PReD-Bench/PRed-Bench huggingface dataset:
Regression of Melanoma Following Intravenous Injection of Plumbagin Entrapped in Transferrin-Conjugated, Lipid–Polymer Hybrid Nanoparticles
Authors: Christine Dufès
Partha Laskar
Intouch Sakpakdeejaroen
Margaret Mullin
Sukrut Somani
Journal: International Journal of Nanomedicine (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: cancer therapy; lipid–polymer hybrid nanoparticles; plumbagin; transferrin; tumor targeting.
Affiliations: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK., College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.

Abstract:  Background: Plumbagin, a naphthoquinone extracted from the officinal leadwort presenting promising anti-cancer properties, has its therapeutic potential limited by its inability to reach tumors in a specific way at a therapeutic concentration following systemic injection. The purpose of this study is to assess whether a novel tumor-targeted, lipid-polymer hybrid nanoparticle formulation of plumbagin would suppress the growth of B16-F10 melanoma in vitro and in vivo. Methods: Novel lipid-polymer hybrid nanoparticles entrapping plumbagin and conjugated with transferrin, whose receptors are present in abundance on many cancer cells, have been developed. Their cellular uptake, anti-proliferative and apoptosis efficacy were assessed on various cancer cell lines in vitro. Their therapeutic efficacy was evaluated in vivo after tail vein injection to mice bearing B16-F10 melanoma tumors. Results: The transferrin-bearing lipid-polymer hybrid nanoparticles loaded with plumbagin resulted in the disappearance of 40% of B16-F10 tumors and regression of 10% of the tumors following intravenous administration. They were well tolerated by the mice. Conclusion: These therapeutic effects, therefore, make transferrin-bearing lipid-polymer hybrid nanoparticles entrapping plumbagin a highly promising anti-cancer nanomedicine. 

Retracted: No

PubPeer comments:
 The two images in Figure 2 appear to overlap, but appear to be described differently. Could the authors please check? *** ![file] ,
Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow
Authors: A Glejzer
L Sommer
P Leprince
E Laudet
B Hennuy
S Wislet-Gendebien
O Shakhova
B Rogister
C Poulet
Journal: Cellular and Molecular Life Sciences (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Neural crest-derived progenitor cells; bone marrow; regenerative medicine; autologous cell replacement therapies; wnt1
Affiliations: GIGA Neurosciences, University of Liege, Tour de Pathologie 2, CHU Avenue de L'hôpital 1, Liège, Belgium.

Abstract:  Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities. 

Retracted: No

PubPeer comments:
 Figure 4. * Sharp vertical transitions are visible between the lanes, suggesting the photos might be composites * Green boxes: The three panels all appear to show the same marker lane * Yellow boxes: JURKAT s lane 4 and U937 s lane 4 look remarkably similar ![file] ,
Aspirin extends the lifespan of Caenorhabditis elegans via AMPK and DAF-16/FOXO in dietary restriction pathway
Authors: Qin-Li Wan
Shan-Qing Zheng
Gui-Sheng Wu
Huai-Rong Luo
Journal: Experimental Gerontology (2013)
Discipline: CLINICAL MEDICINE
Keywords: Aspirin; lifespan extension; Caenorhabditis elegans; health span; stress resistance
Affiliations: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.

Abstract:  Aspirin has been revealed to have many beneficial effects for health since it was discovered as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Here, we investigated the molecular mechanism of aspirin on the lifespan extension of Caenorhabditis elegans. Our results showed that aspirin could extend the lifespan of C. elegans, and increase its health span and stress resistance. The extension of lifespan by aspirin requires DAF-16/FOXO, AMPK, and LKB1, but not SIR-2.1. Aspirin could not extend the lifespan of the mutants of eat-2, clk-1, and isp-1. Aspirin could marginally extend the lifespan of long-live insulin-like receptor mutant daf-2(e1370) III. Taken together, aspirin might act through a dietary restriction-like mechanism, via increasing the AMP:ATP ratio and activating LKB1, subsequently activating AMPK, which stimulates DAF-16 to induce downstream effects through a DAF-16 translocation independent manner. 

Retracted: No

PubPeer comments:
 Lifespan extension by aspirin could not be replicated by the Caenorhabditis Intervention Testing Program in N2. (Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects, 10.1038 ncomms14256) ,
Irinotecan induces steroid and xenobiotic receptor (SXR) signaling to detoxification pathway in colon cancer cells
Authors: Michèle Boisdron-Celle
Olivier Coqueret
Sophie de Carné Trécesson
Alain Morel
Erick Gamelin
Agnes Basseville
Laurence Preisser
Journal: Molecular Cancer (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: chemotherapy resistance; colon cancer; steroid and xenobiotic receptor (SXR); drug resistance; molecular mechanism
Affiliations: Cancer Center Paul Papin, INSERM U892/University of Angers, 2 rue Moll, Angers, F-49033, France.

