PReD-Bench/PRed-Bench huggingface dataset:
Diagnostic and biological significance of microRNA-192 in pancreatic ductal adenocarcinoma
Authors: Chenyan Zhao
Ying Chen
Shuhui Zhang
Minghua Zhu
Qinghua Liu
Jing Zhang
Canrong Ni
Danghui Yu
Min Shi
Journal: Oncology reports (2013)
Discipline: CLINICAL MEDICINE
Keywords: Pancreatic ductal adenocarcinoma; miR-192; biomarker; serum; PDAC
Affiliations: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, P.R. China.

Abstract:  Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of human cancer. In the present study, we evaluated serum microRNA-192 (miR-192) as a potential biomarker in patients with PDAC and investigated its biological functions in this disease. miRNA expression profiling of human PDACs and adjacent normal pancreatic tissues identified 16 upregulated miRNAs including miR-192 and 8 downregulated miRNAs. Quantitative real-time polymerase chain reaction (PCR) revealed elevation of serum miR-192 levels in PDAC patients relative to these levels in duodenal adenocarcinoma patients and healthy controls. Receiver operating characteristic analysis demonstrated that serum miR-192 had a sensitivity of 76% and a specificity of 55% for detecting PDAC. Ectopic expression of miR-192 in PANC-1 pancreatic cancer cells enhanced cell proliferation and migration, reduced apoptosis and promoted cell cycle progression from the G0/G1 to the S phase. Western blot analysis showed that enforced expression of miR-192 decreased the expression of smad-interacting protein 1 (SIP1) and altered a set of cell cycle-related genes in the PANC-1 cells. miR-192 overexpression increased tumor volume in an orthotopic pancreatic cancer mouse model, coupled with suppression of SIP1 and elevation of collagen I. In conclusion, serum miR-192 may serve as a sensitive diagnostic biomarker for PDAC. Overexpression of miR-192 contributes to tumor growth and progression in PDAC, which is associated with repression of SIP1 and alteration of cell cycle regulatory genes. 

Retracted: No

PubPeer comments:
 ![file] I notice that the total patient number is 70 in Characteristic of Gender and Age, but 66 in others. Could the author explain why 4 patients were excludeduff1f ,
The lysine deacetylase Sirtuin 1 modulates the localization and function of the Notch1 receptor in regulatory T cells
Authors: Nimi Marcel
Apurva Sarin
Sanjay K Shukla
Lakshmi R Perumalsamy
Journal: Science Signaling (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cellular functions; nutrient availability; immune homeostasis; Notch; regulatory T cells
Affiliations: National Centre for Biological Sciences, Bengaluru, Karnataka 560065, India., National Centre for Biological Sciences, Bengaluru, Karnataka 560065, India. .

Abstract:  The ability to tune cellular functions in response to nutrient availability has important consequences for immune homeostasis. The activity of the receptor Notch in regulatory T (Treg) cells, which suppress the functions of effector T cells, is indispensable for Treg cell survival under conditions of diminished nutrient supply. Anti-apoptotic signaling induced by the Notch1 intracellular domain (NIC) originates from the cytoplasm and is spatially decoupled from the nuclear, largely transcriptional functions of NIC. We showed that Sirtuin 1 (Sirt1), which is an NAD+ (nicotinamide adenine dinucleotide)-dependent lysine deacetylase that inhibits NIC-dependent gene transcription, stabilized NIC proximal to the plasma membrane to promote the survival and function of activated Treg cells. Sirt1 was required for NIC-dependent protection from apoptosis in cell lines but not for the activity of the anti-apoptotic protein Bcl-xL. In addition, a variant NIC protein in which four lysines were mutated to arginines (NIC4KR) retained anti-apoptotic activity, but was not regulated by Sirt1, and reconstituted the functions of nonnuclear NIC in Notch1-deficient Treg cells. Loss of Sirt1 compromised Treg cell survival, resulting in antigen-induced T cell proliferation and inflammation in two mouse models. Thus, the Sirt1-Notch interaction may constitute an important checkpoint that tunes noncanonical Notch1 signaling. 

Retracted: No

PubPeer comments:
 ![file] ,
Targeting the heme protein hemoglobin by (−)-epigallocatechin gallate and the study of polyphenol–protein association using multi-spectroscopic and computational methods
Authors: Pallavi Sarkhel
Atanu Singha Roy
Anupam Nath Jha
Mostofa Ataur Rohman
Zaved Hazarika
Sourav Das
Sharat Sarmah
Journal: Physical Chemistry Chemical Physics (2020)
Discipline: CHEMISTRY
Keywords: tea polyphenol; (-)-epigallocatechin gallate; bovine hemoglobin; anti-oxidative behavior; anti-glycation property
Affiliations: Department of Chemistry, National Institute of Technology Meghalaya, Shillong-793003, India, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Centre for Advanced Studies, North-Eastern Hill University, Shillong 793022, Birla Institute of Technology Mesra, Jharkhand 835215

