PReD-Bench/PRed-Bench huggingface dataset:
OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin
Authors: Xiaohui Liu
Liqun Chen
Yiguo Wang
Jinbo Han
Tong Li
Haili Shan
Yang Liu
Liangjie Jia
Yuanyuan Zhang
Fangchao Wei
Haiteng Deng
Aijun Long
Erwei Li
Journal: Cell Metabolism (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: OLFR734; asprosin; cAMP; gluconeogenesis.
Affiliations: MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China., National Protein Science Technology Center, Tsinghua University, 100084 Beijing, China., MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, 100084 Beijing, China., MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China. Electronic address: .

Abstract:  Asprosin is a fasting-induced hormone that promotes glucose production in the liver and stimulates appetite in the hypothalamus by activating the cAMP signaling pathway via an unknown G protein-coupled receptor (GPCR). However, the bona fide receptor of Asprosin is unclear. Here, we have identified that the olfactory receptor OLFR734 acts as a receptor of Asprosin to modulate hepatic glucose production. Olfr734 knockout mice show a blunted response to Asprosin, including attenuated cAMP levels and hepatic glucose production, and improved insulin sensitivity. As Olfr734 deficiency dramatically attenuates both fasting and high-fat-diet-induced glucose production, our results demonstrate a critical role of OLFR734 as a receptor of Asprosin to maintain glucose homeostasis during fasting and in obesity. 

Retracted: No

PubPeer comments:
 This is confusing considering that Cell Metabolism previously published that low-endotoxin and non-aggregating asprosin doesn t regulate glucose metabolism: PMID: 30879984 , 
 #1 This paper states  Of note, quality of asprosin protein is critical for its activity , and explains that by using a GST-tag they were able to generate soluble and active asprosin. Thus, seems like PMID: 30879984 made poor quality asprosin protein and then found that it did not have activity. ,
Phosphoproteomic analysis of cells treated with longevity-related autophagy inducers
Authors: Jens S Andersen
Dennis Pultz
Martin V Bennetzen
Nils J Færgeman
Guillermo Mariño
Guido Kroemer
Eugenia Morselli
Journal: Cell Cycle (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Macroautophagy; autophagy; resveratrol; spermidine; phosphoproteome
Affiliations: Center for Experimental BioInformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.

Abstract:  Macroautophagy is a self-cannibalistic process that enables cells to adapt to various stresses and maintain energy homeostasis. Additionally, autophagy is an important route for turnover of misfolded proteins and damaged organelles, with important implications in cancer, neurodegenerative diseases and aging. Resveratrol and spermidine are able to induce autophagy by affecting deacetylases and acetylases, respectively, and have been found to extend the life-span of model organisms. With the aim to reveal the signaling networks involved in this drug-induced autophagic response, we quantified resveratrol and spermidine-induced changes in the phosphoproteome using SILAC and mass spectrometry. The data were subsequently analyzed using the NetworKIN algorithm to extract key features of the autophagy-responsive kinase-substrate network. We found that two distinct sequence motifs were highly responsive to resveratrol and spermidine and that key proteins modulating the acetylation, phosphorylation, methylation and ubiquitination status were affected by changes in phosphorylation during the autophagic response. Essential parts of the apoptotic signaling network were subjected to post-translational modifications during the drug-induced autophagy response, suggesting potential crosstalk and balancing between autophagy and apoptosis. Additionally, we predicted cellular signaling networks affected by resveratrol and spermidine using a computational framework. Altogether, these results point to a profound crosstalk between distinct networks of post-translational modifications and provide a resource for future analysis of autophagy and cell death. 

Retracted: No

PubPeer comments:
 Readers should become aware of a recent paper published in JBC showing that autophagy induction by exogenous polyamines (including spermidine) is an artifact of BSA oxidase activity in culture serum. https: www.jbc.org content early 2020 05 19 jbc.RA120.013867.abstract From the article:  Consequently, considerable caution must be used when interpreting much of the published mechanistic data produced in in vitro cell culture systems as any observed autophagy included in such systems is likely the result of the toxic metabolites formed by BSAO following polyamines addition to the serum-containing medium and not a function of the polyamines themselves ,
Induction of Highly Functional Hepatocytes from Human Umbilical Cord Mesenchymal Stem Cells by HNF4α Transduction
Authors: Qiang Xia
Yabin Yu
Ning Wu
Hualian Hang
Qingfeng Huang
Jianmin Bian
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: HuMSCs; hepatic differentiation; HNF4α; hepatocyte-like cells; differentiation potential
Affiliations: Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Jiao Tong University, Shanghai, China; Department of General Surgery, Nanjing Hospital Affiliated to NanJing Medical University, Nanjing, China., Department of General Surgery, Nanjing Hospital Affiliated to NanJing Medical University, Nanjing, China., Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Jiao Tong University, Shanghai, China.