Abstract:  Background: Resistance to chemotherapy remains one of the principle obstacles to the treatment of colon cancer. In order to identify the molecular mechanism of this resistance, we investigated the role of the steroid and xenobiotic receptor (SXR) in the induction of drug resistance. Indeed, this nuclear receptor plays an important role in response to xenobiotics through the upregulation of detoxification genes. Following drug treatments, SXR is activated and interacts with the retinoid X receptor (RXR) to induce expression of some genes involved in drug metabolism such as phase I enzyme (like CYP), phase II enzymes (like UGT) and transporters (e.g. MDR1). Results: In this study, we have shown that endogenous SXR is activated in response to SN-38, the active metabolite of the anticancer drug irinotecan, in human colon cancer cell lines. We have found that endogenous SXR translocates into the nucleus and associates with RXR upon SN-38 treatment. Using ChIP, we have demonstrated that endogenous SXR, following its activation, binds to the native promoter of the CYP3A4 gene to induce its expression. RNA interference experiments confirmed SXR involvement in CYP3A4 overexpression and permitted us to identify CYP3A5 and MRP2 transporter as SXR target genes. As a consequence, cells overexpressing SXR were found to be less sensitive to irinotecan treatment. Conclusions: Altogether, these results suggest that the SXR pathway is involved in colon cancer irinotecan resistance in colon cancer cell line via the upregulation of select detoxification genes. 

Retracted: No

PubPeer comments:
null, 
 #1 Figure 2. Much more similar than expected. https: imgur.com ZCX0Do6 ,
Long intergenic non-coding RNAs (LincRNAs) identified by RNA-seq in breast cancer
Authors: Ting Ji
Shaoju Gan
Xiping Zhang
Fengmei Wang
Limin Zhu
Ming Zhao
Xianfeng Ding
Hongjian Yang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: lincRNAs; breast cancer; expression; RNA-seq; pathological stage
Affiliations: Institute of Bioengineering, College of Life Science, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, P.R. China., Zhejiang Cancer Research Institute, Department of Breast Tumor Surgery, Zhejiang Cancer Hospital, Banshan Bridge, Hangzhou, Zhejiang, P.R. China., Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.

Abstract:  In an attempt to find the correlation of aberrant expression of long intergenic noncoding RNAs (lincRNAs) with cancer, twenty-five samples of breast cancer tissue and respective adjacent normal tissue were studied for the expression of lincRNAs by RNA-seq. Among the 538 lincRNAs studied, 124 lincRNAs were exclusively expressed in cancer adjacent tissues and 62 lincRNAs were exclusively expressed in the cancer tissues. Furthermore, the expression of 134 lincRNAs was higher while 272 lower in breast cancer tissue compared with adjacent tissue. The expression of four selected lincRNAs (BC2, BC4, BC5, and BC8) was validated by semi-quantitative and real-time PCR. It was revealed that expression of lincRNA-BC5 was positively correlated with patients' age, pathological stage, and progesterone receptor concentration, while lincRNA-BC8 was negatively correlated with progesterone receptor expression. Higher expression of lincRNA-BC4 was seen in advanced breast cancer grade. LincRNA-BC2 showed no specific changes in the pathological features studied. Interactions between selected lincRNAs and breast cancer associated proteins were highly suggested by RPIseq based on the specific secondary structure. The results demonstrated that this group of lincRNAs was aberrantly expressed in breast cancer. They might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of breast cancer. 

Retracted: No

PubPeer comments:
 Figure 2. * Red boxes: The b-actin panels all appear to be the same. It is not clear if the samples are all identical. The description in the text speaks of  pooled samples from five breast cancer tissues and matched adjacent cancer tissues and also mentions  There were twenty (all the numbers are confusing and did not make sense in the current description) breast cancer tissues and matched adjacent tissues used in these experiments . Could the authors please clarify if each panel in Figure 2 represents a different pool? ![file] ,
In vitro and in vivo anti-uveal melanoma activity of JSL-1, a novel HDAC inhibitor
Authors: Jingxuan Pan
Yun Wang
Maoxing Liu
Sheng Jiang
Yanli Jin
Journal: Cancer letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: Cancer stem-like cells; Epigenetics; HDAC inhibitor; Migration and invasion; Uveal melanoma
Affiliations: Jinan University Institute of Tumor Pharmacology, College of Pharmacy, Jinan University; State Key Laboratory of Ophthalmology, Sun Yat-Sen University Zhongshan Ophthalmic Center, Guangzhou, China., Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China., Jinan University Institute of Tumor Pharmacology, College of Pharmacy, Jinan University; State Key Laboratory of Ophthalmology, Sun Yat-Sen University Zhongshan Ophthalmic Center, Guangzhou, China. Electronic address: .