Abstract:  In this work, the interaction of a bioactive tea polyphenol (-)-epigallocatechin gallate (EGCG) with bovine hemoglobin (BHb) along with its anti-oxidative behavior and the anti-glycation property have been explored using multi-spectroscopic and computational techniques. The binding affinity for EGCG towards BHb was observed to be moderate in nature with an order of 104 M-1, and the fluorescence quenching mechanism was characterized by an unusual static quenching mechanism. The binding constant (Kb) showed a continuous enhancement with temperature from 3.468 ± 0.380 × 104 M-1 at 288 K to 6.017 ± 0.601 × 104 M-1 at 310 K. The fluorescence emission measurements along with molecular docking studies indicated that EGCG binds near the most dominant fluorophore of BHb (β2-Trp37, at the interface of α1 and β2 chains) within the pocket formed by the α1, α2 and β2 chains. The sign and magnitude of the thermodynamic parameters, changes in enthalpy (ΔH = +17.004 ± 1.007 kJ mol-1) and in entropy (ΔS = +146.213 ± 2.390 J K-1 mol-1), indicate that hydrophobic forces play a major role in stabilizing the BHb-EGCG complex. The micro-environment around the EGCG binding site showed an increase in hydrophobicity upon ligand binding. The binding of EGCG with BHb leads to a decrease in the α-helical content, whereas that of the β-sheet increased. FTIR studies also indicated that the secondary structure of BHb changed upon binding with EGCG, along with providing further support for the presence of hydrophobic forces in the complexation process. Molecular docking studies indicated that EGCG binds within the cavity of α1, α2, and β2 chains surrounded by residues such as α1- Lys99, α1-Thr134, α1-Thr137, α1-Tyr140, α2-Lys127 and β2-Trp37. Molecular dynamics simulation studies indicated that EGCG conferred additional stability to BHb. Furthermore, moving away from the binding studies, EGCG was found to prevent the glyoxal (GO)-mediated glycation process of BHb, and it was also found to act as a potent antioxidant against the photo-oxidative damage of BHb. 

Retracted: No

PubPeer comments:
 Figure 2A. Splice in p21 panel, but not in other 3 panels. ![file] ,
p66Shc: A novel biomarker of tubular oxidative injury in patients with diabetic nephropathy
Authors: Lin Sun
Xiaoxuan Xu
Chun Hu
Xuejing Zhu
Yachun Han
Yuan Yang
Yashpal S Kanwar
Shuguang Yuan
Fuyou Liu
Mingming Ma
Li Xiao
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: p66Shc expression; diabetic nephropathy; biomarker; tubular oxidative injury; peripheral blood monocytes
Affiliations: Department of Nephrology, 2nd Xiangya Hospital, Central South University, Changsha, Hunan, China., Departments of Pathology &Medicine, Northwestern University, Chicago, USA.

Abstract:  Increased p66Shc expression has been associated with diabetic nephropathy (DN). However, whether p66Shc can serve as a potential biomarker for tubular oxidative injury in DN is unknown. We measured the expression of p66Shc in peripheral blood monocytes (PBMs) and renal biopsy tissues from DN patients and then analysed the relationship between p66Shc expression and the clinical characteristics of patients with DN. Patients were divided into 4 groups (class IIa, class IIb, class III and the control group). qPCR, Western blotting and immunohistochemistry were performed. The results showed that both p66Shc and p-p66Shc expression significantly increased in PBMs and kidney tissues of DN patients. Moreover, Spearman's correlation and multiple regression analyses were carried out. A positive relationship between the p66Shc expression and oxidative stress was found. p66Shc and oxidative stress were significant predictors of the degree of tubular damage. In addition, p66Shc expression was positively correlated with the concentrations of β-NAG, UACR and 8-OHdG, low-density lipoprotein and blood glucose levels, and duration of diabetes in patients with DN from class IIa to class III. These data indicated that increased expression of p66Shc may serve as a therapeutic target and a novel biomarker of DN. 

Retracted: No

PubPeer comments:
 Unexpected similarities in two panels (IIb and III) in the bottom row (DHE) of Figure 2A. Shown with green boxes. , 
 ![file] , 
 https: retractionwatch.com 2019 09 05 northwestern-researcher-has-four-more-papers-retracted-making-five u201cKanwar in an email told us that the work is solid: JBC informed me regarding the retraction. As far as I know **there are no more papers slated for retraction.** The conclusions of all the four articles remains unchanged.u201d Iu2019ve added Dr. Kanwaru2019s email to this thread in case it was previously missing. , 
 Figure 2A appears to have had a second area of overlap (cyan boxes) although the brightness is different. The previously noted correction replaced all of the images in that row. *** ![file] ,
<p>To Develop and Validate the Combination of RNA Methylation Regulators for the Prognosis of Patients with Gastric Cancer</p>
Authors: Zhi-Chao Zheng
Yue Wang
Hai-Yan Piao
Dong Yang
Yan Zhao
Xiang-Yu Meng
Jun Zhang
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: RNA methylation; gastric cancer; least absolute shrinkage and selection operator; prognosis; survival analysis.
Affiliations: Gastric Cancer Department, Liaoning Province Cancer Hospital & Institute (Cancer Hospital of China Medical University), Shenyang City, Liaoning Province 110042, People's Republic of China., Medical Oncology Department of Gastrointestinal Cancer, Liaoning Province Cancer Hospital & Institute (Cancer Hospital of China Medical University), Shenyang City, Liaoning Province 110042, People's Republic of China.

Abstract:  Background: Gastric cancer (GC) accounts for high mortality. RNA methylation has recently gained interest as markers in specific tumors. This study aimed to uncover the function of the roles of 25 RNA methylation regulators in GC. Methods: RNA sequence and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. "STRING" and R were performed to analyze the correlation among the methylase. COX and LASSO were performed to screen for prognostic associated RNA methylation regulators. A prognostic model was established based on the expression of methylase. RT-PCR and immunohistochemistry detected the expression of methylase in GC cells and tissue. Kaplan-Meier curve and Cox analysis were applied to evaluate the effectiveness of the model. Results: The prediction model was established based on the expression of m6A RNA methylation regulators FTO (fat mass and obesity-associated) and RBM15 (RNA binding motif protein 15). Based on the model, GC patients were divided into "high risk" and "low risk" groups to compare the differences in survival. The model was re-evaluated with the clinical data of our center. Conclusion: The two-methylase combination model was an independent prognostic factor of GC. 

