PReD-Bench/PRed-Bench huggingface dataset:
MicroRNA-195 inhibits growth and invasion of laryngeal carcinoma cells by directly targeting DCUN1D1
Authors: Lun Zhang
Chao Li
Xuan Zhou
Yu Shuang
Yongwang Huang
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miR-195; laryngeal squamous cell carcinoma; DCUN1D1; cell proliferation
Affiliations: Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China., Department of Otorhinolaryngology and Maxillofacial Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer; Tianjin 300211, P.R. China.

Abstract:  MicroRNAs (miRNAs) are a class of small, non-coding RNAs that regulate gene expression and are involved in cell biological processes. The aberrant expression of miR-195 has been found in various types of human cancer. However, the effect of miR‑195 on the initiation and development of laryngeal squamous cell carcinoma (LSCC) remains to be elucidated. Accordingly, in the present study, we detected the expression level of miR-195 in the LSCC and the normal tissues and found that miR-195 were significantly down-regulated in the LSCC tissues. Gain-of-function or loss-of-function studies including cell proliferation, wound healing assay, Transwell assay, cell cycle and apoptosis assays were performed to investigate the biological function of miR-195. Luciferase reporter assay and the rescue study confirmed that DCUN1D1 was a target of miR-195. Furthermore, DCUN1D1 expression levels were found to be upregulated in laryngeal tissues and to have a negative correlation with miR-195. We also found that both miR-195 and DCUN1D1 siRNAs can inhibit cell invasion possibly through downregulating Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) at the post-transcriptional level, which can be attenuated by restoring the expression of DCUN1D1. In summary, these data suggest that low expression of miR-195 contributes to the poor prognosis of LSCC and miR-195 regulates the proliferation and invasion ability of LSCC cells in vitro. miR-195 may suppress growth and invasion of LSCC cells possibly through targeting DCUN1D1, which would provide a candidate target for cancer therapy. 

Retracted: No

PubPeer comments:
 *[above]* Fig 3B.  Effects of miR-195 overexpression on the colony formation of TU-177 cells were determined by colony formation assay . *[below]* Fig 6C from [Xiao et al (2018)] .  Colony formation assay was performed . ![file] Could the authors comment on the appearance of one plate in both papers, albeit rotated through 90 deg, and differently identified? , 
 Images in Figure 4C and 8A appeared to overlap. *** ![file] *** ![file] ,
Diabetes-mediated IL-17A enhances retinal inflammation, oxidative stress, and vascular permeability
Authors: Thomas E Zapadka
Patricia R Taylor
Chieh A Lee
Timothy S Kern
Brooklyn E Taylor
Sarah I Lindstrom
Haitao Liu
Sigrun Sigurdardottir
Journal: Cellular immunology (2019)
Discipline: IMMUNOLOGY
Keywords: Diabetic retinopathy; IL-17A; Retinal pathology.

Abstract:  Diabetic retinopathy is a prevailing diabetes complication, and one of the leading causes of blindness worldwide. IL-17A is a cytokine involved in the onset of diabetic complications. In the current study, we examined the role of IL-17A in the development of retinal inflammation and long-term vascular pathology in diabetic mice. We found IL-17A expressing T cells and neutrophils in the retinal vasculature. Further, the IL-17A receptor was expressed on Muller glia, retinal endothelial cells, and photoreceptors. Finally, diabetes-mediated retinal inflammation, oxidative stress, and vascular leakage were all significantly lower in IL-17A-/- mice. These are all clinically meaningful abnormalities that characterize the onset of diabetic retinopathy. 

Retracted: No

PubPeer comments:
 These images are reported as being of different cells (from mouse and human respectively). However, one appears to be very similar to the other - highlighted in blue below. ![file] ,
Gut microbiota is a key modulator of insulin resistance in TLR 2 knockout mice
Authors: José B Carvalheira
Sandro Massao Hirabara
Niels O S Camara
Rui Curi
Eduardo R Ropelle
Andréa M Caricilli
Patrícia O Prada
Ângela Castoldi
Paty K Picardi
Mirian Ueno
Mário J A Saad
Lélia L de Abreu
Pedro Vieira
Journal: PLoS biology (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Environmental factors; host genetics; gut microbiota; obesity; insulin resistance
Affiliations: Department of Internal Medicine, State University of Campinas, Campinas, Brazil.

