PReD-Bench/PRed-Bench huggingface dataset:
Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway
Authors: Joan Massagué
Hediye Erdjument-Bromage
David C Dorn
Paul Tempst
Wei He
Malcolm A S Moore
Journal: Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Tissue homeostasis; TGFbeta; Smad transcription factors; Transcriptional Intermediary Factor 1gamma; hematopoietic cells
Affiliations: Cancer Biology and Genetics Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Abstract:  Tissue homeostasis in mammals relies on powerful cytostatic and differentiation signals delivered by the cytokine TGFbeta and relayed within the cell via the activation of Smad transcription factors. Formation of transcription regulatory complexes by the association of Smad4 with receptor-phosphorylated Smads 2 and 3 is a central event in the canonical TGFbeta pathway. Here we provide evidence for a branching of this pathway. The ubiquitious nuclear protein Transcriptional Intermediary Factor 1gamma (TIF1gamma) selectively binds receptor-phosphorylated Smad2/3 in competition with Smad4. Rapid and robust binding of TIF1gamma to Smad2/3 occurs in hematopoietic, mesenchymal, and epithelial cell types in response to TGFbeta. In human hematopoietic stem/progenitor cells, where TGFbeta inhibits proliferation and stimulates erythroid differentiation, TIF1gamma mediates the differentiation response while Smad4 mediates the antiproliferative response with Smad2/3 participating in both responses. Thus, Smad2/3-TIF1gamma and Smad2/3-Smad4 function as complementary effector arms in the control of hematopoietic cell fate by the TGFbeta/Smad pathway. 

Retracted: No

PubPeer comments:
null, 
null, 
 Figure 3B. Leftmost 3 tubulin lanes appear much narrower than leftmost 3 Jmjd3 lanes. Splice between lanes 2 and 3 Jmjd3 panel, whereas it is not obvious if there are similar splices in the other panels. ![file] ,
Engineering surface atomic structure of single-crystal cobalt (II) oxide nanorods for superior electrocatalysis
Authors: Mietek Jaroniec
Yan Jiao
Shi-Zhang Qiao
Dong-Yang Yan
Zhenpeng Hu
Jing Mao
Xueli Zheng
Xi-Wen Du
Tao Ling
Hui Wang
Yao Zheng
Journal: Nature Communications (2016)
Discipline: Multidisciplinary
Keywords: Engineering; surface structure; atomic level; reactivity; durability
Affiliations: Tianjin Key Laboratory of Composite and Functional Materials, Key Laboratory for Advanced Ceramics and Machining Technology of Ministry of Education, Institute of New-Energy, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China., School of Chemical Engineering, The University of Adelaide, Adelaide, South Australia 5005, Australia., Key Laboratory of Aerospace Materials and Performance (Ministry of Education), School of Materials Science and Engineering, Beihang University, Beijing 100191, China., School of Physics, Nankai University, Tianjin 300071, China., Department of Chemistry and Biochemistry, Kent State University, Kent, Ohio 44242, USA.

Abstract:  Engineering the surface structure at the atomic level can be used to precisely and effectively manipulate the reactivity and durability of catalysts. Here we report tuning of the atomic structure of one-dimensional single-crystal cobalt (II) oxide (CoO) nanorods by creating oxygen vacancies on pyramidal nanofacets. These CoO nanorods exhibit superior catalytic activity and durability towards oxygen reduction/evolution reactions. The combined experimental studies, microscopic and spectroscopic characterization, and density functional theory calculations reveal that the origins of the electrochemical activity of single-crystal CoO nanorods are in the oxygen vacancies that can be readily created on the oxygen-terminated {111} nanofacets, which favourably affect the electronic structure of CoO, assuring a rapid charge transfer and optimal adsorption energies for intermediates of oxygen reduction/evolution reactions. These results show that the surface atomic structure engineering is important for the fabrication of efficient and durable electrocatalysts. 

Retracted: No

PubPeer comments:
 In supplementary Figure 13b and 18a, the CV curves for the capacitance measurements looks very weird. Although it was claimed that the measurements were conducted with RDE, but the rough and jumping points are observed at medium level scan rate, while it not appear at high scan rate, do you really think it was caused by oxygen flow or rotation shafe? ![file] ,
GANT61 plays antitumor effects by inducing oxidative stress through the miRNA‐1286/RAB31 axis in osteosarcoma
Authors: Kuai-Qiang Zhang
Xiang-Dong Chu
Journal: Cell Biology International (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: GANT61; GLI inhibitor; antitumor effects; miRNA-1286; osteosarcoma.
Affiliations: Department of Orthopedic Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine Xianyang Shaanxi China