Abstract:  Uveal melanoma (UM) is the most common intraocular malignant neoplasm in adults. Despite the availability of enucleation, radiation and chemotherapy, the prognosis of patients with metastasis remains poor. Therefore, novel effective therapies for patients with metastatic UM are urgently needed. In the present study, we demonstrated that JSL-1, a novel HDAC inhibitor, effectively inhibited the proliferation. JSL-1 induced apoptosis with increased expression of proapoptotic BH3-only protein BIM in UM cells. JSL-1 suppressed migration and invasion of UM cells with MMP-2 decreased. Furthermore, JSL-1 blocked the canonical Wnt/β-catenin pathway, impaired self-renewal capacity and decreased percentage of ALDH+ cells, thereby reflecting elimination of UM cancer stem-like cells (CSCs) which are believed seeds of metastasis. Importantly, JSL-1 potently inhibited the growth of uveal melanoma xenograft in NOD-SCID mice. These results suggested that JSL-1 may be a promising therapeutic agent for UM. 

Retracted: No

PubPeer comments:
 Indicated areas of two images in Fig. 2C are identical. Could the authors please give explanation? ![file] Two images in Fig. 5A are identical, only with different brightness. ![file] , 
 #1 Dear Dr. Platycheirus Stegnus, I am the first author Yun Wang, and thank you for your interest in our work and for pointing out the errors. I have carefully checked the original data, and found they were indeed errors which inadvertently took place during the stage of figure preparation with photoshop microsoftware. 1. In Fig. 2C, the diagram of flow cytometry in 0.3 u03bcM group was wrongly duplicated with that of 0.1 u03bcM group. The corrected one and its source are shown below.![file] 2. In Fig. 5A, the photos of 92.1 cells treated for 36 h was inadvertently and incorrectly copied and pasted. The corrected one and its original photos are shown below. ![file] Both above-mentioned errors did not impact the conclusions. We have written to the Journal to seek an erratum. We sincerely apologized for these unconscious mistakes which may bring to inconvenience to readers. Best regards, Yun Wang. ,
Combining the differentiating effect of panobinostat with the apoptotic effect of arsenic trioxide leads to significant survival benefit in a model of t(8;21) acute myeloid leukemia
Authors: Peter Atadja
Michael Bots
Jessica M Salmon
Johannes Zuber
Ricky W Johnstone
Eva Vidacs
Kym L Stanley
Journal: Clinical Epigenetics (2015)
Discipline: CLINICAL MEDICINE
Keywords: AML; Apoptosis; Arsenic trioxide; Differentiation; Histone deacetylase inhibitor
Affiliations: Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC Australia ; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3010 VIC Australia., Laboratory of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands., Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC Australia., China Novartis Institutes for Biomedical Research, No. 2 BoYun Road, Pudong, Shanghai 201203 China., Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.

Abstract:  Background: One of the most frequently found abnormalities in acute myeloid leukemia (AML) is the t(8;21)(q22;q22) translocation, which is seen in around 15% of patients. This translocation results in the production of the AML1/ETO (A/E) fusion protein and commonly involves cooperating activating mutations of RAS. AE9a encodes a C-terminally truncated A/E protein of 575 amino acids that retains the ability to recruit histone deacetylases (HDACs). Expression of AE9a leads to rapid development of leukemia in experimental mouse systems. We have recently shown that treatment of mice bearing A/E9a;Nras (G12D) tumors with the histone deacetylase inhibitor (HDACi) panobinostat leads to degradation of the A/E9a fusion protein, cell cycle arrest, differentiation of AML blasts into mature granulocytes and prolonged survival. Herein, we sought to enhance this therapeutic effect. Findings: Combined treatment of mice bearing A/E9a;Nras (G12D) leukemias with panobinostat and arsenic trioxide (ATO) resulted in a significant survival advantage compared to mice treated with either agent alone. Moreover, some of the mice treated with the panobinostat/ATO combination showed complete tumor responses and remained in remission for over 220 days. Panobinostat caused differentiation of A/E9a;Nras (G12D) cells while ATO induced apoptosis of the leukemic cells, an effect that was enhanced following co-treatment with panobinostat. Conclusions: Our results indicate that leukemic blast differentiation mediated by panobinostat combined with induction of apoptosis by ATO could be therapeutically beneficial and should be considered for patients with t(8;21) AML. 

Retracted: No

PubPeer comments:
 Figure 2. Splicing in some panels, but not in others. ![file] ,
A new pharmacological role for donepezil: attenuation of morphine-induced tolerance and apoptosis in rat central nervous system
Authors: Farshid Moradi
Kambiz Hassanzadeh
Mozhdeh Sharifipour
Katayoun Hassanzadeh
Bahram Nikkhoo
Samad Zare
Esmaeal Izadpanah
Ali Abdolmaleki
Journal: Journal of Biomedical Science (2014)
Discipline: CLINICAL MEDICINE
Keywords: opioids; tolerance; analgesic effect; morphine; apoptosis
Affiliations: Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran. .