Abstract:  Environmental factors and host genetics interact to control the gut microbiota, which may have a role in the development of obesity and insulin resistance. TLR2-deficient mice, under germ-free conditions, are protected from diet-induced insulin resistance. It is possible that the presence of gut microbiota could reverse the phenotype of an animal, inducing insulin resistance in an animal genetically determined to have increased insulin sensitivity, such as the TLR2 KO mice. In the present study, we investigated the influence of gut microbiota on metabolic parameters, glucose tolerance, insulin sensitivity, and signaling of TLR2-deficient mice. We investigated the gut microbiota (by metagenomics), the metabolic characteristics, and insulin signaling in TLR2 knockout (KO) mice in a non-germ free facility. Results showed that the loss of TLR2 in conventionalized mice results in a phenotype reminiscent of metabolic syndrome, characterized by differences in the gut microbiota, with a 3-fold increase in Firmicutes and a slight increase in Bacteroidetes compared with controls. These changes in gut microbiota were accompanied by an increase in LPS absorption, subclinical inflammation, insulin resistance, glucose intolerance, and later, obesity. In addition, this sequence of events was reproduced in WT mice by microbiota transplantation and was also reversed by antibiotics. At the molecular level the mechanism was unique, with activation of TLR4 associated with ER stress and JNK activation, but no activation of the IKKβ-IκB-NFκB pathway. Our data also showed that in TLR2 KO mice there was a reduction in regulatory T cell in visceral fat, suggesting that this modulation may also contribute to the insulin resistance of these animals. Our results emphasize the role of microbiota in the complex network of molecular and cellular interactions that link genotype to phenotype and have potential implications for common human disorders involving obesity, diabetes, and even other immunological disorders. 

Retracted: Yes

PubPeer comments:
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 Yet another example of a retracted paper (in 2016) that keeps being frequently cited. Citing papers after retraction: PMID: 31602309 PMID: 31582899 PMID: 31534973 PMID: 30400332 PMID: 30400297 PMID: 30340822 PMID: 30338410 PMID: 30194541 PMID: 29497383 PMID: 29416535 PMID: 29351816 PMID: 29113135 PMID: 29018410 PMID: 28821259 PMID: 28649593 PMID: 28429171 PMID: 28390422 ,
Hispidulin suppresses tumor growth and metastasis in renal cell carcinoma by modulating ceramide-sphingosine 1-phosphate rheostat
Authors: Ming-Quan Gao
Hui Gao
Yan-Tao Han
Jian-Jun Peng
Mei Han
Kai-Li Liu
Journal: American journal of cancer research (2017)
Discipline: CLINICAL MEDICINE
Keywords: Ceramide; Sphk1; hispidulin; renal cell carcinoma; sphingosine 1-phosphate.
Affiliations: Department of Pharmacology, School of Pharmacy, Qingdao UniversityQingdao 266021, China., College of Life Sciences, Chongqing Normal UniversityChongqing 401331, China., Medical College, Qingdao UniversityQingdao 266071, China.

Abstract:  Sphingosine 1-phosphate (S1P) rheostat is considered as a key signal that determines cell fate. This study aimed to report that hispidulin, a polyphenolic flavonoid, exerted anti-growth and anti-metastasis effects against renal cell carcinoma (RCC) by modulating the balance of ceramide-S1P. In vitro studies showed that hispidulin could effectively inhibit cell proliferation, cell migration, cell invasion, and epithelial-mesenchymal transition, and promote cell apoptosis in Caki-2 and A498 cell lines. Moreover, it also increased the ceramide/S1P ratio. Consistent with the in vitro findings, the efficacy of hispidulin in vivo showed that it effectively suppressed tumor growth and lung metastasis. Furthermore, the results revealed that hispidulin significantly suppressed the activity of sphingosine kinase 1 (Sphk1) in RCC cells; however, no significant change was observed in the mRNA or protein expression of Sphk1. The overexpression of Sphk1 could significantly abrogate the anti-growth and anti-metastasis effects of hispidulin, whereas the siRNA-targeting Sphk1 or Sphk1 inhibitor was able to augment the anticancer effects of hispidulin against RCC. Moreover, hispidulin interfered with the phosphorylation and translocation of Sphk1, leading to inhibitory effects of Sphk1 activity. In summary, the findings suggested that hispidulin suppressed tumor growth and metastasis by inhibiting the Sphk1 activity and consequently modulating ceramide-S1P rheostat. It also presented a new explanation for the antitumor mechanisms of hispidulin against RCC. 

