PReD-Bench/PRed-Bench huggingface dataset:
A hypoxia-responsive TRAF6-ATM-H2AX signalling axis promotes HIF1α activation, tumorigenesis and metastasis
Authors: Guoxiang Jin
Liem Phan
Xian Zhang
Abdol-Hossein Rezaeian
Fei Han
Chien-Feng Li
Hui-Kuan Lin
Ping-Chieh Chou
Zhen Cai
Yun Seong Jeong
Dos Sarbassov
Jorge Delacerda
Ching-Yuan Wu
Mien-Chie Hung
Mong-Hong Lee
M James You
Journal: Nature cell biology (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: hypoxia; HIF1α; oncogenic signals; histone H2AX; VHL-independent
Affiliations: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Molecular Medicine, Pasteur Institute, Tehran 13169, Iran., Department of Pathology, Chi-Mei Foundational Medical Center, Tainan 710, Taiwan., National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan., Department of Cancer Biology, Wake Forest University School of Medicine Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA., Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., The University of Texas Graduate School of Biomedical Sciences at Houston, Texas 77030, USA., Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan., Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan., Department of Biotechnology, Asia University, Taichung 413, Taiwan.

Abstract:  The understanding of how hypoxia stabilizes and activates HIF1α in the nucleus with related oncogenic signals could revolutionize targeted therapy for cancers. Here, we find that histone H2AX displays oncogenic activity by serving as a crucial regulator of HIF1α signalling. H2AX interacts with HIF1α to prevent its degradation and nuclear export in order to allow successful VHL-independent HIF1α transcriptional activation. We show that mono-ubiquitylation and phosphorylation of H2AX, which are strictly mediated by hypoxia-induced E3 ligase activity of TRAF6 and ATM, critically regulate HIF1α-driven tumorigenesis. Importantly, TRAF6 and γH2AX are overexpressed in human breast cancer, correlate with activation of HIF1α signalling, and predict metastatic outcome. Thus, TRAF6 and H2AX overexpression and γH2AX-mediated HIF1α enrichment in the nucleus of cancer cells lead to overactivation of HIF1α-driven tumorigenesis, glycolysis and metastasis. Our findings suggest that TRAF6-mediated mono-ubiquitylation and subsequent phosphorylation of H2AX may serve as potential means for cancer diagnosis and therapy. 

Retracted: No

PubPeer comments:
 Supplemental Fig. S2d u2013 more similar than expected (red blue) ![file] Supplemental Fig. S3e u2013 more similar than expected (in red) ![file] ,
Outcomes of Gracilis Muscle Flaps in the Management of Groin Complications after Arterial Bypass with Prosthetic Graft
Authors: Sapan S Desai
Kara A Rothenberg
Christina Rao
Kedar Lavingia
Anahita Dua
Vy T Ho
Journal: Annals of Vascular Surgery (2018)
Discipline: CLINICAL MEDICINE
Keywords: gracilis muscle flap; groin complications; arterial bypass surgery; synthetic graft; ultrasound
Affiliations: Division of Vascular Surgery, Department of Surgery, Stanford Health Care, Stanford, CA., Department of Vascular Surgery, Northwest Community Hospital, Arlington Heights, IL., Department of Vascular Surgery, Northwest Community Hospital, Arlington Heights, IL. Electronic address: .

Abstract:  Background: This study details 2-year outcomes of a modified gracilis muscle flap (GMF) technique in providing tissue coverage for groin complications after arterial bypass surgery with synthetic graft. Methods: All patients who developed groin infections after lower extremity arterial bypass with synthetic graft who underwent a GMF technique were included from June 2014 to March 2017 from a prospectively collected, purpose-built institutional database. Modifications to the standard technique included identification of the muscle using ultrasound to ensure precise skip incisions, preservation of the segmental blood supply, widening of the tunnel through which the muscle is retroflexed, placement of a wound vacuum-assisted closure for healing, and lifelong antibiotics. Demographics, laboratory values, bypass procedure, length of stay (LOS), disposition, and 1-, 3-, 6-, 12-, and 24-month follow-up data were collected. Analysis was performed via descriptive statistics. Results: Over the 3-year study period, 22 patients underwent GMF after complications resulted from arterial bypass surgery. Types of bypass included aortobifemoral (32%), axillobifemoral (14%), femoral-femoral (23%), femoral-popliteal or mixed distal (27%), and thigh graft for dialysis (4%). Forty-five percentage of patients presented with graft infection, 50% with wound dehiscence, and 5% with graft disruption and bleeding. Only 23% of patients were candidates for sartorius muscle flap at the time of their initial procedure. The average case length was 64 + 19 min. Sixty-four percentage of patients were discharged home with home health care and the remainder to a skilled nursing facility. The average LOS was 6.1 + 3.4 days. Fifty-four percentages of wounds were healed at 1 month and 100% at 3 months with adjunctive vacuum-assisted closure therapy and lifelong antibiotics. Sixty percentage of patients were still alive at 24 months, with 33% of grafts still patent at that time. Median survival was 18.1 months, and median graft patency was 17.9 months. Conclusions: GMF is a safe and effective treatment for groin complications after arterial bypass surgery with synthetic graft. Owing to its versatility, area of coverage, ease of use, and durability, it potentially should be considered as a primary form of muscle coverage for groin complications. 

