PReD-Bench/PRed-Bench huggingface dataset:
Eukaryotic expression and purification of anti-epilepsy peptide of Buthus martensii Karsch and its protein interactions
Authors: Junchang Li
Jing Ma
Wei Zhang
Honglei Che
Zhongjun Shao
Jinghua Li
Bifeng Gao
Zongren Wang
Wen Wang
Journal: Molecular and Cellular Biochemistry (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Asian scorpion; Buthus martensil Karsch; anti-epilepsy peptide (AEP); cDNA library; RT-PCR
Affiliations: Department of Traditional Chinese Medicine, Xijing Hospital, The Forth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China. 

Abstract:  The Asian scorpion Buthus martensil Karsch is important in the Chinese traditional medicine where it is used for the treatment of some nervous system diseases. The anti-epilepsy peptide (AEP) is a 61-amino-acid polypeptide extracted from the venom of B. martensil Karsch. Research has confirmed that it has anti-epileptic effects on the rat model of epilepsy. In this experiment, a cDNA library of AEP from the venom of B. martensil Karsch was constructed using RT-PCR; the primer was designed and used for the amplification. An expression vector of AEP was constructed using Pichia pastoris. Vector expression was induced, and protein purification was then performed. Bolting of the interaction molecule of AEP was by His pull down. Experimental results indicate high AEP expression, and the obtained protein was purified and compared with the control group. Four conspicuous protein bands were observed, and mass chromatographic analysis indicated that the four proteins were synaptosomal-associated protein of 25 kDa (SNAP-25), glial fibrillary acidic protein (GFAP), Glutamic acid decarboxylase (GAD) and N-methyl-D: -aspartate (NMDA). Further, the four protein bands were verified by mammalian two-hybrid experiments and co-immunoprecipitation. AEP was found to interact with SNAP2 and NMDA. This provides experimental evidence for the mechanism of AEP's anti-epileptic action and for the manufacture of a novel type anti-epileptic drug. 

Retracted: No

PubPeer comments:
 Figure 5, contrast adjusted to bring out details. * Several panels look more similar to each other than expected, as shown with boxes of the same color. Reported to the journal in October 2015, but no response as of today. ![file] ,
Metabolically Generated Stable Isotope-Labeled Deoxynucleoside Code for Tracing DNA N-Methyladenine in Human Cells
Authors: Xiaoling Liu
Baodong Liu
Hailin Wang
Weiyi Lai
Journal: Analytical Chemistry (2017)
Discipline: CHEMISTRY
Keywords: DNA 6mdA; epigenetic modification; stable isotope-labeled deoxynucleoside; initiation tracer; metabolically differential tracing code
Affiliations: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085, China., University of Chinese Academy of Sciences , Beijing 100049, China.

Abstract:  DNA N6-methyl-2'-deoxyadenosine (6mdA) is an epigenetic modification in both eukaryotes and bacteria. Here we exploited stable isotope-labeled deoxynucleoside [15N5]-2'-deoxyadenosine ([15N5]-dA) as an initiation tracer and for the first time developed a metabolically differential tracing code for monitoring DNA 6mdA in human cells. We demonstrate that the initiation tracer [15N5]-dA undergoes a specific and efficient adenine deamination reaction leading to the loss the exocyclic amine 15N, and further utilizes the purine salvage pathway to generate mainly both [15N4]-dA and [15N4]-2'-deoxyguanosine ([15N4]-dG) in mammalian genomes. However, [15N5]-dA is largely retained in the genomes of mycoplasmas, which are often found in cultured cells and experimental animals. Consequently, the methylation of dA generates 6mdA with a consistent coding pattern, with a predominance of [15N4]-6mdA. Therefore, mammalian DNA 6mdA can be potentially discriminated from that generated by infecting mycoplasmas. Collectively, we show a promising approach for identification of authentic DNA 6mdA in human cells and determine if the human cells are contaminated with mycoplasmas. 

Retracted: No

PubPeer comments:
 Authors should note another well executed study showing that previous reports of 6mA in mammals are artifactual: No evidence for DNA N6-methyladenine in mammals https: advances.sciencemag.org content 6 12 eaay3335  Unfortunately, in the absence of a 6mdA detection technique robust to the multiple sources of error that we have outlined, we conclude that the evidence published to date is not sufficient to support the presence of 6mdA in mammals. ,
Phosphatidylinositol 4-phosphate adaptor protein 2 accelerates the proliferation and invasion of hepatocellular carcinoma cells by enhancing Wnt/β-catenin signaling
Authors: Wanhu Fan
Xiaojing Liu
Fenjing Du
Journal: Journal of Bioenergetics and Biomembranes (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: FAPP2; Hepatocellular carcinoma; Oncogene; Wnt/β-catenin.
Affiliations: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, 710061, People's Republic of China., Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, 710061, People's Republic of China. .