Abstract:  Osteosarcoma (OS) is a rare malignancy of bone associated with poor clinical outcomes. The antitumor effects of GANT61 on OS is unclear. To investigate antitumor effects and mechanism of GANT61 in OS cells and xenograft model. Effects of GANT61 on cell viability, clone formation, cell cycle, apoptosis, migration, and invasion ability of OS cells were assessed. Reactive oxygen species (ROS) levels measured by dichlorofluorescein fluorescence were used to evaluate oxidative stress. The Xenograft model was constructed to investigate the antitumor effects of GANT61 in vivo. The microRNA (miRNA)-1286 was downregulated, while RAB31 upregulated in OS tissues and cells. GANT61 inhibited viability, migration, and invasion ability of OS cells (SaOS-2 and U2OS), and induced apoptosis and the ROS production, along with miRNA-1286 upregulation and RAB13 downregulation. After knockdown of miRNA-1286, GANT6-induced cell inhibition was attenuated, along with RAB31 upregulation. Inversely, miRNA-1286 overexpression downregulated RAB31. Dual-luciferase reporter assay verified that miR-1286 negatively targeted RAB13. Moreover, the knockdown of RAB31 stimulated apoptosis and ROS production while inhibited viability, migration, and invasion of GANT61-treated cells. In vivo experiments further confirmed that GANT61 inhibited tumor growth and RAB13 expression, but enhanced miRNA-1286. The study demonstrated that GANT61 inhibited cell aggressive phenotype and tumor growth by inducing oxidative stress through the miRNA-1286/RAB31 axis. Our findings provided a potential antitumor agent for the OS clinical treatment. 

Retracted: No

PubPeer comments:
 The Western immunoblots presented in this article look very unusual. All blots are diffuse and when you increase the contrast, they look artificial. Can the authors provide raw data (uncut film with MW standards) for the Western blots in Figure 1 and 2? ![file] ,
Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo
Authors: Francesco Tedesco
Fleur Bossi
Paola Secchiero
Federica Corallini
Fabio Fischetti
Claudio Celeghini
Paolo Durigutto
Giorgio Zauli
Journal: Blood (2007)
Discipline: CLINICAL MEDICINE
Keywords: Recombinant osteoprotegerin; adhesion; leukocyte; endothelial cells; PMNs
Affiliations: Department of Biomedicine, University of Trieste, Italy. 

Abstract:  Recombinant osteoprotegerin (OPG) promoted the adhesion of both primary polymorphonuclear neutrophils (PMNs) and leukemic HL60 cells to endothelial cells. Leukocyte/endothelial cell adhesion was promoted by short (peak at 1 hour) preincubation of either endothelial cells or PMNs with OPG, and the peak of proadhesive activity was observed in the same range of OPG concentrations detected in the sera of patients affected by cardiovascular diseases. Although the cognate high-affinity ligands for OPG, membrane receptor activator of nuclear factor-kappaB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were detected at significant levels on both PMNs and HL60 cells, they were not expressed on the surface of endothelial cells. However, preincubation of OPG with heparin abrogated its proadhesive activity, whereas pretreatment of endothelial cells with chondroitinase plus heparinases significantly decreased the proadhesive activity of OPG. Taken together, these findings suggest the involvement of both the ligand binding and the N-terminal heparin-binding domains of OPG in mediating its pro-adhesive activity. The relevance of these in vitro findings was underscored by in vivo experiments, in which the topical administration of recombinant OPG increased leukocyte rolling and adhesion to rat mesenteric postcapillary venules. Our data suggest that a pathological increase of OPG serum levels might play an important role in promoting leukocyte/endothelial cell adhesion. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
null, 
 #2 Figure 5C. How to explain the appearance of the cloud of data points inside the red ellipse in the OPG treated panel, and everything else, down to all the outliers, being the same in the OPG and Untreated panels? , 
 #2 Here is the OPG panel black white reversed and superimposed on the Untreated with 50% transparency. Black dots = unique to Untreated, white dots = unique to OPG, faint blue dots are present in both so they cancel out. ![file] Oddly, there are two populations of shared cells with a slight vertical offset. At left, I superimposed the panels to maximise cancellation within the left-hand quadrants, though there is also a central band of cancelled dots. Over to the right, I shifted them to maximise cancellation within the upper-right quadrant, so the shared dots in the right-hand quadrants appear as black white pairs. , 
null, 
null, 
null, 
 There is a big number of similar dots, I marked some of them till I finished the colors. Some of them are identical, others have just 1 or 2 more. Could authors explain? ![file] It s been 4 years since the first report here, is the Editorial Office of Blood aware of these problems? ,
A beta-arrestin-biased agonist of the parathyroid hormone receptor (PTH1R) promotes bone formation independent of G protein activation
Authors: Leonor Corsino
Diane Gesty-Palmer
Louis M Luttrell
Pat Flannery
Ling Yuan
Robert J Lefkowitz
Robert Spurney
Journal: Science translational medicine (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: therapeutic agents; seven-transmembrane receptors; 7TMRs; ligands; G proteins
Affiliations: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Abstract:  About 40% of the therapeutic agents in use today exert their effects through seven-transmembrane receptors (7TMRs). When activated by ligands, these receptors trigger two pathways that independently transduce signals to the cell: one through heterotrimeric GTP-binding proteins (G proteins) and one through beta-arrestins; so-called biased agonists can selectively activate these distinct pathways. Here, we investigate selective activation of these pathways through the use of a biased agonist for the type 1 parathyroid hormone (PTH)-PTH-related protein receptor (PTH1R), (D-Trp(12),Tyr(34))-PTH(7-34) (PTH-betaarr), which activates beta-arrestin but not classic G protein signaling. In mice, PTH-betaarr induces anabolic bone formation, as does the nonselective agonist PTH(1-34), which activates both mechanisms. In beta-arrestin2-null mice, the increase in bone mineral density evoked by PTH(1-34) is attenuated and that stimulated by PTH-betaarr is ablated. The beta-arrestin2-dependent pathway contributes primarily to trabecular bone formation and does not stimulate bone resorption. These results show that a biased agonist selective for the beta-arrestin pathway can elicit a response in vivo distinct from that elicited by nonselective agonists. Ligands with these properties may form the basis for improved 7TMR-directed pharmacologic agents with enhanced therapeutic specificity. 