Retracted: No

PubPeer comments:
 Can the authors please indicate which institutional review board found the study to be exempt from review? ,
Gain of cellular adaptation due to prolonged p53 impairment leads to functional switchover from p53 to p73 during DNA damage in acute myeloid leukemia cells
Authors: Pallab Ray
Gaurisankar Sa
Dewan Md Sakib Hossain
Sreya Chattopadhyay
Tanya Das
Shuvomoy Banerjee
Juni Chakraborty
Sankar Bhattacharyya
Arghya Adhikary
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Tumor suppressor p53; apoptosis; DNA damage; p73; Chk-1
Affiliations: Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata 700 054, India.

Abstract:  Tumor suppressor p53 plays the central role in regulating apoptosis in response to genotoxic stress. From an evolutionary perspective, the activity of p53 has to be backed up by other protein(s) in case of any functional impairment of this protein, to trigger DNA damage-induced apoptosis in cancer cells. We adopted multiple experimental approaches to demonstrate that in p53-impaired cancer cells, DNA damage caused accumulation of p53 paralogue p73 via Chk-1 that strongly impacted Bax expression and p53-independent apoptosis. On the contrary, when p53 function was restored by ectopic expression, Chk-2 induced p53 accumulation that in turn overshadowed p73 activity, suggesting an antagonistic interaction between p53 family members. To understand such interaction better, p53-expressing cells were impaired differentially for p53 activity. In wild-type p53-expressing cancer cells that were silenced for p53 for several generations, p73 was activated, whereas no such trend was observed when p53 was transiently silenced. Prolonged p53 interference, even in functional p53 settings, therefore, leads to the "gain of cellular adaptation" in a way that alters the cellular microenvironment in favor of p73 activation by altering p73-regulatory proteins, e.g. Chk1 activation and dominant negative p73 down-regulation. These findings not only unveil a hitherto unexplained mechanism underlying the functional switchover from p53 to p73, but also validate p73 as a promising and potential target for cancer therapy in the absence of functional p53. 

Retracted: No

PubPeer comments:
 Fig 5 ![file] Fig 5A: the actin band for upper and lower panel is duplicated. There are seven protein levels are analyzed. Fig 5B: The actin band for upper and lower panel is duplicated. There are seven protein levels are analyzed. It is technically difficult to re-probe 7 times in single blot. Could authors clarify? ,
KDM3 epigenetically controls tumorigenic potentials of human colorectal cancer stem cells through Wnt/β-catenin signalling
Authors: Peng Deng
Sivakumar Ramadoss
Xinmin Li
Jiong Li
Yingduan Cheng
Yongxin Yu
Bo Yu
Cun-Yu Wang
Xiangming Ding
Kareena Kevork
Journal: Nature communications (2017)
Discipline: Multidisciplinary
Keywords: Colorectal cancer stem cells; CSCs; KDM3; Epigenetics; Wnt signaling
Affiliations: Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry and Broad Stem Cell Research Center, UCLA, Los Angeles, California 90095, USA., Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA., Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, UCLA, Los Angeles, California 90095, USA.

Abstract:  Human colorectal cancer stem cells (CSCs) are tumour initiating cells that can self-renew and are highly tumorigenic and chemoresistant. While genetic mutations associated with human colorectal cancer development are well-known, little is known about how and whether epigenetic factors specifically contribute to the functional properties of human colorectal CSCs. Here we report that the KDM3 family of histone demethylases plays an important role in tumorigenic potential and survival of human colorectal CSCs by epigenetically activating Wnt target gene transcription. The depletion of KDM3 inhibits tumorigenic growth and chemoresistance of human colorectal CSCs. Mechanistically, KDM3 not only directly erases repressive H3K9me2 marks, but also helps to recruit histone methyltransferase MLL1 to promote H3K4 methylation, thereby promoting Wnt target gene transcription. Our results suggest that KDM3 is a critical epigenetic factor in Wnt signalling that orchestrates chromatin changes and transcription in human colorectal CSCs, identifying potential therapeutic targets for effective elimination of CSCs. 

Retracted: No

PubPeer comments:
 Microscope photographs from completely different conditions in Fig.4B are the same. # **Fig.4B** ![file] , 
 November 2019 correction, which reads: *This Article contains errors in Figure 4 and Supplementary Figure 3. In Figure 4b, the image representing ALDHu2212 EpCAM+ Control siRNA was taken from the ALDH+ EpCAM+ KDM3A+B siRNA image. In Supplementary Figure 3b, the image representing CD133+ EpCAM+ was taken from CD133+ EpCAM+ Control siRNA image of panel a. The correct versions of Figure 4 and Supplementary Figure 3 are shown below. The error has not been corrected in the PDF or HTML versions of the Article.* https: www.nature.com articles s41467-019-12878-z ,
Inhibition of protein phosphatase-2A with LB-100 enhances antitumor immunity against glioblastoma
Authors: John S Kovach
Mark R Gilbert
Stuart Walbridge
Rongze O Lu
Dominic Maggio
Rebecca Breese
Jing Cui
Zhengping Zhuang
Winson S Ho
John D Heiss
Herui Wang
Journal: Journal of Neuro-Oncology (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: GBM; Immunotherapy; LB-100; PP2A.
Affiliations: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA., Department of Neurosurgery, Dell Medical School, University of Texas at Austin, Austin, TX, 78701, USA. ., University of Texas at Austin, 1601 Trinity St, Bldg. B HDB 3.214, Austin, TX, 78701, USA. ., Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Lixte Biotechnology Holdings, Inc., East Setauket, NY, 11733, USA., University of Texas at Austin, 1601 Trinity St, Bldg. B HDB 3.216, Austin, TX, 78701, USA. ., Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. ., National Institutes of Health, BLDG 35, Rm 2B203, Bethesda, MD, 20892, USA. .