Abstract:  Background: Tolerance to the analgesic effect of opioids is a pharmacological phenomenon that occurs after their prolonged administration. It has been shown that morphine-induced tolerance is associated with apoptosis in the central nervous system and neuroprotective agents which prevented apoptosis signaling could attenuate tolerance to the analgesic effects. On the other hand donepezil, an acetylcholinesterase inhibitor, has been reported to have neuroprotective effects. Therefore in this study, the effect of systemic administration of donepezil on morphine-induced tolerance and apoptosis in the rat cerebral cortex and lumbar spinal cord was evaluated. Various groups of rats received morphine (ip) and different doses of donepezil (0, 0.5, 1, 1.5 mg/kg/day). Nociception was assessed using tail flick apparatus. Tail flick latency was recorded when the rat shook its tail. For apoptosis assay other groups of rats received the above treatment and apoptosis was evaluated by in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Results: The results showed that administration of donepezil (0.5, 1, 1.5 mg/kg, ip) delayed the morphine tolerance for 9, 12 and 17 days, respectively. Furthermore pretreatment injection of donepezil attenuated the number of apoptotic cells in the cerebral cortex and lumbar spinal cord compared to the control group. Conclusion: In conclusion, we found that systemic administration of donepezil attenuated morphine-induced tolerance and apoptosis in the rat cerebral cortex and lumbar spinal cord. 

Retracted: No

PubPeer comments:
 two image duplications ![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. ,
Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta
Authors: Anindita Das
Lei Xi
Rakesh C Kukreja
Journal: Journal of Biological Chemistry (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Sildenafil; phosphodiesterase-5; myocardial ischemia-reperfusion injury; cGMP; protein kinase
Affiliations: Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia 23298, USA.

Abstract:  Sildenafil, a potent inhibitor of phosphodiesterase-5 (PDE-5) induces powerful protection against myocardial ischemia-reperfusion injury. PDE-5 inhibition increases cGMP levels that activate cGMP-dependent protein kinase (PKG). However, the cause and effect relationship of PKG in sildenafil-induced cardioprotection and the downstream targets of PKG remain unclear. Adult ventricular myocytes were treated with sildenafil and subjected to simulated ischemia and reoxygenation. Sildenafil treatment significantly decreased cardiomyocyte necrosis and apoptosis. The PKG inhibitors, KT5823, guanosine 3',5'-cyclic monophosphorothioate, 8-(4-chloro-phenylthio) (R(p)-8-pCPT-cGMPs), or DT-2 blocked the anti-necrotic and anti-apoptotic effect of sildenafil. Selective knockdown of PKG in cardiomyocytes with adenoviral vector containing short hairpin RNA of PKG also abolished sildenafil-induced protection. Furthermore, intra-coronary infusion of sildenafil in Langendorff-isolated mouse hearts prior to ischemia-reperfusion significantly reduced myocardial infarct size after 20 min ischemia and 30 min reperfusion, which was abrogated by KT5823. Sildenafil significantly increased PKG activity in intact hearts and cardiomyocytes. Sildenafil also enhanced the Bcl-2/Bax ratio, phosphorylation of Akt, ERK1/2, and glycogen synthase kinase 3beta. All these changes (except Akt phosphorylation) were significantly blocked by KT5823 and short hairpin RNA of PKG. These studies provide the first evidence for an essential role of PKG in sildenafil-induced cardioprotection. Moreover, our results demonstrate that sildenafil activates a PKG-dependent novel signaling cascade that involves activation of ERK and inhibition of glycogen synthase kinase 3beta leading to cytoprotection. 

Retracted: No

PubPeer comments:
 Fig 2 ![file] Fig 6 ![file] ![file] Same Actin probe was used in Fig 2 A and B and Fig Fig 6 C. Duplicated image. ,
Evasion of Plant Innate Defense Response by on Lettuce
Authors: Harsh Bais
Pushpinder K Litt
Nicholas Johnson
Kalmia E Kniel
Journal: Frontiers in microbiology (2020)
Discipline: MICROBIOLOGY
Keywords: L. monocytogenes; S. enterica; T3SS; food safety; hormonal response
Affiliations: Department of Plant and Soil Sciences, University of Delaware, Newark, DE, United States., Delaware Biotechnology Institute, University of Delaware, Newark, DE, United States., Department of Animal and Food Sciences, University of Delaware, Newark, DE, United States.