Abstract:  Aim: To investigate the differentiation potential of human umbilical mesenchymal stem cells (HuMSCs) and the key factors that facilitate hepatic differentiation. Methods: HuMSCs were induced to become hepatocyte-like cells according to a previously published protocol. The differentiation status of the hepatocyte-like cells was examined by observing the morphological changes under an inverted microscope and by immunofluorescence analysis. Hepatocyte nuclear factor 4 alpha (HNF4α) overexpression was achieved by plasmid transfection of the hepatocyte-like cells. The expression of proteins and genes of interest was then examined by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods. Results: Our results demonstrated that HuMSCs can easily be induced into hepatocyte-like cells using a published differentiation protocol. The overexpression of HNF4α in the induced HuMSCs significantly enhanced the expression levels of hepatic-specific proteins and genes. HNF4α overexpression may be associated with liver-enriched transcription factor networks and the Wnt/β-Catenin pathway. Conclusion: The overexpression of HNF4α improves the hepatic differentiation of HuMSCs and is a simple way to improve cellular sources for clinical applications. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have a repeated image, although oddly the color and cropping appear different. *** ![file] ,
Quercetin Attenuates Atherosclerosis Modulating Oxidized LDL-Induced Endothelial Cellular Senescence
Authors: Yue-Hua Jiang
Du-Fang Ma
Xiao Li
Ling-Yu Jiang
Yong-Cheng Wang
Journal: Frontiers in pharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ApoE-/- mice; atherosclerosis; endothelial cellular senescence; oxidized low-density lipoprotein; quercetin.
Affiliations: Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China., First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China., Cardiovascular Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

Abstract:  Background and aims: Endothelial senescence is an important risk factor leading to atherosclerosis. The mechanism of quercetin against endothelial senescence is worth exploring. Methods: Quercetin (20 mg/kg/d) was administered to ApoE-/- mice intragastrically to evaluate the effectiveness of quercetin on atherosclerotic lesion in vivo. In vitro, human aortic endothelial cells (HAECs) were used to assess the effect of quercetin on cellular senescence induced by oxidized low-density lipoprotein (ox-LDL). Transcriptome microarray and quantitative RT-PCR was conducted to study the pharmacological targets of quercetin. Results: ApoE-/- mice demonstrated obvious lipid deposition in arterial lumina, high level of serum sIcam-1 and IL-6, and high density of Vcam-1 and lower density of Sirt1 in aorta. Quercetin administration decreased lipid deposition in arterial lumina, serum sIcam-1, and IL-6 and Vcam-1 in aorta, while increased the density of Sirt1 in aorta of ApoE-/- mice. In vitro, quercetin (0.3, 1, or 3 μmol/L) decreased the expression of senescence-associated β-galactosidase and improved cell morphology of HAECs. And quercetin decreased the cellular apoptosis and increased mitochondrial membrane potential (ΔΨm) in dose-dependent manner, and decreased ROS generation simultaneously. Transcriptome microarray suggested 254 differentially expressed (DE) mRNAs (110 mRNAs were upregulated and 144 mRNAs were downregulated) in HAECs after quercetin treatment (fold change &gt; 1.5, P &lt; 0 .05, Que vs Ox-LDL). GO and KEGG analysis indicated nitrogen metabolism, ECM-receptor interaction, complement, and coagulation cascades, p53 and mTOR signaling pathway were involved in the pharmacological mechanisms of quercetin against ox-LDL. Conclusions: Quercetin alleviated atherosclerotic lesion both in vivo and in vitro. 

Retracted: No

PubPeer comments:
 Two images in figure 3C appear to overlap. *** ![file] *** ![file] , 
 I m really sorry that this is a proof mistakes. We just found out about this mistake and actively contacted the magazine to change the picture. Thank you for pointing it out! ,
Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage
Authors: Xing Hua Wang
Fa Gang Jiang
Zhi Rong Xu
Jia Hua Fang
Journal: BMC Neuroscience (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Glutamate-mediated excitotoxicity; N-methyl-D-aspartate (NMDA) receptors; retinal ganglion cells (RGCs); Bis(7)-tacrine; neuroprotective effects
Affiliations: Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Abstract:  Background: Glutamate-mediated excitotoxicity, primarily through N-methyl-D-aspartate (NMDA) receptors, may be an important cause of retinal ganglion cells (RGCs) death in glaucoma and several other retinal diseases. Bis(7)-tacrine is a noncompetitive NMDA receptors antagonist that can prevent glutamate-induced hippocampal neurons damage. We tested the effects of bis(7)-tacrine against glutamate-induced rat RGCs damage in vitro and in vivo. Results: In cultured neonatal rats RGCs, the MTT assay showed that glutamate induced a concentration- and time-dependent toxicity. Bis(7)-tacrine and memantine prevented glutamate-induced cell death in a concentration-dependent manner with IC50 values of 0.028 microM and 0.834 microM, respectively. The anti-apoptosis effects of bis(7)-tacrine were confirmed by annexin V-FITC/PI staining. In vivo, TUNEL analysis and retrograde labeling analysis found that pretreatment with bis(7)-tacrine(0.2 mg/kg) induced a significant neuroprotective effect against glutamate-induced RGCs damage. Conclusions: Our results showed that bis(7)-tacrine had neuroprotective effects against glutamate-induced RGCs damage in vitro and in vivo, possibly through the drug's anti-NMDA receptor effects. These findings make bis(7)-tacrine potentially useful for treating a variety of ischemic or traumatic retinopathies inclusive of glaucoma. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Preparation of a MoS2/carbon nanotube composite as an electrode material for high-performance supercapacitors
Authors: Jing Jiang
Xiaobo Chen
Guoce Zhuang
Jingguo Ding
Zhihai Zhang
Peizhi Yang
Journal: RSC Advances (2018)
Discipline: CHEMISTRY
Keywords: MoS2; MoS2/C; anodes; supercapacitors; carbon-based materials
Affiliations: School of New Energy and Electronic Engineering, Yancheng Teachers University, Yancheng, P. R. China, Key Laboratory of Education Ministry for Advance Technique and Preparation of Renewable Energy Materials, Institute of Solar Energy, Yunnan Normal University, Kunming