Abstract:  Purpose: Glioblastoma (GBM) carries a dismal prognosis despite standard multimodal treatment with surgery, chemotherapy and radiation. Immune checkpoint inhibitors, such as PD1 blockade, for treatment of GBM failed to show clinical benefit. Rational combination strategies to overcome resistance of GBM to checkpoint monotherapy are needed to extend the promise of immunotherapy to GBM management. Emerging evidence suggests that protein phosphatase 2A (PP2A) plays a critical role in the signal transduction pathways of both adaptive and innate immune cells and that inhibition of PP2A could enhance cancer immunity. We investigated the use of a PP2A inhibitor, LB-100, to enhance antitumor efficacy of PD1 blockade in a syngeneic glioma model. Methods: C57BL/6 mice were implanted with murine glioma cell line GL261-luc or GL261-WT and randomized into 4 treatment arms: (i) control, (ii) LB-100, (iii) PD1 blockade and (iv) combination. Survival was assessed and detailed profiling of tumor infiltrating leukocytes was performed. Results: Dual PP2A and PD1 blockade significantly improved survival compared with monotherapy alone. Combination therapy resulted in complete regression of tumors in about 25% of mice. This effect was dependent on CD4 and CD8 T cells and cured mice established antigen-specific secondary protective immunity. Analysis of tumor lymphocytes demonstrated enhanced CD8 infiltration and effector function. Conclusion: This is the first preclinical investigation of the effect of combining PP2A inhibition with PD1 blockade for GBM. This novel combination provided effective tumor immunotherapy and long-term survival in our animal GBM model. 

Retracted: No

PubPeer comments:
 Figure 1d, two images are exactly the same. Pixel by pixel ![file] ![file] ,
The human Frizzled 6 (HFz6) acts as a negative regulator of the canonical Wnt. beta-catenin signaling cascade
Authors: Abraham Yaniv
Arnona Gazit
Tamar Golan
Anna Bafico
Guizhong Liu
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Frizzled 6; Canonical Wnt pathway; Repression; Beta-catenin; TCF/lymphoid enhancer factor
Affiliations: Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Abstract:  Previously we have cloned the human Frizzled 1 (HFz1) and shown that it transmits the Wnt-3a-induced canonical pathway. We also cloned the human Frizzled 6 (HFz6) and show in the present study that, as opposed to HFz1, HFz6 did not activate the canonical Wnt pathway following exposure to various Wnts, whether belonging to the Wnt-1 or to the Wnt-5a group. Moreover we show that HFz6 repressed Wnt-3a-induced canonical signaling when co-expressed with HFz1. HFz6 repressed the canonical Wnt cascade activated also by various Wnt signaling intracellular mediators such as Dishevelled-1, a stabilized beta-catenin(S33Y) mutant, and LiCl-mediated repression of glycogen synthase kinase-3beta activity. Removal of HFz6 N'- or C'-terminal sequences abolished HFz6 repressive activity. As the HFz6 repressive effect was not associated with a decrease in the level of beta-catenin, it is suggested that HFz6 does not affect beta-catenin stabilization, implying that HFz6 transmits a repressive signaling that cross-talks with and inhibits the canonical Wnt pathway downstream of beta-catenin destruction complex. HFz6 did not affect the level of nuclear T-cell factor 4 (TCF4) nor did it affect beta-catenin.TCF4 complex formation. However, electrophoretic mobility shift assays indicated that HFz6 repressed the binding of TCF/lymphoid enhancer factor transcription factors to target DNA. Moreover we present data suggesting that HFz6 activates the transforming growth factor-beta-activated kinase-NEMO-like kinase pathway that blocks TCF/lymphoid enhancer factor binding to target promoters, thereby inhibiting the ability of beta-catenin to activate transcription of Wnt target genes. 

Retracted: No

PubPeer comments:
 ![file] ,
Expression of luciferase plasmid (pCMVLuc) entrapped in DPPC/cholesterol/DDAB liposomes in HeLa cell lines
Authors: Korakot Thathang
Aranya Manosroi
Jiradej Manosroi
Rolf G Werner
Regine Peschka-Süss
Rolf Schubert
Journal: Journal of Liposome Research (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: luciferase gene expression; lipoplexes; liposome; HeLa cell lines; cationic liposomes
Affiliations: Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. 

