PReD-Bench/PRed-Bench huggingface dataset:
GADD45β Loss Ablates Innate Immunosuppression in Cancer
Authors: Mariafausta Fischietti
Federica Begalli
Marcella De Maglie
Jason Bennett
Stuart J Forbes
Guido Franzoso
Daria Capece
Daniel D&#x27;Andrea
Antonio Sica
Toby Lawrence
Francesca Zazzeroni
Davide Vecchiotti
Barbara Di Francesco
Camilla Recordati
Fabio Pasqualini
Daniela Verzella
Edoardo Alesse
Anil K Thotakura
Salvatore Papa
Laura Tornatore
Journal: Cancer Research (2018)
Discipline: CLINICAL MEDICINE
Keywords: T-cell exclusion; tumor microenvironment; myeloid-intrinsic mechanism; NF-κB effector molecule; GADD45β
Affiliations: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Centre for Cell Signalling and Inflammation, Department of Medicine, Imperial College London, London, United Kingdom., Mouse & Animal Pathology Laboratory, Fondazione Filarete, Milan, Italy., Department of Inflammation and Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy., Current address: Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, United Kingdom., Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Inserm, CNRS, Marseille, France., Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom., Department of Pharmaceutical Sciences, Università del Piemonte Orientale 'Amedeo Avogadro', Novara, Italy., Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.  ., Centre for Cell Signalling and Inflammation, Department of Medicine, Imperial College London, London, United Kingdom.  .

Abstract:  T-cell exclusion from the tumor microenvironment (TME) is a major barrier to overcoming immune escape. Here, we identify a myeloid-intrinsic mechanism governed by the NF-κB effector molecule GADD45β that restricts tumor-associated inflammation and T-cell trafficking into tumors. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma and ovarian adenocarcinoma, Gadd45b inhibition in myeloid cells restored activation of proinflammatory tumor-associated macrophages (TAM) and intratumoral immune infiltration, thereby diminishing oncogenesis. Our results provide a basis to interpret clinical evidence that elevated expression of GADD45B confers poor clinical outcomes in most human cancers. Furthermore, they suggest a therapeutic target in GADD45β for reprogramming TAM to overcome immunosuppression and T-cell exclusion from the TME.Significance: These findings define a myeloid-based immune checkpoint that restricts T-cell trafficking into tumors, with potentially important therapeutic implications to generally improve the efficacy of cancer immunotherapy. Cancer Res; 78(5); 1275-92. ©2017 AACR. 

Retracted: No

PubPeer comments:
 Figure 1A. https: imgur.com 2VqMrcn ,
The Yin Yang-1 (YY1) protein undergoes a DNA-replication-associated switch in localization from the cytoplasm to the nucleus at the onset of S phase
Authors: Hank W Bass
Myra M Hurt
Linda Palko
Maroun J Beyrouthy
Journal: Journal of Cell Science (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: YY1; zinc-finger transcription factor; cell cycle; DNA-binding activity; histone genes
Affiliations: Department of Biological Science, Florida State University, Tallahassee, Florida 32306-4370, USA.

Abstract:  The essential Yin Yang-1 gene (YY1) encodes a ubiquitous, conserved, multifunctional zinc-finger transcription factor in animals. The YY1 protein regulates initiation, activation, or repression of transcription from a variety of genes required for cell growth, development, differentiation, or tumor suppression, as well as from genes in some retroviruses and DNA viruses. Among the specific functions attributed to YY1 is a role in cell-cycle-specific upregulation of the replication-dependent histone genes. The YY1 protein binds to the histone alpha element, a regulatory sequence found in all replication-dependent histone genes. We therefore examined the abundance, DNA-binding activity and localization of the YY1 protein throughout the cell cycle in unperturbed, shake-off-synchronized Chinese hamster ovary and HeLa cells. We found that, whereas the DNA-binding activity of YY1 increased dramatically early in S phase, the YY1 mRNA and protein levels did not. YY1 changed subcellular distribution patterns during the cell cycle, from mainly cytoplasmic at G1 to mainly nuclear at early and middle S phase, then back to primarily cytoplasmic later in S phase. Nuclear accumulation of YY1 near the G1/S boundary coincided with both an increase in YY1 DNA-binding activity and the coordinate up-regulation of the replication-dependent histone genes. The DNA synthesis inhibitor aphidicolin caused a nearly complete loss of nuclear YY1, whereas addition of caffeine or 2-aminopurine to aphidicolin-treated cells restored both DNA synthesis and YY1 localization in the nucleus. These findings reveal a mechanism by which YY1 localization is coupled to DNA synthesis and responsive to cell-cycle signaling pathways. Taken together, our results provide insight into how YY1 might participate in the cell-cycle control over a variety of nuclear events required for cell division and proliferation. 

Retracted: No

PubPeer comments:
 ![file] ,
MicroRNA-218 modulates activities of glioma cells by targeting HMGB1
Authors: Yaxing Li
Shousen Wang
Rong Xu
Jianjun Gu
Jianhe Zhang
Journal: American journal of translational research (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: apoptosis; glioma; high mobility group box 1 (HMGB1); invasion; microRNA-218
Affiliations: Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College 156 Road Xi'erhuanbei, Fuzhou 350025, Fujian, P. R. China., Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University Shanghai 200040, P. R. China., Department of Oncology, Taizhou People's Hospital Affiliated to Medical College of The Nantong University Taizhou 225300, Jiangsu, P. R. China.