Abstract:  MoS2 and MoS2/carbon allotrope (MoS2/C) composites for use as anodes in supercapacitors were prepared via a facile hydrothermal method. In this study, we report the effects of various carbon-based materials (2D graphene nanosheet (GNS), 1D carbon nanotube (CNT), and 0D nano carbon (NC)) on the electrochemical performances. Among all nanocomposites studied, MoS2/CNT exhibited the best electrochemical performance. Specifically, the MoS2/CNT composite exhibits remarkable performances with a high specific capacitance of 402 F g-1 at a current density of 1 A g-1 and an outstanding cycling stability with 81.9% capacitance retention after 10 000 continuous charge-discharge cycles at a high current density of 1 A g-1, making it adaptive for high-performance supercapacitors. The superiority of MoS2/CNT was investigated by field emission scanning electron microscopy and transmission electron microscopy, which showed that MoS2 nanosheets were uniformly loaded into the three-dimensional interconnected network of nanotubes, providing an excellent three dimensional charge transfer network and electrolyte diffusion channels while effectively buffering the collapse and aggregation of active materials during charge-discharge processes. Overall, the MoS2/CNT nanocomposite synthesized by a simple hydrothermal process presents a new and promising candidate for high-performance anodes for supercapacitors. 

Retracted: No

PubPeer comments:
 Figure 1 shows two identical XRD patterns for different samples. ![file] ,
Treatment with Panax ginseng antagonizes the estrogen decline in ovariectomized mice
Authors: Zhi-Qiang Liu
Ying-Hui Ma
Na Lin
Jie Ding
Xiao-Ping Ma
Ying Xu
Journal: International journal of molecular sciences (2014)
Discipline: CHEMISTRY
Keywords: Ginseng; menopausal symptoms; estrogenic efficacy; OVX mice; estrus cycle
Affiliations: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Dongzhimen Nanxiao Road 16, Beijing 100700, China. ., Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Renmin Road 5625, Changchun 130022, China. .

Abstract:  Ginseng is a popular herb for alleviating menopausal symptoms; however, no conclusive scientific data has shown ginseng as being efficient in such therapies. The present study was designed to evaluate the estrogenic efficacy of ginseng on reproductive target tissues of ovariectomized (OVX) mice. The OVX mice were treated with ginseng at doses of 12.0, 18.0 and 24.0 g/kg per day for four weeks. Ginseng treatments restored the estrus cycle and demonstrated significant estrogenic activity, as indicated by the reversal of the atrophy of the uterus and vagina, upregulation of estrogen receptor (ER) α and ER β expression at the protein and mRNA level in the reproductive tissues, where ER α upregulation was stronger than that of ER β. Meanwhile, treatment with ginseng significantly increased adrenal gland weight and serum estradiol and clearly decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in circulation. Notably, the largest changes in these parameters were found at the highest dose of 24.0 g/kg. Moreover, ginseng at 18.0 g/kg resulted in the greatest decrease in weight gain caused by ovariectomy. The data suggest that ginseng estrogenic responses show tissue variation that reflects different affinities of ERs for ginseng components. This study demonstrates that ginseng activity is mediated through estrogenic components and provides further evidence for ginseng treatment of postmenopausal symptoms. 

Retracted: Yes

PubPeer comments:
  Figure 6. The effects of ginseng (GS) treatment on the expressions of estrogen receptor (ER) u03b1 and (ER) u03b2 in the uterus and vagina. ER u03b1 and ER u03b2 expressions were assessed by quantitative immunohistochemistry. Representative photomicrographs taken at 400u00d7 magnification of uterus and vagina sections from each treatment group are shown: (i) sham-operated mice; (ii) untreated ovariectomized (OVX) mice; (iii) OVX mice treated with estradiol valerate; (iv) OVX mice treated with GS 12.0 g kg; **(vi) 18.0 g kg** (v) and 24.0 g kg.  ![] Please compare with Fig 4 from [Jie et al (2015)] ,  The effects of GS treatment on the expressions of ERu03b1 and ERu03b2 in the uterus and vagina .... F1-J1: the expression of ERu03b1 of Con, EV, GS 12.0, **18.0** and 24.0 g kg in the vagina; F2-J2: the expression of ERu03b2 of Con, EV, GS 12.0, 18.0 and 24.0 g kg in the vagina. ![file] One panel appears in both Figures. Can the authors indicate whether these were the same or separate studies? Also, were the mice immature or ovariectomised? ,
Pharmaceutical and immunological evaluation of mucoadhesive nanoparticles based delivery system(s) administered intranasally
Authors: D S V Raman Rao
S P Vyas
Neeraj K Garg
K S Jaganathan
Arvind K Jain
Sharad Mangal
Dilip Pawar
Journal: Vaccine (2011)
Discipline: IMMUNOLOGY
Keywords: Tri-methyl chitosan; synthesis; polymer chain scission; carrier properties; adjuvant properties
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar 470003, Madhya Pradesh, India.

