cells, PC1/3 is localized at the Trans-Golgi network and traffics to lysosome related vesicles upon lipopolysaccharide stimulation. Moreover, we report the co-localization of PC1/3 and Toll-like receptor 4 upon lipopolysaccharide stimulation. Down regulation of PC1/3 by shRNA produce a similar phenotype in NR8383 to what we previously reported in isolated peritoneal macrophages. PC1/3 shRNA induced changes in the cellular organization and expression of the specific trafficking regulator RAB GTPase. As a consequence, NR8383 down-regulated for PC1/3, present an abnormal cytokine secretion profile. We conclude that the NR8383 cell line represents a good model to study PC1/3 in macrophages and we present PC1/3 as an important regulator of vesicle trafficking and secretion in macrophages. 

Retracted: No

PubPeer comments:
 Figure 1D * Red boxes: Lane 1 in the PC1 3 panel looks similar to lane 2 in the 18S panel * Blue boxes: Lane 1 in the 18S panel looks similar to lane 3 in the 18S panel ![file] , 
 Figure 2B. * Green arrows: the high MW bands in lanes NT and shPC1 3 are separated from the lower MW part of the gel by a sharp horizontal background transition ![file] , 
 #1 If you overlay both you will see that are different. The V Shaped of the PC1 3 result is more pronounced than the loading control you highlight. The results was also confirmed by QPCR in the paper. #2 It s an adjustment of the contrast to be able to see band below the very intense non-specific band on top. If you zoom you will see that the horizontal background transition is even between NT and shPC1 3 , 
 Dear Dr. Gagnon, do you have an update to share? Could you perhaps share the original blots here? , 
 #3 Here is a false color illustration that confirms for me the original concern about Figure 1D. *** ![file] ,
Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs
Authors: Zhipeng Fan
Khalid Al Hezaimi
Xuedong Zhou
Ling Ye
No-Hee Park
Bo Yu
Cun-Yu Wang
Jia Chang
Journal: Cell stem cell (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Human bone marrow; mesenchymal stem/stromal cells; MSCs; osteogenesis; adipogenesis
Affiliations: State Key Laboratory of Oral Disease and Department of Endodontics, West China School of Stomatology, Sichuan University; Chengdu, Sichuan 610041, China.

Abstract:  Human bone marrow mesenchymal stem/stromal cells (MSCs) are multipotent progenitor cells with multilineage differentiation potentials including osteogenesis and adipogenesis. While significant progress has been made in understanding transcriptional controls of MSC fate, little is known about how MSC differentiation is epigenetically regulated. Here we show that the histone demethylases KDM4B and KDM6B play critical roles in osteogenic commitment of MSCs by removing H3K9me3 and H3K27me3. Depletion of KDM4B or KDM6B significantly reduced osteogenic differentiation and increased adipogenic differentiation. Mechanistically, while KDM6B controlled HOX expression by removing H3K27me3, KDM4B promoted DLX expression by removing H3K9me3. Importantly, H3K27me3- and H3K9me3-positive MSCs of bone marrow were significantly elevated in ovariectomized and aging mice in which adipogenesis was highly active. Since histone demethylases are chemically modifiable, KDM4B and KDM6B may present as therapeutic targets for controlling MSC fate choices and lead to clues for new treatment in metabolic bone diseases such as osteoporosis. 