Retracted: No

PubPeer comments:
 What happened to the ROC curve in this study (Figure 7a)? ![file] , 
 To Develop and Validate the Combination of RNA Methylation Regulators for the Prognosis of Patients with Gastric Cancer. ![file] Table 1 Patients Characteristics and Univariate Analysis of total N were inconsistent, all other indicators were 128, while the total number of TNM was 32+40+64+2=138. It s not logical. ,
The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells
Authors: Denis Mottet
Vincent Hennequière
Akeila Bellahcène
Andrei Turtoi
Alain Colige
Paul Peixoto
Christophe Deroanne
Bruno Dumont
Nicolas Matheus
Vincent Castronovo
Edwin De Pauw
Journal: Angiogenesis (2012)
Discipline: CLINICAL MEDICINE
Keywords: Histone deacetylases; angiogenesis; HDAC7; endothelial cells; proteomic analysis
Affiliations: Metastasis Research Laboratory, GIGA-Cancer, University Hospital, University of Liège, Bat. B23, CHU Sart Tilman, 4000, Liège, Belgium. 

Abstract:  Histone deacetylases (HDACs) are a family of 18 enzymes that deacetylate lysine residues of both histone and nonhistone proteins and to a large extent govern the process of angiogenesis. Previous studies have shown that specific inhibition of HDAC7 blocks angiogenesis both in vitro and in vivo. However, the underlying molecular mechanisms are not fully understood and hence preclude any meaningful development of suitable therapeutic modalities. The goal of the present study was to further the understanding of HDAC7 epigenetic control of angiogenesis in human endothelial cells using the proteomic approach. The underlying problem was approached through siRNA-mediated gene-expression silencing of HDAC7 in human umbilical vein endothelial cells (HUVECs). To this end, HUVEC proteins were extracted and proteomically analyzed. The emphasis was placed on up-regulated proteins, as these may represent potential direct epigenetic targets of HDAC7. Among several proteins, A-kinase anchor protein 12 (AKAP12) was the most reproducibly up-regulated protein following HDAC7 depletion. This overexpression of AKAP12 was responsible for the inhibition of migration and tube formation in HDAC7-depleted HUVEC. Mechanistically, H3 histones associated with AKAP12 promoter were acetylated following the removal of HDAC7, leading to an increase in its mRNA and protein levels. AKAP12 is responsible for protein kinase C mediated phosphorylation of signal transducer and activator of transcription 3 (STAT3). Phosphorylated STAT3 increasingly binds to the chromatin and AKAP12 promoter and is necessary for maintaining the elevated levels of AKAP12 following HDAC7 knockdown. We demonstrated for the first time that AKAP12 tumor/angiogenesis suppressor gene is an epigenetic target of HDAC7, whose elevated levels lead to a negative regulation of HUVEC migration and inhibit formation of tube-like structures. 

Retracted: No

PubPeer comments:
 Figure 3A of this paper shows 2D migration assay. Image from AKAP12 irrelevant siRNA is the same than the AKAP12 HDAC7 one with a short vertical shift. ![file] ,
Serum metabolomics strategy for understanding the therapeutic effects of Yin-Chen-Hao-Tang against Yanghuang syndrome
Authors: Ai-Hua Zhang
Qi Song
Meng-Xi Li
Heng Fang
Xi-Jun Wang
Le Yang
Xing-Yuan Liu
Meng-Die Yu
Jing Su
Journal: RSC Advances (2018)
Discipline: CHEMISTRY
Keywords: Yin-Chen-Hao-Tang; YCHT; Yanghuang syndrome; YHS; Chinese medicine syndrome
Affiliations: Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Laboratory of Metabolomics, Department of Pharmaceutical Analysis

Abstract:  Yin-Chen-Hao-Tang (YCHT), a classic Chinese herbal formula, is characterized by its strong therapeutic effects of liver regulation and relief of jaundice, especially Yanghuang syndrome (YHS). YHS is a type of jaundice with damp-heat pathogenesis, and it is considered a complicated Chinese medicine syndrome (CMS). The accurate mechanism for healing YHS has not yet been completely reported. The purpose of the current research is to investigate the expression of endogenous biomarkers in YHS mice and evaluate the clinical therapeutic effect of YCHT. Serum samples were analyzed using UPLC-Q/TOF-MS techniques in order to determine differential metabolites to elucidate the functional mechanism of YCHT on YHS through metabolite profiling combined with multivariate analysis. Simultaneously, the exact diversification of YHS mice was elucidated using blood biochemistry indexes and histopathological examination, and the results indicated that YHS is markedly improved by YCHT. Unsupervised principal component analysis (PCA) patterns were constructed to dissect the variances of metabolic profiling. Overall, 22 potential biomarkers were identified using a metabolomics approach based on an accurate MS/MS approach, clustering and distinguishing analysis. The present work demonstrates that the effectiveness of YCHT against YHS prompts distinct discrepancies in metabolic profiles by adjusting biomarkers and regulating metabolic disorders. A total of 15 metabolic pathways were involved in biological disturbance. This demonstrates that metabolomic techniques are powerful means to explore the pathogenesis of CMS and the therapeutic effects of traditional Chinese formulae. 