Abstract:  Tri-methyl chitosan synthesis accompanies polymer chain scission, which may affect the carrier and adjuvant properties of the polymer. The main objective of this study was to synthesize the tri-methylated chitosan using mild (TMC-M) and conventional (TMC) method and compare their efficacy as nasal vaccine delivery vehicle. During in vitro studies TMC-M nanoparticles showed the lowest nasal clearance rate when compared with chitosan (CS) and TMC nanoparticles. The immunogenicity of nanoparticles based delivery system(s) was assessed by measuring anti-HBsAg antibody titer in mice serum and secretions after intranasal administration. The alum based HBsAg vaccine injected subcutaneously was used as positive control. Results indicated that alum based HBsAg induced strong humoral but negligible mucosal immunity. However, TMC-M nanoparticles induced stronger immune response at both of the fronts as compared to generated by CS or TMC nanoparticles. Present study demonstrates that TMC-M can be a better carrier adjuvant for nasal subunit vaccines. 

Retracted: No

PubPeer comments:
  Fig. 1. SEMphotomicrographs:[A] TMCnanoparticles and[B] TMC-Mnanoparticles . ![file] Who did this to you, Fig 1? , 
 Also of interest: ![file] Below is Fig 1A from [Mangal et al (2014)] . , 
 Fig. 5.  Nasal uptake studies: fluorescent microscopy images showing the nasal uptake of dye (FITCu2013BSA) loaded nanoparticles. (A) FITCu2013BSA; (B) CS nanoparticles; (C) TMC nanoparticles; (D) TMC-M nanoparticles. (B) and (D) overlap, in a partial way that shakes my faith in the integrity of the images: (D) is a composite of two sections of (B), one rotated through 180 deg. ![file] , 
 Two other versions of Fig 5(B). Middle, Fig 4 from [Jain et al (2009)] .  Fluorescent microscopy images showing the uptake of FITCu2013BSA loaded different nanoparticles by mucosal surface after intranasal administration. (A) Soluble FITCu2013BSA (control); (B) AB NPs; **(C) ABA NPs**; (D) BAB NPs. At right, Fig 3 from [Pawar et al (2010)] .  Fluorescence microscopy images showing the uptake of FITC-BSA loaded microparticles in NALT. a Soluble FITC-BSA (PBS, pH 7.4). b Plain poly(lactic-co-glycolic acid) (PLGA) microparticles. **c PLGAC microparticles**. d PLGA-TMC microparticles.  ![file] Mustn t forget Fig 7 from [Mangal et al (2014)] , here at bottom.  Fluorescence photograph of mice peyer u2019 s patch. (A). Mice treated with FITC-BSA solution; **(B). Mice treated with A-CHMps loaded with FITC u2013 BSA. Hot-Spot indicated by arrows showing the uptake of A-CHMps by peyeru2019s patch of mice**. ![] ,
A screen for genes of heme uptake identifies the FLC family required for import of FAD into the endoplasmic reticulum
Authors: Olga Protchenko
Rachel Androphy
Caroline C Philpott
Roberto Rodriguez-Suarez
Howard Bussey
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Candida albicans; Saccharomyces cerevisiae; iron uptake; heme; CaFLC1
Affiliations: Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract:  Although Candida albicans and Saccharomyces cerevisiae express very similar systems of iron uptake, these species differ in their capacity to use heme as a nutritional iron source. Whereas C. albicans efficiently takes up heme, S. cerevisiae grows poorly on media containing heme as the sole source of iron. We identified a gene from C. albicans that would enhance heme uptake when expressed in S. cerevisiae. Overexpression of CaFLC1 (for flavin carrier 1) stimulated the growth of S. cerevisiae on media containing heme iron. In C. albicans, deletion of both alleles of CaFLC1 resulted in a decrease in heme uptake activity, whereas overexpression of CaFLC1 resulted in an increase in heme uptake. The S. cerevisiae genome contains three genes with homology to CaFLC1, and two of these, termed FLC1 and FLC2, also stimulated growth on heme when overexpressed in S. cerevisiae. The S. cerevisiae Flc proteins were detected in the endoplasmic reticulum and the FLC genes encoded an essential function, as strains deleted for either FLC1 or FLC2 were viable, but deletion of both FLC1 and FLC2 was synthetically lethal. FLC gene deletion resulted in pleiotropic phenotypes related to defects in cell wall integrity. High copy suppressors of this synthetic lethality included three mannosyltransferases, VAN1, KTR4, and HOC1. FLC deletion strains exhibited loss of cell wall mannose phosphates, defects in cell wall assembly, and delayed maturation of carboxypeptidase Y. Permeabilized cells lacking FLC proteins exhibited dramatic loss of FAD import activity. We propose that the FLC genes are required for import of FAD into the lumen of the endoplasmic reticulum, where it is required for disulfide bond formation. 