Abstract:  To explore the effects of microRNA-218 (miR-218) on glioma cell lines and the related mechanism. U251 and U87 cells were transfected with negative control, miR-218 mimic or miR-218 inhibitor using lipofectamine 2000. The expressions of mRNA and proteins were detected with qRT-PCR and Western blotting. The cell proliferation, apoptosis, migration and invasion were studied using MTT, flow cytometry, Transwell assay and scratch-wound assay, respectively. The targeting effect of HMGB1 by miR-218 was measured with luciferase reporter assay. The results showed that miR-218 was significantly downregulated while HMGB1 was upregulated in both glioma cell lines. Transfection of miR-218 significantly reduced the cell viability and colony formation, increased cell apoptosis and arrested cell in G0/G1 phase. Transfection of miR-218 also decreased the invasion and migration of glioma cells. The expressions of HMGB1, RAGE, cyclin D1 and MMP-9 were downregulated while the expression of caspase-9 was upregulated by miR-218. Silencing HMGB1 increased the expression of RAGE, cyclin D1, MMP-9 but decreased the expression of caspase-9 in U251 and U87 cells. Co-transfection with pcHMGB1 and miR-218 significantly decreased the growth inhibition and increased the apoptosis of glioma cells while these effects were abolished in glioma cells co-transfected with HMGB1 siRNA and miR-218 inhibitor. In addition, co-transfection with pcHMGB1 and miR-218 inhibitor increased the invasiveness of U251 and U87 cells. These findings suggested that miR-218 may negatively regulate HMGB-mediated suppression of RAGE to regulate cell proliferation, apoptosis and invasion, and that intervention of miR-218-HMGB1-RAGE may be useful for developing potential clinical strategies. 

Retracted: No

PubPeer comments:
 Two of the U87 panels: ![file] I have not tried to mark all copies of the tuning fork cell. , 
 Fig 6.  Showing the effects of different treatments on the... invasion (E, F) of U85 and U251 cells . ![] Unexpected appearance of a cluster of cells in two unrelated panels (with 180-deg flip). Unexpected similarity within the U251 NC panel: ![file] ,
Electron Transport Chain Complex II Regulates Steroid Metabolism
Authors: Randy M Whittal
Brendan Marshall
Dilip K Debnath
Elizabeth W Perry
Himangshu S Bose
Journal: iScience (2020)
Discipline: Multidisciplinary
Keywords: Biochemistry; Biological Sciences; Molecular Biology.
Affiliations: Biomedical Sciences, Mercer U School of Medicine, Memorial University Medical Center, 1250 East 66th Street, Savannah, GA 31404, USA; Anderson Cancer Institute, Savannah, GA, USA. Electronic address: ., Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA, USA., Biomedical Sciences, Mercer U School of Medicine, Memorial University Medical Center, 1250 East 66th Street, Savannah, GA 31404, USA., Department of Chemistry, University of Alberta, Edmonton, Canada.

Abstract:  The first steroidogenic enzyme, cytochrome P450-side-chain-cleavage (SCC), requires electron transport chain (ETC) complexes III and IV to initiate steroid metabolic processes for mammalian survival. ETC complex II, containing succinate dehydrogenase (quinone), acts with the TCA cycle and has no proton pumping capacity. We show that complex II is required for SCC activation through the proton pump, generating an intermediate state for addition of phosphate by succinate. Phosphate anions in the presence of succinate form a stable mitochondrial complex with higher enthalpy (-ΔH) and enhanced activity. Inhibition of succinate action prevents SCC processing at the intermediate state and ablates activity and mitochondrial protein network. This is the first report directly showing that a protein intermediate state is activated by succinate, facilitating the ETC complex II to interact with complexes III and IV for continued mitochondrial metabolic process, suggesting complex II is essential for steroid metabolism regulation. 

Retracted: No

PubPeer comments:
 Fig 2C.  Hoechst 33342 dye exclusion assay showing the effect of miR-1207 overexpression cells or vector cells on the distribution of SP+ (C) and CD133+ cells (D) determined using flow cytometric analysis . ![file] Fig 2C from [Zhou et al (2015)] .  Hoechst 33342 dye exclusion assay showing the effect of pMSCV-miR-744-overexpressing cells or pMSCV-vector cells on side population cells . ![file] Different experiments at different institutions. No authors in common. One panel is the same. ![file] , 
 Fig 3C from [Zhao et al (2015)] . ![file] Fig 3C. ![file] Three panels are shared. ,
Withdrawn: Hair Analysis for Drug‐Facilitated Crime: The Critical Role of Hair Growth Rate
Authors: Karen Maman
Gideon Koren
Elad Bellaish
Journal: Journal of Forensic Sciences (2019)
Discipline: CLINICAL MEDICINE
Keywords: 7 amino flunitrazepam; benzodiazepines; drug-facilitated crime; flunitrazepam; forensic science
Affiliations: Maccabi Kahn Research Institute, 4 Koifman Street, 8th Floor, Tel Aviv, Israel., Israeli Ministry of Law, Nazeret Ilit, Israel 21735-070.