Retracted: Yes

PubPeer comments:
 Figure 6B. Much more similar than expected. https: imgur.com ARx2Ni7 ,
Activation of protein kinase C triggers its ubiquitination and degradation
Authors: D Liu
M Pagano
W Devonish
Z Lu
D A Foster
A Hornia
Journal: Molecular and Cellular Biology (1998)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: phorbol esters; protein kinase C; ubiquitin-proteasome pathway; cell cycle control; 3Y1 rat fibroblasts
Affiliations: <!--label omitted: 1-->Department of Biological Sciences, Hunter College and the Graduate School of the City University of New York, New York, New York 10021, 1  and, <!--label omitted: 2-->Department of Pathology, New York University Medical Center, New York, New York 100162

Abstract:  Treatment of cells with tumor-promoting phorbol esters results in the activation but then depletion of phorbol ester-responsive protein kinase C (PKC) isoforms. The ubiquitin-proteasome pathway has been implicated in regulating the levels of many cellular proteins, including those involved in cell cycle control. We report here that in 3Y1 rat fibroblasts, proteasome inhibitors prevent the depletion of PKC isoforms alpha, delta, and epsilon in response to the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Proteasome inhibitors also blocked the tumor-promoting effects of TPA on 3Y1 cells overexpressing c-Src, which results from the depletion of PKC delta. Consistent with the involvement of the ubiquitin-proteasome pathway in the degradation of PKC isoforms, ubiquitinated PKC alpha, delta, and epsilon were detected within 30 min of TPA treatment. Diacylglycerol, the physiological activator of PKC, also stimulated ubiquitination and degradation of PKC, suggesting that ubiquitination is a physiological response to PKC activation. Compounds that inhibit activation of PKC prevented both TPA- and diacylglycerol-induced PKC depletion and ubiquitination. Moreover, a kinase-dead ATP-binding mutant of PKC alpha could not be depleted by TPA treatment. These data are consistent with a suicide model whereby activation of PKC triggers its own degradation via the ubiquitin-proteasome pathway. 

Retracted: No

PubPeer comments:
 Figure 1 and Figure 3 appear to have an repeated image. It is not clear to me that this is intentional. Apologies if I ve misunderstood. *** ![file] *** ![file] ,
Mitochondrial and nuclear genomic responses to loss of LRPPRC expression
Authors: Roland Nilsson
Casey A Belcher-Timme
Vishal M Gohil
Vamsi K Mootha
David E Root
Biao Luo
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Genotyping; Sequencing technology; Genes; Human disease; LRPPRC
Affiliations: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Abstract:  Rapid advances in genotyping and sequencing technology have dramatically accelerated the discovery of genes underlying human disease. Elucidating the function of such genes and understanding their role in pathogenesis, however, remain challenging. Here, we introduce a genomic strategy to characterize such genes functionally, and we apply it to LRPPRC, a poorly studied gene that is mutated in Leigh syndrome, French-Canadian type (LSFC). We utilize RNA interference to engineer an allelic series of cellular models in which LRPPRC has been stably silenced to different levels of knockdown efficiency. We then combine genome-wide expression profiling with gene set enrichment analysis to identify cellular responses that correlate with the loss of LRPPRC. Using this strategy, we discovered a specific role for LRPPRC in the expression of all mitochondrial DNA-encoded mRNAs, but not the rRNAs, providing mechanistic insights into the enzymatic defects observed in the disease. Our analysis shows that nuclear genes encoding mitochondrial proteins are not collectively affected by the loss of LRPPRC. We do observe altered expression of genes related to hexose metabolism, prostaglandin synthesis, and glycosphingolipid biology that may either play an adaptive role in cell survival or contribute to pathogenesis. The combination of genetic perturbation, genomic profiling, and pathway analysis represents a generic strategy for understanding disease pathogenesis. 