Retracted: No

PubPeer comments:
 The authors describe a mouse model of Yang Huang Syndrome (YHS), where  YHS is a type of jaundice with damp-heat pathogenesis, and it is considered a complicated Chinese medicine syndrome (CMS) . The mouse model appears to be a rebranding of the existing u03b1-naphthylisothiocyanate-poisoning mouse model of biliary injury and hepatic fibrosis. They compare a group of YHS-model mice (poisoned with ANIT) against a group of **unpoisoned** mice dosed with a herbal decoction *instead*, to see how the herbal decoction cures YHS. ![file] Am I missing something? ,
Understanding the survival mechanisms of Deinococcus radiodurans against oxidative stress by targeting thioredoxin reductase redox system
Authors: Veeramani Kandan Ponniresan
Kanimozhi Govindasamy
Illiyas Maqbool
Nagarajan Rajendra Prasad
Journal: Archives of microbiology (2019)
Discipline: MICROBIOLOGY
Keywords: Antioxidants; Deinococcus radiodurans; EGCG; Inhibitors; Resistance
Affiliations: Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, 608 002, India., Dharumapurm Gnanambikai Government Arts College, Dharumapuram Road, Nagapattinam, Mayiladuthurai, Tamil Nadu, 609001, India., Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, 608 002, India. .

Abstract:  The principal objective of this study is to determine the resistance of Deinococcus radiodurans to hydrogen peroxide (H2O2) induced oxidative stress by inhibiting its thioredoxin reductase (TrxR) antioxidant system. Treatment of D. radiodurans with different TrxR inhibitors such as ebselen, epigallocatechin gallate and auranofin displayed this organism sensitivity to H2O2 treatment in a concentration-dependent manner. We observed that D. radiodurans showed greater resistance to H2O2 treatment. Further, it has also been noticed that TrxR redox system was suppressed by TrxR inhibitors and that this response might be associated with the oxidative stress-mediated cell death in D. radiodurans. Thus, TrxR inhibitors affect the resistance of the D. radiodurans through suppression of its thioredoxin redox pathway via the inhibition of TrxR. Results from this study proved that TrxR plays an important role as an antioxidant enzyme by scavenging intracellular ROS, and thus contributing to the resistance of D. radiodurans towards oxidative stress. 

Retracted: No

PubPeer comments:
 Figure 3A. The  10 mM and  20 mM panels appear to look unexpectedly similar. The aspect ratio is slightly different, and there is a bright spot on one photo that is not present on the other, but otherwise, the position and size of the colonies appear to be remarkably similar. Shown with red boxes. ![file] , 
 June 20, 2020 correction, found here: https: link.springer.com article 10.1007%2Fs00203-020-01953-5  In the original article, an image in Fig. 3(aii), namely the u201c10 mM of HP treatmentu201d published incorrect. The correction does not affect the discussion or conclusions of the article. The correct image (Fig. 3) is given below. I thank the authors for correcting this duplication. ,
FGD5-AS1 facilitates glioblastoma progression by activation of Wnt/β-catenin signaling via regulating miR-129-5p/HNRNPK axis
Authors: Mengguo Guo
Lixin Wu
Dongming Yan
Junxin Liang
Xuqiang Zhu
Zhenyu Song
Journal: Life Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: FGD5-AS1; Glioblastoma; HNRNPK; Wnt/β-catenin signaling; miR-129-5p.
Affiliations: Department of Neurosurgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China., Department of Neurosurgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: .

Abstract:  Aims: Accumulating evidence elucidates the biological significance of long non-coding RNA (lncRNAs) in tumorigenesis and development. FGD5 antisense RNA 1 (FGD5-AS1) was previously revealed as an oncogene in several types of malignancies. However, the roles of FGD5-AS1 in glioblastoma (GBM) and its potential molecular mechanisms remain unclear. Materials and methods: The expression of FGD5-AS1, miR-129-5p, and heterogeneous nuclear ribonucleoprotein K (HNRNPK) mRNA were measured by qRT-PCR. Cell proliferation, invasion and apoptosis were determined by MTT, colony formation, transwell and flow cytometry assays. The protein levels of Ki-67, HNRNPK and Wnt signaling-associated genes were examined by western blot assay. The possible action mechanism of FGD5-AS1 was detected by bioinformatic tools, luciferase reporter, RIP and TOP/FOP Flash reporter assays. A nude mouse xenograft model was built to analyze the function of FGD5-AS1 in vivo. Key findings: FGD5-AS1 expression was increased in GBM tumor tissues and cells. Knockdown of FGD5-AS1 inhibited cell proliferation and invasion in vitro, and slowed tumor growth in vivo. Mechanistically, FGD5-AS1 served as a sponge of miR-129-5p to relieve its suppression on HNRNPK. Moreover, down-regulation of HNRNPK repressed cell proliferation and invasion, while enhanced apoptosis. Additionally, si-FGD5-AS1-mediated suppression of cell proliferation and invasion was obviously reversed by the decrease of miR-129-5p or restoration of HNRNPK. Furthermore, FGD5-AS1 promoted cell growth and invasion by stimulating Wnt/β-catenin signaling via regulation of miR-129-5p/HNRNPK. Significance: FGD5-AS1 promoted GBM progression at least partly by regulating miR-129-5p/HNRNPK to activate Wnt/β-catenin signaling, suggesting the potential of FGD5-AS1 as a candidate target to improve GBM therapy. 