Abstract:  Hair analysis is increasingly used in detecting drug-facilitated crime (DFC) claiming success in identifying even single dose exposures. The calculation of accurate deposition time of the drug in hair is typically based on the assumption of mean hair growth of 1 cm/month. We describe a case of potential exposure to flunitrazepam. Assuming the literature average hair growth rate of 1 cm/month, the alleged victim had measurable amounts of the 7 amino flunitrazepam a month after the alleged drug exposure. However, in this case, due to hair dying, the true growth rate could be quantified at 1.5 cm/month. This difference has led to different interpretation from the one based on the average assumed hair growth of 1 cm/month. In conclusion, hair growth rate can be a critical variable in verifying the alleged time of drug exposure. 

Retracted: No

PubPeer comments:
 Withdrawn, on account of litigation. The following article from the Journal of Forensic Sciences, u201cHair Analysis for Drug-Facilitated Crime: The Critical Role of Hair Growth Rateu201d by Koren G, Bellaish E, Maman K, published online on 3rd September 2019 (1) on Wiley Online Library has been withdrawn at the authorsu2019 request, and in agreement between the authors, the Journalu2019s Editorial Office, and John Wiley Sons, Inc. The withdrawal has been agreed to by all parties due to material included in the article being involved in current litigation. ,
Inhibition of adipogenic differentiation of human SGBS preadipocytes by androgen-regulated microRNA miR-375
Authors: Matthias Kraus
Carina Wenzel
Thomas Greither
Martin Wabitsch
Hermann M Behre
Daniela Bräuer-Hartmann
Journal: Molecular and cellular endocrinology (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ADIPOR2; Androgens; Insulin resistance; Late-onset hypogonadism; miR-375.
Affiliations: Center for Reproductive Medicine and Andrology of the Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle, Germany., Division of Hematology and Oncology, University of Leipzig, Johannisallee 32a, 04103 Leipzig, Germany., Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Eythstr. 24, 89075 Ulm, Germany., Center for Reproductive Medicine and Andrology of the Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle, Germany. Electronic address: .

Abstract:  Late-onset hypogonadism (LOH), defined as a combination of low serum testosterone (T) levels in combination with clinical signs and symptoms of androgen deficiency in ageing men, is nowadays a well-characterized disease. Testosterone therapy in males affected by hypogonadism leads to a significant decrease of fat mass. In humans, the exact molecular mechanism of T effects on inhibition of adipogenesis is still unknown. We hypothesized that specific microRNAs could be regulated by androgens which might cause an inhibition of adipogenic differentiation. To confirm this hypothesis, human mesenchymal stem cells and a preadipocyte cell line were differentiated into mature adipocytes and in parallel treated with testosterone and dihydrotestosterone. The expression level of miR-375 was upregulated during adipogenic differentiation and downregulated after androgen treatment. Furthermore, we could show that after androgen treatment the decreased expression of miR-375 led to increased expression levels of adiponectin receptor 2 (ADIPOR2) compared to untreated adipocytes. Moreover, inhibition of miR-375 also mediated a decreased adipogenic differentiation and increased ADIPOR2 expression levels. In summary, we identified miR-375 as an androgen regulated microRNA, which could play an important role for understanding the mechanism of the increase in visceral fat mass and the associated insulin resistance caused by testosterone deficiency. 

Retracted: No

PubPeer comments:
 There is a set of repeated bands in Figure 1 that are more similar than can be expected by chance. ![file] ,
GX1-conjugated poly(lactic acid) nanoparticles encapsulating Endostar for improved in vivo anticolorectal cancer treatment
Authors: Chongwei Chi
Jie Tian
Yaqian Li
Xiaolong Liang
Qian Zhang
Xin Yang
Zhifei Dai
Lijia Jing
Yang Du
Journal: International Journal of Nanomedicine (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Endostar; GX1 peptide; IRDye 800CW; angiogenesis; colorectal cancer
Affiliations: Key laboratory of Molecular Imaging, The state Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People's Republic of China., Department of Biomedical Engineering, College of Engineering, Peking University, Beijing People's Republic of China.

Abstract:  Tumor angiogenesis plays a key role in tumor growth and metastasis; thus, targeting tumor-associated angiogenesis is an important goal in cancer therapy. However, the efficient delivery of drugs to tumors remains a key issue in antiangiogenesis therapy. GX1, a peptide identified by phage-display technology, is a novel tumor vasculature endothelium-specific ligand and possesses great potential as a targeted vector and antiangiogenic agent in the diagnosis and treatment of human cancers. Endostar, a novel recombinant human endostatin, has been shown to inhibit tumor angiogenesis. In this study, we developed a theranostic agent composed of GX1-conjugated poly(lactic acid) nanoparticles encapsulating Endostar (GPENs) and labeled with the near-infrared dye IRDye 800CW to improve colorectal tumor targeting and treatment efficacy in vivo. The in vivo fluorescence molecular imaging data showed that GPENs (IRDye 800CW) more specifically targeted tumors than free IRDye 800CW in colorectal tumor-bearing mice. Moreover, the antitumor efficacy was evaluated by bioluminescence imaging and immunohistology, revealing that GPENs possessed improved antitumor efficacy on subcutaneous colorectal xenografts compared to other treatment groups. Thus, our study showed that GPENs, a novel GX1 peptide guided form of nanoscale Endostar, can be used as a theranostic agent to facilitate more efficient targeted therapy and enable real-time monitoring of therapeutic efficacy in vivo. 