Abstract:  Phosphatidylinositol 4-phosphate adaptor protein 2 (FAPP2) has been recently identified as a tumor-associated regulator that is closely related to tumorigenesis. Yet, the precise role of FAPP2 in hepatocellular carcinoma (HCC) is still largely unknown. This study was designed to determine the function and molecular mechanisms of FAPP2 in HCC. Elevated expression of FAPP2 commonly occurred in the tumor tissue of HCC compared with normal controls. High expression of FAPP2 was also detected in HCC cell lines and its knockdown markedly decreased the proliferation, colony formation and invasion of HCC cells. Upregulation of FAPP2 by using a FAPP2 expression vector markedly promoted the proliferation, colony formation and invasion of HCC cells. FAPP2 was found to promote the activation of Wnt/β-catenin signaling. Importantly, inhibition of Wnt/β-catenin signaling abrogated the FAPP2 overexpression-conferred oncogenic effect in HCC cells. In addition, xenograft tumor experiments revealed that knockdown of FAPP2 significantly decreased the tumorigenicity of HCC cells in vivo. Taken together, the data of our study reported a tumor-promotion function of FAPP2 in HCC and demonstrate that knockdown of FAPP2 was capable of suppressing HCC cell proliferation and invasion through downregulation of Wnt/β-catenin signaling. This study indicated that FAPP2 might be an attractive candidate anticancer target for HCC. 

Retracted: No

PubPeer comments:
 This article and the paper by Kong L, Dong L. FAPP2 Accelerates the Proliferation and Invasion of Hepatocellular Carcinoma Cells via Wnt u03b2-Catenin Signaling. J Environ Pathol Toxicol Oncol. 2020;39(4):309-316. doi: 10.1615 JEnvironPatholToxicolOncol.2020035441. have almost identical word-for-word abstracts and report identical results. Although I do not have access to the full content, it strikes me as imossible that different authors could have such identical submissions to two different journals? ,
Characterization of a novel cAMP-binding, cAMP-specific cyclic nucleotide phosphodiesterase (TcrPDEB1) from Trypanosoma cruzi
Authors: Thomas R Hinds
Rocío Díaz-Benjumea
Sunil Laxman
Ana Rascón
Joseph A Beavo
Journal: Biochemical Journal (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Trypanosoma cruzi; Chagas disease; cAMP-specific PDE; TcrPDEB1; TcrPDEB2
Affiliations: Instituto de Biología Experimental, Universidad Central de Venezuela, Box 47069, Caracas, Venezuela, Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195-7280, U.S.A.

Abstract:  Trypanosoma cruzi, the causative agent of Chagas disease, encodes a number of different cAMP-specific PDE (phosphodiesterase) families. Here we report the identification and characterization of TcrPDEB1 and its comparison with the previously identified TcrPDEB2 (formerly known as TcPDE1). These are two different PDE enzymes of the TcrPDEB family, named in accordance with the recent recommendations of the Nomenclature Committee for Kinetoplast PDEs [Kunz, Beavo, D'Angelo, Flawia, Francis, Johner, Laxman, Oberholzer, Rascon, Shakur et al. (2006) Mol. Biochem. Parasitol. 145, 133-135]. Both enzymes show resistance to inhibition by many mammalian PDE inhibitors, and those that do inhibit do so with appreciable differences in their inhibitor profiles for the two enzymes. Both enzymes contain two GAF (cGMP-specific and -stimulated phosphodiesterases, Anabaena adenylate cyclases and Escherichia coli FhlA) domains and a catalytic domain highly homologous with that of the T. brucei TbPDE2/TbrPDEB2 family. The N-terminus+GAF-A domains of both enzymes showed significant differences in their affinities for cyclic nucleotide binding. Using a calorimetric technique that allows accurate measurements of low-affinity binding sites, the TcrPDEB2 N-terminus+GAF-A domain was found to bind cAMP with an affinity of approximately 500 nM. The TcrPDEB1 N-terminus+GAF-A domain bound cAMP with a slightly lower affinity of approximately 1 muM. The N-terminus+GAF-A domain of TcrPDEB1 did not bind cGMP, whereas the N-terminus+GAF-A domain of TcrPDEB2 bound cGMP with a low affinity of approximately 3 muM. GAF domains homologous with those found in these proteins were also identified in related trypanosomatid parasites. Finally, a fluorescent cAMP analogue, MANT-cAMP [2'-O-(N-methylanthraniloyl)adenosine-3',5'-cyclic monophosphate], was found to be a substrate for the TcPDEB1 catalytic domain, opening the possibility of using this molecule as a substrate in non-radioactive, fluorescence-based PDE assays, including screening for trypanosome PDE inhibitors. 

Retracted: No

PubPeer comments:
 Figure 1A appears to show an unexpected white rectangular patch (red arrow). Could the authors please comment? ![file] , 
 Figure 1B appears to show repeated portions of background (blue boxes). Could the authors please comment? ![file] , 
 #2 There are even more in Figure 1B: ![file] ,
L-butyl phthalein improves neural function of vascular dementia mice by regulating the PI3K/AKT signaling pathway
Authors: Z-Z Hu
S-H Hou
M-S Chen
D-P Chen
Z-J Zhang
Y-G Chen
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: L-3-n-butylphthalide; vascular dementia; PI3K/AKT signaling pathway; Bcl-2 expression; cell apoptosis
Affiliations: Department of Neurology, The Affiliated Longyan First Hospital of Fujian Medical University, Longyan, Fujian, China. .