Retracted: No

PubPeer comments:
 Figure 7C appears to have two images which overlap. *** ![file] ,
Highly porous copper-supported magnetic nanocatalysts: made of volcanic pumice textured by cellulose and applied for the reduction of nitrobenzene derivatives
Authors: Mahdi Saeidirad
Fateme Sadat Qazi
Ahmed Esmail Shalan
Atefeh Fazeli
Ali Maleki
Reza Taheri-Ledari
Journal: RSC Advances (2021)
Discipline: CHEMISTRY
Keywords: Volcanic pumice magnetic particles; Cellulose; Copper nanoparticles; Iron oxide nanoparticles; Green chemistry
Affiliations: Catalysts and Organic Synthesis Research Laboratory, BC Materials

Abstract:  Herein, a novel designed heterogeneous catalytic system constructed of volcanic pumice magnetic particles (VPMPs), cellulose (CLS) as a natural polymeric matrix, and copper nanoparticles (Cu NPs) is presented. Also, to enhance the inherent magnetic property of VPMP, iron oxide (Fe3O4) nanoparticles have been prepared and incorporated in the structure via an in situ process. As its first and foremost excellent property, the designed composite is in great accordance with green chemistry principles because it contains natural ingredients. Another brilliant point in the architecture of the designed composite is the noticeable porosity of VPMP as the core of the composite structure (surface area: 84.473 m2 g-1). This great porosity leads to the use of a small amount (0.05 g) of the particles for catalytic purposes. However, the main characterization methods, such as Fourier-transform infrared and energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and electron microscopy, revealed that the spherical metallic particles (Fe and Cu oxides) were successfully distributed onto the surface of the VPMP and CLS matrices. Further, vibrating-sample magnetometer analysis confirmed the enhancement of the magnetic property (1.5 emu g-1) of the composite through the addition of Fe3O4 nanoparticles. Further, the prepared (Fe3O4@VPMP/CLS-Cu) nanocomposite has been applied to facilitate the reduction reaction of hazardous nitrobenzene derivatives (NBDs) to their aniline analogs, with 98% conversion efficiency in eight minutes under mild conditions. Moreover, the good reusability of the catalytic system has been verified after recycling it ten times without any significant decrease in the performance. 

Retracted: No

PubPeer comments:
 Fig. 3g shows SEM energy-mapping images, assumed to be elemental mapping using EDX. The mappings I am used to show a grainy structure due to the limited number of X-ray photons one detects, combined with the specifics of the visualization software that tends to use some smoothing. Because of this, localization of edges is also limited. The SEM-EDX maps in this paper are strikingly different. They have a neon-like appearance and the elemental maps accurately trace out the particle outlines in the SEM image, panel e. For example, the neon-yellow Fe EDX map seems to accurately trace the brightest ridges and spots in the SEM image. What SEM EDX and what software did the authors use to generate elemental maps with this striking appearance and resolution? Fig. 3g: ![file] Comparison of SEM Fe EDX map (animated, click): ![file] ,
The role of irreversible electroporation in promoting M1 macrophage polarization via regulating the HMGB1-RAGE-MAPK axis in pancreatic cancer
Authors: Shuxin Sun
Chaobin He
Shengping Li
Fengxiao Xie
Yu Zhang
Journal: OncoImmunology (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Irreversible electroporation; immunogenic cell death; macrophage; pancreatic cancer; polarization.
Affiliations: Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China

Abstract:  Irreversible electroporation (IRE) is an effective method for treating pancreatic ductal adenocarcinoma (PDAC). It remains unclear whether IRE can induce a specific immune response by stimulating macrophages. Here, the associated markers of macrophages were analyzed after exposure to tumor culture supernatant (TSN) of tumor cells treated with electroporation. Subcutaneous and orthotopic PDAC models were also used to evaluate the effect of macrophage polarization induced by IRE. Aside from its direct killing effect, IRE could induce the immunogenic cell death of tumor cells by increasing the synthesis and secretion of damage associated molecular patterns. Moreover, IRE could increase the release of HMGB1, which activates the MAPK-p38 pathway and leads to the increased expression of M1 markers in macrophages, through binding to the receptor of the advanced glycation end-product (RAGE) receptor. M1 polarization was inhibited by the inhibitors of HMGB1 release, the RAGE receptor, and the MAPK-p38 signaling pathway, but it was activated by rHMGB1 or the stimulator of MAPK-p38. In addition, the promotion of M1 macrophage polarization was enhanced by the positive-feedback release or expression of HMGB1 and RAGE through the MAPK-ERK pathway in macrophages. The promotion of M1 macrophage polarization induced by IRE provided a specific rationale for the combination of IRE and immune therapy in treating PDAC. 

Retracted: No

PubPeer comments:
 Images in Figure 4A and 4F appear to be the same. *** ![file] ,
Enhancing the chemotherapy effect of Apatinib on gastric cancer by co-treating with salidroside to reprogram the tumor hypoxia micro-environment and induce cell apoptosis
Authors: Hongxing Liu
Wei Yang
Qi Ma
Zhandong Zhang
Yonglei Zhang
Bin Zhang
Fei Ma
Yawei Hua
Yingqiang Liu
Journal: Drug Delivery (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: drug delivery; drug-resistance; hypoxic microenvironment; nanoparticles; tumor targeting.
Affiliations: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Henan, Zhengzhou.

Abstract:  Hypoxic microenvironment commonly occurred in the solid tumors considerably decreases the chemosensitivity of cancer cells. Salidroside (Sal), the main active ingredient of Rhodiola rosea, was shown to be able of regulating the tumor hypoxia micro-environment and enhancing the chemotherapeutic efficacy of drug-resistant cancer. Therefore, in this study, the Sal was co-loaded with Apatinib (Apa) by the PLGA-based nanoparticles (NPs) to improve the chemosensitivity of gastric cancer cells. Additionally, to improve the drug delivery efficacy, the tumor-homing peptide (iVR1 peptides) was further decorated on the surface of NPs. The tumor targeting ability of the peptides-functionalized nanoparticles (iVR1-NPs-Apa/Sal) was evaluated by in vitro and in vivo experiments. As the obtained results revealed that the iVR1-NPs-Apa/Sal displayed excellent tumor affinity than the unmodified ones (NPs-Apa/Sal), which in turn resulted in more efficient of anti-proliferation of gastric cancer cells and anti-tumor effect in vivo. In addition, compared with the cells or tumor-bearing mice only treaded by monotherapy of Apa, the cells or mice received combinational treatment of Apa and Sal showed obvious lower rate of growth, invasion, and migration or tumor growth and progress. Underlying mechanisms were further investigated and it was revealed that the anti-gastric cancer effect of Apa was signally improved by Sal through down-regulation the proliferation factors and increase the pro-apoptotic genes, as well as reprograming the tumor hypoxia micro-environment. In a word, the study showed that the Sal was able of improving the chemosensitivity of gastric cancer to Apa and the iVR1-NPs-Apa/Sal was capable of realizing highly efficient of tumor-targeting drug delivery. 