Abstract:  The luciferase gene expression of lipoplexes, a liposome containing luciferase plasmid (pCMVLuc), in HeLa cell lines, was investigated. Cationic liposomes were prepared by the chloroform film method with sonication. The lipoplex was formed by loading the liposome with pCMVLuc. The lipoplex with an optimal weight ratio of dimethyl dioctadecyl ammonium bromide (DDAB)/pCMVLuc protected from DNaseI was determined by an agarose gel electrophoresis. The selected lipoplexes were assayed for luciferaase activity by using a luminometer. The effect on cell proliferation was evaluated by WST-1 assay. The highest luciferase activity of 1.5 x 10(6) RLU was observed in the cholesterol (Chol)/DDAB (2:1 molar ratio) lipoplex at the DDAB/pCMVLuc weight ratio of 10:1 at 48 hours, which was about 10, 100, and 1,000 times higher than the DDAB, L-alpha-dipalmitoyl phosphatidylcholine (DPPC)/Chol/DDAB (1:2:1 molar ratio), and DPPC/Chol/DDAB (2:2:1 molar ratio) lipoplexes, respectively. The liposome with the smallest particle size was obtained from the cationic liposome composed of DPPC/Chol/DDAB (7:1:1 molar ratio) with the zeta potential of 7.17 +/- 0.73. The optimal weight ratio of DDAB/pCMVLuc that protected pCMVLuc from DNaseI digestion was 4:1 in the DDAB formulation. The Chol/DDAB (2:1 molar ratio) lipoplex with the DDAB/pCMVLuc of 10:1 showed the highest luciferase activity of 1.5 x 10(6) RLU and the highest cytotoxicity as well. DPPC/Chol/DDAB (1:1:1 molar ratio)-lipoplex (DDAB/pCMVLuc = 14:1), which had the amount of DPPC and cholesterol not exceeding 33 and 50% mol, respectively, gave the lower gene expression of about 4 times, but lower cytoxicity of about 14 times, than the Chol/DDAB lipoplex (2:1 molar ratio) and was considered to be the most suitable formulation. The results from this study can be applied as a model for the development of a gene-therapeutic dosage form. 

Retracted: No

PubPeer comments:
 The gel appears to be duplicated for two completely different almond populations. Could the authors please check. https: imgur.com a JsknjjA , 
 The third author (Attila Hegedu0171s) and last author (Ju00falia Halu00e1sz) are Associate Editors of this journal, so there may be a conflict of interest in correcting this error: https: ojs.lib.unideb.hu IJHS about editorialTeam ,
Involvement of hTERT in apoptosis induced by interference with Bcl-2 expression and function
Authors: D Del Bufalo
M R Torrisi
G Cardinali
A Rizzo
U Zangemeister-Wittke
G Zupi
A Biroccio
D Trisciuoglio
Journal: Cell Death and Differentiation (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: telomerase; Bcl-2; apoptosis; hTERT; HA14-1
Affiliations: Experimental Chemotherapy Laboratory, Experimental Research Center, Regina Elena Cancer Institute, Rome 00158, Italy.

Abstract:  Here, we investigated the role of telomerase on Bcl-2-dependent apoptosis. To this end, the 4625 Bcl-2/Bcl-xL bispecific antisense oligonucleotide and the HA14-1 Bcl-2 inhibitor were used. We found that apoptosis induced by 4625 oligonucleotide was associated with decreased Bcl-2 protein expression and telomerase activity, while HA14-1 triggered apoptosis without affecting both Bcl-2 and telomerase levels. Interestingly, HA14-1 treatment resulted in a profound change from predominantly nuclear to a predominantly cytoplasmic localization of hTERT. Downregulation of endogenous hTERT protein by RNA interference markedly increased apoptosis induced by both 4625 and HA14-1, while overexpression of wild-type hTERT blocked Bcl-2-dependent apoptosis in a p53-independent manner. Catalytically and biologically inactive hTERT mutants showed a similar behavior as the wild-type form, indicating that hTERT inhibited the 4625 and HA14-1-induced apoptosis regardless of telomerase activity and its ability to lengthening telomeres. Finally, hTERT overexpression abrogated 4625 and HA14-1-induced mitochondrial dysfunction and nuclear translocation of hTERT. In conclusion, our results demonstrate that hTERT is involved in mitochondrial apoptosis induced by targeted inhibition of Bcl-2. 

Retracted: No

PubPeer comments:
null, 
null, 
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 Figure 2c. Much more similar than expected. ![file] , 
 Figure 4. Much more similar than expected. ![file] ,
Hydrophobic Modification on the Surface of SiO Nanoparticle: Wettability Control
Authors: Xiao-Chun Liu
Yu-Xiu Cai
Yong-Li Yan
Man-Xue Wang
Guo-Wei Ma
Wei Lv
Journal: Langmuir (2020)
Discipline: CHEMISTRY
Keywords: silica nanoparticles; surface wettability; chemical modifier; scanning electron microscopy; Fourier transform infrared spectroscopy
Affiliations: College of Chemistry & Chemical Engineering, Xi'an Shiyou University, Xi'an 710065, China., Oil and Gas Technology Research Institute, CNPC Changqing Oilfield Company, Xi'an 710018, China., Shaanxi Key Laboratory of Lacustrine Shale Gas Accumulation and Exploitation, Xi'an 710075, China.

