PReD-Bench/PRed-Bench huggingface dataset:
Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen modulates K1 expression through its cis-acting elements within the terminal repeats
Authors: Erle S Robertson
Subhash C Verma
Ke Lan
Tathagata Choudhuri
Journal: Journal of virology (2006)
Discipline: MICROBIOLOGY
Keywords: Kaposi's sarcoma-associated herpesvirus (KSHV); K1; transmembrane glycoprotein; immunoreceptor tyrosine-based activation motif (ITAM); B-cell receptor signaling
Affiliations: Department of Microbiology and Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Abstract:  K1 is the first open reading frame encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) and lies positionally to the immediate right of the terminal repeats. K1 is a transmembrane glycoprotein having a functional immunoreceptor tyrosine-based activation motif (ITAM) capable of activating B-cell receptor signaling. K1 is expressed mostly during the lytic cycle of the virus and its promoter lies within the terminal repeat which contains the binding sites for latency-associated nuclear antigen (LANA). The K1 promoter (K1p) having LANA binding sites assayed by reporter assay demonstrated that LANA is capable of down-regulating K1 promoter transcriptional activity. However, the KSHV replication transcription activator RTA up-regulates K1p transcriptional activity. The promoter deleted of LANA binding sites showed loss in LANA-mediated down-regulation but was unaffected for RTA-mediated up-regulation. Increasing amounts of RTA rescued LANA-mediated repression of K1p transcriptional activity in cotransfection experiments. Reporter assay data suggest that LANA binding to its cognate sequence is critical for LANA-mediated repression of K1p as a LANA construct lacking the DNA binding domain was unable to repress K1p transcription. Additionally, KSHV primary infection experiments suggest that K1 is expressed during early infection but is repressed on the establishment of latency and so follows an expression profile similar to that of RTA during infection. Analysis of the promoter sequence revealed the presence of Oct-1 transcription factor binding sites within the -116 to +76 region. Mutational analysis of the Oct-1 sites abolished RTA-mediated transcriptional activation, suggesting that RTA up-regulates K1p transcription through binding to this transcription factor. 

Retracted: No

PubPeer comments:
 Figure 8. Much more similar than you would expect. https: imgur.com EMMYz3f , 
 Last author appears to be on this journalu2019s editorial board: https: jvi.asm.org content board-editors , 
 Figures 6 and 7F. Much more similar than expected. ![file] ,
Dual Feedforward Loops Modulate Type I Interferon Responses and Induce Selective Gene Expression during TLR4 Activation
Authors: Jie Zhou
Tingzhe Sun
Shouheng Jin
Jun Cui
Zhiyong Guo
Journal: iScience (2020)
Discipline: Multidisciplinary
Keywords: Biological Sciences; Cell Biology; Integrative Aspects of Cell Biology; Mathematical Biosciences.
Affiliations: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China., School of Life Sciences, Anqing Normal University, Anqing, Anhui 246011, China., Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China., MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. Electronic address: .

Abstract:  Although the dynamic features of type I coherent feedforward loop (C1-FFL) has been well studied, how C1-FFL shapes cell-to-cell heterogeneity remains unclear. Here, we found that C1-FFL with OR logic serves as "noise reducer," whereas C1-FFL with AND logic functions as "noise propagator" to fine-tune the heterogeneity of signaling molecule's activation. Within Toll-like receptor 4 (TLR4) signaling pathway, we demonstrated that MyD88 together with TRIF generates a C1-FFL to control TBK1 phosphorylation and reduce its cell-to-cell heterogeneity, whereas noisy TRIF activation induced high heterogeneity of IRF3 activation through another C1-FFL. We further developed a mathematical model with dual C1-FFLs to uncover how MyD88 and TRIF encoded differential dynamics for TBK1 and IRF3 activation. Integration of dual FFLs drives MyD88-TBK1 axis to determine the specificity of IFN-stimulated genes transcription. Collectively, our work elucidates a paradigm that tunable TLR4-mediated type I IFN responses are subtly controlled by dual FFLs. 

Retracted: No

PubPeer comments:
 In Figure 2A and E, a Western blot panel has been duplicated and presented as something else (red squares). Another Western blot panel also show similar patterns, but the quality is too poor to conclude (blue squares). ![file] , 
 Thank you for your attention. Upon noticing these comments, we immediately reviewed our raw data about these figures carefully and confirmed that there was no intentional misconduct during figure editing. For Figure 2A and Figure 2E, we will provide the uncropped original images to the editor to erratum. ,
Salidroside mitigates hydrogen peroxide-induced injury by enhancement of microRNA-27a in human trabecular meshwork cells
Authors: Jun Zhao
Peiyao Yang
Meng Wang
Juanmei Zhang
Xiujuan Du
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Glaucoma; PI3K/AKT; Salidroside; Wnt/β-catenin; hydrogen peroxide
Affiliations: Department of Ophthalmology, Linyi People’s Hospital, Linyi, China;, Department of Ophthalmology, Eye Institute of Shandong University of Traditional Chinese Medicine, Affiliated Eye Hospital of Shandong University of TCM, Jinan, China;, Qingdao University, Qingdao, China