Abstract:  To establish host association, the innate immune system, which is one of the first lines of defense against infectious disease, must be circumvented. Plants encounter enteric foodborne bacterial pathogens under both pre- and post-harvest conditions. Human enteric foodborne pathogens can use plants as temporary hosts. This unique interaction may result in recalls and illness outbreaks associated with raw agricultural commodities. The purpose of this study was to determine if Salmonella enterica Typhimurium applied to lettuce leaves can suppress the innate stomatal defense in lettuce and utilization of UD1022 as a biocontrol against this ingression. Lettuce leaves were spot inoculated with S. Typhimurium wild type and its mutants. Bacterial culture and confocal microscopy analysis of stomatal apertures were used to support findings of differences in S. Typhimurium mutants compared to wild type. The persistence and internalization of these strains on lettuce was compared over a 7-day trial. S. Typhimurium may bypass the innate stomatal closure defense response in lettuce. Interestingly, a few key T3SS components in S. Typhimurium were involved in overriding stomatal defense response in lettuce for ingression. We also show that the T3SS in S. Typhimurium plays a critical role in persistence of S. Typhimurium in planta. Salmonella populations were significantly reduced in all UD1022 groups by day 7 with the exception of fliB and invA mutants. Salmonella internalization was not detected in plants after UD1022 treatment and had significantly higher stomatal closure rates (aperture width = 2.34 μm) by day 1 compared to controls (8.5 μm). S. Typhimurium SPI1 and SPI2 mutants showed inability to reopen stomates in lettuce suggesting the involvement of key T3SS components in suppression of innate response in plants. These findings impact issues of contamination related to plant performance and innate defense responses for plants. 

Retracted: No

PubPeer comments:
 Flagellin nomenclature is used inconsistently. Authors correctly note the two flagellin genes (fliC, fljB), but appear to call the latter fliB throughout the paper. FliB is a methylase, and it should be clarified which gene was actually knocked out in their experiments. , 
 This clearly seems to be a repeated measures design--yet, the Statistical Analysis section of methods states:  A Studentu2019s t-test was used where needed to compare the means, at a significance level of p 0.05. ,
High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress
Authors: Zafer Gurel
Christine M Sorenson
Qiong Huang
Eui Seok Shin
Nader Sheibani
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Astrocytes; retinal vasculature; blood-retina-barrier; diabetes; high glucose conditions
Affiliations: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America., Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America., Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America; McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.

Abstract:  Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB). Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC) leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration. 

Retracted: No

PubPeer comments:
 Figure 11B * Red boxes: two panels appear to look very similar. Reported to the journal in October 2015, but no action taken as of today. ![file] ,
Rebamipide Mitigates Impairments in Mitochondrial Function and Bioenergetics with α-Synuclein Pathology in 6-OHDA-Induced Hemiparkinson's Model in Rats
Authors: Sairam Krishnamurthy
Akanksha Mishra
Journal: Neurotoxicity research (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Glucocerebrosidase; Mitochondrial bioenergetics; Oxidative stress; Parkinson’s disease; Rebamipide
Affiliations: Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, UP, 221005, India., Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, UP, 221005, India. .

Abstract:  Parkinson's disease (PD) is one of the widely reported neurodegenerative disorders affecting more than ten million people worldwide. Due to therapeutic limitations and several adverse effects associated with currently used drugs, it is crucial to search for safe and effective options for treatment of PD. Oxidative stress, mitochondrial dysfunction, α-synuclein oligomeric aggregates, and glucocerebrosidase (GCase) deficiency are involved in PD pathogenesis. Rebamipide, an anti-ulcer drug, is a proven free-radical scavenger and antioxidant. The drug has shown neuroprotective effects in cultured SH-SY5Y cells. Therefore, we investigated the pharmacological effect of rebamipide in 6-hydroxydopamine (6-OHDA)-induced experimental PD model. Rebamipide was given to adult male albino rats of Charles-Foster strain in 20, 40, and 80 mg/kg (R-20, R-40, and R-80) oral dose twice daily for 24 days (day 4 to day 27) after 6-OHDA intrastriatal injection. The drug inhibited 6-OHDA-induced motor deficits and nigral α-synuclein aggregates in dose-dependent manner. R-40 and R-80 dose dependently increased striatal mitochondrial complex I, II, IV, and V activities; mitochondrial bioenergetics; and nigral GCase activity. 6-OHDA-induced lipid peroxidation was decreased. Highest dose (R-80) also decreased apoptotic proteins and upregulated striatal dopamine concentration in 6-OHDA-induced hemiparkinson's rat model. Therefore, the anti-PD effect of rebamipide may involve stabilization of mitochondrial bioenergetics, enhancement of GCase enzymatic activity as well as decreased oxidative stress with α-synuclein pathology, and apoptosis in 6-OHDA-induced hemiparkinson's rat model. Hence, preclinical evidence indicates rebamipide to be a potential drug for management of PD. 