Retracted: No

PubPeer comments:
 Fig. 4A Vehicle WT vs Beta-Arrestin2- - seems to share the same common image. Could the authors check please? ![file] ,
Aberrant upregulation of KLK10 promotes metastasis via enhancement of EMT and FAK/SRC/ERK axis in PDAC
Authors: Min-Wei Yang
Shu-Heng Jiang
Yong-Wei Sun
Qing Li
Xiao-Yan Cao
Li-Li Zhu
Xiao-Xin Zhang
Zhi-Gang Zhang
Li-Peng Hu
Guang-Ang Tian
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: EMT; KLK10; Metastasis; Pancreatic ductal adenocarcinoma.
Affiliations: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, PR China., Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200217, PR China., Shanghai Medical College of Fudan University, Shanghai 200032, PR China., Shanghai Medical College of Fudan University, Shanghai 200032, PR China. Electronic address: ., Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200217, PR China. Electronic address: ., State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: .

Abstract:  Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors. However, the specific member of kallikrein family and its function in PDAC remain unexplored. In this study, by data mining of GEO datasets, we have identified KLK10 is upregulated gene in PDAC. We found that KLK10 was significantly overexpressed in tissues of pancreatic intraepithelial neoplasia (PanIN) and PDAC from Pdx1-Cre; LSL-KrasG12D/+ mice (KC) and Pdx1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ mice (KPC) by immunohistochemical analysis. Moreover, KLK10 is extremely elevated in the PDAC tissues, especially that from the PDAC patients with lymphatic and distant metastasis. Aberrant KLK10 expression is significantly correlated with poor prognosis and shorter survival by univariable and multivariable analysis. Functionally, knockdown of KLK10 observably inhibits invasion and metastatic phenotype of PDAC cells in vitro and metastasis in vivo. In addition, blockade of KLK10 attenuates epithelial-mesenchymal transition and activation of FAK-SRC-ERK signaling, which explains the mechanism of KLK10 in promoting metastasis. Collectively, KLK10 should be considered as a promising biomarker for diagnosis and potential target for therapy in PDAC. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have some image duplications or overlaps. ![file] ,
miR-656 inhibits glioma tumorigenesis through repression of BMPR1A
Authors: Mian Guo
Zhenfeng Jiang
Zhichao Wu
Albert Duy Ha
Li Hu
Dunyue Lu
Xiaoming Zhang
Wenzhong Du
Kevork Khadarian
Jia Shen
Jiahang Sun
Zhiguo Lin
Journal: Carcinogenesis (2014)
Discipline: CLINICAL MEDICINE
Keywords: Bone morphogenetic protein-2 (BMP-2); microRNAs; glioma; BMP receptor, type 1A (BMPR1A); proliferation
Affiliations: Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China., Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China., Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China, Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA., Dental School, University of California, Los Angeles, Los Angeles, CA 90095, USA and., Dental School, University of California, Los Angeles, Los Angeles, CA 90095, USA and  ., Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China, .

Abstract:  Bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor-β family, plays critical roles in cell differentiation, modeling and regeneration processes in several tissues. BMP-2 is also closely associated with various malignant tumors. microRNAs negatively and posttranscriptionally regulate gene expression and function as oncogenes or tumor suppressors. Herein, we report that miR-656 expression was significantly downregulated in glioma cell lines and tissues. We identified and confirmed that BMP receptor, type 1A (BMPR1A) is a direct target of miR-656. The expression of BMPR1A was negatively correlated with that of miR-656 in human glioma tissues. We further demonstrated that miR-656 suppressed glioma cell proliferation, neurosphere formation, migration and invasion with or without exogenous BMP-2. Engineered knockdown of BMPR1A diminished the antiproliferation effect of miR-656 in vitro. Moreover, the canonical BMP/Smad and non-canonical BMP/mitogen-activated protein kinase (MAPK) pathways were inhibited by miR-656 overexpression. Several cancer-related signaling molecules, including cyclin B, cyclin D1, matrix metalloproteinase-9, p21 and p27, were also involved in miR-656 function in glioma cells. The tumor-suppressing function of miR-656 was validated using an in vivo intracranial xenograft mouse model. Notably, ectopic expression of miR-656 markedly reduced tumor size and prolonged the survival of mice treated with or without BMP-2. These results elucidate the function of miR-656 in glioma progression and suggest a promising application for glioma treatment. 