Abstract:  Objective: L-3-n-butylphthalide (L-NBP) is a type of anti-ischemic cranial nerve protective drug that may act on vascular dementia (VD). Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway can up-regulate B-cell lymphoma 2 (Bcl-2) expression, reduce reactive oxygen species (ROS) production, and alleviate cell apoptosis. This study aimed at investigating the role of L-NBP on neurological function and cell apoptosis in VD mouse through regulating PI3K/AKT signaling pathway. Materials and methods: The mice were divided into four groups, including Sham, VD, VD + solvent, and VD + L-NBP. HT22 cells were cultured in vitro and treated by ischemia/reperfusion (I/R). HT22 cells were divided into four groups, including I/R, VD + solvent, VD + L-NBP, and VD + L-NBP + LY294002 groups. Phosphorylated AKT (p-AKT) and Bcl-2 expressions were tested. ROS content in hippocampus tissue was detected by flow cytometry. Cell apoptosis was evaluated by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Results: ROS content and cell apoptosis increased, while p-AKT and Bcl-2 expressions reduced in hippocampus tissue from VD group compared with sham group. L-NBP significantly up-regulated p-AKT and Bcl-2 expressions and decreased ROS content and cell apoptosis in hippocampus tissue. I/R treatment markedly induced HT22 cell apoptosis and ROS production, and reduced p-AKT and Bcl-2 expressions. L-NBP treatment markedly up-regulated p-AKT and Bcl-2 levels, restrained cell apoptosis, and reduced ROS content in TH22 cells intervened by I/R. LY294002 apparently attenuated the protective effect of L-NBP on HT22 cells. Conclusions: L-NBP protects VD by up-regulating PI3K/AKT signaling pathway, elevating Bcl-2 expression, reducing nerve cell apoptosis, and restraining ROS production. 

Retracted: No

PubPeer comments:
 For those interested by the previous comment, this *Science* article has been cited 561 times over 15 years. Articles citing the *Science* article have been cited 14,800 times (*h* = 65). Data taken from Clarivate Analytics. Figures are significantly different using GS: [1327 citations](http: scholar.google.com citations?hl=en user=60c67g0AAAAJ view_op=list_works). ![file] , 
 A replication study with larger samples failed to replicate these results. It is therefore unscientific to cite this article as evidence for the theoretical claims made in this article. Unfortunately, citation counts do not (yet) show any signs of self-correction. https: www.tandfonline.com doi abs 10.1080 01973533.2013.856792?journalCode=hbas20 ,
Amino acid signaling in yeast: post-genome duplication divergence of the Stp1 and Stp2 transcription factors
Authors: Cathy Jean
Bruno André
Stéphan Vissers
Kevin Wielemans
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Yeast cells; amino acids; Ssy1 sensor; Stp1; Stp2
Affiliations: Laboratoire de Physiologie Moléculaire de la Cellule, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, rue des Pr Jeener et Brachet, 6041 Gosselies, Belgium.

Abstract:  When yeast cells detect external amino acids via their permease-like Ssy1 sensor, the cytosolic precursor forms of Stp1 and Stp2 transcription factors are activated by endoproteolytic removal of their N-terminal domains, a reaction catalyzed by the Ssy5 endoprotease. The processed Stp factors then migrate into the nucleus, where they activate transcription of several amino acid permease genes including AGP1. We report here that the STP1 and STP2 genes most likely derive from the whole genome duplication that occurred in a yeast ancestor. Although Stp1 and Stp2 have been considered redundant, we provide evidence that they functionally diverged during evolution. Stp2 is the only factor processed when amino acids are present at low concentration, and the transcriptional activation of AGP1 promoted by Stp2 is moderate. Furthermore, only Stp2 can sustain Agp1-dependent utilization of amino acids at low concentration. In contrast, Stp1 is only processed when amino acids are present at high concentration, and it promotes higher level transcriptional activation of AGP1. Domain swapping experiments show that the N-terminal domains of Stp1 and Stp2 are responsible for these proteins being cleaved at different amino acid concentrations. Last, induction of the DIP5 permease gene by amino acids depends on Stp2 but not Stp1. We propose that post-whole genome duplication co-conservation of the STP1 and STP2 genes was favored by functional divergence of their products, likely conferring to cells an increased ability to adapt to various amino acid supply conditions. 

Retracted: No

PubPeer comments:
 Fig 2B: more similar than expected in the gap1u0394 and the gap1u0394uga35u0394stp2u0394 group. Could authors check please? ![file] ,
Macrophage Activation Marker Soluble CD163 Associated with Fatal and Severe Ebola Virus Disease in Humans
Authors: Stuart T Nichol
Roosecelis B Martines
G Marshall Lyon
Aneesh K Mehta
Anita K McElroy
Sherif R Zaki
Luciana Silva-Flannery
Jessica R Harmon
Punya Shrivastava-Ranjan
Christina F Spiropoulou
Timothy D Flietstra
Bruce S Ribner
Jay B Varkey
Colleen S Kraft
Journal: Emerging infectious diseases (2019)
Discipline: IMMUNOLOGY
Keywords: CD163; Ebola; Ebola virus; Ebola virus disease; HLH

Abstract:  Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreactivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD. 

Retracted: No

PubPeer comments:
 Apparent duplicated areas in some images in this paper. Two examples below from Figure 2 (there are others). I suspect this was done for cosmetic purposes when labels were moved from the lower left corner to the upper left corner. While this may not affect the conclusions, altering data for any reason wouldnu2019t be considered a best practice; especially considering the author affiliations. ![file] *** ![file] *** ![file] ,
LncRNA ANRIL Regulates Ovarian Cancer Progression and Tumor Stem Cell-Like Characteristics via miR-324-5p/Ran Axis [Retraction]
Authors: Cong Ye
Ke Wang
Yu-Bo Hu
Ye Zhao
Journal: OncoTargets and Therapy (2021)
Discipline: CLINICAL MEDICINE
Keywords: Retraction; Article; DOI; OTT; S273614

Abstract:  [This retracts the article DOI: 10.2147/OTT.S273614.]. 