Abstract:  Good control of the morphology, particle size, and wettability of silica nanoparticles is of increasing importance to their use in a variety of fields. Here, we propose a strategy to tune the surface wettability of nanosilica by changing the dosage of a chemical modifier. A series of measurements, including scanning electron microscopy (SEM), laser scatting technique, Fourier transform infrared (FTIR) spectroscopy, thermogravimetry, and surface hydroxyl number and water contact angle measurement, were conducted to verify the surface chemistry and wettability of these nanoparticles. Through controlled chemical modification, the contact angle of the treated nanoparticles increases from 34.7 to 155° with increasing amount of dichlorodimethylsilane (DCDMS) within a molar ratio (MR) between DCDMS and nanoparticles of 5.17. The number of hydroxyl groups covered on the particle surface decreases gradually from 1.79 to 0.47, and the surface grafting rate could reach 73.7%. As the addition of dichlorodimethylsilane equals MR 5.17, the contact angle reaches the maximum value of 155°, which displays excellent superhydrophobicity. After surpassing the point of MR 5.17, the contact angle does not increase but starts to decrease, ultimately remaining stable at 135°. It can be concluded that the surface wettability of nano-SiO2 particles can be precisely modulated by varying the amounts of the modifier. Furthermore, the modulating mechanism of the process occurring on the surface of SiO2 particles has been investigated at the molecular level. 

Retracted: No

PubPeer comments:
 Figure 1 and Figure 2 look remarkably similar. Based on the legends, Figure 2 maybe should have shown something else. Could the authors please check? They might also want to check the spelling of the affiliated city,  *Marrseille* . ![file] ,
Insular cortex processes aversive somatosensory information and is crucial for threat learning
Authors: Shriya Palchaudhuri
Wei Tang
Olexiy Kochubey
Emmanuelle Berret
Denys Osypenko
Michael Kintscher
Ralf Schneggenburger
Journal: Science (2019)
Discipline: Multidisciplinary
Keywords: threat learning; amygdala; insula; optogenetic techniques; fear behavior
Affiliations: Laboratory of Synaptic Mechanisms, Brain Mind Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Laboratory of Synaptic Mechanisms, Brain Mind Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. .

Abstract:  Learning about threats is essential for survival. During threat learning, an innocuous sensory percept such as a tone acquires an emotional meaning when paired with an aversive stimulus such as a mild footshock. The amygdala is critical for threat memory formation, but little is known about upstream brain areas that process aversive somatosensory information. Using optogenetic techniques in mice, we found that silencing of the posterior insula during footshock reduced acute fear behavior and impaired 1-day threat memory. Insular cortex neurons respond to footshocks, acquire responses to tones during threat learning, and project to distinct amygdala divisions to drive acute fear versus threat memory formation. Thus, the posterior insula conveys aversive footshock information to the amygdala and is crucial for learning about potential dangers in the environment. 

Retracted: Yes

PubPeer comments:
 The videos in the supplementary information, in particular video 3, appear as though opto stimulation is producing behavior induced seizure activity that the authors describe as  aversive behavior . , 
 #1 Dear  Lataxenia thank you for sharing this important observation with us. If you would like to discuss it more, please reveal your name, or write me an e-mail. best regards, R.S. , 
 This paper has been retracted due to data falsification: https: science.sciencemag.org content sci 366 6472 1460.1.full.pdf  ....the mouse behavior data reported in Figs. 1C, 3C, 3F, and 6B, and the corresponding data in supplementary figures, had been manipulated... The first author, who performed these measurements, has admitted to having committed the data falsification. ,
Kirenol attenuates experimental autoimmune encephalomyelitis by inhibiting differentiation of Th1 and th17 cells and inducing apoptosis of effector T cells
Authors: Wenwei Liu
Wenbin Deng
Rongbing Yang
Xiaohang Fan
Juan Xiao
Lin Yang
Journal: Scientific Reports (2015)
Discipline: Multidisciplinary
Keywords: Experimental autoimmune encephalomyelitis; EAE; multiple sclerosis; CNS demyelination; autoreactive T cells
Affiliations: 1] Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China [2] Department of Biological Treatment, Handan Central Hospital, Handan, Hebei, China [3] Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA, USA., Department of Biological Treatment, Handan Central Hospital, Handan, Hebei, China., Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China., 1] Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China [2] Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA, USA.

Abstract:  Experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is characterized by CNS demyelination mediated by autoreactive T cells. Kirenol, a biologically active substance isolated from Herba Siegesbeckiae, has potent anti-inflammatory activities. Here we investigated effects of kirenol on EAE. Kirenol treatment markedly delayed onset of disease and reduced clinical scores in EAE mice. Kirenol treatment reduced expression of IFN-γ and IL-17A in the serum and proportion of Th1 and Th17 cells in draining lymph nodes. Priming of lymphocytes was reduced and apoptosis of MOG-activated CD4+ T cells was increased in kirenol treated EAE mice. Kirenol treatment of healthy animals did not affect the lymphocytes in these non-immunized mice. Further in vitro studies showed that kirenol inhibited viability of MOG-specific lymphocytes and induced apoptosis of MOG-specific CD4+ T cells in a dose- and time-dependent manner. Kirenol treatment upregulated Bax,downregulated Bcl-2,and increased activation of caspase-3 and release of cytochrome c, indicating that a mitochondrial pathway was involved in kirenol induced apoptosis. Moreover, pretreatment with either a pan-caspase inhibitor z-VAD-fmk or a more specific caspase 3 inhibitor Ac-DEVD-CHO in lymphocytes reduced kirenol induced apoptosis. Our findings implicate kirenol as a useful agent for the treatment of MS. 