Retracted: No

PubPeer comments:
 there appears to be a splice betw control and kd1 blots in Fig 1E, the passage 10 ![file] , 
 2020 correction. https: www.jbc.org content 295 16 5533.short In Fig. 1E, passage 10, the splicing of a non-adjacent lane from the same immunoblot was not marked. This error has now been corrected and does not affect the results or conclusions of this work. ,
An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation
Authors: Ming Li
Xiao-Nan Jia
Kai-Jiang Yu
Yue Bu
Ruijin Liu
Xiao-Hui Ma
Lei Sun
Si-Cong Wang
Journal: BioMed Research International (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Mitochondria; Energy metabolism; Oxygen deprivation; Free radicals; Sepsis
Affiliations: Department of Critical Care Medicine, The Harbin Medical University Cancer Hospital, Harbin, 150081 Heilongjiang Province, China, Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081 Heilongjiang Province, China, Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 Heilongjiang Province, China, Institute of Critical Care Medicine and Institute of Sino Russian Medical Research Center of Harbin Medical University, 150 Hapin Road, Harbin 150081, China

Abstract:  Mitochondria play an essential role in energy metabolism. Oxygen deprivation can poison cells and generate a chain reaction due to the free radical release. In patients with sepsis, the kidneys tend to be the organ primarily affected and the proximal renal tubules are highly susceptible to energy metabolism imbalances. Dynamin-related protein 1 (DRP1) is an essential regulator of mitochondrial fission. Few studies have confirmed the role and mechanism of DRP1 in acute kidney injury (AKI) caused by sepsis. We established animal and cell sepsis-induced AKI (S-AKI) models to keep DRP1 expression high. We found that Mdivi-1, a DRP1 inhibitor, can reduce the activation of the NOD-like receptor pyrin domain-3 (NLRP3) inflammasome-mediated pyroptosis pathway and improve mitochondrial function. Both S-AKI models showed that Mdivi-1 was able to prevent the mitochondrial content release and decrease the expression of NLRP3 inflammasome-related proteins. In addition, silencing NLRP3 gene expression further emphasized the pyroptosis importance in S-AKI occurrence. Our results indicate that the possible mechanism of action of Mdivi-1 is to inhibit mitochondrial fission and protect mitochondrial function, thereby reducing pyroptosis. These data can provide a potential theoretical basis for Mdivi-1 potential use in the S-AKI prevention. 

Retracted: No

PubPeer comments:
 ![file] , 
 In Fig.1B, lower panel has undisclosed splicing ![file] ,
Feasibility, Acceptability, and Accuracy of Vaginal Self-Sampling for Screening Human Papillomavirus Types in Women from Rural Areas in Senegal
Authors: Jean-Christophe Lagier
Nafissatou Diagne
Ndeye Safietou Fall
Catherine Tamalet
Didier Raoult
Cheikh Sokhna
Florence Fenollar
Journal: American Journal of Tropical Medicine and Hygiene (2019)
Discipline: CLINICAL MEDICINE
Keywords: Vaginal self-sampling; HPV DNA testing; feasibility; acceptability; high-risk HPV prevalence
Affiliations: Aix-Marseille Université, IRD, AP-HM, SSA, VITROME, IHU Méditerranée Infection, Marseille, France., Assistance Publique-Hôpitaux de Marseille, IHU Méditerranée Infection, Laboratoire de Microbiologie, Marseille, France., Aix Marseille Université, IRD, AP-HM, MEPHI, IHU Méditerranée Infection, Marseille, France.

Abstract:  Vaginal self-sampling and human papillomavirus (HPV) DNA testing can be useful tools for women with limited access to health care living in sub-Saharan Africa. To assess the feasibility and acceptability of vaginal self-sampling and high-risk HPV prevalence in two villages of central Senegal, women were asked to self-sample vaginal swabs for HPV detection in May, 2016. Vaginal swabs were collected from 133 women and were tested for HPV genotyping. The acceptability rate of vaginal self-sampling was 98.5%, and 99.2% of the women (133/134) used the device correctly. The quality of self-sampling was satisfactory in 100% of the samples; 10.5% of the samples were positive for HPV, including 6% with high-risk HPV types and 4% with low-risk HPV types. This preliminary study indicates that vaginal self-sampling is a valuable strategy for high-risk HPV detection and cervical cancer screening in a population of women not attending gynecologic screening in rural areas of Senegal. 