Abstract:  Salidroside (Sal) exerted widely pharmacological effects in multitudinous diseases had been certified. The actual study clarified the protective activity of Sal in H2O2-injured human trabecular meshwork (HTM) cells. HTM cells were disposed with H2O2 to construct an oxidative damage model in vitro. Then, Sal was utilized to administrate HTM cells, and cell viability, apoptosis, apoptosis-interrelated proteins and ROS production were appraised using CCK-8, flow cytometry, western blot and DCFH-DA staining. MiR-27a inhibitor and its control were transfected into HTM cells, and the influences of miR-27a inhibition in HTM cells stimulated with H2O2 and Sal were detected. PI3K/AKT and Wnt/β-catenin pathways were ultimately investigated to uncover the underlying mechanism. We found that H2O2 evoked HTM cells oxidative damage, as evidenced by repressing cell viability, inducing apoptosis, activating cleaved-caspase-3/-9 expression and increasing ROS production. Sal significantly lightened H2O2-evoked oxidative damage in HTM cells. Additionally, miR-27a was up-regulated by Sal, and miR-27a suppression significantly reversed the protective effect of Sal on H2O2-injured HTM cells. Finally, Sal activated PI3K/AKT and Wnt/β-catenin pathways through enhancement of miR-27a in H2O2-injured HTM cells. In conclusion, these discoveries suggested that Sal could protect HTM cells against H2O2-evoked oxidative damage by activating PI3K/AKT and Wnt/β-catenin pathways through enhancement of miR-27a. Highlights H2O2 evokes HTM cells oxidative damage; Sal relieves H2O2-induced oxidative damage in HTM cells; Sal enhances miR-27a expression in H2O2-injured HTM cells; Repressed miR-27a reverses the protective impacts of Sal on H2O2-injured HTM cells; Sal activates PI3K/AKT and Wnt/β-catenin pathways by increasing miR-27a. 

Retracted: No

PubPeer comments:
 In Figure 4. The F5A Mutation Blocks Amino Acid Signaling via mTOR toward S6K1 2nd lanes look a bit weird of the S6K assay. If one increases the saturation, it becomes apparent the backgrounds are clearly not aligned. ![file] ,
Cancer-Associated Fibroblasts-Derived Exosomes Suppress Immune Cell Function in Breast Cancer via the miR-92/PD-L1 Pathway
Authors: Xinxing Wang
Mingli Han
Xiaodong Xu
Yuanting Gu
Xin Ge
Xiaoyang Ren
Dongwei Dou
Journal: Frontiers in Immunology (2020)
Discipline: IMMUNOLOGY
Keywords: CAF; PD-L1; YAP1; breast cancer; miR-92.
Affiliations: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Department of Information, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract:  Cancer-associated fibroblasts (CAFs) are an essential component in the tumor microenvironment and have been reported to contribute to tumor progression through many mechanisms; however, the detailed mechanism underlying the immune-suppression effect of CAFs is not clearly defined. In this study, human breast cancer-derived CAFs were cultured, and CAF-derived exosomes in a culture medium were isolated. Using a miRNA profiles assay, we identify a significantly higher level of microRNA-92 isolated in CAFs exosomes. After treatment by CAF-derived exosomes, breast cancer cells express higher programmed cell death receptor ligand 1 (PD-L1), accompanied with increased miR-92 expression. Increased PD-L1 expression, which was induced by CAF-derived exosomes, significantly promotes apoptosis and impaired proliferation of T cells. The underlying mechanism of this effect was studied, proliferation and migration of breast cancer cells were increased after the transfection of miR-92, LATS2 was recognized as a target gene of miR-92, and further confirmed by a luciferase assay. Immunoprecipitation showed that LATS2 can interact with YAP1, chromatin immunoprecipitation confirmed that after nuclear translocation YAP1 could bind to the enhancer region of PD-L1 to promotes transcription activity. Furthermore, the animal study confirmed that CAFs significantly promoted tumor progression and impaired the function of tumor-infiltrated immune cells in vivo. Our data revealed a novel mechanism that can induce immune suppression in the tumor microenvironment. 

Retracted: No

PubPeer comments:
 Figure 2F and 3G appear to have an image which overlaps. Could the authors please review and confirm that this is intentional? *** ![file] , 
 rtyhtryhrth hg hgf ,
Interruption of nuclear factor kappaB signaling by the androgen receptor facilitates 12-O-tetradecanoylphorbolacetate-induced apoptosis in androgen-sensitive prostate cancer LNCaP cells
Authors: Wen-Jye Lin
Hui-Kuan Lin
LeRoy A Hanchett
Yanqing Zhang
Hong-Yo Kang
Kuang-Hsiang Chuang
Lin Yang
Chawnshang Chang
Meng-Ying Tsai
Mujib M Rahman
Saleh Altuwaijri
Shuyuan Yeh
Journal: Cancer research (2003)
Discipline: CLINICAL MEDICINE
Keywords: TPA; apoptosis; androgen; prostate cancer; LNCaP cells
Affiliations: George Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.