Retracted: No

PubPeer comments:
 Duplicated blots....Could authors please check. Scans of source data would help to clarify the issue. ![file] ![file] ,
Effect of microRNA-129-5p targeting HMGB1-RAGE signaling pathway on revascularization in a collagenase-induced intracerebral hemorrhage rat model
Authors: Xin-Long Ma
Feng Shang
Shu-Ya Li
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HMGB1-RAGE signaling pathway; Highmobility group box 1 protein; Intracerebral hemorrhage; MicroRNA-129-5p; Receptor for advanced glycation end-products
Affiliations: Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China., Department of Neurology, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, PR China., Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China. Electronic address: .

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. An Expression of Concern for this article was previously published while an investigation was conducted (see related editorial: https://doi.org/10.1016/j.biopha.2022.113812). This retraction notice supersedes the Expression of Concern published earlier. Concern was raised about the reliability of the Western blot data in Figure 2A, which contain suspected image duplications within the β-actin blot, and appear to represent a distinct phenotype as found in many other publications, as detailed here: https://pubpeer.com/publications/83FD53A8F4C5B60E2187CBF9F29B01; and here: https://docs.google.com/spreadsheets/d/1r0MyIYpagBc58BRF9c3luWNlCX8VUvUuPyYYXzxWvgY/edit#gid=262337249. Independent analysis confirmed these findings and also identified additional suspected image duplications within Figures 3 and 4A. The journal requested the corresponding author comment on these concerns and provide the associated raw data. The authors did not respond to this request and therefore the Editor-in-Chief decided to retract the article. 

Retracted: No

PubPeer comments:
 Fig 2  A. Electrophoresis results of HMGB1 and RAGE proteins in brain tissue homogenates of rats on day 7 and 14 after surgery . ![file] The loading control here appears to be a composite. Note in particular the bubble under one blob and the eye in two. These distinctive blobs turn up in loading controls across a number of papers. ![] ![] ![] https: docs.google.com spreadsheets d 1r0MyIYpagBc58BRF9c3luWNlCX8VUvUuPyYYXzxWvgY edit#gid=262337249 ,
LncRNA LINC00689 promotes the growth, metastasis and glycolysis of glioma cells by targeting miR-338-3p/PKM2 axis
Authors: Linjun Hu
Yang Guo
Xin Liu
Qiuran Xu
Qiaojuan Zhu
Zunqiang Xiao
Journal: Biomedicine & Pharmacotherapy (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Glioma growth; Glycolysis; LINC00689; Metastasis; PKM2
Affiliations: Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, 310014, China., Department of Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310000, China., Graduate Department, BengBu Medical College, BengBu, Anhui Province, 233030, China., The Medical College of Qindao University, Qindao, Shandong Province, 266071, China., Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, 310014, China. Electronic address: .

Abstract:  Accumulating evidence supports that long non-coding RNAs (lncRNAs) are implicated in the tumorigenesis and progression of glioma. Recent studies find that lncRNA long intergenic non-protein coding RNA 689 (LINC00689) is associated with obesity and participates in eukaryotic gene expression. However, whether LINC00689 plays a critical role in glioma progression remains unknown. Here, we identified a highly expressed lncRNA LINC00689 in gliomas compared to normal brain tissues based on the GSE dataset (GSE4290). The analysis of our data indicated that the expression of LINC00689 was up-regulated in glioma tissues and cell lines. Moreover, the high expression of LINC00689 was closely correlated with tumor size ≥3 cm, high tumor grade, low KPS scores and poor prognosis of glioma patients. Further investigation demonstrated that LINC00689 knockdown markedly repressed the proliferation, migration, invasion and glycolysis of glioma cells. Additionally, silencing of LINC00689 significantly suppressed the growth of glioma cells in vivo. Mechanistically, LINC00689 functioned as a competing endogenous RNA (ceRNA) by directly interacting with miR-338-3p to promote pyruvate kinase M2 (PKM2) expression. Notably, we also revealed that restoration of PKM2 abolished the effects of LINC00689 silencing on glioma cell proliferation, migration, invasion and glycolysis. In summary, our results suggested that LINC00689/miR-338-3p/PKM2 axis might play an essential role in glioma progression. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have a partial image duplication. Although they have the same treatment, they are different cell lines, and should not have overlaps. There are some differences between the overlapping box. I have circled the differences in red. I do not know how only part of the image could be so similar. I did not look further. ![file] ,
Contrasting patterns of Bim induction and neuroprotection in Bim-deficient mice between hippocampus and neocortex after status epilepticus
Authors: R Meller
A Paucard
R P Simon
M Dunleavy
D C Henshall
G Mouri
K Tanaka
B M Murphy
I Woods
T Engel
L P Tuffy
E M Jimenez-Mateos
J H M Prehn
H P Bonner
S Hatazaki
A Strasser
Journal: Cell death and differentiation (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Prolonged seizures; status epilepticus; apoptosis; BH3; Bcl-2
Affiliations: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.