Retracted: No

PubPeer comments:
 The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. It was bought to the journalu2019s attention that several figures within the article appeared to have duplicated images, specifically: Figure 4E panel 0 h si-ANRIL R2 appears to be duplicated with Figure 4E panel 0 h miR-NC. Figure 5A panel si-NC appears to share duplicated regions with Figure 5A panel miR-NC. Figure 5C row ALDH CD133, the far left and centre right flow cytometry panels appear to show duplicated regions. Figure 5C row ALDH CD133, the centre left and far right flow cytometry panels appear to show duplicated regions. Figure 5C row CD117 CD44, the far left and centre right flow cytometry panels appear to show duplicated regions. Figure 5C row CD117 CD44, the centre left and far right flow cytometry panels appear to show duplicated regions. Figure 5C row Notch1 CD24, the far left and centre right flow cytometry panels appear to show duplicated regions. Figure 5C row Notch1 CD24, the centre left and far right flow cytometry panels appear to show duplicated regions. Figure 6D panel si-NC appears to share duplicated regions with Figure 6D panel si-ANRIL R2+pcDNA-Ran. Figure 6D panel si-ANRIL R2 appears to share duplicated regions with Figure 6D panel si-ANRIL R2+pcDNA. The authors were unable to provide a satisfactory explanation for the alleged duplication and were unable to provide the original images used in the figures. The editor determined the findings of the article were no longer valid and requested for the article to be rejected. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. , 
 Original post is in this thread: https: pubpeer.com publications 073FDAD0E6C85E6EAC3C9E275031A0 ,
Downregulating long non-coding RNA CCAT5 inhibits tumor growth, invasion and metastasis in colorectal cancer through suppressing STAT3
Authors: Y Wang
X-L Yan
S-K Tian
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; CCAT5; colorectal cancer; tumorigenesis; RT-qPCR
Affiliations: Department of Outpatient, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. .

Abstract:  Objective: Recent researches have proved that long noncoding RNAs (lncRNAs) play an important role in tumorigenesis. In this research, lncRNA CCAT5 was explored to identify its role in the development of colorectal cancer (CRC). Patients and methods: Real time-quantitative polymerase chain reaction (RT-qPCR) was utilized to measure CCAT5 expression of CRC tissues. Besides, function assays including wound healing assay and transwell assay were conducted. Furthermore, RT-qPCR and Western blot assay were used to explore the underlying mechanism. Results: By comparison with CCAT5 expression in adjacent tissues, the CCAT5 expression level was significantly higher in CRC samples. Moreover, after CCAT5 was downregulated, cell migration and cell invasion of CRC cells were suppressed. Besides, after knockdown of CCAT5, the mRNA and protein expression of STAT3 was repressed. Furthermore, it was found that STAT3 expression was positively correlated to CCAT5 expression in CRC tissues. Conclusions: Results suggest that CCAT5 could promote cell migration and invasion of CRC by upregulating STAT3, which may offer a potential therapeutic target in CRC. 

Retracted: Yes

PubPeer comments:
 Figure 4A. * Red arrows: Lanes 2 and 4 in the p65(N) panel appear to look similar * Blue arrows: Lanes 1, 4, and 5 in the Lamin B panel appear to look similar Could the authors please show the un-cropped blots to take away any concerns? ![file] ,
RETRACTED ARTICLE: Improved Endovascular Coiling of Wide-Neck Intracranial Aneurysms in Elderly Patients by Double-Microcatheter Technique
Authors: Xiang Xu
Xiaoming Shang
Dayong Wang
Jianzhong Cui
Yu Zheng
Journal: Cell Biochemistry and Biophysics (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Aneurysm; Coiling; Double-microcatheter; Elderly; Embolization
Affiliations: Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, 063000, Hebei, China. ., Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, 063000, Hebei, China., Department of Cardiology, Tangshan Gongren Hospital, Tangshan, 063000, Hebei, China.

Abstract:  Elderly patients are more susceptible to intracranial aneurysms. However, many of them are poor surgical candidates and often have to undergo endovascular treatment. The purpose of this study was to evaluate the efficacy and safety of double-microcatheter technique as an alternative to a balloon- or stent-assisted techniques for wide-neck aneurysms in elderly patients. A retrospective review of 58 patients with 58 wide-neck aneurysms treated with the double-microcatheter technique between October 2010 and December 2012 was performed. Immediate post-embolization angiograms were evaluated using a conventional angiographic scale, and clinical evaluation was performed using the Glasgow Outcome Scale. Clinical and imaging follow-ups were available in 32 (55%) patients, with a mean of 12.5 months. Post-embolization angiograms demonstrated total occlusion in 46 of 58 (79%) aneurysms, a neck remnant in 7 (13%), and body filling in 5 (8%). The technique-related complication rate was 5% (3/58), and the procedural-related mortality rate was 0. Of the 32 aneurysms with follow-ups, recanalization developed in 3 (9%) aneurysms, and none received re-treatment. Using double-microcatheter technique for embolization of wide-neck intracranial aneurysms is safe and effective in the elderly patients. This technique is feasible and safe for coil embolization of wide-neck aneurysms, especially in cases, which are not suitable for balloon- or stent-assisted techniques. 