Abstract:  12-O-tetradecanoylphorbolacetate (TPA) influences proliferation, differentiation, and apoptosis in a variety of cells including prostate cancer cells. Here, we show that androgen treatment potentiates TPA-induced apoptosis in androgen-sensitive prostate cancer LNCaP cells but not in androgen-independent prostate cancer cell lines DU145 and PC-3. The use of the antiandrogen bicalutamide (Casodex) rescued LNCaP cells from 5-alpha-dihydrotestosterone (DHT)/TPA-induced apoptosis, suggesting that DHT/TPA-induced apoptosis is mediated by androgen/androgen receptor (AR). In addition, a caspase-3 inhibitor (Ac-DEVD-CHO) reduced the level of apoptosis, suggesting that DHT/TPA-mediated apoptosis occurs through a caspase-3-dependent pathway. A functional reporter assay using nuclear factor (NF) kappaB-luciferase and an electromobility gel shift assay showed that DHT suppressed NFkappaB activity. In addition, apoptosis mediated by combined DHT/TPA treatment was abrogated by overexpression of the NFkappaB subunit p65 in LNCaP-p65 cells, suggesting that NFkappaB may play an important role in regulating the effects of androgen/AR and TPA on apoptosis. Furthermore, use of the c-Jun N-terminal kinase (JNK) inhibitor SB202190 showed that the combination of DHT/TPA increased JNK activation in LNCaP cells but not in LNCaP-p65 cells, demonstrating that NFkappaB may be able to suppress JNK activity. These results indicate that androgen/AR facilitates TPA-induced apoptosis by interruption of the NFkappaB signaling pathway, leading to activation of JNK in LNCaP cells. These data describe a signaling pathway that could potentially be useful in proposed therapeutic treatment strategies exploiting combinations of different agents that control apoptosis in prostate tumors. 

Retracted: No

PubPeer comments:
 Figure 3A appears to have a repeated image. Figure 3C appears to have two images which overlap (green boxes). These types of errors are sometimes seen in paper mill products. *** ![file] ,
RETRACTED ARTICLE: Regulation function of MMP-1 downregulated by siRNA on migration of heat-denatured dermal fibroblasts
Authors: Youfen Fan
Jinhua Dai
Xianghui He
Xihong Zhao
Chun Zhang
Journal: Bioengineered (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MMP-1; TIMP; heat-denatured dermal fibroblast; migration; siRNA.
Affiliations: a Department of Burn , Ningbo No. 2 Hospital, Ningbo , China., b Department of Clinical Laboratory , Ningbo No. 2 Hospital, Ningbo , China., c Key Laboratory for Green Chemical Process of Ministry of Education , School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology , Wuhan , China.

Abstract:  Cutaneous wound healing is a complex physiological process that requires the efforts of various cell types and signaling pathways and often results in thickened collagen-enriched healed tissue called a scar. Therefore, the identification of the mechanism of cutaneous wound healing is necessary and has great value in providing better treatment. Here, we demonstrated that MMP-1 inhibition could promote cell proliferation in dermal fibroblasts via the MTT assay. Meanwhile, we investigated cell migration by flow cytometry and tested type I collagenase activity. We found that MMP-1 inhibition promoted cell proliferation and inhibited cell migration and type I collagenase activity. In conclusion, our study demonstrated that MMP-1 might be a potential therapeutic target in cutaneous wound healing. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: www.tandfonline.com doi full 10.1080 21655979.2020.1770001 We, the Editor, Publisher and authors have retracted the following article from Bioengineered: Xianghui He, Jinhua Dai, Youfen Fan, Chun Zhang Xihong Zhao, Regulation function of MMP-1 downregulated by siRNA on migration of heat-denatured dermal fibroblasts, Bioengineered (2017) 8(6): 333-346, DOI:10.1080 21655979.2016.1267885 The above article has been retracted at the request of the authors who have, subsequent to publication, found that the experiments reported are not reproducible and that the conclusions made are therefore unreliable. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u2018Retractedu2019. ,
Proteomic view of the venom from the fire ant Solenopsis invicta Buren
Authors: Anally R da Silva Menegasso
Odair C Bueno
Ednildo A Machado
Mario S Palma
Daniel M Saidemberg
Lucilene D Santos
José R A dos Santos Pinto
Eliúde Costa-Manso
Eduardo G P Fox
Journal: Journal of Proteome Research (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Fire ants; venom; proteomic characterization; proteins; biochemistry
Affiliations: Institute of Biosciences, Center of the Study of Social Insects/Department of Biology, University of São Paulo State-UNESP, Rio Claro, SP, Brazil., Laboratório
de Entomologia Médica e Molecular, Instituto de Biofísica
Carlos Chagas Filho, Federal University of Rio de Janeiro (IBCCF/UFRJ), Rio de Janeiro, Brazil, Institute of Biosciences, Center
of the Study of Social Insects/Department of Biology, University of São Paulo State (UNESP), Rio Claro,
SP, Brazil, Clinic of Allergology, Pouso
Alegre, MG, Brazil

Abstract:  Fire ants are well-known by their aggressive stinging behavior, causing many stinging incidents of medical importance. The limited availability of fire ant venom for scientific and clinical uses has restricted, up to now, the knowledge about the biochemistry, immunology, and pharmacology of these venoms. For this study, S. invicta venom was obtained commercially and used for proteomic characterization. For this purpose, the combination of gel-based and gel-free proteomic strategies was used to assign the proteomic profile of the venom from the fire ant S. invicta. This experimental approach permitted the identification of 46 proteins, which were organized into four different groups according to their potential role in fire ant venom: true venom components, housekeeping proteins, body muscle proteins, and proteins involved in chemical communication. The active venom components that may not present toxic roles were classified into three subgroups according to their potential functions: self-venom protection, colony asepsis, and chemical communication. Meanwhile, the proteins classified as true toxins, based on their functions after being injected into the victims' bodies by the fire ants, were classified in five other subgroups: proteins influencing the homeostasis of the victims, neurotoxins, proteins that promote venom diffusion, proteins that cause tissue damage/inflammation, and allergens. 