Retracted: No

PubPeer comments:
 Photographs of stainings from different conditions in Fig.3E F and Fig.S2B C are the same. Moreover, these photos were published before in 2009 (DOI:10.1038 ncb1913; Fig.1D and 4C) as completely different experiments. # **Fig.3** ![file] # **Fig.S2** ![file] # **Fig.1D** (DOI:10.1038 ncb1913) ![file] # **Fig.4C** (DOI:10.1038 ncb1913) ![file] , 
 Thank you very much for detecting our errors. We were able to locate our original images, and are working with the journal to make corrections. , 
 December 2018 correction, which is hard to find at the original paper s website: https: www.cell.com action showPdf?pii=S1934-5909%2818%2930538-1 It reads: *During the assembly of Figures 3E, 3F, S2B, and S2C, we inadvertently used the wrong control staining photographs (0 day wk panel). These control experiments were performed on separate plates from those used for the induction experiments, and the images were very similar. This resulted in a duplication of the control panels in Figures 3E and S2B, and a duplication of the control panels in Figures 3F and S2C. We have tracked down our original scans, and below we have replaced the control staining panels with the correct images. This does not affect our original conclusions. We sincerely apologize for any inconvenience this may have caused our readers.* Thank you, authors, for correcting the figures. ,
Lipopolysaccharide (LPS) regulates TLR4 signal transduction in nasopharynx epithelial cell line 5-8F via NFkappaB and MAPKs signaling pathways
Authors: Xiaolin Li
Houde Zhou
Chen Huang
Weisong Li
Ming Zhou
Minghua Wu
Cong Peng
Yanghong Zhou
He Huang
Yixin Yang
Guiyuan Li
Wei Xiong
Yunbo Yang
Zhaoyang Zeng
Journal: Molecular Immunology (2007)
Discipline: IMMUNOLOGY
Keywords: Lipopolysaccharide; Gram-negative bacteria; cytokines; proinflammatory genes; TLR4 signaling pathway
Affiliations: Cancer Research Institute, Central South University, 110 Xiangya Road, Changsha, 410078 Hunan, PR China.

Abstract:  The lipopolysaccharide (LPS) of Gram-negative bacteria induces the expression of cytokines and proinflammatory genes via the TLR4 signaling pathway in diverse cell types. The purpose of the present study was to test the hypothesis that the nasopharynx epithelial cells (NECs) could recognize and respond to LPS. The underlying molecular mechanisms were further elucidated in the NEC line 5-8F for its ability to activate the NFkappaB and TNF-alpha reporter genes, in response to LPS. After LPS stimulation, the TNF-alpha promoter activity and the relevant production of TNF-alpha were significantly increased in 5-8F cells. Moreover, LPS activated NFkappaB p65, ERK1/2 and JNK1/2 and induced their translocation to the nucleus. Western blot analysis showed that the expression of NFkappaB p65, MEK1, ERK1/2, JNK1/2, phospho-ERK1/2 and phospho-JNK1/2 proteins also was increased in NEC 5-8F cells, following the LPS stimulation. Additionally, the expression of TLR1-6, MD2 and CD14 was examined by RT-PCR, and the CD14 expression was determined by flow cytometry analysis. We demonstrated that the expression of CD14, TLR4 and MD2 was crucial for the NEC responses to LPS. In conclusion, our results provide novel mechanisms for the response of nasopharnyx epithelial cells to LPS stimulation, through NFkappaB and MAPKs signaling pathways. 

Retracted: No

PubPeer comments:
 For the HRTEM images in both supplementary Figure 45 and 46, all the claimed distance of lattice fringes for either Sn or SnO2 are quite weird. Based on the scale bar, the lattice d for Sn(200) and SnO2(110) is as high as 2.5-3.0 nm, really? Some of the lattice area is not clear to resolved the distance as well. Can the author check explain how this happened here? ![file] ![file] , 
 #1 In the original figures, we provided two lines in Figures S45 and S46 that indicate the crystal planes of Sn and of SnO2. There is more than one lattice fringe between each of the line pairs. To calculate the lattice spacing, we need to divide the distance between the two lines by the number of fringes. We now attach the original HRTEM images with analyses, and these show: - Materials marked in red font in the annotated images have line spacing 1.45 nm, 5 fringes, for a lattice spacing of 0.29 nm. This agrees with the lattice spacing of 2.91 u00c5 for Sn (200). - Materials marked in yellow in the annotated images have line spacing 1.70 nm, 5 fringes, for a lattice spacing of 0.34 nm. This agrees with the lattice spacing of 3.35 u00c5 for SnO2 (110). ![file] ![file] ![file] ![file] ![file] ![file] ,
Prediction-based neural mechanisms for shielding the self from existential threat
Authors: Y Dor-Ziderman
A Lutz
A Goldstein
Journal: NeuroImage (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: mortality; prediction-based mechanisms; death-denial; neuronal level; self-specific predictive processes
Affiliations: Gonda Brain Research Center, Bar Ilan University, Ramat-Gan, Israel. Electronic address: ., Lyon Neuroscience Research Center, INSERM, U1028, CNRS UMR5292, Lyon 1 University, Lyon, 69500, France., Gonda Brain Research Center, Bar Ilan University, Ramat-Gan, Israel; Department of Psychology, Bar Ilan University, Ramat-Gan, Israel.