Retracted: Yes

PubPeer comments:
 Retraction, January 2022, found here: https: link.springer.com article 10.1007 s12013-022-01059-3  The Editor in Chief has retracted this article because it contains material that substantially overlaps with the following article [1]. The editor and publisher were not able to obtain current email addresses for Xiang Xu, Yu Zheng, Dayong Wang, Jianzhong Cui and Xiaoming Shang. Reference: * Lee, J. Y. et al. (2011). Endovascular treatment of wide-neck intracranial aneurysms using a microcatheter protective technique: results and outcomes in 75 aneurysms. AJNR American Journal of Neuroradiology, 32, 917u201322. ,
Targeted brain delivery of AZT via transferrin anchored pegylated albumin nanoparticles
Authors: Praveen Dubey
Vivek Mishra
Suresh P Vyas
Sunil Mahor
Prem N Gupta
Kapil Khatri
Amit Rawat
Journal: Journal of drug targeting (2006)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Hydrophilic drugs; Blood-brain permeability; Drug delivery systems; Albumin nanoparticles; Brain specific delivery
Affiliations: Dr Hari Singh Gour Vishvavidyalaya, Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Sagar, (M.P.), 470 002, India.

Abstract:  Hydrophilic drugs/peptides have poor cross Blood-brain permeability. Various drug delivery systems with diverse surfacial characteristics have been reported for effective translocation of drugs across Blood-brain barrier. In present investigation, the potential of engineered albumin nanoparticles was evaluated for brain specific delivery after intravenous administration. Long circulatory PEGylated albumin nanoparticles encapsulating water-soluble antiviral drug azidothymidine (AZT) were prepared by ultra-emulsification method using chemical cross-linking by glutaraldehyde. Surface of the PEGylated nanoparticles was modified by anchoring transferrin as a ligand for brain targeting. Nanoparticles were characterized for their size, polydispersity, surfacial charge, drug loading and in vitro drug release. Fluorescence studies revealed the enhanced uptake of transferrin-anchored nanoparticles in the brain tissues when compared with unmodified nanoparticles. In vivo evaluation was carried out on albino rats to evaluate tissue distribution of engineered nanoparticles after intravenous administration. A significant ((*)P &lt; 0.01) enhancement of brain localization of AZT was observed for transferrin anchored pegylated albumin nanopariticles (Tf-PEG-NPs). Hence, the specific role of transferrin ligand on nanoparticles for brain targeting was confirmed. 

Retracted: No

PubPeer comments:
 Left: Figure 3.  Transmission electron microscopic image of transferrin modified albumin nanoparticles (Tf-PEG-NPs) Right: Figure 2 from [Dubey et al (2010)] .  Transmission electron microscopic image of YIGSR modified albumin nanoparticles (YIGSR-SN). ![file] Were the NPs modified with transferrin, for targeted brain delivery of AZT, or with YIGSR peptide, for tumor targeting? , 
 Figure 5. Fluorescence distributed in the brain tissue of the rat after 45min of intravenous injection under a fluorescence microscope using (a) Tf-PEG-NPs and (b) Plain NPs. ![file] Fig 5(b) seems to have tripped and fallen into a kaleidoscope. Here it is lightened and marked up. ![file] Its lower 40% consists of horizontally-compressed versions of the same motifs comprising the upper 60%. ,
Autophagy inhibition sensitizes hepatocellular carcinoma to the multikinase inhibitor linifanib
Authors: Liming Jiang
Weidong Han
Liangkun You
Zhao Jing
Wendong Huang
Hongming Pan
Zhanggui Wang
Jiansheng Xie
Weiting Ge
Xiujun Cai
Jiawei Shou
Xinbing Sui
Journal: Scientific Reports (2014)
Discipline: Multidisciplinary
Keywords: Autophagy; Linifanib; Hepatocellular carcinoma (HCC); Drug resistance mechanism; PDGFR-β
Affiliations: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China., Laboratory of Cancer Biology; Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China., Cancer Institute, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China., Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China., Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA.

Abstract:  Autophagy is a critical survival pathway for cancer cells under conditions of stress. Thus, induction of autophagy has emerged as a drug resistance mechanism. This study is to determine whether autophagy is activated by a novel multikinase inhibitor linifanib, thereby impairing the sensitivity of hepatocellular carcinoma (HCC) cells to this targeted therapy. Here, we found that linifanib induced a high level of autophagy in HCC cells, which was accompanied by suppression of phosphorylation of PDGFR-β and its downstream Akt/mTOR and Mek/Erk signaling pathways. Cell death induced by linifanib was greatly enhanced after autophagy inhibition by the pharmacological inhibitors or siRNAs against autophagy related genes, ATG5 and ATG7, in vitro. Moreover, HCQ, an FDA-approved drug used to inhibit autophagy, could significantly augment the anti-HCC effect of linifanib in a mouse xenograft model. In conclusion, linifanib can induce cytoprotective autophagy by suppression of PDGFR-β activities in HCC cells. Thus, autophagy inhibition represents a promising approach to improve the efficacy of linifanib in the treatment of HCC patients. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. * Red boxes. In Figure S1, the 3-MA-Linifanib panels appear to look similar to the siATG5+Linifanib panels in Figure S2A. ![file] , 
 Thank you for your query. I will investigate and reply as soon as possible. , 
 We will investigate the issue thoroughly and will deal with it as soon as possible. , 
 Correction, October 2020, found here: https: www.nature.com articles s41598-020-74205-7  *This Article contains errors in Supplementary Figure 1, where the images of Linifanib and 3-MAu2009+u2009Linifanib are duplications of the images of Linifanib and siATG5u2009+u2009Linifanib in Supplementary Figure 2A, respectively. The correct Supplementary Figure 1 appears here as Figure 1.* I thank the authors and journal for quickly addressing this duplication. ,
Curcumin synergistically augments bcr/abl phosphorothioate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells
Authors: Jian-Hua Xu
Kun-Zhong Zhang
Xiu-Wang Huang
Yuan-Zhong Chen
Li-Xian Wu
Yu Su
Journal: Acta Pharmacologica Sinica (2007)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: growth inhibition; bcr/abl; curcumin; chronic myelogenous leukemia; K562 cell line
Affiliations: Institute of Clinical Pharmacology, School of Pharmacy, Fujian Medical University, Fujian 350004, China. .