Retracted: No

PubPeer comments:
 This was using CRISPR on the exact spot in the N-terminal of the spike protein (in the related TGEV coronavirus), [which is the most perturbed] . This [500bp is completely unique] to the nCoV - and can be used for diagnosis (which is including [SARS] ), vaccine or even inhibition. ,
Circular RNA circ_0074027 indicates a poor prognosis for NSCLC patients and modulates cell proliferation, apoptosis, and invasion via miR‐185‐3p mediated BRD4/MADD activation
Authors: Xuan Jiao
Yue Yao
Zhanliang Hu
Ping Gao
Zhidong Wang
Journal: Journal of Cellular Biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BRD4; MADD; NSCLC; circRNA; circ_0074027
Affiliations: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Harbin, China., Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China., Department of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract:  Circular RNAs play an imperative role in cancer development and metastasis by regulating oncogenic and tumor-suppressive pathways. However, the role and mechanism of circ_0074027 in non-small-cell lung cancer (NSCLC) have not been elucidated. The expression levels of circ_0074027 were detected by qRT-PCR. The link between circ_0074027 expression and clinicopathologic parameters was analyzed by Fisher's exact test. The prognostic role of circ_0074027 was investigated by Kaplan-Meier and Cox regression analysis. Cell counting kit-8 and flow cytometric assays were utilized to evaluate NSCLC cell proliferation and apoptosis, respectively. Wound scratch and Transwell tests were applied to detect cell migratory and invasive capacities. The interaction potential of circ_0074027 and miR-185-3p was analyzed by the circBank database, and verified by dual-luciferase reporter assay. The downstream gene of miR-185-3p was also investigated. Circ_0074027 was elevated in NSCLC specimens and cell lines. Overexpressed circ_0074027 was related to more advanced TNM stages, poorer differentiation grade, and worse overall survival. Upregulated circ_0074027 increased the proliferation of H1299 cells by inhibiting cell apoptosis. Cell migration and invasion were enhanced after circ_0074027 overexpression. Silenced circ_0074027 caused the opposite effects in the A549 cell line. For mechanism investigation, circ_0074027 directly sponges miR-185-3p to enhance bromodomain-containing protein 4 (BRD4) and MAPK-activating death domain-containing protein (MADD) expression levels at the posttranscriptional level. Furthermore, we found the oncogenic function of circ_0074027 is attributed to its modulation of BRD4 and MADD. Collectively, upregulated circ_0074027 in NSCLC accelerates cell progression via miR-185-3p/BRD4/MADD pathway as a competing endogenous RNA. 

Retracted: No

PubPeer comments:
 Figures 2F and 4D: * Yellow boxes: Two panels appear to show an overlap. ![file] ,
Elucidation of the dimeric interplay of dual MRAP2 proteins in the zebrafish
Authors: Qi Liu
Daofu Cheng
Chao Zhang
Meng Wang
Song Xue
Cong Zhang
Na Li
Liumei Lu
Yue Zhai
Shaliu Fu
Journal: Journal of Cellular Physiology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MC4R; MRAP2; heterodimer; homodimer; zebrafish.
Affiliations: Department of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China, Shanghai Key Laboratory of Signaling and Disease Research, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology Tongji University  Shanghai China, Yantai Derui Bio‐Tech Co.,Ltd  Yantai Shandong China

Abstract:  The melanocortin receptor accessory protein 2 (MRAP2) plays an essential role in the regulation of metabolic homeostasis and deletion of which results in severe obesity syndrome in mice and human. Mammalian MRAP2 is recognized as an endogenous physiological mediator through the potentiation of the MC4R signaling in vivo. Two isoforms of MRAP2 are identified in zebrafish genome, zMRAP2a and zMRAP2b. However, the mechanism of assembling dual topology and the regulatory roles of each complex on the melanocortin cascades remains unclear. In this study, we showed the bidirectional homo- and hetero-dimeric topologies of two zebrafish MRAP2 isoforms on the plasma membrane. Orientation fixed chimeric proteins could affect the trafficking and pharmacological properties of zMC4R signaling. Reciprocal replacement of zMRAP2a and zMRAP2b proteins elucidated the major participation of the carboxyl terminal as the functional domain for modulating zMC4R signaling. Our findings revealed the complex and dynamic conformational regulation of dual zebrafish MRAP2 proteins in vitro. 

Retracted: No

PubPeer comments:
 At right, Fig 2,  TEM images of Fe-CMC nanoparticles . At left, Fig 6 from from [Bajpai Bundela (2010)] .  TEM image showing the crystal size of HA particles in nano range. ![file] . Which is it? ,
Amentoflavone induces apoptosis and suppresses glycolysis in glioma cells by targeting miR-124-3p
Authors: Zhang Xiaohua
Wang Zhaohui
Wu Liugeng
Lin Hongli
Zhang Hui
Yang Linfeng
Wang Haijing
Tian Feng
Niu Yingli
Fang Chao
Jiang Hong
Journal: Neuroscience letters (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Amentoflavone; Apoptosis; DNMT1; Glioma; Glycolysis
Affiliations: The Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao, Shandong, China., The Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao, Shandong, China. Electronic address: .

Abstract:  Malignant glioma is the most common type of brain tumor with poor clinical outcome and survival. Therefore, it is imperative to develop novel therapeutic agents for managing glioma. The aim of this study was to investigate the role of amentoflavone (AF), an active flavonoid component in Selaginella tamariscina Spring, in glioma cells and the underlying mechanism of its action. Our results showed that miR-124-3p expression was significantly down-regulated in glioma tissues relative to normal brain tissues. AF decreased cell viability and triggered apoptosis in both glioma cell lines in a dose-dependent manner. AF induced apoptosis and inhibited glycolysis in the glioma cells by upregulating miR-124-3p. Furthermore, AF upregulated miR-124-3p by repressing DNMT1 through Sp1, which in turn was caused by the activation of ROS/AMPK signaling pathway by AF. In conclusion, AF could induce apoptosis and inhibited glycolysis in glioma cells via miR-124-3p. Our findings provide preliminary experimental data that support further investigation on the therapeutic efficacy of AF in glioma. 