Retracted: No

PubPeer comments:
 In Figure 7, two images of a mouse are identical except for the bioluminescence signal. ![file] , 
 In Figure 5A the upper portion of one image appears to be spliced (red arrow) from another image. White arrows in original. *** ![file] , 
 #2 ![file] ,
Beta1-adrenergic receptors promote focal adhesion signaling downregulation and myocyte apoptosis in acute volume overload
Authors: Steven R Houser
Mikhail A Kolpakov
Abdelkarim Sabri
Rachid Seqqat
Khadija Rafiq
Jianfen Guo
Walter J Koch
Louis J Dell&#x27;italia
Xinji Guo
Journal: Journal of Molecular and Cellular Cardiology (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: extracellular matrix (ECM); focal adhesion (FA); beta1-adrenergic receptors (β(1)-ARs); myocyte apoptosis; hemodynamic stress
Affiliations: Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA.

Abstract:  Numerous studies demonstrated increased expression of extracellular matrix (ECM) proteins and activation of focal adhesion (FA) signaling pathways in models of pressure overload-induced cardiac hypertrophy. However, little is known about FA signaling in response to volume overload where cardiac hypertrophy is associated with ECM loss. This study examines the role of beta1-adrenergic receptors (β(1)-ARs) in FA signaling changes and myocyte apoptosis induced during acute hemodynamic stress of volume overload. Rats with eccentric cardiac hypertrophy induced after aorto-caval fistula (ACF) develop reduced interstitial collagen content and decreased tyrosine phosphorylation of key FA signaling molecules FAK, Pyk(2) and paxillin along with an increase in cardiac myocyte apoptosis. ACF also increased activation of PTEN, a dual lipid and protein phosphatase, and its interaction with FA proteins. β(1)-AR blockade (extended-release of metoprolol succinate, 100mg QD) markedly attenuated PTEN activation, restored FA signaling and reduced myocyte apoptosis induced by ACF at 2days, but failed to reduce interstitial collagen loss and left ventricular dilatation. Treating cultured myocytes with β(1)-AR agonists or adenoviral expression of β(1)-ARs caused PTEN activation and interaction with FA proteins, thus leading to FA signaling downregulation and myocyte apoptosis. Adenoviral-mediated expression of a catalytically inactive PTEN mutant or wild-type FAK restored FA signaling downregulation and attenuated myocyte apoptosis induced by β(1)-ARs. Collectively, these data show that β(1)-AR stimulation in response to ACF induces FA signaling downregulation through an ECM-independent mechanism. This effect involves PTEN activation and may contribute to adverse cardiac remodeling and function in the course of volume overload. 

Retracted: No

PubPeer comments:
 Figure 4C. Much more similar than expected. https: imgur.com IFeRq2l , 
 Figure 4F. Much more similar than expected. https: imgur.com Wj7Est7 ,
Evaluation of Single-Cell Cytokine Secretion and Cell-Cell Interactions with a Hierarchical Loading Microwell Chip
Authors: Ning Shao
Pengchao Zhang
Xin Liu
Lidong Qin
Ricardo Bessa de Castro
Yuan Ma
Feizhou Huang
Yufu Zhou
Rong-Fu Wang
Journal: Cell Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: T cell function; adoptive cell therapy; cell-bead pairing; cell-cell interaction; cytokine detection
Affiliations: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; The Third Xiangya Hospital, Central South University, Changsha 410008, China; Center for inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA., Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA., Center for inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Medicine and Norris Comprehensive Cancer Center, The Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., The Third Xiangya Hospital, Central South University, Changsha 410008, China., Center for inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Pediatrics, Children's Hospital of Los Angeles, The Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA; Department of Medicine and Norris Comprehensive Cancer Center, The Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: ., Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: .

Abstract:  Comprehensive evaluation of single T cell functions such as cytokine secretion and cytolysis of target cells is greatly needed in adoptive cell therapy (ACT) but has never been fully fulfilled by current approaches. Herein, we develop a hierarchical loading microwell chip (HL-Chip) that aligns multiple cells and functionalized beads in a high-throughput microwell array with single-cell/bead precision based on size differences. We demonstrate the potential of the HL-Chip in evaluating single T cell functions by three applications: high-throughput longitudinal secretory profiling of single T cells, large-scale evaluation of cytolytic activity of single T cells, and integrated T cell-tumor cell interactions. The HL-Chip is a simple and robust technology that constructs arrays of defined cell/object combinations for multiple measurements and material retrieval. 

Retracted: No

PubPeer comments:
 In Figure 1, the beads laying in the so called microwell chip do not look like beads, but perfect circles. The size of the microwell chip is not impressive given the presented scale bars... ![file] ,
Distinct and redundant roles of the two protein kinase A isoforms Tpk1p and Tpk2p in morphogenesis and growth of Candida albicans
Authors: A Sonneborn
J F Ernst
S Krishnamurthy
M Gerads
D P Bockmühl
Journal: Molecular Microbiology (2002)
Discipline: MICROBIOLOGY
Keywords: TPK1; TPK2; protein kinase A; Candida albicans; hyphal morphogenesis
Affiliations: Institut für Mikrobiologie, Heinrich-Heine-Universität, Universitätsstr. 1/26.12, 40225 Düsseldorf, Germany.