Retracted: No

PubPeer comments:
 Figure 4B appears to have several overlapping images. ![file] ,
Co-delivery of brinzolamide and miRNA-124 by biodegradable nanoparticles as a strategy for glaucoma therapy
Authors: Ye Wang
Jiahao Chen
Xiaoshu Gao
Tingting Li
Siqi Pan
Xinrong Zhou
Yu Su
Journal: Drug Delivery (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Glaucoma; IOP; brinzolamide; miRNA-124; nanoparticle
Affiliations: Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai engineering center for precise diagnosis and treatment of eye diseases, Shanghai, China, Department of Ophthalmology, Peking University Shenzhen Hospital, Shenzhen, China, Department of Biological pharmacy, School of Pharmacy, Jilin University, Changchun, China

Abstract:  Co-delivery nanoparticles with characteristics of intracellular precision release drug have been generally accepted as an effective therapeutic strategy for eye diseases. In this study, we designed a new co-delivery system (miRNA/NP-BRZ) as a lasting therapeutic approach to prevent the neuro-destructive after the long-term treatment of glaucoma. Neuroprotective and intraocular pressure (IOP) response were assessed in in vivo and in vitro models of glaucoma. At the meaning time, we describe the preparation of miRNA/NP-BRZ, drug release characteristics, intraocular tracing, pharmacokinetic and pharmacodynamics study and toxicity test. We found that miRNA/NP-BRZ could remarkably decrease IOP and significantly prevent retinal ganglion cell (RGC) damages. The new formula of miRNA-124 encapsulated in PEG-PSA-BRZ nanoparticles exhibits high encapsulation efficiency (EE), drug-loading capacity (DC), and stable controlled-release efficacy (EC). Moreover, we also verified that the miRNA/NP-BRZ system is significantly neuroprotective and nontoxic as well as lowering IOP. This study shows our co-delivery drug system would have a wide potential on social and economic benefits for glaucoma. 

Retracted: No

PubPeer comments:
 The nanoparticles presented in Figure 2 are too perfect. The halo effect seen around the particles are also odd. In the Materials and Methods a description of the preparation for TEM is not described, eg. fixative used. The attached picture is adjusted (increased contrast). ![file] ,
Targetting an LncRNA P5848-ENO1 axis inhibits tumor growth in hepatocellular carcinoma
Authors: Zhangrui Zeng
Hui Yu
Xidan Zhu
Guangrong Li
Jing Quan
Baolin Li
Jinbo Liu
Journal: Bioscience reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ENO1; Hepatocellular carcinoma (HCC); LncRNA P5848; Therapeutic target.
Affiliations: Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.

Abstract:  Hepatocellular carcinoma (HCC) has a high recurrence rate and poor clinical outcome after currently used therapies, including radiofrequency ablation. To explore the possible mechanisms for the relapse of HCC, in the present study we focussed on long non-coding RNA (LncRNA), which has been reported to be involved in tumorigenesis. We identified an LncRNA P5848, whose expression level was up-regulated in tumor samples from HCC patients after radiofrequency ablation. As such, we speculated that LncRNA P5848 may play a role in tumor growth. Here we showed that LncRNA P5848, whose up-regulation can lead to HCC cancer cell proliferation and migration. In vitro and in vivo overexpression of LncRNA P5848 promoted cell growth, cell survival, and cell invasion, whereas LncRNA P5848 depletion exerts opposite effects. Mechanistically, we have found that ENO1 was the target of LncRNA P5848. LncRNA P5848 up-regulated the gene and protein expression level of ENO1, promoting tumor growth and cell survival. However, siRNA-mediated knockdown of ENO1 counteracted the effects of LncRNA P5848 on cancer cell growth, cell survival, and migration. Taken together, LncRNA P5848 promotes HCC development by up-regulating ENO1, indicating that LncRNA P5848-ENO1 axis is a potential therapeutic target for the treatment of HCC. 

Retracted: No

PubPeer comments:
 Figure 4D appears to have two sets of repeated images. I also wish to note that the email address for the corresponding author does not seem to, um, correspond with their name. *** Closeup ![file] *** Full figure ![file] , 
 https: doi.org 10.1042 BSR-20180896_EOC The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. ,
A bioengineered metastatic pancreatic tumor model for mechanistic investigation of chemotherapeutic drugs
Authors: Xing Zhang
Zhiren Fu
Xiaohui Wang
Hao Yin
Journal: Journal of Biotechnology (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chemotherapy; Electrospun scaffold; Metastasis; Orthotopic model; Pancreatic cancer.
Affiliations: Department of General Surgery, Bayinguoleng Menggu Zizhizhou People's Hospital, Korla, Xinjiang, China.

Abstract:  Here we bioengineered a metastatic pancreatic tumor model with homogenous human CD133(+)CXCR4(+) cancer stem cells (CSC) and a polyglyconate/gelatin electrospun scaffold. The scaffold sported a highly porous microstructure with the majority of fibers possessing a diameter between 500μm and 1500μm. The scaffold supported the growth of tumor cells without provoking apoptosis. The homogeneous CD133(+)CXCR4(+) CSC was transplanted with the scaffold into the pancreas of nude mice to establish a metastatic pancreatic tumor. After 8 weeks, the tumor volume and weight in the scaffold model were 40.52% and 51.49% greater than the traditional model, respectively. The scaffold also increased the incidence of tumor formation and readily induced a hepatic metastasis. In this model we found that FOLFIRINOX possessed a superior capability of preventing the hepatic metastasis of pancreatic tumor cells than gemcitabine. A mechanistic study attributed this superiority to the fact that FOLFIRINOX could induce a greater apoptosis of CD133(+)CXCR4(+) CSC, thus depriving the driving force of hepatic metastasis. This metastatic tumor model showed an increased incidence of tumor formation, an accelerated tumorigenesis and a significant hepatic metastasis, therefore offering scientists a proven platform to study chemotherapeutic drugs. 