Retracted: No

PubPeer comments:
 Image artefacts? Supplementary Figure S1 presenting seemingly identical experimental lanes as results. Unique images indicated in blue red boxes in the annotated image in link. https: pasteboard.co J2L2bYv.png ![file] In same image, orange arrowhead signals for possible border artefact between gel bands. ,
Regulation of the p53 homolog p73 by adenoviral oncogene E1A
Authors: Kumaravel Somasundaram
Sanjeev Das
Wafik S El-Deiry
Journal: Journal of Biological Chemistry (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: p73; E1A; transcriptional activation; tumor suppressor; p53 homolog
Affiliations: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.

Abstract:  p73 is a p53 homolog, as they are similar structurally and functionally. Unlike p53, p73 is not inactivated by the products of viral oncogenes such as SV40 T antigen and human papilloma virus E6. Here we show that the product of adenoviral oncogene E1A inhibits the transcriptional activation by both p73alpha and p73beta. Electrophoretic mobility shift assays revealed that E1A does not inhibit the sequence-specific DNA binding by p73. Transcriptional activation by a fusion protein containing the Gal4 DNA-binding domain and either of the activation domains of p73 was inhibited by wild-type (WT) E1A, but not by the N-terminal deletion mutant E1A(Delta2-36). E1A(Delta2-36), which does not bind to the p300/CBP family of coactivators, failed to inhibit p73-mediated transcription, whereas E1A(DeltaCR2), a deletion mutant that does not bind to the pRb family of proteins, inhibited p73-mediated transcription as efficiently as WT E1A. Consistent with these observations, growth arrest induced by p73 expressed from a recombinant adenovirus was abrogated by WT E1A, which correlated with inhibition of p73-mediated induction of p21(WAF1/CIP1) by E1A. However, p73 was able to induce p21(WAF1/CIP1) and to mediate growth arrest in the presence of E1A(Delta2-36). Furthermore, the expression of either wild-type E1A or E1A(Delta2-36) resulted in the stabilization of endogenous p73. However, p73 stabilized in response to the expression of E1A(Delta2-36), but not WT E1A, was able to activate the expression of p21(WAF1/CIP1). These results suggest that the transcriptional activation function of p73 is specifically targeted by E1A through a mechanism involving p300/CBP proteins during the process of transformation and that p73 may have a role to play as a tumor suppressor. 

Retracted: No

PubPeer comments:
 ![file] , 
 Outliers more similar than you would expect (after horizontal stretching compression). ![file] ,
APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase
Authors: Daniele Guardavaccaro
Michele Pagano
Sheng Ge
Virginia Amador
Patricia G Santamaría
Journal: Molecular Cell (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p21; Skp2; Cdc20; APC/C; ubiquitylation
Affiliations: Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue MSB 599, New York, NY 10016, USA.

Abstract:  During the G1/S transition, p21 proteolysis is mediated by Skp2; however, p21 reaccumulates in G2 and is degraded again in prometaphase. How p21 degradation is controlled in mitosis remains unexplored. We found that Cdc20 (an activator of the ubiquitin ligase APC/C) binds p21 in cultured cells and identified a D box motif in p21 necessary for APC/C(Cdc20)-mediated ubiquitylation of p21. Overexpression of Cdc20 or Skp2 destabilized wild-type p21; however, only Skp2, but not Cdc20, was able to destabilize a p21(D box) mutant. Silencing of Cdc20 induced an accumulation of p21, increased the fraction of p21 bound to Cdk1, and inhibited Cdk1 activity in p21(+/+) prometaphase cells, but not in p21(-/-) cells. Thus, in prometaphase Cdc20 positively regulates Cdk1 by mediating the degradation of p21. We propose that the APC/C(Cdc20)-mediated degradation of p21 contributes to the full activation of Cdk1 necessary for mitotic events and prevents mitotic slippage during spindle checkpoint activation. 