Retracted: No

PubPeer comments:
 An unexpected similarity betwen an area of the image of HIF-1alpha expression of NPs-Sal in Figure 6E and that of MKN-45 in Figure 1E, after a rotation of 180 deg before adjusting their size. ![file] ,
Tyrosine kinase inhibitors for the treatment of acute myeloid leukemia: delineation of anti-leukemic mechanisms of action
Authors: Pierre Fenaux
Lionel Adès
Marie Sébert
Stéphane de Botton
André Baruchel
Claude Gardin
Elodie Lainey
Sylvain Thépot
Simone Boehrer
Guido Kroemer
Maximilien Tailler
Cyrielle Bouteloup
Journal: Biochemical pharmacology (2011)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: tyrosine kinase inhibitors; off-target effects; EGFR inhibitors; antineoplastic effects; myelodysplastic syndrome
Affiliations: INSERM, U848, 94805 Villejuif, France.

Abstract:  Initially, tyrosine kinase inhibitors (TKIs) were developed as targeted therapies that would solely interfere with aberrant tyrosine kinase activation in malignant cells. Nevertheless, preclinical and clinical studies demonstrated that TKI also exhibit "off-target" effects, that is effects not mediated by the assumed mechanisms of action. We and others showed that the epidermal growth factor receptor (EGFR) inhibitors erlotinib and gefitinib exert potent antineoplastic effects on EGFR-negative myeloblasts from patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Here, we undertook a side-by-side comparison of the anti-leukemic efficacy of four different TKI in MDS and AML. Besides the EGFR inhibitor erlotinib, which served as a point of reference, we employed the dual EGFR/HER2 TKI lapatinib, as well as the multikinase inhibitors dasatinib and sorafenib. All four drugs had anti-leukemic effects on cell line models of MDS/AML in vitro as well as on malignant blasts from MDS/AML patients ex vivo. We explored the biological phenomena underlying this anti-leukemic efficacy. Since it is established that a therapeutic benefit in MDS/AML can be conveyed by induction of cell cycle arrest, apoptosis and/or differentiation, we deciphered the individual contribution of these three phenomena to the anti-leukemic action of each of the four TKI. The concomitant assessment of the panel of TKI enables us thus to define (and quantify) their differential capacity to impact on the three biological phenomena, and provide further evidence that these mechanisms are not solely explained by on-target effects. 

Retracted: No

PubPeer comments:
 Fig. 1A - more similar than expected. Could authors check it please? ![file] ,
MicroRNA-93 promotes cell proliferation by directly targeting P21 in osteosarcoma cells
Authors: Yu He
Bo Yu
Journal: Experimental and Therapeutic Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: P21; cell cycle; cell proliferation; cyclin-dependent kinase inhibitor 1A; microRNA
Affiliations: Department of Radiology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China., Department of Critical Care Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.

Abstract:  MicroRNAs (miRNAs) are small, non-coding RNAs that are key regulators of gene expression by directly binding to the 3'-untranslated region of their target mRNAs, resulting in translational repression or degradation of mRNA. It has been demonstrated that miRNAs have key roles in a variety of human malignancies, including osteosarcoma. The present study aimed to assess the molecular mechanism of miR-93 in the regulation of osteosarcoma cell proliferation. Reverse-transcription quantitative PCR and western blot assays were used to examine mRNA and protein expression. An MTT assay and flow cytometry were performed to determine the cell proliferation and cell cycle distribution. A luciferase reporter assay was performed to confirm the direct targeting of cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as P21, by miR-93, which was suggested by a bioinformatics analysis. The results showed that the expression of miR-93 was frequently and significantly increased in a total of 19 osteosarcoma tissues compared to their matched adjacent non-tumor tissues, and the upregulation of miR-93 was associated with the malignant progression of osteosarcoma. Furthermore, miR-93 was also upregulated in the human osteosarcoma cell lines Saos-2, U2OS, SW1353 and MG63 when compared with that in the human osteoblast cell line hFOB1.19. Transfection with miR-93 inhibitor significantly reduced the miR-93 levels and inhibited the proliferation of U2OS and MG63 osteosarcoma cells. The protein levels of P21 were negatively regulated by miR-93 in U2OS and MG63 cells. Knockdown of miR-93 caused cell cycle arrest at G1 stage in U2OS and MG63 cells, identical to the effect of P21 overexpression. Finally, P21 was found to be significantly downregulated in osteosarcoma tissues compared to their matched adjacent non-tumor tissues, suggesting that the inhibition of P21 may be due to increased miR-93 expression in osteosarcoma tissues. In conclusion, the present study demonstrated that miR-93 enhances the proliferation of osteosarcoma cells, at least in part via inhibiting P21 expression and thus promoting cell cycle progression. 