Abstract:  Aim: To investigate the growth inhibition effect of the combination of bcr/abl phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur), and the possible mechanisms of cur on the chronic myelogenous leukemia cell line K562. Methods: The K562 cell line was used as a P210( bcr/abl )-positive cell model in vitro and was exposed to different concentrations of PS-ASODN (0-20 micromol/L), cur (0-20 micromol/L), or a combination of both. Growth inhibition and apoptosis of K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respectively. The expression levels of P210( bcr/abl ), NF-kappaB and heat shock protein 90 (Hsp90) were assessed by Western blot. Results: Exposure to cur (5-20 micromol/L) and PSASODN (5-20 micromol/L) resulted in a synergistic inhibitory effect on cell growth. Growth inhibition was associated with the inhibition of the proliferation and induction of apoptosis. Western blot analysis showed that the drugs synergistically downregulated the level of P210( bcr/abl ) and NF-kappaB. Cur downregulated Hsp90, whereas no synergism was observed when cur was combined with PS-ASODN. Conclusion: PS-ASODN and cur exhibited a synergistic inhibitory effect on the cell growth of K562. The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210( bcr/abl ). 

Retracted: No

PubPeer comments:
 Figure 4. Some cells appear to be visible in multiple panels, as shown by boxes of the same color. Legend: (A) Control; (B) Cur 10 u03bcmol L; (C) PS- ASODN, 10 u03bcmol L; (D) PS-ASODN, 10 u03bcmol L+cur, 10 u03bcmol L. ![file] , 
 Figure 8. Some of the bands appear to look similar to each other, in particular in the 2nd panel from the top. Of note, the Acknowledgements say:  *We thank Dr Qun-hao ZHANG from Harvard Medical School who helped in our analysis of Western blot. * ![file] ,
Human marrow stromal cells secrete microRNA-375-containing exosomes to regulate glioma progression
Authors: Chun-Hua Xu
Jian-Guo Kuang
Hao-Ran Zhang
You-Ping Li
Sheng-Ze Deng
Min-Fang Lai
Journal: Cancer Gene Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: hMSCs; tumor microenvironments; microRNAs; exosomes; glioma
Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China., Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China., Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China. .

Abstract:  It is well established that human marrow stromal cells (hMSCs) can directly migrate towards tumor microenvironments associated with tumor formation and intracellular communication. Gene regulatory networks in tumors may be targeted by microRNAs (miRNAs), especially those derived in exosomes from hMSCs. However, the potential functional roles of hMSCs in glioma cell growth still remain controversial. Therefore, this study aimed at exploring the regulatory mechanisms of hMSC exosomal microRNA-375 (miR-375) in glioma. Microarray analysis was used to initially screen out glioma-related genes. The interaction between miR-375 and solute carrier family 31 member 1 (SLC31A1) was confirmed by dual-luciferase reporter gene assay. miR-375 and SLC31A1 expression in glioma cells were determined. Glioma cells were initially exposed to exosomes derived from hMSCs treated with miR-375. Subsequently, the rates of proliferation, migration, invasion and apoptosis were determined in glioma cells using in vitro assays. The effects of exosomal miR-375 from hMSCs on tumor growth in vivo were also measured using xenograft tumor in nude mice. We found that miR-375 and SLC31A1 showed significantly lower and higher expression of glioma cells respectively. Additionally, restored miR-375 expression resulted in suppressed cell proliferation, migration and invasion, and increased apoptosis by targeting SLC31A1. Next, in vitro experiments demonstrated that hMSC-derived exosomes overexpressing miR-375 promoted apoptosis while suppressing proliferation, migration and invasion. Furthermore, in vivo experiments confirmed the negative regulatory effects of hMSC-derived exosomes with overexpressed miR-375. We conclude that exosomal miR-375 from hMSCs inhibits glioma cell progression through SLC31A1 suppression, and ultimately serves as a potential target in the treatment of gliomas. 

Retracted: No

PubPeer comments:
 In Figure 8D, a micrograph has been duplicated and presented as something else. ![file] , 
 Figs 2B, 4E, 7I. ![file] WBs of this unusual stylised form have appeared in a number of problematic papers. I prepared a montage: ![] Is it possible for the authors to upload scans of their original gels, to allay any concerns? ,
Moringa oleifera Alkaloids Inhibited PC3 Cells Growth and Migration Through the COX-2 Mediated Wnt/β-Catenin Signaling Pathway
Authors: Chong-Ying Shi
Xiao-Yu Gao
Tian-Yi Dai
Jun Sheng
Liang Tao
Yang Tian
Lei Peng
Shuang Song
Ming-Rong Yang
Jing Xie
Feng-Xian Luo
Ying-Yan Qian
Wei-Wei Jiang
Journal: Frontiers in Pharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: COX-2-wnt/β-catenin signaling pathway; Moringa oleifera alkaloids; cell growth and migration; prostate cancer PC3 cells.
Affiliations: College of Food Science and Technology, Yunnan Agricultural University, Kunming, China., Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China., National Research and Development Professional Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China., College of Science, Yunnan Agricultural University, Kunming, China., Yunnan Province Engineering Research Center of Functional Food of Homologous of Drug and Food, Yunnan Agricultural University, Kunming, China., Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China.