Retracted: No

PubPeer comments:
 Figure 7. Some bands look more similar than expected. Arrows of the same color show bands that look similar as well as their orientation. ![file] ,
Effects of growth hormone replacement therapy on levels of cortisol and cortisol-binding globulin in hypopituitary adults
Authors: H Grasberger
M Tschöp
A F Attanasio
O E Janssen
C J Strasburger
H Lahner
K M Morrison
H Feldmeier
Journal: European journal of endocrinology (2000)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: human growth hormone; hydrocortisone; pharmacokinetics; hypopituitary adults; cortisol-binding globulin
Affiliations: Innenstadt University Hospital, Munich, Germany.

Abstract:  Objective: To determine if human growth hormone (hGH) replacement therapy alters pharmacokinetics of hydrocortisone (CS) substitution in hypopituitary adults. Design: To this aim, we analysed serum and salivary CS profiles 270 min after oral CS administration at baseline and 6 and 12 months after initiation of hGH replacement therapy. Methods: Serum IGF-I, cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG) and sex hormone-binding hormone (SHBG) were measured using commercially available radioimmunoassays. In-house immunofluorometric assays were employed for measurements of CS and hGH. Results: hGH replacement did not change total serum CS bioavailability (area under the serum cortisol profile curve). Interference of orally administered CS with salivary measurement of free CS (fCS) caused significant bias. Therefore, fCS levels were calculated from their total CS and cortisol-binding globulin (CBG) levels. CBG decreased by approximately 30% after both 6 and 12 months of hGH replacement therapy (n=20, P&lt;0.01). A significant negative correlation between deltaCBG (CBG6months-CBGbaseline) and deltaIGF-I (IGF-I6months-IGF-Ibaseline) was observed (P=0.04). The calculated values of free CS tended to increase with physiological hGH replacement, but this effect was marginal and did not reach statistical significance. In contrast to the CBG concentrations, plasma levels of sex hormone-binding globulin and thyroxine-binding globulin were essentially stable. Conclusion: Given that no clinically relevant alterations in pharmacokinetics of CS were evoked by initiation of hGH replacement in hypopituitary adults, we conclude that CS substitution does not require dose adjustment after initiation of hGH replacement. 

Retracted: No

PubPeer comments:
 How can formula V-36 in this paper been derived from V-35 in Ref 7? And can V-36 been solved as V-37? Maybe the authors could explain in more detail. ![file] ,
Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma
Authors: Mei Xu
Xin-yi Wang
Hao-shu Fang
Ke-ke Yu
Li Chen
You-zhi Xu
Jin-Lian Yang
Si-Ying Wang
Fei Wang
Zhong-qian Hu
Lixin Kan
Yan-min Lu
Fei-fei Li
Jia Luo
Journal: Molecular Cancer (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hepatocellular carcinoma; alcohol; progression; metastasis; TNM stages
Affiliations: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China. ., Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, P.R. China. ., Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA. ., Department of Clinical Medicine, Anhui Medical University, Hefei, Anhui, 230032, P.R. China. .

Abstract:  Background: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC. Methods and results: We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in a 3-D tumor/endothelial co-culture system, we found that alcohol enhanced the migration/invasion of HepG2 cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1 and NF-κB was observed in HCC tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-κB signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-κB signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis. Conclusion: This study suggested that chronic moderate alcohol consumption may promote the progression and metastasis of HCC; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-ĸB-dependent VEGF and MCP-1 up-regulation. 

Retracted: No

PubPeer comments:
 Figure 5C: * Red boxes: One of the panels looks very similar to a panel in another figure by Minghui Chen et al, J Cell Physiol (2020), DOI: 10.1002 jcp.29347 - https: pubpeer.com publications B8A9E7761524560ACEEEF0EFEB23CB Note that the two panels represent very different experiments and cell lines. Can the authors please provide an explanation? Both research groups are affiliated with the Second Affiliated Hospital of Harbin Medical University. ![file] ,
Quercetin regulates oxidized LDL induced inflammatory changes in human PBMCs by modulating the TLR-NF-κB signaling pathway
Authors: Shobha Bhaskar
A Helen
V Shalini
Journal: Immunobiology (2011)
Discipline: IMMUNOLOGY
Keywords: Toll-like receptors; TLR2; TLR4; NF-κB; cytokines
Affiliations: Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India.