Retracted: No

PubPeer comments:
 This paper appears to duplicate IHC results presented at by the same corresponding author. See figure below. ![file] , 
 The tumors density seems to be much lower than expected. The authors should realized some facts: the density of human body is about 1g cm^3; the highest density of soft tissue is muscle (about 1.12 g cm^3); the lowest density of soft tissue is adipose tissue (about 0.8 g cm^3). But the tumor density in this research is about 0.13 g cm^3 (Mean data in Fig3B divides in mean data in Fig3B )! Could the author explain? ,
<p>Long Non-Coding RNA LUCAT1 Promotes Progression of Thyroid Carcinoma by Reinforcing ADAM10 Expression Through Sequestering microRNA-493</p>
Authors: Meng Lian
Jiaming Chen
Jugao Fang
Guofeng Xiong
Shizhi He
Zhen Wu
Journal: International Journal of General Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: ADAM10; JAK-STAT signaling pathway; long non-coding RNA LUCAT1; microRNA-493; thyroid carcinoma.
Affiliations: Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China., Department of Otolaryngology, Head and Neck Surgery, Wenzhou Central Hospital, Wenzhou 325000, People's Republic of China.

Abstract:  Background: Long non-coding RNA (lncRNA) LUCAT1 has recently been recognized as an oncogene in several malignancies. This study was launched to probe its role in thyroid carcinoma (TC) development and the implicated molecules. Methods: LUCAT1 expression in TC cell lines and in normal thyroid follicular epithelial cell line Nthy-ori3-1 was determined by RT-qPCR. Binding relationships between LUCAT1 and microRNA (miR)-493, and between miR-493 and a disintegrin and metalloproteinase-10 (ADAM10) were predicted on a bioinformatics system and then validated through luciferase reporter gene assays. Expression of miR-493 and ADAM10 in TC cells was determined. Gain- and loss-of functions of LUCAT1, miR-493 and ADAM10 were performed to explore their influences on the behaviors of TC cells. Xenograft tumors were induced in nude mice for in vivo studies. Results: LUCAT1 and ADAM10 were highly expressed, while miR-493 was poorly expressed in TC cell lines. LUCAT1 served as a miR-493 sponge to upregulate ADAM10 expression. Silencing of LUCAT1 discouraged proliferation, invasion, and migration but triggered apoptosis of TC cells. By contrast, these changes were abrogated by further miR-493 inhibition or ADAM10 upregulation. The in vitro experiment results were reproduced in vivo. In addition, miR-493 inhibition or ADAM10 overexpression was found to increase the phosphorylation of STAT3 in cells. Conclusion: This study evidenced that LUCAT1 increases ADAM10 expression through sequestering miR-493, leading to JAK-STAT activation and TC cell growth and metastasis. LUCAT1 and ADAM10 may serve as therapeutic targets for TC treatment. 

Retracted: No

PubPeer comments:
 Figs 1G, 3E, 5C. ![file] Flow-cytometry cell-cycle plots should include a histogram of the raw data; the smooth red and hatched curves of theoretical distributions, produced by cells in each cycle phase; and another smooth curve, combining those theoretical distributions, which fits the observed histogram as closely as possible. Something must have gone seriously wrong to produce alarming overhangs, multiple superimposed squiggly lines, and red hatched templates that vary in shape from panel to panel. ![file] , 
 Fig 1H.  protein levels of Bax and Bcl-2 in cells determined by Western blot analysis . Similar profiles. ![file] ![file] ,
Anti-inflammatory effect of up-regulated microRNA-221-3p on coronary heart disease via suppressing NLRP3/ASC/pro-caspase-1 inflammasome pathway activation
Authors: Hua Zhou
Ting Mou
Qian Liu
Jijie Xu
Hao Chi
Xuhua Zhang
Jingfeng Rong
Jianjun Xu
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Coronary heart disease; MicroRNA-221-3p; NLR pyrin domain containing 3; a caspase recruitment domain; anti-inflammatory effect
Affiliations: Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Chinese Medicine , Shanghai, China., Cardiovascular Medicine Institute, Shuguang Hospital Affiliated to Shanghai University of Chinese Medicine , Shanghai, China., Cardiothoracic Surgery Department, Shuguang Hospital Affiliated to Shanghai University of Chinese Medicine , Shanghai, China., Department of Cardiovascular, Shuguang Hospital Affiliated to Shanghai University of Chinese Medicine , Shanghai, China.