Abstract:  The human mind has an automatic tendency to avoid awareness of its mortality. How this protective mechanism is implemented at the neuronal level is unknown. Here we test the hypothesis that prediction-based mechanisms mediate death-denial by shielding the self from existential threat. We provide evidence that self-specific predictive processes are downregulated during the perception of death-related linguistic stimuli and that this mechanism can predict fear-of-death. Using a magnetoencephalography visual mismatch paradigm, we show that the brain's automatic prediction response to deviancy is eliminated when death words and self-face representations are coupled, but remains present when coupled to other-face or to negative words. We further demonstrate a functional link between how death impacts self-image vs. Other-image, and show that it predicts fear-of-death. Finally, we confirm this effect in a behavioral active inference experiment showing that death-related words bias perceptual judgment on facial self and other morphed video clips. Together these results lay out, for the first time, a plausible neural-based mechanism of death-denial. 

Retracted: No

PubPeer comments:
 I wonder how the researchers controlled their experiment on the presence of a conscious brain that knows it is not dead? , 
 #1 Dear Sir Madam, I m not sure I understand your question. If you will clarify what is concerning you I will be happy to answer. Best wishes, Yair ,
Cytogenetic markers applied to cytotaxonomy in two soybean pests: Anticarsia gemmatalis (Hübner, 1818) and Chrysodeixis includens (Walker, 1858)
Authors: Jaqueline Fernanda Dionísio
Joana Neres Da Cruz Baldissera
Daniel Ricardo Sosa-Goméz
Brenda Rafaella Da Silva Magalhães
Matheus Pires Rincão
Felipe Cordeiro Dias
Renata Da Rosa
Journal: PLoS ONE (2020)
Discipline: Multidisciplinary
Keywords: Anticarsia gemmatalis; Chrysodeixis includens; Lepidoptera; chromosomal organization; cytogenetic markers
Affiliations: Laboratório de Citogenética Animal, Departamento de Biologia Geral, Universidade Estadual de Londrina, Brasil., Laboratório de Biologia Molecular de Artrópodes e Entomopatógenos, Embrapa Soja, Londrina, Brasil.

Abstract:  Anticarsia gemmatalis (Hübner, 1818) and Chrysodeixis includens (Walker, 1858) are species of Lepidoptera that cause great damages in the soybean plantations of Brazil. Despite the importance they have in this regard, there are no studies on the chromosomal organization of these species and recently, A. gemmatalis, which belonged to the Noctuidae family, was allocated to the Erebidae family. Therefore, the objective of this paper was to analyze, through conventional and molecular cytogenetic markers, both species of Lepidoptera. A 2n = 62 was observed, with ZZ/ZW sex chromosome system and holokinetic chromosomes for both species. There was homogeneity in the number of 18S rDNA sites for both species. However, variations in heterochromatin distribution were observed between both species. The cytogenetic analyses enabled separation of the species, corroborating the transference of A. gemmatalis, from the family Noctuidae to the family Erebidae, suggesting new cytotaxonomic characteristics. 

Retracted: No

PubPeer comments:
 Phylogeny in this manuscript is discussed in a confused manner.  Thus, our data support the proposed by Zahiri et al. [4], confirming the chromosome differentiation between the species studied and the phylogenetic position of the genus Anticarsia in Erebidae. - Anticarsia is in principle included in Noctuidae, no?  Thus, our cytogenetic data corroborate the new position of the species, and bring to light the differences between the representative species of the orders Erebidae and Noctuidae. - Erebidae and Noctuidae are *families*, not  orders . Maybe the authors were confusing concepts when discussing this part of the manuscript? ,