Retracted: No

PubPeer comments:
 Fig 4C:  MiR-124-3p mediates the anti-proliferative and pro-apoptotic effect of AF on glioma cells. ... MiR124-3p inhibitor attenuated AF-induced... C. apoptosis ![file] 8B:  Figure 8. Suppression of Sp1 DNMT1 by ROS AMPK activation mediates the antitumor effects of AF...., B. AF-induced apoptosis was inhibited . ![file] Resolution is not ideal, but it can be seen that one pair of panels are identical except for the lower-right quadrant - even quadrant percentages are the same - while the same is true for another set of four panels. Other versions of these panels can be found across a sprawling oeuvre of papers, as in this montage: ![] ,
Orientia tsutsugamushi stimulates an original gene expression program in monocytes: relationship with gene expression in patients with scrub typhus
Authors: Duangdao Waywa
Eric Ghigo
Jean-Louis Mege
Chanin Limwongse
Wiwit Tantibhedhyangkul
Adil El Filali
Christian Capo
Didier Raoult
Yupin Suputtamongkol
Wanna Thongnoppakhun
Thanavadee Prachason
Journal: PLoS neglected tropical diseases (2011)
Discipline: IMMUNOLOGY
Keywords: Orientia tsutsugamushi; scrub typhus; monocytes; microarray analysis; type I interferon
Affiliations: Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, Centre National de la Recherche Scientifique - Institut de Recherche pour le Développement Unité Mixte de Recherche 6236, Université de la Méditerranée, Faculté de Médecine, Marseille, France.

Abstract:  Orientia tsutsugamushi is the causal agent of scrub typhus, a public health problem in the Asia-Pacific region and a life-threatening disease. O. tsutsugamushi is an obligate intracellular bacterium that mainly infects endothelial cells. We demonstrated here that O. tsutsugamushi also replicated in monocytes isolated from healthy donors. In addition, O. tsutsugamushi altered the expression of more than 4,500 genes, as demonstrated by microarray analysis. The expression of type I interferon, interferon-stimulated genes and genes associated with the M1 polarization of macrophages was significantly upregulated. O. tsutsugamushi also induced the expression of apoptosis-related genes and promoted cell death in a small percentage of monocytes. Live organisms were indispensable to the type I interferon response and apoptosis and enhanced the expression of M1-associated cytokines. These data were related to the transcriptional changes detected in mononuclear cells isolated from patients with scrub typhus. Here, the microarray analyses revealed the upregulation of 613 genes, which included interferon-related genes, and some features of M1 polarization were observed in these patients, similar to what was observed in O. tsutsugamushi-stimulated monocytes in vitro. This is the first report demonstrating that monocytes are clearly polarized in vitro and ex vivo following exposure to O. tsutsugamushi. These results would improve our understanding of the pathogenesis of scrub typhus, during which interferon-mediated activation of monocytes and their subsequent polarization into an M1 phenotype appear critical. This study may give us a clue of new tools for the diagnosis of patients with scrub typhus. 

Retracted: No

PubPeer comments:
 All the figures published in FIg. 3 of this study were already published in a previous article of this group, however, this is not mentioned in the figure legends neither in the article ![file] ,
Phosphatidylinositol 3-kinase p85{alpha} subunit-dependent interaction with BCR/ABL-related fusion tyrosine kinases: molecular mechanisms and biological consequences
Authors: Shu-Yue Ren
Andrea Morrione
Benjamin G Neel
Elisabeth Bolton
M Golam Mohi
Tomasz Skorski
Journal: Molecular and Cellular Biology (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p85alpha; phosphatidylinositol 3-kinase; oncogenic fusion tyrosine kinases; BCR/ABL; TEL/ABL
Affiliations: Molecular Carcinogenesis Section, Center for Biotechnology, College of Science and Technology, Temple University, BLSB 419, 1900 N. 12th Street, Philadelphia, PA 19122, USA., Molecular Carcinogenesis Section, Center for Biotechnology, College of Sciences and Technology, Temple University, Philadelphia, Pennsylvania 19122, Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Institute of Medicine, Boston, Massachusetts 02215, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Abstract:  The p85alpha subunit of phosphatidylinositol 3-kinase (PI-3k) forms a complex with a protein network associated with oncogenic fusion tyrosine kinases (FTKs) such as BCR/ABL, TEL/ABL, TEL/JAK2, TEL/PDGFbetaR, and NPM/ALK, resulting in constitutive activation of the p110 catalytic subunit of PI-3k. Introduction of point mutations in the N-terminal and C-terminal SH2 domain and SH3 domain of p85alpha, which disrupt their ability to bind phosphotyrosine and proline-rich motifs, respectively, abrogated their interaction with the BCR/ABL protein network. The p85alpha mutant protein (p85mut) bearing these mutations was unable to interact with BCR/ABL and other FTKs, while its binding to the p110alpha catalytic subunit of PI-3k was intact. In addition, binding of Shc, c-Cbl, and Gab2, but not Crk-L, to p85mut was abrogated. p85mut diminished BCR/ABL-dependent activation of PI-3k and Akt kinase, the downstream effector of PI-3k. This effect was associated with the inhibition of BCR/ABL-dependent growth of the hematopoietic cell line and murine bone marrow cells. Interestingly, the addition of interleukin-3 (IL-3) rescued BCR/ABL-transformed cells from the inhibitory effect of p85mut. SCID mice injected with BCR/ABL-positive hematopoietic cells expressing p85mut survived longer than the animals inoculated with BCR/ABL-transformed counterparts. In conclusion, we have identified the domains of p85alpha responsible for the interaction with the FTK protein network and transduction of leukemogenic signaling. 