Retracted: No

PubPeer comments:
 Figs 4C,D.  Western blot analysis was used to examine the protein levels of P21. Non-transfected were used as a Control . ![file] For comparison, Figs 4C D from [Zhou et al (2016)] .  Western blot was used to examine the protein levels of EMT-related genes . Other manifestations are linked in that thread. ![file] How to explain the similarities? ,
Downregulation of Survivin Gene Expression Affects Ionizing Radiation Resistance of Human T98 Glioma Cells
Authors: Youxin Zhou
Dai Zhou
Ming Ye
Hangzhou Wang
Jicheng Li
Yong Han
Ziwei Du
Journal: Cellular and Molecular Neurobiology (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Apoptosis; Glioma; Ionizing radiation; Proliferation; Survivin.
Affiliations: Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, People's Republic of China., Department of Neurosurgery, Children's Hospital of Soochow University, Suzhou, 215000, Jiangsu, People's Republic of China., Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, People's Republic of China. ., Department of Neurosurgery, Children's Hospital of Soochow University, Suzhou, 215000, Jiangsu, People's Republic of China. .

Abstract:  Survivin is a tumor-associated gene, which has been detected in a wide variety of human tumors. Previous research has shown that Survivin can affect hepatoma carcinoma cell radiosensitivity. However, little is known about the role of Survivin in ionizing radiation resistance in glioma cells. In this study, we aimed to identify the effects of Survivin on ionizing radiation resistance in glioma cell line T98. Our results showed that downregulation of Survivin gene expression and ionizing irradiation could both inhibit T98 cell proliferation by assays in vitro including CCK-8 and immunohistochemistry. The inhibitory effect of downregulation of Survivin combined with irradiation was the most significant compared with other groups. Results of Western blotting and flow cytometric analysis also showed that downregulation of Survivin combined with the irradiation group achieved the highest apoptosis rate. Experimental results in vivo by intracranial implanting into nude mice were consistent with those in vitro. These findings indicated that ionizing radiation resistance of human T98 glioma cells can be inhibited effectively after Survivin gene silencing. 

Retracted: No

PubPeer comments:
 Figure 2b the right 2 figures share a substantial area ![file] ,
MiR-223-3p promotes the growth and invasion of neuroblastoma cell via targeting FOXO1
Authors: X Chen
X-W Hao
F-J Li
Q Dong
L-L Han
X-J Zhou
Z Jiang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MicroRNAs; miR-223-3p; neuroblastoma; cell proliferation; cell invasion
Affiliations: Department of Operation Room, The Affiliated Hospital of Qingdao University (Laoshan Branch Courts), Qingdao, China. .

Abstract:  Objective: MicroRNAs (miRNAs) have been demonstrated to have crucial roles in cancer development. We investigated the involvement of miR-223-3p in neuroblastoma (NB). Materials and methods: MiR-223-3p expression in NB cell lines and normal cell line was analyzed with real-time quantitative PCR method. Cell proliferation, cell invasion, and cell apoptosis were assessed by cell counting kit-8 (CCK-8), transwell invasion assay, and flow cytometry assay, respectively. Bioinformatics analysis, Dual-Luciferase reporter assays, and Western blot analysis were conducted to identify the connection of miR-223-3p and forkhead box O1 (FOXO1). Results: MiR-223-3p level was found highly expressed in NB cell lines compared with normal cell line. Knockdown miR-223-3p expression decreased cell growth and invasion but increased cell apoptosis. MiR-223-3p was able to bind with the 3'-untranslated region of FOXO1, and thereby resulting in a reduction of FOXO1 expression. The knockdown of FOXO1 increased the malignant capacity of NB cells. Conclusions: Therefore, given the fact that miR-223-3p suppressed FOXO1 expression to promote NB progression, targeting miR-223-3p may be an effective method for NB treatment. 

Retracted: No

PubPeer comments:
  Figure 4. Knockdown of FOXO1 partially reversed the effects of miR-223-3p. A, FOXO1 expression . ![file] Stylised WB blobs, with a mottled background pattern repeating across bands and across figures. AT right, contrast-enhanced. , 
 Figure 3D,  Cell apoptosis in NB cells transfected with synthetic miRNAs. miR223-3p: microRNA-223-3p . Fig 4D,  Cell apoptosis in NB cells transfected with si-FOXO1; siR-NC; or si-FOXO1 and miR-223-3p inhibitor . ![file] These peculiar strawberries do not look much like flow-cytometry plots. Whatever their origins, they repeat within and between diagrams. ,
Chinese herbal formula QHF inhibits liver cancer cell invasion and migration
Authors: Tao Chen
Yunxiao Li
Hefei Huang
Wei Hu
Quan Wang
Journal: Experimental and Therapeutic Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: Chinese herbal formula; QHF; hepatocellular carcinoma; invasion; migration
Affiliations: College of Medical Sciences, China Three Gorges University, Yichang, Hubei 443002, P.R. China; Third-Grade Pharmacological Laboratory on Traditional Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Yichang, Hubei 443002, P.R. China.