Retracted: No

PubPeer comments:
  The investigation was approved by the Ethics Committee of the hospital, and all patients had signed informed consent. This is unconvincing, as the investigation was supposedly distributed over **two** hospitals - The First Affiliated Hospital of Gannan Medical University, Ganzhou, and Fuxin Central Hospital, Fuxin. Fig 1C:  Kaplan-Meier survival curve of NSCLC patients based on USP3 expression. The prognosis of patients with high expression of USP3 was significantly worse than that of low expression group . ![file] Versions of this pair of K-M plots (resembling combs, or walls made of Lego) appear in a great number of papers in this journal. The precipitous nose-dive to 0% Survival at 75 months is especially remarkable and I hope that it doesn t reflect a widespread policy of euthanasia. , 
 Another recurrent feature of this tradition of papers is a Table 1 in which the column heads promise to convert the numbers in each patient subgroup into percentages, but the promise remains unfulfilled. ![file] , 
 A colony-formation plate is re-used between Figs 2C and 4C,  Colony formation assay was performed to detect relative colony number in H1299 and SPCA1 cell lines ...  Colony formation assay was performed to detect the number of colonies in co-transfected cells . ![file] ,
Connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal sheep
Authors: Laura Bennet
Colin R Green
Paul P Drury
Louise F Nicholson
Alistair J Gunn
Joanne O Davidson
Journal: PloS one (2014)
Discipline: Multidisciplinary
Keywords: Asphyxia; Preterm birth; Connexin hemichannels; Neurodevelopmental disability; Brain activity
Affiliations: Department of Physiology, The University of Auckland, Auckland, New Zealand., Department of Ophthalmology, The University of Auckland, Auckland, New Zealand., Department of Anatomy with Radiology, The University of Auckland, Auckland, New Zealand.

Abstract:  Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete umbilical cord occlusion in preterm fetal sheep (103-104 d gestational age). Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic peptide starting 90 min after asphyxia at a concentration of 50 µM/h for one hour followed by 50 µM/24 hour for 24 hours (occlusion-peptide group, n = 6) or vehicle infusion for controls (occlusion-vehicle group, n = 7). Peptide infusion was associated with earlier recovery of electroencephalographic power after asphyxia compared to occlusion-vehicle (p&lt;0.05), with reduced neuronal loss in the caudate and putamen (p&lt;0.05), but not in the hippocampus. In the intragyral and periventricular white matter, peptide administration was associated with an increase in total oligodendrocyte numbers (p&lt;0.05) and immature/mature oligodendrocytes compared to occlusion-vehicle (p&lt;0.05), with a significant increase in proliferation (p&lt;0.05). Connexin hemichannel blockade was neuroprotective and reduced oligodendrocyte death and improved recovery of oligodendrocyte maturation in preterm fetuses after asphyxia. 

Retracted: No

PubPeer comments:
 Figure 9 appears to include at least one repeated image. *** ![file] ,
LINC01510 suppresses cell proliferation and invasion by inhibiting Wnt/β-catenin signaling in renal cell carcinoma
Authors: Zhaohui Zhang
Chenhui Zhao
Jianian Zhang
Binbin Ma
Tao Huang
Wenlong Zhou
Chenlong Chu
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell invasion; Cell proliferation; LINC01510; Wnt/β-catenin.
Affiliations: Department of Urology, Rui Jin Hospital Lu Wan Branch, School of Medicine, Shanghai Jiaotong University, No.149, South Chongqing Road, Shanghai, 200020, China., Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, No.301, Yanchangzhong Road, Shanghai, 200072, China., Department of Urology, Rui Jin Hospital Lu Wan Branch, School of Medicine, Shanghai Jiaotong University, No.149, South Chongqing Road, Shanghai, 200020, China. Electronic address: .

Abstract:  The role of long non-coding RNA in Renal cell carcinoma (RCC) tumorigenesis and progression remains largely unknown. Here, we found that LINC01510 functions as a tumor suppressor in RCC tumorigenesis. We screened TCGA database and then found that LINC01510 is significantly down-regulated in malignant RCC tissues, and the lower expression of LINC01510 predicts poor prognosis. Moreover, the down-regulated LINC01510 was further confirmed in our fresh tissues and cell lines. Biological functions assays shown that Ectopic expression of LINC01510 not only inhibits RCC cell proliferation both in vitro and in vivo, but also impairs cell invasion ability. Moreover, we found overexpression of LINC01510 inhibits the expression of CCND1 and CCNE1, as well as MMPs (MMP2, MMP7 and MMP9), and thus affecting RCC cell cycle and invasion. Meanwhile, Western blot assays revealed that the expression of β-catenin is regulated by LINC01510; overexpression of β-catenin could partly rescue the cell viability and invasion ability caused by ectopic expression of LINC01510. Taken together, we found that LINC01510 regulates cell proliferation and invasion by modulating Wnt/β-catenin signaling in RCC. 

Retracted: No

PubPeer comments:
 *[below]* Fig. 2.  Overexpression of LINC01510 inhibits RCC cell proliferation and invasion. .... (E) Xenograft tumor formation assays showed that heightening the expression of LINC01510 significantly inhibits the ability of subcutaneous tumor formation in 786-O. *[above]* Fig. 3 from [Tang, Zheng Zhang (2018)] .  Knockdown of CRNDE inhibits HCC cell proliferation in vivo. (A) The representative images of tumors which formed by indicated stable cell lines, scale bar, 1 cm . There are no scale bars, only rulers with cm and inches. ![file] Could the authors of either paper comment on the duplication? ,
Effect of caloric restriction on base-excision repair (BER) in the aging rat brain
Authors: Gaobin Bao
Steven G Kohama
Rafael de Cabo
Mona Churchwell
Donald K Ingram
Yoke W Kow
Edward Spangler
Antoinette Olivas
Daniel Doerge
Barry Imhof
Glen E Kisby
Journal: Experimental Gerontology (2010)
Discipline: CLINICAL MEDICINE
Keywords: Apyrimidinic/apurinic endonuclease; base-excision DNA repair; oxidative DNA lesions; frontal/parietal cortex; cerebellum
Affiliations: Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, OR 97239, USA. 