Retracted: No

PubPeer comments:
 Figure 4B. Much more similar than you would expect. https: imgur.com hOrGaaI ,
TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1
Authors: Dietmar E Martin
Michael N Hall
Alexandre Soulard
Journal: Cell (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ribosome biogenesis; TOR signaling pathway; Ribosomal protein genes; Protein kinase A; YAK1
Affiliations: Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.

Abstract:  The regulation of ribosome biogenesis in response to environmental conditions is a key aspect of cell growth control. Ribosomal protein (RP) genes are regulated by the nutrient-sensitive, conserved target of rapamycin (TOR) signaling pathway. TOR controls the subcellular localization of protein kinase A (PKA) and the PKA-regulated kinase YAK1. However, the target transcription factor(s) of the TOR-PKA pathway are unknown. We show that regulation of RP gene transcription via TOR and PKA in yeast involves the Forkhead-like transcription factor FHL1 and the two cofactors IFH1 (a coactivator) and CRF1 (a corepressor). TOR, via PKA, negatively regulates YAK1 and maintains CRF1 in the cytoplasm. Upon TOR inactivation, activated YAK1 phosphorylates and activates CRF1. Phosphorylated CRF1 accumulates in the nucleus and competes with IFH1 for binding to FHL1 at RP gene promoters, and thereby inhibits transcription of RP genes. Thus, we describe a signaling mechanism linking an environmental sensor to ribosome biogenesis. 

Retracted: No

PubPeer comments:
 Figure 5B u2013 It seems that bcy1 and yak1 mutants were represented with a duplicated inverted image. Could authors check please? ![file] , 
 Another possible concern with Fig. 5 ![file] ,
Attomolar DNA detection with chiral nanorod assemblies
Authors: Li Ding
Libing Wang
Wei Ma
Chuanlai Xu
Nicholas A Kotov
Liguang Xu
Hua Kuang
Journal: Nature Communications (2013)
Discipline: Multidisciplinary
Keywords: Nanoscale plasmonic assemblies; chiral optical activity; gold nanorods; DNA-bridged chiral systems; chiroplasmonic activity
Affiliations: 1] State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China [2].

Abstract:  Nanoscale plasmonic assemblies display exceptionally strong chiral optical activity. So far, their structural design was primarily driven by challenges related to metamaterials whose practical applications are remote. Here we demonstrate that gold nanorods assembled by the polymerase chain reaction into DNA-bridged chiral systems have promising analytical applications. The chiroplasmonic activity of side-by-side assembled patterns is attributed to a 7-9 degree twist between the nanorod axes. This results in a strong polarization rotation that matches theoretical expectations. The amplitude of the bisignate 'wave' in the circular dichroism spectra of side-by-side assemblies demonstrates excellent linearity with the amount of target DNA. The limit of detection for DNA using side-by-side assemblies is as low as 3.7 aM. This chiroplasmonic method may be particularly useful for biological analytes larger than 2-5 nm which are difficult to detect by methods based on plasmon coupling and 'hot spots'. Circular polarization increases for inter-nanorod gaps between 2 and 20 nm when plasmonic coupling rapidly decreases. Reaching the attomolar limit of detection for simple and reliable bioanalysis of oligonucleotides may have a crucial role in DNA biomarker detection for early diagnostics of different diseases, forensics and environmental monitoring. 

Retracted: No

PubPeer comments:
 Figure 2. The TEM photos of the nanorods, generated after different PCR cycles, appear to show some unexpected features. The nanorods appear to be  floating on the background, surrounded by light edges and background transitions. IN addition, three of the panels appear to be showing the same background. Some areas that look similar are shown here with boxes of the same color. The same backgrounds also appear to be visible in Figure 3 and several of the supplemental figures. Could the authors please provide some explanation? Are these microscopy artifacts? ![file] , 
 #1 Thanks for your interests in our paper and helped us to find this point. We have checked the related original files, found this is from camera lens that the speckles appear on the samples. See the original pictures we observed. This comment is very important for our future scientific research. We could provide more results by email to you. Thank you very much. ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] , 
 YES, it was caused by camera lens. We would like to provide more original images by email. , 
 Thank you, Dr. Xu, for your reply. Much appreciated. ,
Clinically relevant concentration of anti-viral drug ribavirin selectively targets pediatric osteosarcoma and increases chemosensitivity
Authors: Xiaoming Xu
Jianguo Chen
Junjun Chen
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chemosensitivity; Erk/EZH2/Snail; Osteosarcoma; Ribavirin.
Affiliations: Department of Pediatric Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, People's Republic of China. Electronic address: ., Department of Orthopedic Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, People's Republic of China., Department of Spine Surgery, The Second Hospital of Jingzhou, Jingzhou, People's Republic of China.