Abstract:  Toll-like receptors (TLRs) have been shown to play a pivotal role in both innate and adaptive immune responses. TLR family is the essential recognition and signaling component of mammalian host defense. Both genetic and biochemical data support a common signaling pathway that finally leads to the activation of NF-κB and induction of the cytokines and co-stimulatory molecules required for the activation of the adaptive immune response. The present study was designed to examine the involvement of TLR2 and TLR4 in the oxidized LDL induced inflammation in human PBMCs and the effect of flavonoid quercetin on TLR-NF-κB signaling mechanism. LDL was isolated from human plasma and oxidation of LDL was done by incubating with 10 μM CuSO₄ overnight at 37°C. The isolated human PBMCs in culture were used as the model system. 50 μg/ml ox-LDL treatment significantly up regulated TLR2 and TLR4 expression in isol human PBMCs after 24 h of culture and this was down regulated by quercetin at 25 μM concentration. ox-LDL caused a significant activation of NF-κB as evidenced by the detection of enhanced p65 subunit in nuclear extracts. Supplementation of quercetin significantly modulates the NF-κB p65 nuclear translocation. The cytokine IL-6 production was significantly increased in ox-LDL treated group and was decreased by quercetin treatment. Quercetin mediated reduction of TLR2 and TLR4 expression and the inhibition of nuclear translocation of NF-κB p65 in turn decreased the inflammatory enzymes like 5-LOX and COX and also decreased the mRNA expression of inducible enzymes like COX-2 and iNOS. Quercetin inhibited the ox-LDL induced TLR2 and TLR4 expression at mRNA level and modulated the TLR-NF-κB signaling pathway thereby inhibited the cytokine production and down regulated the activity of inflammatory enzymes thus have protective effect against the ox-LDL induced inflammation in PBMCs. 

Retracted: No

PubPeer comments:
 This paper contains tortured phrases, suggesting the use of paraphrasing software to avoid plagiarism detection. Examples include: * breast malignancy - breast cancer * X-beams - X-rays * full field advanced mammography (FFDM) - full field digital mammography * bosom tumor - breast cancer * district of intrigue - region of interest * will bite the dust from breast growth - will die from breast cancer Another phrase that appears tortured is **assume a noteworthy job**, which never appeared in the literature before 2018, had some popularity in 2019 and 2020, and now seems to be falling out of favour again. Anyone have an idea what it is supposed to be? ![file] ,
Aflatoxin-induced upregulation of protein arginine methyltransferase 5 is mediated by protein kinase C and extracellular signal-regulated kinase
Authors: Md Sajid Ghufran
Santosh R Kanade
Priyanka Soni
Journal: Cell Biology and Toxicology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Aflatoxin B1; Arginine methylation; Aspergillus; ERK; PKC
Affiliations: Department of Biochemistry and Molecular Biology, School of Biological Sciences, Riverside transit Campus, Central University of Kerala, Nileshwaram, Kasargod District, Kerala, 671314, India., Department of Biochemistry and Molecular Biology, School of Biological Sciences, Riverside transit Campus, Central University of Kerala, Nileshwaram, Kasargod District, Kerala, 671314, India. .

Abstract:  Aflatoxins are fungal metabolites classified into four major groups such as B1, B2, G1, and G2. These natural aflatoxins are designated as group I carcinogen by the International Agency for Research on Cancer. Among these, the aflatoxin B1 is more potent. Protein arginine methyltransferase 5, an epigenetic modulator, emerged as an oncoprotein, is overexpressed in diverse forms of cancers. The present study aims to explore the AFB1-mediated overexpression of PRMT5. The AFB1 at nanomolar concentrations increased the cell viability, as well as the expression of PRMT5 and its binding partner methylosome protein 50 level significantly in L-132 and HaCaT cells. The knockdown of PRMT5 by its siRNA is attenuated by AFB1, thus substantiating AFB1-mediated PRMT5 overexpression. The PKC isoform-specific inhibitor study revealed direct relation with PKCα and an inverse relation with PKCδ. The analysis of mitogen-activated protein kinase pathway revealed reduced p38 phosphorylation with increased phosphorylation of ERK1/2 upon exposure to AFB1. The combination of MEK and PKC inhibitors with AFB1 treatment revealed that PKCα activates downstream kinase ERK which leads to overexpression of PRMT5. In summary, we propose that PKCα and extracellular signal-regulated kinases are conjointly involved in the induction of PRMT5 upon AFB1 exposure. 

Retracted: No

PubPeer comments:
 In Figure 4a,b, a Western immunoblot has been duplicated,modified and presented as something else. This is seen by increasing the contrast. ![file] ,
Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms
Authors: Wen Ye
Danying Chen
Haiwei Chen
Huanhuan Liang
Qian Zhou
Hongbing Shu
Zhenlin Yang
Ying Li
Joy Fleming
Yingfang Liu
Journal: Cell Research (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Interferon-stimulated gene 56; ISG54; RNA-binding structure; crystal structure; tetratricopeptide repeat-like motifs
Affiliations: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.