Abstract:  Moringa oleifera Lam. (M. oleifera) is valuable plant distributed in many tropical and subtropical countries. It has a number of medicinal uses and is highly nutritious. M. oleifera has been shown to inhibit tumor cell growth, but this effect has not been demonstrated on prostate cancer cells. In this study, we evaluated the inhibitory effect of M. oleifera alkaloids (MOA) on proliferation and migration of PC3 human prostate cancer cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that MOA inhibited proliferation of PC3 cells and induced apoptosis and cell cycle arrest. Furthermore, MOA suppressed PC3 cell migration and inhibited the expression of matrix metalloproteinases (MMP)-9. In addition, MOA significantly downregulated the expression of cyclooxygenase 2 (COX-2), β-catenin, phosphorylated glycogen synthase 3β, and vascular endothelial growth factor, and suppressed production of prostaglandin E2 (PGE2). Furthermore, FH535 (β-catenin inhibitor) and MOA reversed PGE2-induced PC3 cell proliferation and migration, and the effects of MOA and FH535 were not additive. In vivo experiments showed that MOA (150 mg/kg) significantly inhibited growth of xenograft tumors in mice, and significantly reduced the protein expression levels of COX-2 and β-catenin in tumor tissues. These results indicate that MOA inhibits the proliferation and migration, and induces apoptosis and cell cycle arrest of PC3 cells. Additionally, MOA inhibits the proliferation and migration of PC3 cells through suppression of the COX-2 mediated Wnt/β-catenin signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 1C appears to have a repeated image. *** ![file] ,
CircHMGCS1 Promotes Hepatoblastoma Cell Proliferation by Regulating the IGF Signaling Pathway and Glutaminolysis
Authors: Nan Huang
Zhongqi Cui
Fenyong Sun
Qiuhui Pan
Jing Wang
Jiabei Zhu
Minzhi Yin
Zhixuan Bian
Ni Zhen
Min Xu
Ji Ma
Song Gu
Journal: Theranostics (2019)
Discipline: CLINICAL MEDICINE
Keywords: GLS; IGF2; circHMGCS1; competing endogenous RNAs; hepatoblastoma.
Affiliations: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China., Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of medicine, Shanghai Jiaotong University, Shanghai, 200127, China., Department of Surgery, Shanghai Children's Medical Center, School of medicine, Shanghai Jiaotong University, Shanghai, 200127, China., Department of Pathology, Shanghai Children's Medical Center, School of medicine, Shanghai Jiaotong University, Shanghai, 200127, China.

Abstract:  Circular RNAs (circRNAs), a novel class of endogenous RNAs, have been recently shown to participate in cellular development and several pathophysiological processes. The identification of dysregulated circRNAs and their function in cancer have attracted considerable attention. Nevertheless, the expression profile and role of circRNAs in human hepatoblastoma (HB) remain to be studied. In this report, we analyzed the expression prolife of circRNAs in HB tissues and identified circHMGCS1 (3-hydroxy-3-methylglutaryl-CoA synthase 1; hsa_circ_0072391) as a remarkably upregulated circRNA. Methods: The expression prolife of circRNAs in HB tissues were investigated through circRNA sequencing analyses. ISH and qRT-PCR assays were performed to measure the expression level of circHMGCS1. The effect of knocking down circHMGCS1 in HB cells in vitro and in vivo were evaluated by colony formation assay, flow cytometry, xenograft tumors assay and untargeted metabolomics assay. MRE analysis and dual luciferase assay were performed to explore the underlying molecular mechanisms. Results: HB patients with high circHMGCS1 expression have shorted overall survival. Knockdown of circHMGCS1 inhibits HB cells proliferation and induces apoptosis. CircHMGCS1 regulates IGF2 and IGF1R expression via sponging miR-503-5p, and affects the downstream PI3K-Akt signaling pathway to regulate HB cell proliferation and glutaminolysis. Conclusions: The circHMGCS1/miR-503-5p/IGF-PI3K-Akt axis regulates the proliferation, apoptosis and glutaminolysis of HB cells, implying that circHMGCS1 is a promising therapeutic target and prognostic marker for HB patients. 

Retracted: No

PubPeer comments:
 It s strange the blots for Total-Akt show 1 bands in Fig. 10J but 2 bands in Fig. 10K and Fig. 10L. ![file] ,
The Olive Biophenols Oleuropein and Hydroxytyrosol Selectively Reduce Proliferation, Influence the Cell Cycle, and Induce Apoptosis in Pancreatic Cancer Cells
Authors: Paul D Roach
Chloe D Goldsmith
Helen Jankowski
Judith Weidenhofer
Christopher J Scarlett
Danielle R Bond
Costas E Stathopoulos
Journal: International Journal of Molecular Sciences (2018)
Discipline: CHEMISTRY
Keywords: HPDE; MIA PaCa-2; anti-cancer; chemoprevention; hydroxytyrosol
Affiliations: Pancreatic Cancer Research Group, School of Environmental & Life Sciences, University of Newcastle, Ourimbah 2258, NSW, Australia. ., Faculty of Science, The University of Newcastle, Ourimbah 2258, NSW, Australia. ., Faculty of Health, The University of Newcastle, Ourimbah 2258, NSW, Australia. ., Hunter Medical Research Institute (HMRI), New Lambton Heights 2305, NSW, Australia. ., School of Science, Engineering and Technology, University of Abertay, Dundee, Scotland DD1 1HG, UK. .