Abstract:  Objective: As some evidence has demonstrated the role of microRNA-221 (miR-221) on coronary heart disease (CHD), the aim of the present study was to investigate the effect of miR-221-3p on CHD via regulating NLRP3/ASC/pro-caspase-1 inflammasome pathway. Methods: Sixty CHD patients and 60 healthy controls were collected to detect the expression of miR-221-3p, NLRP3, ASC, pro-caspase-1 in peripheral blood and the contents of related factors in serum. The rats model of CHD was injected with miR-221-3p agomir or miR-221-3p antagomir to explore its functions in miR-221-3p, NLRP3, ASC and pro-caspase-1 expression, electrocardiogram data, cardiomyocytes apoptosis, myocardial injury, inflammatory reaction and oxidative stress of CHD rats. Results: MiR-221-3p declined and NLRP3, ASC and pro-caspase-1 raised in CHD. Up-regulated miR-221-3p reduced the change value of J-point and T-wave, decreased NLRP3, ASC and pro-caspase-1 expression, suppressed apoptosis in cardiomyocytes, as well as suppressed myocardial injury, inflammatory reaction and oxidative stress in CHD rats. Conclusion: This study highlights that up-regulated miR-221-3p suppresses the overactivation of NLRP3/ASC/pro-caspase-1 inflammasome pathway and has an anti-inflammatory effect in CHD. Thus, miR-221-3p may serve as a potential target for the treatment of CHD. 

Retracted: No

PubPeer comments:
 Why are we limiting to embryos? The same genotoxicity will happen to any human cells, be it Tcells or [Stem-cells, as in this study] People are [dying in cancer human CRISPR trials] u2013 which are being either ignored or attributed to tumor progression. , 
 Excellent point. We lack access to the tools that would tell us what happens. , 
 Thanks, there is enough data to show that [potential off-targets] are huge for any gRNA. It wont always cut - efficiency goes down the greater the mismatches - but still enough off-targets will be cleaved. And, CRISPR is meant to be non-specific - else viruses would evade it in a day. ,
Just Took a DNA Test, Turns Out 100% Not That Phase
Authors: Aaron D Gitler
Taekjip Ha
Sua Myong
James Shorter
Journal: Molecular Cell (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Heterochromatin protein 1; HP1; heterochromatin formation; liquid-liquid phase separation; digital compaction states
Affiliations: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: ., Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: ., Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: .

Abstract:  Heterochromatin protein 1 (HP1) has been proposed to drive heterochromatin formation by liquid-liquid phase separation. In this issue of Molecular Cell, however, Erdel et al. establish that heterochromatin can adopt digital compaction states that are independent of HP1 phase separation. 

Retracted: No

PubPeer comments:
 ![file] In the family JS-O2, the authors described vermis agenesis (VA). Does it mean that the vermis is totally absent? or not? If the vermis is totally absent, the cerebellar inferior peduncle should be totally absent. Is it the case here? A figure of brain MRI should be very appreciated! , 
 Eucyrtidium Calvertense #1 You are right, the terminology used by Thomas *et al*. is not very rigorous. Indeed, in this paper, one can read: ![file] References 18 and 19 on *KIF7* mutations do not describe vermis agenesis in the patients. Putoux *et al*.: ![file] The fastigium is evidenced on these sagittal sections showing that the vermis is present even if it is hypoplastic. Dafinger *et al*.: ![file] My yellow arrows point to the vermis. On sagittal sections this cerebellar structure could be easily observed. In conclusion, vermis agenesis is not a constant feature of acrocallosal syndrome. It is not a malformation that could be observed in Meckel or Joubert syndromes. Terminology is very important since the mechanisms involved should be radically different. Vermis agenesis supposes that the vermis is never formed suggesting an early event affecting the two primordia of this structure (ventricular zone and rhombic lip). In contrast, vermis hypoplasia suggests that cell proliferation is impaired. Granular cells of the cerebellum proliferate thanks to Sonic Hedgehog (a pathway that is impaired in ciliopathy). This could easily explains the feature of vermis hypoplasia. , 
 ![file] ![file] ![file] Contradiction between the text and the table. Brain anomalies of case 10047 seems to be attributed to case 860. A correction should be proposed. ,
A methylotrophic origin of methanogenesis and early divergence of anaerobic multicarbon alkane metabolism
Authors: Tom A Williams
Gunter Wegener
Jialin Hou
Yinzhao Wang
Xiang Xiao
Ruize Xie
Fengping Wang
Journal: Science Advances (2021)
Discipline: Multidisciplinary
Keywords: Methanogens; anaerobic methane-oxidizing archaea; alkane metabolism; Archaea; evolution
Affiliations: State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China., Max Planck Institute for Marine Microbiology, 28359 Bremen, Germany., MARUM, Center for Marine Environmental Sciences, University of Bremen, 28359 Bremen, Germany., School of Biological Sciences, University of Bristol, BS8 1TH Bristol, UK., School of Oceanography, Shanghai Jiao Tong University, Shanghai 200240, China., Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, Guangdong, China., State Key Laboratory of Ocean Engineering, School of Naval Architecture, Ocean & Civil Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Abstract:  Methanogens are considered as one of the earliest life forms on Earth, and together with anaerobic methane-oxidizing archaea, they have crucial effects on climate stability. Yet, the origin and evolution of anaerobic alkane metabolism in the domain Archaea remain controversial. Here, we show that methanogenesis was already present in the common ancestor of Euryarchaeota, TACK archaea, and Asgard archaea likely in the late Hadean or early Archean eon and that the ancestral methanogen was dependent on methylated compounds and hydrogen. Carbon dioxide-reducing methanogenesis developed later through the evolution of tetrahydromethanopterin S-methyltransferase, which linked methanogenesis to the Wood-Ljungdahl pathway for energy conservation. Multicarbon alkane metabolisms in Archaea also originated early, with genes coding for the activation of short- or even long-chain alkanes likely evolving from an ethane-metabolizing ancestor. These genes were likely horizontally transferred to multiple archaeal clades including Candidatus (Ca) Bathyarchaeota, Ca. Helarchaeota, Ca Hadesarchaeota, and the methanogenic Ca. Methanoliparia. 