Abstract:  The aim of the present study was to observe the effects of the Chinese herbal formula QHF (Q, Qingrejiedu; H, Huoxuehuayu; and F, Fuzhengguben) on the migration and invasion of hepatocellular carcinoma (HCC) HepG2 cells and to elucidate the potential molecular mechanisms involved. HepG2 cells were treated with various concentrations of QHF, and scratch and Transwell® migration assays were used to qualitatively analyze differences in the migration and invasion activity of these cells. Extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) inhibitors were subsequently introduced in order to study the association between QHF and the invasion of HepG2 cells. The protein expression levels of the mitogen-activated protein kinase (MAPK) signaling pathway in HepG2 cells in the presence and absence of QHF were additionally determined using western blot analysis. The results showed that QHF significantly inhibited the proliferation of the HepG2 cells in a concentration-dependent manner, in addition to inhibiting cell movement, which reduced the ability of the cells to invade and migrate. Western blot analysis indicated that the effects of QHF on HCC HepG2 cells after 24 h were to significantly decrease the expression of phosphorylated- (p-)ERK and to increase the expression of p-p38 and p-JNK; however, the total quantity of ERK, p38 and JNK protein remained unchanged. The administration of an inhibitor of ERK altered p38 and JNK expression and promoted the anti-invasion effects of QHF, whereas p38 and JNK inhibitors only partially reversed this effect. The results of the present study indicate, therefore, that QHF is able to inhibit the migratory and invasive activity of HepG2 cells. A possible underlying mechanism involves the activation of the p38 and JNK MAPK signaling pathway and the attenuation of the ERK signaling pathway. 

Retracted: No

PubPeer comments:
 February 15, 2016 This article has been retracted: please see Elsevier Policy on Article Withdrawal (http: www.elsevier.com locate withdrawalpolicy). This article has been retracted at the request of the Editor. In Fig. 5A different intensities of the same image were used to represent different experimental conditions: the extent of cell death of TUNEL Vehicle (left image) and the extent of cell death of TUNEL Curcumin (2nd image from the left). The article has been retracted because the data integrity has become questionable. ,
Maturation of hepatic lipase. Formation of functional enzyme in the endoplasmic reticulum is the rate-limiting step in its secretion
Authors: Mark H Doolittle
Osnat Ben-Zeev
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hepatic lipase; Lipase gene family; Intracellular specific activity; Endoplasmic reticulum; Sedimentation profile
Affiliations: Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.

Abstract:  Among three lipases in the lipase gene family, hepatic lipase (HL), lipoprotein lipase, and pancreatic lipase, HL exhibits the lowest intracellular specific activity (i.e. minimal amounts of catalytic activity accompanied by massive amounts of inactive lipase mass in the endoplasmic reticulum (ER)). In addition, HL has a distinctive sedimentation profile, where the inactive mass overlaps the region containing active dimeric HL and trails into progressively larger molecular forms. Eventually, at least half of the HL inactive mass in the ER reaches an active, dimeric conformation (t(1/2) = 2 h) and is rapidly secreted. The remaining inactive mass is degraded. HL maturation occurs in the ER and is strongly dependent on binding to calnexin in the early co-/post-translational stages. Later stages of HL maturation occur without calnexin assistance, although inactive HL at all stages appears to be associated in distinct complexes with other ER proteins. Thus, unlike other lipases in the gene family, HL maturation is the rate-limiting step in its secretion as a functional enzyme. 

Retracted: Yes

PubPeer comments:
 2019 retraction. http: www.jbc.org content 294 33 12566 This article has been withdrawn by the authors. Figs. 1, 3B, and 6A were inappropriately manipulated. Figs. 4C and 7 were spliced. ,
LncRNA KCNQ1OT1 regulates the invasion and migration of hepatocellular carcinoma by acting on S1PR1 through miR-149
Authors: Ji-Lun Cheng
Xiang-Yu Liu
Ming-Yang Lv
Yi-Jin Pei
Xiu-Juan Zhang
Lin Li
Ai-Hui Fan
Du-Juan Li
Journal: Cancer Gene Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: lncRNA KCNQ1OT1; HCC; miR-149; S1PR1; qRT-PCR assay
Affiliations: School of Pharmacy, Guangdong Medical University, 523808, Dongguan, P.R. China., Department of Pathology, Henan Provincial People's Hospital, 453000, Zhengzhou, P.R. China., Department of Emergency Intensive Care Unit, General Hospital of Pingmei Shenma Medical Group, 467200, Pingdingshan, P.R. China., Department of Physiology, Guangdong Medical University, 523808, Dongguan, P.R. China., Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, 510515, Guangzhou, P.R. China., Guangdong Medical University, 523808, Dongguan, P.R. China., Department of Physiology, Guangdong Medical University, 523808, Dongguan, P.R. China. .

Abstract:  The aim of this study was to investigate the effect of lncRNA KCNQ1OT1 on HCC and to explore the possible underlying mechanisms. The expression levels of KCNQ1OT1, miR-149 and S1PR1 were detected by qRT-PCR assay. A dual luciferase reporter assay was used to detect the interaction between KCNQ1OT1 and miR-149, as well as miR-149 and S1PR1. The interaction between KCNQ1OT1 and miR-149 was further investigated by RNA pull-down assay. Wound healing assays and Transwell assays were carried out to determine cell migration and invasion. A xenograft tumour assay was used to validate the role of KCNQ1OT1 in vivo. KCNQ1OT1 and S1PR1 were significantly increased, but miR-149 was decreased in HCC cells. Luciferase reporter assays and RNA pull-down assays revealed that KCNQ1OT1 directly targeted miR-149. In addition, miR-149 bound to the 3'-UTR of S1PR1. Knockdown of KCNQ1OT1 or overexpression of miR-149 inhibited the invasion and migration of HCC cells. However, suppression of miR-149 could abrogate the effect of KCNQ1OT1 knockdown on the invasion and migration abilities of HCC cells. In vivo assays showed that KCNQ1OT1 knockdown suppressed tumour growth. This work suggests that lncRNA KCNQ1OT1 might act as a potential therapeutic target in HCC. 

Retracted: No

PubPeer comments:
 Though the study does not involve patients or tissue samples from patients it is stated that:  Consent for publication The informed consent was obtained from the study participants. Ethics approval and consent to participate The protocol has been approved by the Ethics Committee of Guangdong Medical University. All patients were informed of the study and signed the written consent. ,