Abstract:  Apyrimidinic/apurinic endonuclease (APE) is a key protein involved in the base-excision DNA repair (BER) pathway of oxidative DNA lesions. Using a novel oligonucleotide substrate, we demonstrate that APE activity in the frontal/parietal cortex (F/PCTX), cerebellum, brainstem, midbrain and hypothalamus declined with age in rats on an ad libitum (AL) diet. In contrast, APE activity for these brain regions was approximately 1.5-3 times higher in young, caloric restricted (CR) rats. Despite continuous CR treatment in all animals since six weeks of age, APE activity in the CR group started to decline by middle-age and continued into old age. However, CR maintained APE activity at a level that was significantly higher than that in AL rats across age and in the brain regions examined. Because Western analysis of APE, DNA polymerase beta and DNA ligase III levels in the F/PCTX of both CR and AL rats remained unchanged with age, this suggests that the increased APE activity in CR rats is the result of differential post-translational modification of APE. 

Retracted: No

PubPeer comments:
 Figure 4A. https: imgur.com XQ85AEZ ,
Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K/Akt/FoxO dependent anti-apoptotic effect
Authors: Chia-Chi Chang
Hsieh-Hsing Lee
Ming-Jium Shieh
Yi-Te Chen
Tai-Horng Young
Jung-Pan Wang
Shih-Chieh Hung
Journal: Scientific Reports (2013)
Discipline: Multidisciplinary
Keywords: Hypoxia; chondrogenic differentiation; mesenchymal stem cells; gene expression; protein expression
Affiliations: 1] Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan [2] Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan [3] Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.

Abstract:  Hypoxia, a common environmental condition, influences cell signals and functions. Here, we compared the effects of hypoxia (1% oxygen) and normoxia (air) on chondrogenic differentiation of human mesenchymal stem cells (MSCs). For in vitro chondrogenic differentiation, MSCs were concentrated to form pellets and subjected to conditions appropriate for chondrogenic differentiation under normoxia and hypoxia, followed by the analysis for the expression of genes and proteins of chondrogenesis and endochondral ossification. MSCs induced for differentiation under hypoxia increased in chondrogenesis, but decreased in endochondral ossification compared to those under normoxia. MSCs induced for differentiation were more resistant to apoptosis under hypoxia compared to those under normoxia. The hypoxia-dependent protection of MSCs from chondrogenesis-induced apoptosis correlated with an increase in the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/FoxO pathway. These results suggest that the PI3K/Akt/FoxO survival pathway activated by hypoxia in MSCs enhances chondrogenesis and plays an important role in preventing endochondral ossification. 

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. , 
 #1 These samples are described as follows: (d) Cell pellets of 7 days were assayed by ICC staining for active caspase-8. (e) (Left panel) Cell pellets of 7 days were assayed for active caspase-3 by ICC staining. ,
Evolution of human papillomavirus carcinogenicity
Authors: Robert D Burk
Koenraad Van Doorslaer
Journal: Advances in virus research (2010)
Discipline: MICROBIOLOGY
Keywords: Alphapapillomavirus; cervical cancer; HPV16; oncoproteins; E6
Affiliations: Department of Microbiology and Immunology, Albert Einstein Cancer Center, Albert Einstein College of Medicine, New York, USA.

Abstract:  Members of the Alphapapillomavirus genus are the causative agent for virtually all cases of cervical cancer. However, strains (commonly referred to as types) within this genus span the entire range of pathogenicity from highly carcinogenic (e.g., HPV16, odds ratio = 281.9, responsible for 50% of all cervical cancers), moderately carcinogenic (e.g., HPV31) to not carcinogenic (e.g., HPV71). The persistent expression of the viral oncoproteins (E6 and E7) from HPV16 has been shown to be necessary and sufficient to transform primary human keratinocytes in vitro. A plethora of functions have been described for both oncoproteins, and through functional comparisons between HPV16 and HPV6, a subset of these functions have been suggested to be oncogenic. However, extrapolating functional differences from these comparisons is unlikely to tease apart the fine details. In this review, we argue that a thorough understanding of the molecular mechanisms differentiating oncogenic from nononcogenic types should be obtained by performing functional assays in an evolutionary and epidemiological framework. We continue by interpreting some recent results using this paradigm and end by suggesting directions for future inquiries. 

Retracted: No

PubPeer comments:
 Hi, Thank you for putting together this review. I think it provided an interesting way to visualize some information. In Figure 7, you say  *The epi. column shows the epidemiological classification (oncogenic, OT; nonOT, NOT, insufficient data, N A) according to Bouvard et al. (2010)* , with the following reference: Bouvard, V., Baan, R., Straif, K., Grosse, Y., Secretan, B., El Ghissassi, F., Benbrahim- Tallaa, L., Guha, N., Freeman, C., Galichet, L., and Cogliano, V. (2010). A review of human carcinogensu2014Part B: Biological agents. Lancet Oncol. 10(4):321u2013322. However, I think this is the wrong year (2010, instead of 2009). For example, you can see a PubMed entry for the same issue information in 2009: https: www.ncbi.nlm.nih.gov pubmed 19350698 While not linked in PubMed, I could view this version of that citation: https: www.thelancet.com journals lanonc article PIIS1470-2045(09)70096-8 fulltext So, I think the year for the Bouvard et al. citation should be corrected? Sincerely, Charles ,
Hypothermia protects the brain from transient global ischemia/reperfusion by attenuating endoplasmic reticulum response-induced apoptosis through CHOP
Authors: Huailong Chen
Fei Shi
Yanlin Bi
Mingshan Wang
Xiaojie Liu
Ying Li
Fuguo Ma
Yunliang Guo
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Endoplasmic reticulum stress; cerebral ischemia; apoptosis; hypothermia; TNF
Affiliations: Department of Anesthesiology, Qingdao Municipal Hospital, Shandong, China.