Abstract:  Current chemotherapy drugs for pancreatic cancer only offer an increase in survival of up to six months. Additionally, they are highly toxic to normal tissues, drastically affecting the quality of life of patients. Therefore, the search for novel agents, which induce apoptosis in cancer cells while displaying limited toxicity towards normal cells, is paramount. The olive biophenols, oleuropein, hydroxytyrosol and tyrosol, have displayed cytotoxicity towards cancer cells without affecting non-tumorigenic cells in cancers of the breast and prostate. However, their activity in pancreatic cancer has not been investigated. Therefore, the aim of this study was to determine the anti-pancreatic cancer potential of oleuropein, hydroxytyrosol and tyrosol. Pancreatic cancer cells (MIA PaCa-2, BxPC-3, and CFPAC-1) and non-tumorigenic pancreas cells (HPDE) were treated with oleuropein, hydroxytyrosol and tyrosol to determine their effect on cell viability. Oleuropein displayed selective toxicity towards MIA PaCa-2 cells and hydroxytyrosol towards MIA PaCa-2 and HPDE cells. Subsequent analysis of Bcl-2 family proteins and caspase 3/7 activation determined that oleuropein and hydroxytyrosol induced apoptosis in MIA PaCa-2 cells, while oleuropein displayed a protective effect on HPDE cells. Gene expression analysis revealed putative mechanisms of action, which suggested that c-Jun and c-Fos are involved in oleuropein and hydroxytyrosol induced apoptosis of MIA PaCa-2 cells. 

Retracted: No

PubPeer comments:
 Two images in Figure 2 appear to overlap yet are described differently. Puzzling that the magnification would be different for the original images. *** Closeup ![file] *** Full figure ![file] ,
Investigation of magnetically controlled water intake behavior of Iron Oxide Impregnated Superparamagnetic Casein Nanoparticles (IOICNPs)
Authors: Anil Kumar Bajpai
Anamika Singh
Jaya Bajpai
Journal: Journal of nanobiotechnology (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Iron oxide impregnated casein nanoparticles; in-situ precipitation; characterization; SEM; TEM
Affiliations: BMRL, Department of Chemistry, Government Model Science College, Jabalpur, India. .

Abstract:  Iron oxide impregnated casein nanoparticles (IOICNPs) were prepared by in-situ precipitation of iron oxide within the casein matrix. The resulting iron oxide impregnated casein nanoparticles (IOICNPs) were characterized by Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR), Vibrating sample magnetometer (VSM) and Raman spectroscopy. The FTIR analysis confirmed the impregnation of iron oxide into the casein matrix whereas XPS analysis indicated for complete oxidation of iron (II) to iron(III) as evident from the presence of the observed representative peaks of iron oxide. The nanoparticles were allowed to swell in phosphate buffer saline (PBS) and the influence of factors such as chemical composition of nanoparticles, pH and temperature of the swelling bath, and applied magnetic field was investigated on the water intake capacity of the nanoparticles. The prepared nanoparticles showed potential to function as a nanocarrier for possible applications in magnetically targeted delivery of anticancer drugs. 

Retracted: No

PubPeer comments:
  Figure 4 TEM images of IOICNPs containing varying amount of casein 0.5 g, 1.0 g, 1.5 g, 2.0 g, and glutaraldehyde 5 mM, 10 mM, 15 mM and 20 mM. (A) TEM images of IOICNPs containing varying amounts of casein **a) 0.5 g, b) 1.0 g**, c) 1.5 g, d) 2.0 g. (B) TEM images of IOICNPs containing varying amounts of glutaralehyde a) 5 mM, b) 10 mM, c) 15 mM, d) 20 mM. ![file] It is unlikely that Aa and Ab contain different amounts of casein, since both images overlap with Bc. Ad and Ba are the same image, which is consistent with the labelling but not consistent with their scale bars. ,
Recent perspectives of electronic medical record systems
Authors: Peiying Zhang
Xiao-Ying Zhang
Journal: Experimental and Therapeutic Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: electronic medical record; health information system; patient care.
Affiliations: Nanjing University of Chinese Medicine, Information Institute, Nanjing, Jiangsu 221009, P.R. China., Department of Cardiology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China.

Abstract:  Implementation of electronic medical record (EMR) systems within developing contexts as part of efforts to monitor and facilitate the attainment of health-related aims has been on the increase. However, these efforts have been concentrated on urban hospitals. Recent findings showed that development processes of EMR systems are associated with various discrepancies between protocols and work practices. These discrepancies were mainly caused by factors including high workload, lack of medical resources, misunderstanding of the protocols by health workers, and client/patient practices. The present review focused on the effects of EMRs on patient care work, and on appropriate EMR designs principles and strategies to ameliorate these systems. 

Retracted: No

PubPeer comments:
  Figure 1. - Detection of the number of apoptotic cells in 7 days with TUNEL method. (A) Sham operation group, (B) model group, (C) SDF-1 intervention group and (D) SDF-1 antibody group . Panels B and D are the same, apart from a partial duplication within D. ![file] Suggested by an anonymous colleague via social media. ,