Abstract:  TPK1 and TPK2 encode both isoforms of protein kinase A (PKA) catalytic subunits in Candida albicans. Mutants lacking both TPK1 alleles showed defective hyphal morphogenesis on solid inducing media, whereas in liquid hypha, formation was affected slightly. In contrast, tpk2 mutants were only partially morphogenesis defective on solid media, whereas a strong block was observed in liquid. In addition, the yeast forms of tpk2-- but not tpk1-- mutants were completely deficient in invading agar. Because Tpk1p and Tpk2p differ in their N-terminal domains of approximately 80--90 amino acids, while the catalytic portions are highly homologous, the functions of hybrid Tpk proteins with exchanged N-terminal domains were tested. The results demonstrate that the catalytic portions mediate Tpk protein specificities with regard to filamentation, whereas agar invasion is mediated by the N-terminal domain of Tpk2p. Homozygous tpk1 and tpk2 mutants grew normally; however, a tpk2 mutant strain containing a single regulatable TPK1 allele (PCK1p-TPK1) at low expression levels was severely growth defective. It was completely blocked in hyphal morphogenesis and was stress resistant to high osmolarities or temperatures. Thus, both Tpk isoforms in C. albicans share growth functions but, unlike Saccharomyces cerevisiae isoforms, they have positive, specific roles in filament formation in different environments. 

Retracted: No

PubPeer comments:
 Figures 6, 7, and 8 * Boxes of the same color highlight panels that look similar. The orange and blue boxed-panels might represent the same experiments, but I am not sure about the other ones. Could the authors please clarify? ![file] ,
MicroRNA-424 inhibits cell migration, invasion and epithelial-mesenchymal transition in human glioma by targeting KIF23 and functions as a novel prognostic predictor
Authors: Y-H Zhang
X-B Wang
C Zhao
W-C Yao
Q Yin
Y-M Zhou
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-424; glioma; KIF23; tumor-suppressor; metastasis
Affiliations: Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, China. .

Abstract:  Objective: To investigate the expressions, biological effects and potential mechanism of miR-424 in glioma. Methods and methods: A total of 54 glioma tissues and 12 normal brain tissues were collected. Human glioma cells (A172, SHG-44, T98, LN18, and LN229) and normal human astrocytes (NHAs) were cultured. Cell invasion and migration capacities were detected by transwell assay. KIF23 was predicted and confirmed as a direct target of miR-424 by TargetScan prediction and Dual-luciferase reporter assay. Six-week-old female nude mice were used for Xenograft tumor formation assay. Results: Results of this study demonstrated a significant decrease of miR-424 expressions both in glioma cells and tissues. Moreover, the declined miR-424 expressions were observed to be correlated with the poor OS and worse clinicopathological parameters of glioma patients. Functional assays indicated that miR-424 restoration could inhibit the glioma cell epithelial-to-mesenchymal transition (EMT) and metastasis, as well as the tumor growth rate and tumor size of glioma mice. Additionally, kinesin family member 23 (KIF23) expressions were found to be significantly enhanced in glioma specimens, and KIF23 was considered to be a functional target for miR-424 in glioma. Conclusions: MiR-424, considered as a tumor-suppressor, inhibited cell metastasis and EMT by targeting KIF23 in glioma, which may provide a novel insight into tumorigenesis and the basis for the development of miRNA-targeting therapies against glioma. 

Retracted: No

PubPeer comments:
 Figure 2E appears to have an image duplication ![file] ,
The long non-coding RNA-ROR promotes osteosarcoma progression by targeting miR-206
Authors: Zhao Dongxu
Long Tan
Dan Fei
Kewei Zhang
Guoqing Sui
Yang Lu
Journal: Journal of Cellular and Molecular Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ROR; invasion; lncRNA; miR-206; osteosarcoma
Affiliations: Ultrasonographic Department, China-Japan Union Hospital of Jilin University, Changchun, P.R. China., Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, P.R. China., Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, P.R. China.

Abstract:  The long intergenic non-protein coding RNA regulator of reprogramming (lncRNA-ROR) has been reported to play crucial regulatory roles in the pathogenesis and progression of multiple cancers. However, whether ROR is associated with the initiation and development of osteosarcoma (OS) remains unclear. Here, we found that ROR expression level was significantly up-regulated in OS tissue samples compared to adjacent normal tissues, and the elevated ROR was closely correlated with advanced tumour-node-metastasis (TNM) stage and lymph node metastasis and poor overall survival rate. Functional assays showed that ROR knockdown suppressed the OS cell proliferation, colony formation, migration and invasion in vitro, and retarded tumour growth in vivo. In addition, miR-206 was verified to be a target miRNA of ROR using bioinformatics online program and luciferase report assay. miR-206 inhibition partially rescued the inhibitory effects on OS cells induced by ROR knockdown. In conclusion, these results suggested that ROR function as an oncogene in OS by sponging miR-206 and might be a potential therapeutic target for patients with OS. 