Abstract:  Endoplasmic reticulum (ER) stress has been implicated in the pathology of cerebral ischemia. Apoptotic cell death occurs during prolonged period of stress or when the adaptive response fails. Hypothermia blocked the TNF or Fas-mediated extrinsic apoptosis pathway and the mitochondria pathway of apoptosis, however, whether hypothermia can block endoplasmic reticulum mediated apoptosis is never known. This study aimed to elucidate whether hypothermia attenuates brain cerebral ischemia/reperfusion (I/R) damage by suppressing ER stress-induced apoptosis. A 15 min global cerebral ischemia rat model was used in this study. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in hippocampus CA1 were assessed after reperfusion of the brain. The expressions of C/EBP-homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) in ischemic hippocampus CA1 were measured at 6, 12, 24 and 48 h after reperfusion. The results showed that hypothermia significantly attenuated brain I/R injury, as shown by reduction in cell apoptosis, CHOP expression, and increase in GRP78 expression. These results suggest that hypothermia could protect brain from I/R injury by suppressing ER stress-induced apoptosis. 

Retracted: Yes

PubPeer comments:
 Figure 6C. * Marked in red. The photo representing the  NK ESC line appears to show an overlap (albeit stretched differently) with the  NK-YY1-DN ESC lines photo. ![file] , 
 Supplemental Figure IV. The YY1 Isl-1 double stained image appears to show similarities to the YY1 Gata4 double stained image, if one of the two images is flipped, and if the areas shown in yellow and aqua are shifted with respect to each other. Could the authors please explain? I could imagine a double stain if both antibodies have a different origin (e.g. mouse and rabbit), with 2 secondary antibodies with 2 different colors, but were three different antibodies used here? And how can the height ratio of the 2 tissue structures be so different between the two images, while the colored pixels are nearly identical albeit of a different color? ![file] ,
Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration
Authors: Lai-Chu Wu
Giancarlo R Valiente
Nicholas A Young
Michael S Bruss
Zhongfa Liu
Yu Cao
Mark Gardner
Wael N Jarjour
Xiaokui Mo
William L Willis
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: curcumin; nano-emulsion; inflammation; NFκB; bioavailability
Affiliations: Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America., Center for Biostatistics, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America., College of Pharmacy, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America., College of Pharmacy, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America; Comprehensive Cancer Center, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America.

Abstract:  Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC) that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response. 

Retracted: No

PubPeer comments:
 Figure 6C appears two images which overlap. *** ![file] ,
Hepatocyte growth factor promotes proliferation, invasion, and metastasis of myeloid leukemia cells through PI3K-AKT and MAPK/ERK signaling pathway
Authors: Xiao-Lan Lian
Yong Wu
Xiao-Hui Zheng
Yuan-Zhong Chen
Jiang-Rui Guo
Wei Li
Xin Li
Lin-Qing Wu
Hui-Fang Huang
Ya-Fei Guo
Journal: American journal of translational research (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: AML; HGF; MAPK/Erk; PI3K-AKT; c-Met.
Affiliations: Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital Fuzhou, China., School of Pharmacy, Fujian Medical University Fuzhou, China., Department of Immunology, Fujian Medical University Fuzhou, China.

Abstract:  This study aims to investigate effects of HGF expression on biological behaviors of Kasumi-1 and HL60. Expression of HGF and c-Met gene were detected using qRT-PCR. Short hairpin RNA (shRNA) was used to reduce HGF expression. Silencing effect of shRNA was verified by qRT-PCR and western blot. Cell reproductive capacity, cell clonality and cell cycle (apoptosis) were detected by CCK-8, clone formation, flow cytometry (FCM), respectively. Cell adhesion, cell invasion ability and cell proliferation were also examined. Changes of PI3K-AKT, MAPK/ERK signaling factors were detected by western blot. HGF and c-Met expression in first-vist AML group was significantly higher than in AML-relief and normal control group. HGF shRNA can inhibit cell proliferation, inhibit cloning ability. Compared with control group, apoptosis ratios of Kasumi-1 and HL60 cell in interference groups were significantly higher. After shRNA interference, the number of adherent cells and transmembrane cells were significantly decreased compared with control group. Meanwhile, shRNA also down-regulated Bad, Bcl-XL, Bcl-2, CDK1, Cyclin B, MMP2, MMP9, and up-regulated cleaved caspase9, cleaved caspase3, cleaved PARP, Bax, and P21. Moreover, phosphorylated c-Met, AKT, Erk, and mTOR were also reduced. In conclusion, HGF and c-Met gene highly expressed among first-visit AML patients, but decreased after relief treatment. HGF may promote proliferation, invasion, and metastasis of AML cells through PI3K-AKT and MAPK/ERK signaling pathway. Therefore, proliferation and invasion ability of AML cell can be inhibited by down-regulating HGF gene to retardate cell in G2/M stage. 