Abstract:  Prolonged seizures (status epilepticus) are associated with brain region-specific regulation of apoptosis-associated signaling pathways. Bcl-2 homology domain 3-only (BH3) members of the Bcl-2 gene family are of interest as possible initiators of mitochondrial dysfunction and release of apoptogenic molecules after seizures. Previously, we showed that expression of the BH3-only protein, Bcl-2 interacting mediator of cell death (Bim), increased in the rat hippocampus but not in the neocortex after focal-onset status epilepticus. In this study, we examined Bim expression in mice and compared seizure damage between wild-type and Bim-deficient animals. Status epilepticus induced by intra-amygdala kainic acid (KA) caused extensive neuronal death within the ipsilateral hippocampal CA3 region. Hippocampal activation of factors associated with transcriptional and posttranslational activation of Bim, such as CHOP and c-Jun NH(2)-terminal kinases, was significant within 1 h. Upregulation of bim mRNA was evident after 2 h and Bim protein increased between 4 and 24 h. Hippocampal CA3 neurodegeneration was reduced in Bim-deficient mice compared with wild-type animals after seizures in vivo, and short interfering RNA molecules targeting bim reduced cell death after KA treatment of hippocampal organotypic cultures. In contrast, neocortical Bim expression declined after status epilepticus, and neocortex damage in Bim-deficient mice was comparable with that in wild-type animals. These results show region-specific differential contributions of Bim to seizure-induced neuronal death. 

Retracted: No

PubPeer comments:
 An image seems to appear in both Figure 1a and Figure 1b. *** ![file] ,
Knockdown of long non-coding RNA LUCAT1 reverses high glucose-induced cardiomyocyte injury via targeting CYP11B2
Authors: L-Q Zhou
Y Yin
Y-J Zhang
Z-F Yang
B Yang
X-H Li
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Diabetic cardiomyopathy; long noncoding RNAs; lncRNA LUCAT1; cardiomyocyte injury; apoptosis
Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China. .

Abstract:  Objective: Diabetic cardiomyopathy (DCM) is one of the major complications in patients with diabetes mellitus. Recently, long noncoding RNAs (lncRNAs) have been well concerned for their roles in the progression of multiple diseases, including DCM. In this research, we aimed to explore the role of lncRNA LUCAT1 in cardiomyocyte injury and apoptosis induced by high glucose (HG) in vitro. Materials and methods: High glucose-induced (HG-induced) AC16 cardiomyocytes transfected with LUCAT1 shRNA were constructed. LUCAT1 expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Subsequently, cell proliferation and cell apoptosis were detected after LUCAT1 knockdown in HG-induced AC16 cells. Moreover, RT-qPCR and Western blot assay were performed to explore the potential underlying mechanism of LUCAT1 in DCM. Results: The expression of LUCAT1 was significantly upregulated in HG-treated AC16 cardiomyocytes. Moreover, knockdown of LUCAT1 could reverse cardiomyocyte injury and apoptosis through downregulating CYP11B2. Conclusions: We first demonstrated that knockdown of LUCAT1 could reverse HG-induced cardiomyocyte injury by down-regulating CYP11B2. Our findings might offer a new direction for interpreting the mechanism of DCM development. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. ,
Silibinin ameliorates LPS-induced memory deficits in experimental animals
Authors: Debapriya Garabadu
Gangineni Ravi Teja
Ritu Joshi
Sairam Krishnamurthy
Journal: Neurobiology of Learning and Memory (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Acetylcholine; Aβ; LPS; Neuroinflammation; Silibinin
Affiliations: Neurotherapeutics Lab, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India., Neurotherapeutics Lab, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India. Electronic address: .

Abstract:  Neuroinflammation is considered as one of the predisposing factor in the etiology of several neurodegenerative disorders. Therefore, the objective of the present study was to evaluate the protective effect of silibinin (SIL) in the lipopolysaccharide (LPS)-induced neuroinflammatory model. The effect of SIL on memory function was also evaluated on normal rats without LPS administration. In the first experiment, male rats were divided into five groups. Except control group animals, all rats received bilateral intracerebroventricular injection of LPS (5 μg/5 μl) into lateral ventricles on the first day of the experimental schedule. Control rats received bilateral intracerebroventricular injection of artificial cerebrospinal fluid into lateral ventricles. SIL in doses of 50, 100 and 200 mg/kg, p.o. was administered 1h before LPS injection and continued for 7 days. On Day-7, SIL attenuated the LPS-induced long-term and working memory loss in elevated plus and Y-maze test respectively. Further, SIL dose-dependently attenuated LPS-induced decrease in acetylcholine level and increase in the acetylcholinestrase activity in hippocampus and pre-frontal cortex. SIL ameliorated LPS-induced decrease in the mitochondrial complex activity (I, IV and V) and integrity, increase in lipid peroxidation and decrease in the activity of superoxide dismutase in both the brain regions. SIL attenuated amyloidogenesis in the hippocampus, while it decreased the LPS-induced increase in the level of NFκB in the pre-frontal cortex. In another study, SIL dose-dependently, enhanced memory functions in the normal rats, indicating its nootropic activity. Hence, SIL could be a potential candidate in the management of neuroinflammation-related memory disorders. 