Retracted: No

PubPeer comments:
 *[right]* Fig 2C.  Colony formation assay was employed to evaluate the effect of ROR knockdown on U2OS cell colony formation. *[left]* Fig 2C from [Lin et al (2017)] .  Estimation of colonies in SKOV3 cells stable expressing miR-363 and miR-NC . ![file] Quite different experiments, no authors in common, a panel shared in common. However, the repeated details on other panels cast suspicion on the authenticity of these images. , 
 Fig 6B.  The tumour image . ![file] This appears to be a composite of photographs taken on different occasions, with different lighting conditions, hence the absence of any consistent direction of shadowing. This reduces the value of including a ruler in the composition. , 
 *[left]* Fig 3B,  Transwell invasion assay was employed to evaluate the effect of ROR knockdown on U2OS cell invasive capacity . *[right]* Fig 5a b from  The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K AKT signaling in hepatocellular carcinoma ([Huang et al 2018] ). ![file] Panels match apart from flips and manipulation. , 
 *[left]* Fig 6D. The panels were sourced from *[right]* Fig 6C of  HMGA1 exacerbates tumor growth through regulating the cell cycle and accelerates migration invasion via targeting miR-221 222 in cervical cancer ([Fu et al 2018] ). ![file] ,
The Protective Effect of Mitochondrial ATP-Sensitive K+ Channel Opener, Nicorandil, Combined With Na+/Ca2+ Exchange Blocker KB-R7943 on Myocardial Ischemia–Reperfusion Injury in Rat
Authors: Dalin Jia
Journal: Cell Biochemistry and Biophysics (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: mitochondrial ATP-sensitive K(+) channel; nicorandil; Na(+)/Ca(2+) exchange blocker; myocardial ischemia-reperfusion injury; rat hearts
Affiliations: Department of Cardiology, The First Affiliated Hospital, University of China Medical, China Medical University, 155th North of Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China. 

Abstract:  To study the protective effect of mitochondrial ATP-sensitive K(+) channel (mitoK(ATP) channel) opener, nicorandil, combined with Na(+)/Ca(2+) exchange blocker KB-R7943 on myocardial ischemia-reperfusion injury in isolated rat hearts; the isolated rat heart was perfused by modified Langendorff device, after 15-min balanced perfusion, 45-min ischemia (about left and right coronary perfusion flow reduced to 5% of the original irrigation flow), and 2-h reperfusion were performed. Forty Wistar rats were randomly divided into four groups: control group, nicorandil group, KB-R7943 group, and the combination of nicorandil and KB-R7943 group. After 45-min ischemia and then 2-h reperfusion, the myocardial infarct size was 34.31% in control group, 26.35% in nicorandil group, 28.74% in KB-R7943 group, and 19.23% in combination of nicorandil and KB-R7943 group. SOD activity in coronary perfusion fluid was the highest in the combination of nicorandil and KB-R7943 group, and MDA content was the lowest. In the combination drug group compared with the control group, myocardial ultrastructural injury was significantly reduced. The combination of nicorandil and KB-R7943 significantly reduced myocardial infarct size, significantly reduced myocardial ultrastructural damage, could increase coronary perfusion fluid SOD activity, and reduced MDA levels. 

Retracted: No

PubPeer comments:
 The images in figure 1B and 1C appear to overlap. *** Closeup ![file] *** Full figure ![file] ,
Comprehensive Modeling in Predicting Biodiesel Density Using Gaussian Process Regression Approach
Authors: Issam Alruyemi
Bingxian Wang
Journal: BioMed Research International (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Gaussian process regression; biodiesel density; kernel functions; pressure; temperature
Affiliations: School of Mathematics and Statistics, Huaiyin Normal University, Huaian, Jiangsu 223300, China, Fouman Faculty of Engineering, College of Engineering, University of Tehran, Fouman, Iran

Abstract:  In this study, four Gaussian process regression (GPR) approaches by various kernel functions have been proposed for the estimation of biodiesel density as the functions of pressure, temperature, molecular weight, and the normal melting point of fatty acid esters. Comparing the actual values with GPR outputs shows that these approaches have good accuracy, but the performance of the rational quadratic GPR model is better than others. In this GPR model, RMSE = 0.47, MSE = 0.22, MRE = 0.04, R 2 = 1, and STD is equal to 0.3. In addition, for the first time, this study shows that the effective parameters affect the biodiesel density. According to this analysis, it was shown that among the input parameters, pressure has the greatest effect on the target values with a relevancy factor of 0.59. This study can be used as a suitable and valuable work/tool for chemical and petroleum engineers who attempt environment protection and recovery improvement. 

Retracted: No

PubPeer comments:
 I don t really understand why the authors use reservoir simulation paper in here. ![file] ![file] ,
Retracted: The Role of MicroRNA‐143‐5p in the Differentiation of Dental Pulp Stem Cells into Odontoblasts by Targeting Runx2 via the OPG / RANKL Signaling Pathway
Authors: Fu-Liang Zhan
Xing-Bo Wang
Xin-Yang Liu
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DENTAL PULP REGENERATION; DENTAL PULP STEM CELLS; MICRORNA-143-5P; OPG/RANKL SIGNALING PATHWAY; RUNT-RELATED TRANSCRIPTION FACTOR 2.
Affiliations: Department of Endodontics, School of Stomatology, China Medical University, Shenyang, 110002, P.R. China.