Abstract:  Interferon-stimulated gene 56 (ISG56) family members play important roles in blocking viral replication and regulating cellular functions, however, their underlying molecular mechanisms are largely unclear. Here, we present the crystal structure of ISG54, an ISG56 family protein with a novel RNA-binding structure. The structure shows that ISG54 monomers have 9 tetratricopeptide repeat-like motifs and associate to form domain-swapped dimers. The C-terminal part folds into a super-helical structure and has an extensively positively-charged nucleotide-binding channel on its inner surface. EMSA results show that ISG54 binds specifically to some RNAs, such as adenylate uridylate (AU)-rich RNAs, with or without 5' triphosphorylation. Mutagenesis and functional studies show that this RNA-binding ability is important to its antiviral activity. Our results suggest a new mechanism underlying the antiviral activity of this interferon-inducible gene 56 family member. 

Retracted: No

PubPeer comments:
 Fluorescence image reused in Fig.4A. Could authors give an explanation? ![file] ,
Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN)
Authors: Jun Ma
Ying-Qin Li
Yin Zhao
Na Liu
Yang Chen
Ling-Long Tang
Wei-Jie Luo
Xiao-Jing Yang
Xiao-Hong Hong
Qing-Mei He
Ye-Lin Liang
Ya-Qin Wang
Shi-Wei He
Yuan Lei
Pan-Pan Zhang
Jun-Yan Li
Journal: Cells (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CTTN; UCHL1; metastasis; methylation; nasopharyngeal carcinoma.
Affiliations: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, China.

Abstract:  Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the UCHL1 promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment. 

Retracted: No

PubPeer comments:
 Figure 6A appears to have two images which overlap. *** ![file] , 
 Figures 3F and 6D appear to overlap. The the authors please review and confirm whether this is intentional; I am uncertain? *** ![file] *** ![file] , 
 Iu2019m Yin Zhao, the first author of this article. Thanks for your comments. After having carefully checked the manuscript and the raw data, we found that the mentioned image has indeed been mismatched during the preparation of Figure 6A and 6D. We apologize for this mistake and thanks for your concern. Please see below for the corrected Figure 6A and 6D. We emphasize that this correction does not affect the conclusions or any other aspect of this article. We have already contacted the journal office to issue a correction. Sincerely yours! ![Uploading file...]() , 
 ![file] ,
Activation of protein kinase Tel1 through recognition of protein-bound DNA ends
Authors: Kenzo Fukunaga
Katsunori Sugimoto
Youngho Kwon
Patrick Sung
Journal: Molecular and Cellular Biology (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Double-strand breaks; ATM protein kinase; Tel1; MRX complex; DNA ends
Affiliations: Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07101, USA.

Abstract:  Double-strand breaks (DSBs) in chromosomal DNA elicit a rapid signaling response through the ATM protein kinase. ATM corresponds to Tel1 in budding yeast. Here we show that the catalytic activity of Tel1 is altered by protein binding at DNA ends via the Mre11-Rad50-Xrs2 (MRX) complex. Like ATM, Tel1 is activated through interaction with the MRX complex and DNA ends. In vivo, Tel1 activation is enhanced in sae2Δ or mre11-3 mutants after camptothecin treatment; both of these mutants are defective in the removal of topoisomerase I from DNA. In contrast, an sae2Δ mutation does not stimulate Tel1 activation after expression of the EcoRI endonuclease, which generates "clean" DNA ends. In an in vitro system, tethering of Fab fragments to DNA ends inhibits MRX-mediated DNA end processing but enhances Tel1 activation. The mre11-3 mutation abolishes DNA end-processing activity but does not affect the ability to enhance Tel1 activation. These results support a model in which MRX controls Tel1 activation by recognizing protein-bound DNA ends. 

Retracted: No

PubPeer comments:
 July 2017 Correction found here: https: mcb.asm.org content 37 16 e00263-17 It reads:  *Fig. 1A and C: In the Rad53 and Tel1 panels, which were generated from the same Western blot and autoradiography images, the splice lines were not properly indicated and images were mixed up. The correct versions are shown below (left, A; right, C). Note that identical images were used for the WT cell lanes.*  *Fig. 2A: An incorrect Western blot image was inadvertently used. The correct version is shown below. Note that the Tel1-HA lanes are identical to the ones used in Fig. 1A and C.*  *Fig. 2C: A Western blot image was inadvertently duplicated and presented. Since we could not locate the original image, a set of data directly relevant to the experiment is shown below.* Here is the original Figure 1, with the duplication marked in red (same experiment) and blue (mixed up lanes), as well as the duplication in Figure 2A and 2C, marked in orange. ![file] I thank the authors for addressing these issues. However, I am not sure why the Tel1-HA lanes in Figure 2A can be the same as in Figures 1A and 1C? They appear to show different deletions. This paper was part of a structured search for image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long ,