Retracted: No

PubPeer comments:
 Figure 8A. * Red and blue arrows highlight bands that appear to look similar within or across different panels. ![file] , 
 Figure 9A. * Green arrows highlight bands that appear to look similar within the same panel. ![file] ,
Effect of celecoxib on protein expression of FAK and Cx43 in DMBA induced rat tongue carcinoma cells
Authors: B-Z Shan
X-F Sun
B Guo
Y-S Li
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Tongue cancer; Cyclooxygenase-2; Focal adhesion kinase; Connexin 43; Celecoxib
Affiliations: Department of Stomatology, Jinan Central Hospital Affiliated to Shandong University, Jinan, P.R. China. .

Abstract:  Objective: The pathogenesis of tongue cancer (TA) has not been fully illustrated. Cyclooxygenase-2 (COX-2) is correlated with the precancerous lesion of oral cavity mucosa and malignant transformation. The focal adhesion kinase (FAK) and gap junction protein connexin 43 (Cx43) are involved in the occurrence and progression of tumors. This study aimed to investigate the effect of celecoxib on the proliferation, malignant transformation, and expression of FAK and Cx43 proteins. Materials and methods: Healthy male Sprague-Dawley (SD) rats (4 months old) were divided into control, model and celecoxib group. 7,12-dimethylbenzanthracene (DMBA) was used to generate tongue mucosal carcinoma, coupled with celecoxib intervention. At 8, 12, 16, and 20 weeks after induction, the rat survival status, the tumor formation rate and the tongue tissue morphology were observed. Meanwhile, the expression of FAK and Cx43 was also evaluated by using immunohistochemistry (IHC). Results: Tumor occurrence rates after induction were 0, 26.67%, 66.67%, and 80% at 8, 12, 16, and 20 weeks, respectively. The celecoxib treatment decreased such rats to 0, 0, 0, and 13.33%, respectively (p&lt;0.05 compared to model group). No significant change was observed in control group, whilst model group had mild to severe hyperplasia and squamous carcinoma with elongated time. Celecoxib treatment significantly improved the tissue morphology (p&lt;0.05). The model group also had elevated FAK and depressed Cx43 protein expression (p&lt;0.05). With elongated time, the FAK expression was further increased whilst Cx43 protein was depressed (p&lt;0.05 compared to model group). Conclusions: The focal application of celecoxib effectively inhibited the DMBA-induced rat TA, possibly via regulating FAK and CX43 protein expression, and inhibiting oral epidermal hyperplasia. 

Retracted: No

PubPeer comments:
 Figure 1 https: imgur.com a KJBaQay ,
Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Authors: Sergio Poli
Suchita Kamle
Chun Geun Lee
Bing Ma
Chuan-Hua He
Bedia Akosman
Jin Wook Park
Changwan Ryu
Xueyan Peng
Erica L Herzog
Yang Zhou
Roberto Cotez
Jae Hyun Lee
Augustine M Choi
Jack A Elias
Ivan O Rosas
Carol Feghali Bostwick
Emily Chen
Chang-Min Lee
Journal: Life Science Alliance (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: TGF-β1; CHIT1; fibrosis; SMAD7; TGFBRAP1
Affiliations: Molecular Microbiology and Immunology, Brown University, Providence, RI, USA., Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea., Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA., Brigham and Women's Hospital, Boston, MA, USA., Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC, USA., Weill Cornell Medicine Pulmonary and Critical Care Medicine, New York, NY, USA., Molecular Microbiology and Immunology, Brown University, Providence, RI, USA ., Division of Medicine and Biological Sciences, Brown University, Warren Alpert School of Medicine, Providence, RI, USA.

Abstract:  TGF-β1 is a critical mediator of tissue fibrosis in health and disease whose effects are augmented by chitinase 1 (CHIT1). However, the mechanisms that CHIT1 uses to regulate TGF-β1-mediated fibrotic responses have not been defined. Here, we demonstrate that CHIT1 enhances TGF-β1-stimulated fibrotic cellular and tissue responses and TGF-β1 signaling. Importantly, we also demonstrate that these effects are mediated by the ability of CHIT1 to inhibit TGF-β1 induction of its feedback inhibitor, SMAD7. CHIT1 also interacted with TGF-β receptor associated protein 1 (TGFBRAP1) and forkhead box O3 (FOXO3) with TGFBRAP1 playing a critical role in CHIT1 enhancement of TGF-β1 signaling and effector responses and FOXO3 playing a critical role in TGF-β1 induction of SMAD7. These pathways were disease relevant because the levels of CHIT1 were increased and inversely correlated with SMAD7 in tissues from patients with idiopathic pulmonary fibrosis or scleroderma-associated interstitial lung disease. These studies demonstrate that CHIT1 regulates TGF-β1/SMAD7 axis via TGFBRAP1 and FOXO3 and highlight the importance of these pathways in the pathogenesis of pulmonary fibrosis. 

Retracted: No

PubPeer comments:
 Figure 2D. Much more similar than expected. https: imgur.com 7wFgCgm ,