Retracted: No

PubPeer comments:
 Retracted. Copy pasted from https: advances.sciencemag.org content 7 8 eabh1051 :  In our Research Article, u201cA methylotrophic origin of methanogenesis and early divergence of anaerobic multicarbon alkane metabolismu201d (1), we unintentionally included some embargoed data in our analyses. These data had been deposited in the open-access NCBI SRA database without propagation of the embargo from the original database. We deeply regret our oversight and to protect the interests of the generators of these data, we have requested retraction of the paper. Science Advances 17 Feb 2021. See https: retractionwatch.com 2021 02 17 no-malicious-intent-authors-retract-week-old-paper-based-on-embargoed-data for backgrounds. ,
MicroRNA-204, a direct negative regulator of ezrin gene expression, inhibits glioma cell migration and invasion
Authors: Kun Lv
Jie Mao
Yingying Zhang
Min Zhong
Mengying Zhang
Journal: Molecular and Cellular Biochemistry (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ezrin; miR-204; Glioma; Migration; Invasion
Affiliations: Department of Neurosurgery of The first affiliated Hospital, Wannan Medical College, 2 West Zheshan Road, Wuhu, 241001, Anhui, People's Republic of China.

Abstract:  Ezrin is overexpressed in a variety of neoplastic cells and involved in the later stages of tumor progression and metastasis. Ezrin expression can be regulated at both the transcriptional and post-transcriptional levels. We used a combination of bioinformatics and experimental techniques to demonstrate that the miR-204 is a direct negative regulator of ezrin. Overexpression of miR-204 mimics decreased the activity of a luciferase reporter containing the ezrin 3' UTR and led to repression of ezrin protein. In contrast, ectopic expression of miR-204 inhibitor elevated ezrin expression. We also show that miR-204 is down-regulated in a panel of glioma tissues and in high invasive glioma cell lines we examined. Moreover, miR-204 mimics significantly reduced glioma cell migration and invasion, while miR-204 inhibitor generated the opposite results. Finally, overexpression of miR-204 and knockdown of ezrin reduced glioma cell invasion, and these effects could be rescued by re-expression of ezrin. These findings reveal that miR-204 could be partly due to its inhibitory effects on glioma cell migration and invasion through regulating ezrin expression. 

Retracted: No

PubPeer comments:
 Figures 4E and 5C. * Red boxes: two panels appear to show an overlap. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. ![file] ,
Reversibility of epithelial-mesenchymal transition (EMT) induced in breast cancer cells by activation of urokinase receptor-dependent cell signaling
Authors: Boryana Eastman
Valerie Montel
Robin D Lester
Minji Jo
Steven L Gonias
Shinako Takimoto
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hypoxia; urokinase receptor (uPAR); epithelial-mesenchymal transition (EMT); cancer cells; cell signaling
Affiliations: Department of Pathology, University of California, San Diego, California 92093, USA.

Abstract:  Hypoxia induces expression of the urokinase receptor (uPAR) and activates uPAR-dependent cell signaling in cancer cells. This process promotes epithelial-mesenchymal transition (EMT). uPAR overexpression in cancer cells also promotes EMT. In this study, we tested whether uPAR may be targeted to reverse cancer cell EMT. When MDA-MB 468 breast cancer cells were cultured in 1% O(2), uPAR expression increased, as anticipated. Cell-cell junctions were disrupted, vimentin expression increased, and E-cadherin was lost from cell surfaces, indicating EMT. Transferring these cells back to 21% O(2) decreased uPAR expression and reversed the signs of EMT. In uPAR-overexpressing MDA-MB 468 cells, EMT was reversed by silencing expression of endogenously produced urokinase-type plasminogen activator (uPA), which is necessary for uPAR-dependent cell signaling, or by targeting uPAR-activated cell signaling factors, including phosphatidylinositol 3-kinase, Src family kinases, and extracellular signal-regulated kinase. MDA-MB 231 breast cancer cells express high levels of uPA and uPAR and demonstrate mesenchymal cell morphology under normoxic culture conditions (21% O(2)). Silencing uPA expression in MDA-MB-231 cells decreased expression of vimentin and Snail, and induced changes in morphology characteristic of epithelial cells. These results demonstrate that uPAR-initiated cell signaling may be targeted to reverse EMT in cancer. 