Abstract:  This study aims to elucidate the mechanisms by which microRNA-143-5p (miR-143-5p) targets runt-related transcription factor 2 (Runx2) in the differentiation of dental pulp stem cells (DPSCs) into odontoblasts, through regulating the osteoprotegerin receptor activator of the nuclear factor-κB ligand (OPG/RANKL) signaling pathway. Following transfection, DPSCs were divided into blank, control, miR-143-5p mimics, miR-143-5p inhibitors, miR-143-5p inhibitors + siRunx2 and siRunx2 groups. Alkaline phosphatase (ALP) activity and mineralized nodules were detected using ALP kit and alizarin red staining. Quantitative reverse transcriptase real time PCR (qRT-PCR) was conducted to measure mRNA expressions of miR-143-5p, Runx2, OPG, and RANKL. Western blotting was used to assess protein expression of odontoblast differentiation-related proteins. Transwell assay and an extracellular matrix (ECM) adhesion cell assay were employed to examine cell migration and cell adhesion. Compared with the blank group, the miR-143-5p mimics and siRunx2 groups showed decreased ALP activity, decreased mineralized nodules and displays of calcium. Fewer migrated cells, weakened cell adhesion, decreased protein expression of dentin phosphoprotein (DPP), dentin sialoprotein (DSP), dentin matrix protein 1 (DMP1), osteopontin (OPN), bone sialoprotein (BSP), osteocalcin (OCN), OPG and Runx2, and increased RANKL protein expressions were observed. Additionally, opposite results were observed in the miR-143-5p inhibitors group, demonstrating that down-regulated miR-143-5p promotes the differentiation of DPSCs into odontoblasts by enhancing Runx2 expression via the OPG/RANKL signaling pathway. Based on findings in this study, it is postulated that the enhancement of Runx2 expression via the regulation of the OPG/RANKL signaling pathway could be a beneficial approach for dental pulp regeneration. J. Cell. Biochem. 119: 536-546, 2018. © 2017 Wiley Periodicals, Inc. 

Retracted: Yes

PubPeer comments:
 See https: doi.org 10.35122 jospi.2019.1.875441 (open access) for extensive comments on this article. ,
Development, characterization and in vivo assessment of effective lipidic nanoparticles for dermal delivery of fluconazole against cutaneous candidiasis
Authors: Madhu Gupta
Suresh P Vyas
Journal: Chemistry and physics of lipids (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Nanoparticulate carrier systems; solid lipid nanoparticles; nanostructured lipid carriers; skin penetration; fluconazole
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Viswavidyalaya, Sagar 470 003, MP, India. 

Abstract:  The nanoparticulate carrier systems as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have gained interest for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Therefore in this study, SLNs and NLCs loaded fluconazole (FLZ) were prepared by solvent diffusion method in an aqueous system and characterized for different parameters. In addition, antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed albino rats. The results showed that SLNs and NLCs represent the respective mean particle sizes of approx. 178 and 134 nm with encapsulation efficiency of 75.7±4.94% and 81.4±3.89%, respectively. The skin-retention studies of FLZ from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of NLCs formulation. The in vivo cumulative amount of FLZ retention from NLCs was more than 5-fold that of the plain solution, while it was 3.3-fold more in the case of an equivalent-dose application in the form of SLNs at 12h after administration. The antifungal study also confirmed the maximum therapeutic efficacy of NLCs, as the lowest number of cfu/ml was recorded. It can be concluded from this study that NLCs provide a good skin targeting effect and may be a promising carrier for topical delivery of FLZ offering the sustained release and maintain the localized effect, resulting in an effective treatment of a life-threatening cutaneous fungal infection. 

Retracted: No

PubPeer comments:
  Fig. 1. SEM photographs of FLZ loaded ... NLCs formulations (B) ![file] The boxed part reappears, heavily revised, as Fig 2(a) of [Gupta et al (2014)] . ![] ,
Low-dose X-ray radiotherapy–radiodynamic therapy via nanoscale metal–organic frameworks enhances checkpoint blockade immunotherapy
Authors: Chunbai He
Yang-Xin Fu
Michael T Spiotto
Guangxu Lan
Charles Pelizzari
Haidong Tang
Christina Chan
Ralph R Weichselbaum
Wenbin Lin
Nining Guo
Kaiyuan Ni
Kuangda Lu
Journal: Nature Biomedical Engineering (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Checkpoint blockade immunotherapy; cytotoxic T cells; tumour tissue; T cell infiltration; radiotherapy
Affiliations: Department of Chemistry, The University of Chicago, Chicago, IL, USA., The Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, USA., Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA., Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Chemistry, The University of Chicago, Chicago, IL, USA. .

Abstract:  Checkpoint blockade immunotherapy relies on energized cytotoxic T cells attacking tumour tissue systemically. However, for many cancers, the reliance on T cell infiltration leads to low response rates. Conversely, radiotherapy has served as a powerful therapy for local tumours over the past 100 years, yet is rarely sufficient to cause systemic tumour rejection. Here, we describe a treatment strategy that combines nanoscale metal-organic framework (nMOF)-enabled radiotherapy-radiodynamic therapy with checkpoint blockade immunotherapy for both local and systemic tumour elimination. In mouse models of breast and colorectal cancer, intratumorally injected nMOFs treated with low doses of X-ray irradiation led to the eradication of local tumours and, when loaded with an inhibitor of the immune checkpoint molecule indoleamine 2,3-dioxygenase, the irradiated nMOFs led to consistent abscopal responses that rejected distal tumours. By combining the advantages of local radiotherapy and systemic tumour rejection via synergistic X-ray-induced in situ vaccination and indoleamine 2,3-dioxygenase inhibition, nMOFs may overcome some of the limitations of checkpoint blockade in cancer treatment. 