Abstract:  Ribavirin is an anti-viral drug but has recently gained attention as a potential candidate for cancer treatment. In line with these efforts, our work is the first to demonstrate that ribavirin, at clinically relevant concentration, selectively targets pediatric osteosarcoma and increases chemosensitivity. Using preclinical osteosarcoma cell and xenograft models, we found that ribavirin is active against osteosarcoma bulk and subpopulations with highly proliferative and invasive properties via inhibiting growth, inducing apoptosis and suppressing colony formation. At the same concentrations, ribavirin either did not or affected human normal osteoblastic cell and fibroblast cells in a less extent than osteosarcoma cells. Notably, the combination of ribavirin with doxorubicin resulted in greater efficacy than single drug alone. The combination completely arrested the osteosarcoma growth in vivo throughout the whole duration of drug treatment. We further showed that ribavirin acted on osteosarcoma largely via targeting eIF4E. In addition to eIF4E, ribavirin also modulated phosphorylation of Erk and expression of EZH2 and Snail without affecting Akt and mTOR. Lastly, we found that eIF4E expression and phosphorylation were elevated in osteosarcoma compared to normal cells, which might explain the selective anti-osteosarcoma activity of ribavirin. eIF4E depletion mimics the inhibitory effects of ribavirin, further confirm that eIF4E is the essential target of ribavirin in osteosarcoma. Our work provides fundamental evidence of repurposing ribavirin for the treatment of osteosarcoma. Our findings also highlight the therapeutic value of inhibiting eIF4E in osteosarcoma. 

Retracted: No

PubPeer comments:
 Figure 1C appears to have a repeated image. *** ![file] ,
MiR-4262 inhibits the development of esophageal cancer by negatively regulating KLF6 level
Authors: Lijun Lu
Shuangqing Gao
Zhanye Liu
Shixia Du
Chunlong Zhao
Journal: Experimental and Molecular Pathology (2020)
Discipline: CLINICAL MEDICINE
Keywords: Development; Esophageal cancer; KLF6; MiR-4262.
Affiliations: Department of Thoracic Surgery, Caoxian People's Hospital, Heze, China., Department of Respiratory Medicine, Caoxian People's Hospital, Heze, China., Department of Thoracic Surgery, Caoxian People's Hospital, Heze, China. Electronic address: .

Abstract:  Objective: To uncover the expression pattern and the prognosis of miR-4262 in these patients with esophageal cancer, and its potential mechanism. Methods: MiR-4262 levels in 57 esophageal cancer and paracancerous specimens were detected. The relationship between miR-4262 level and clinical features of esophageal cancer was analyzed. After overexpression of miR-4262 in OE19 and EC-109 cells, changes in proliferative potential and apoptosis were examined. The interaction between miR-4262 and KLF6 was explored by dual-luciferase reporter assay. Their involvement in the development of esophageal cancer was finally determined. Results: MiR-4262 was downregulated in esophageal cancer specimens and cell lines. Low level of miR-4262 predicted advanced pathological staging and poor prognosis in esophageal cancer patients. Overexpression of miR-4262 reduced proliferative potential and enhanced apoptosis in esophageal cancer cells. KLF6 was the downstream gene binding to miR-4262. The interaction between miR-4262 and KLF6 was responsible for alleviating the malignant development of esophageal cancer. Conclusions: MiR-4262 is downregulated in esophageal cancer and linked to its pathological staging and prognosis. MiR-4262 inhibits the malignant development of esophageal cancer by down-regulating KLF6. 

Retracted: No

PubPeer comments:
 Potential duplications in figure 3B ![file] , 
 Also see some potential duplications in 4G ![file] There may be more , 
 Retracted [October 31 2020] .  This article has been retracted: Authors concluded that the experimental results are not solid enough to support their conclusions. Thus, they have made the decision to retract the article upon the agreement of all listed authors. ,
Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases
Authors: Alexis De Haven Brandon
Paul A Clarke
Florence Raynaud
Robin Ketteler
Simon R Stockwell
Angela Hayes
Jamie Freeman
May Elbanna
Bissan Al-Lazikani
Sibylle Mittnacht
Suzanne Eccles
Chi Zhang
Paul Workman
Journal: Oncogene (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CDK4/6; cancer; inhibitors; MET; FAK
Affiliations: UCL Cancer Institute, University College London, London, WC1E 6DD, UK., Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research, London, SM2 5NG, UK., MRC Laboratory for Molecular Cell Biology, University College London, London, WC1E 6BT, UK., Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research, London, SM2 5NG, UK. ., UCL Cancer Institute, University College London, London, WC1E 6DD, UK. .

Abstract:  Deregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer; yet, inhibitors against these kinases are currently used only in restricted tumour contexts. The extent to which cancers depend on CDK4/6 and the mechanisms that may undermine such dependency are poorly understood. Here, we report that signalling engaging the MET proto-oncogene receptor tyrosine kinase/focal adhesion kinase (FAK) axis leads to CDK4/6-independent CDK2 activation, involving as critical mechanistic events loss of the CDKI p21CIP1 and gain of its regulator, the ubiquitin ligase subunit SKP2. Combined inhibition of MET/FAK and CDK4/6 eliminates the proliferation capacity of cancer cells in culture, and enhances tumour growth inhibition in vivo. Activation of the MET/FAK axis is known to arise through cancer extrinsic and intrinsic cues. Our work predicts that such cues support cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases and identifies MET/FAK as a tractable route to broaden the utility of CDK4/6 inhibitor-based therapies in the clinic. 

Retracted: No

PubPeer comments:
 2020 correction. https: www.nature.com articles s41388-020-1221-8 After publication of the article, the authors became aware of an error in Fig. 5e. In the published article, the immunoblot panels for p21CIP and SKIP2 for cell lines MCF7 and A549 in Fig. 5e were interchanged. A correct version of the Figure is published below. This has now been corrected in both the PDF and HTML versions of the article. ,