Retracted: No

PubPeer comments:
 ![file] Undeclared splicing sites in Fig 1D. The two panels are from different images. could the author show the original data? ,
Quantification and evaluation of thymoquinone loaded mucoadhesive nanoemulsion for treatment of cerebral ischemia
Authors: Md Aftab Alam
Mohd Samim
Niyaz Ahmad
Zeenat Iqbal
Rizwan Ahmad
Farhan Jalees Ahmad
Journal: International Journal of Biological Macromolecules (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Brain pharmacokinetics; Cerebral ischemia; Nanoemulsion; Thymoquinone; UPLC-PDA method validation.
Affiliations: Department of Pharmaceutics, College of Clinical Pharmacy, University of Dammam, Dammam 31441, Saudi Arabia. Electronic address: ., Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, University of Dammam, Dammam 31441, Saudi Arabia., Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Gautam Budh Nagar, Greater Noida 201310, India., Department of Chemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India., Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.

Abstract:  Stroke is an important cause of deaths worldwide, resulting in an irreversible deterioration of the central nervous system. Finally, production of more free radicals. Therefore, Thymoquinone is having antioxidant property and reported to have a potential role in the amelioration of cerebral ischemia but due to low solubility and poor absorption; they exhibit low serum and tissue levels. Present work aims to prepare nanoemulsions in order enhance the bioavailability of drug and hence evaluate the drug targeting in brain via non-invasive nasal route administration. Thymoquinone Mucoadhesive Nanoemulsion (TMNE) was prepared by ionic gelation method; characterized for particles size, entrapment efficiency, zeta potential, and ex vivo permeation study. Optimized TMNE ended up with a mean globule size 94.8±6.61nm; zeta potential -13.5±1.01mV; drug content 99.86±0.35% and viscosity 110±12cp. Ultra Performance Liquid Chromatography-Photodiode Array (UPLC-PDA) based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (628.5786±44.79%) and brain drug-targeting potential (89.97±2.94%) studies via post intranasal administration which revealed enhanced bioavailability of TQ in brain as compared to intravenous administration. Improved neurobehavioural activity (locomotor and grip strength) was observed in middle cerebral artery occlusion induced cerebral ischemic rats after i.n. administration of TMNE. 

Retracted: No

PubPeer comments:
 *[Right]* Fig 4,  Transmission electron microscopy (TEM) images of optimized Thymoquinone Mucoadhesive Nanoemulsion . *[Left]* Figure 2 from [Ahmad et al (2018)] ,  Scanning electron microscopy (SEM) ... (B) images of DTX-loaded-CS-coated-PLGA-NPs. ![file] ,
Long non-coding RNA DLGAP1-AS1 facilitates tumorigenesis and epithelial–mesenchymal transition in hepatocellular carcinoma via the feedback loop of miR-26a/b-5p/IL-6/JAK2/STAT3 and Wnt/β-catenin pathway
Authors: Xiangling Wei
Renguo Guan
Ye Lin
Haosheng Jin
Xiongfeng Zou
Zhixiang Jian
Jianfeng Huang
Journal: Cell death & disease (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hepatocellular carcinoma; epithelial-mesenchymal transition; long noncoding RNAs; lncRNA DLGAP1-AS1; tumorigenesis
Affiliations: Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, China. ., Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, China.

Abstract:  Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide, and epithelial-mesenchymal transition (EMT) is a crucial factor affecting HCC progression and metastasis. Long noncoding RNAs (lncRNAs) have been validated to act as critical regulators of biological processes in various tumors. Herein, we attempted to elucidate the uncharacterized function and mechanism of lncRNA DLGAP1-AS1 in regulating tumorigenesis and EMT of HCC. In our study, DLGAP1-AS1 was shown to be upregulated in HCC cell lines and capable to promote HCC progression and EMT. Besides, DLGAP1-AS1 was proven to serve as a molecular sponge to sequester the HCC-inhibitory miRNAs, miR-26a-5p and miR-26b-5p, thus enhancing the level of an oncogenic cytokine IL-6, which could activate JAK2/STAT3 signaling pathway and reciprocally elevate the transcriptional activity of DLGAP1-AS1, thus forming a positive feedback loop. Moreover, we elaborated that the cancerogenic effects of DLGAP1-AS1 in HCC cells could be effectuated via activating Wnt/β-catenin pathway by positively regulating CDK8 and LRP6, downstream genes of miR-26a/b-5p. In conclusion, our results demonstrated the detailed molecular mechanism of DLGAP1-AS1 in facilitating HCC progression and EMT in vitro and in vivo, and suggested the potentiality of DLGAP1-AS1 as a therapeutic target for HCC. 

Retracted: No

PubPeer comments:
 Figure 8, Western-blot bands for CDK8 was totally inconsistent with the authorsu2019 text description. As the authors said, both CDK8 and LRP6 have been identified to be a hallmark regulator to activate Wnt u03b2-catenin signaling. Besides, both CDK8 and LRP6 have been reported to act as oncogenes in HCC. As a consequence, these two genes were chosen as their study objects, and should have the same expression trend in Figure 8E. Surprisingly, Figure 8E, the expression level of CDK8 showed in the Western-blot was ultimately opposite to the other experiments. ![file] ![file] ,