Retracted: No

PubPeer comments:
 Figures 6 through 9: some panels look unexpectedly similar to each other, but represent different proteins or cell lines. Boxes of the same color highlight panels that show similarities. I did not mark the upside-down GAPDH in the top left of Figure 6A. ![file] ,
Rat inositol 1,4,5-trisphosphate 3-kinase C is enzymatically specialized for basal cellular inositol trisphosphate phosphorylation and shuttles actively between nucleus and cytoplasm
Authors: Hartwig Schmale
Uwe Bertsch
Georg W Mayr
Malte C Stockebrand
Werner Fanick
Marcus M Nalaskowski
Journal: Journal of Biological Chemistry (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Inositol 1,4,5-trisphosphate; Ins(1,3,4,5)P4; IP3Ks; isoforms; HsIP3K-C

Abstract:  The calcium-liberating second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) is converted to inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) by Ins(1,4,5)P3 3-kinases (IP3Ks) that add a fourth phosphate group to the 3-position of the inositol ring. Two isoforms of IP3Ks (named A and B) from different vertebrate species have been well studied. Recently the cloning and examination of a human full-length cDNA encoding a novel isoform, termed human IP3K-C (HsIP3K-C), has been reported. In the present study we report the cloning of a full-length cDNA encoding a rat homologue of HsIP3K-C with a unique mRNA expression pattern, which differs remarkably from the tissue distribution of HsIP3K-C. Of the rat tissues examined, rat IP3K-C (RnIP3K-C) is mainly present in heart, brain, and testis and shows the strongest expression in an epidermal tissue, namely tongue epithelium. RnIP3K-C has a calculated molecular mass of approximately 74.5 kDa and shows an overall identity of approximately 75% with HsIP3K-C. A bacterially expressed, enzymatically active and Ca2+-calmodulin-regulated fragment of this isoform displays remarkable enzymatic properties like a very low Km for Ins(1,4,5)P3 ( approximately 0.2 microm), substrate inhibition by high concentrations of Ins(1,4,5)P3, allosteric product activation by Ins(1,3,4,5)P4 in absence of Ca2+-calmodulin (Ka(app) 0.52 microm), and the ability to efficiently phosphorylate a second InsP3 substrate, inositol 2,4,5-trisphosphate, to inositol 2,4,5,6-tetrakisphosphate in the presence of Ins(1,3,4,5)P4. Furthermore, the RnIP3K-C fused with a fluorescent protein tag is actively transported into and out of the nucleus when transiently expressed in mammalian cells. A leucine-rich nuclear export signal and an uncharacterized nuclear import activity are localized in the N-terminal domain of the protein and determine its nucleocytoplasmic shuttling. These findings point to a particular role of RnIP3K-C in nuclear inositol trisphosphate phosphorylation and cellular growth. 

Retracted: No

PubPeer comments:
 Undeclared gel splice in Fig. 2B ![file] ,
LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells
Authors: Baoguo Li
Changfu Liu
Zhi Guo
Rui Mao
Yong Tang
Weihao Zhang
Journal: Life sciences (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Exosome; HCC; LncRNA FAL1; ceRNA mechanism; miR-1236.
Affiliations: Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, Chinese National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: ., Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, Chinese National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.

Abstract:  Background: Long non-coding RNAs (LncRNAs) have been demonstrated to play crucial role in tumor growth and metastasis for hepatocellular carcinoma (HCC). LncRNA FAL1 has been indicated to promote the progression of various cancers. However, the role of lncRNA FAL1 in HCC was poorly understood. Methods: The expression levels of lncRNA FAL1 in HCC tissues and cells were determined by RT-qPCR. The roles of lncRNA FAL1 on HCC cells were investigated by MTT, colony formation, transwell, RT-qPCR, and Western blotting. The miRNA binding sites of lncRNA FAL1 was predicted using RegRNA 2.0 and miR-1236 was validated to target lncRNA FAL1 by luciferase reporter assays and RT-qPCR. Finally, the expression levels of lncRNA FAL1 in serum exosome of HCC patients was also investigated and the role of exosome-mediated lncRNA FAL1 was further investigated by co-culturing with HCC cells. Results: This study first showed that lncRNA FAL1 was up-regulated in HCC tissues and functioned as an oncogene in HCC. LncRNA FAL1 could accelerate cell proliferation and metastasis as a ceRNA mechanism by competitively binding to miR-1236. Moreover, lncRNA FAL1 was also up-regulated in serum exosome of HCC patients and could transfer lncRNA FAL1 to HCC cells to increase their abilities of cell proliferation and migration. Conclusions: Taken together, this study indicated that lncRNA FAL1 functions as an oncogenic in HCC and may be a novel diagnostic biomarker or a novel target for the treatment of HCC in future. 

Retracted: No

PubPeer comments:
 A micrograph has been duplicated and presented as something else (Figure 2E and 4C (2nd micrograph from left, top panel). ![file] ,