Retracted: No

PubPeer comments:
 For Supplementary Figure 26, the CT scan images at Day 0.5 and Day 1.5 is totally the same, while obvious changes were observed for longer term retention. Could the author clarify this is normal condition or misuse of duplicated images? ![file] ,
Expression of NF-κB in juvenile rats with nephrotic syndrome and its effects on inflammatory changes and renal injury
Authors: Z-Y Li
J Wu
C-J Yuan
X-M Sun
X-H Sun
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: NF-κB; nephrotic syndrome; inflammatory changes; renal injury; Sprague-Dawley rats
Affiliations: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China. .

Abstract:  Objective: The aim of this study was to investigate the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in juvenile rats with nephrotic syndrome, and to explore its effects on inflammatory changes and renal injury. Materials and methods: 24 Sprague-Dawley (SD) rats were randomly divided into the normal group (n=12) and model group (n=12). Rats in the normal group were intraperitoneally injected with normal saline. Meanwhile, rats in the model group were given azithromycin hydrochloride injection to establish the model of nephrotic syndrome. After 24 h of modeling, the samples were collected. The expression of NF-κB was detected via immunohistochemistry. Moreover, the protein expression of NF-κB was determined through Western blotting. Quantitative Polymerase Chain Reaction (qPCR) was used to measure the messenger ribonucleic acid (mRNA) expression levels of interleukin-1 (IL-1) and IL-6. Meanwhile, the content of IL-1 and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA). The serum levels of urea nitrogen and serum creatinine were measured by an automatic biochemical analyzer. Furthermore, the correlation between NF-κB protein with IL-1 and IL-6 were studied via Pearson analysis. Results: Compared with the normal group, rats in the model group exhibited significantly increased expression and protein expression of NF-κB (p&lt;0.05). Meanwhile, the mRNA expression levels and content of IL-1 and IL-6 (p&lt;0.05), as well as the serum levels of urea nitrogen and creatinine (p&lt;0.05) of the model group were markedly higher than those of the normal group. Furthermore, NF-κB protein was positively correlated with IL-1 and IL-6 contents. Conclusions: NF-κB is highly expressed in juvenile rats with nephrotic syndrome, which promotes the expressions of inflammatory factors (IL-1 and IL-6) and aggravates the renal injury. 

Retracted: No

PubPeer comments:
 Clockwise from upper left: Figure 3.  NF-u03baB protein expression determined through Western blotting ; Fig 3 from [Long et a (2019)] ; Fig 4 from [Lou et al (2019)] ; and Figure 5 from [Pan et al (2019)] . ![file] That is a versatile loading control. No putative authors in common across the papers. ,
Erythropoietin improves hypoxic-ischemic encephalopathy in neonatal rats after short-term anoxia by enhancing angiogenesis
Authors: Chao Jiang
Lie Yu
Huijuan Li
Youcai Tang
Xiaojie Fu
Meimei Zhang
Fangfang Yan
Yan Meng
Journal: Brain Research (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Angiogenesis; Anoxia; Erythropoietin; Neonatal Rats; VEGF.
Affiliations: Department of Neurology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China., Department of Pediatric Neurology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: ., Department of Pediatric Neurology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.

Abstract:  Erythropoietin (EPO) is important for angiogenesis after hypoxia/ischemia. In this study, we investigated whether recombinant human erythropoietin (rhEPO) can enhance angiogenesis, and promote cognitive function through vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway in a rat model of hypoxic-ischemic encephalopathy (HIE). RhEPO, selective VEGFR2 inhibitor (SU5416) or vehicle was administrated by intraperitoneal injection. The assessment for cognitive function begins on day 60 after anoxia. Vascular density in hippocampus and white matter damage within corpus callosum were examined on day 28 after anoxia. The expression of erythropoietin receptor (EPOR), VEGF, rapidly accelerated fibrosarcoma 1 (Raf1), and extracellular-signal-regulated kinases 1 and 2 (ERK1/2) in hippocampus were evaluated on day 7 after anoxia. RhEPO-treated anoxia rats had better cognitive recovery, higher vascular density, and less white matter damage than in the vehicle anoxia rats. These protective effects associated with increased expression of EPOR, VEGF; and increased phosphorylation of Raf1 and ERK1/2. While this up-regulation, and changes in the histopathologic and functional outcomes were abolished by SU5416. Our data indicate that rhEPO can enhance angiogenesis, reduce white matter damage, and promote cognitive recovery through VEGF/VEGFR2 signaling pathway in anoxia rats. 

Retracted: No

PubPeer comments:
  Fig. (2). Scanning Electron Photomicrographs of (B) u0001 Cyclodextrin (C) CPDX-PR (P) Physical mixture (1:2) (S) Solvent evaporation (1:2) (F) Freeze dried (1:2) ![file] Repeated area in the (S) panel: ![file] And in the (F) panel: ![file] (B) panel: ![file] (P) panel. ![file] It is as if the areas overwritten with the microscopy metadata originally contained other information which needed to be covered over so that new metadata could be written there. ,