Retracted: No

PubPeer comments:
 In this paper, the authors describe HPV DNA testing of self-sampled vaginal specimens from women in low-resource settings, in this case in Senegal. Although the samples were shipped to France and analyzed by PCR there, the paper does make a case for point-of-care (POC) laboratories. One of the authors of this paper, Didier Raoult, is one of the founders of a company that sells small machines for molecular analysis in POC labs, called POCramu00e9 and founded in 2014, before this paper was submitted. See: http: backup.mediterranee-infection.com article.php?laref=368 titre=pocrame and http: pocrame.com The company s name stands for Point Of Care RAoult Mu00c9ditu00e9rannu00e9e according to this article: https: thearabhospital.com articles-eng pocrame-the-start-up-at-the-forefront-of-the-fight-against-the-coronavirus-and-all-its-variants A paper that makes a point of implementing POC labs in rural areas e.g. in Senegal, could be advantageous for a company that sells machines specifically for POC labs. Yet, I could not find any disclosure of this perceived conflict of interest. Could the authors please comment? ![file] ,
Human adipose tissue-derived multipotent stem cells differentiate in vitro and in vivo into osteocyte-like cells
Authors: Christian Elabd
Ali Massoudi
Gérard Ailhaud
Pierre Weiss
Olivia Cochet
Nathalie Rochet
Christophe Trojani
Jean-François Michiels
Chiara Chiellini
Laure-Emmanuelle Zaragosi
Ez-Zoubir Amri
Georges Carle
Claude A Dechesne
Christian Dani
Journal: Biochemical and Biophysical Research Communications (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell-based therapies; bone defects; hMADS cells; differentiation; osteocyte-like cells
Affiliations: ISBDC, Université de Nice Sophia-Antipolis, CNRS, 28 Avenue de Valrose, 06100 Nice, France.

Abstract:  Cell-based therapies are used to treat bone defects. We recently described that human multipotent adipose-derived stem (hMADS) cells, which exhibit a normal karyotype, self renewal, and the maintenance of their differentiation properties, are able to differentiate into different lineages. Herein, we show that hMADS cells can differentiate into osteocyte-like cells. In the presence of a low amount of serum and EGF, hMADS cells express specific molecular markers, among which alkaline phosphatase, CBFA-1, osteocalcin, DMP1, PHEX, and podoplanin and develop functional gap-junctions. When loaded on a hardening injectable bone substitute (HIBS) biomaterial and injected subcutaneously into nude mice, hMADS cells develop mineralized woven bone 4 weeks after implantation. Thus hMADS cells represent a valuable tool for pharmacological and biological studies of osteoblast differentiation in vitro and bone development in vivo. 

Retracted: No

PubPeer comments:
 Fig. 2A: More similar than expected (Contrast enhanced). Could authors check please? ![file] , 
 I believe Coryphantha Nickelsiae means the comparison between 1% and 0% FCS (with 0 ng mL of EGF) ,
The anti-tumor efficacy of 20(S)-protopanaxadiol, an active metabolite of ginseng, according to fasting on hepatocellular carcinoma
Authors: Hongliu Sun
Xiaohong Pan
Xinbo Zhou
Xue Gao
Junhong Lü
Shayan Chen
Yifan Wang
Zeping Xie
Wenzhen Li
Journal: Journal of Ginseng Research (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 20(S)-protopanaxadiol; fasting-mimicking; hepatocellular carcinoma; intermittent fasting.

Abstract:  Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the main active metabolites of ginseng, performs a broad spectrum of anti-tumor effects. Our aims are to search out new strategies to enhance anti-tumor effects of natural products, including 20(S)-PPD. In recent years, fasting has been shown to be multi-functional on tumor progression. Here, the effects of fasting combined with 20(S)-PPD on hepatocellular carcinoma growth, apoptosis, migration, invasion and cell cycle were explored. Methods: CCK-8 assay, trypan blue dye exclusion test, imagings photographed by HoloMonitorTM M4, transwell assay and flow cytometry assay were performed for functional analyses on cell proliferation, morphology, migration, invasion, apoptosis, necrosis and cell cycle. The expressions of genes on protein levels were tested by western blot. Tumor-bearing mice were used to evaluate the effects of intermittent fasting combined with 20(S)-PPD. Results: We firstly confirmed that fasting-mimicking increased the anti-proliferation effect of 20(S)-PPD in human HepG2 cells in vitro. In fasting-mimicking culturing medium, the apoptosis and necrosis induced by 20(S)-PPD increased and more cells were arrested at G0-G1 phase. Meanwhile, invasion and migration of cells were decreased by down-regulating the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in fasting-mimicking medium. Furthermore, the in vivo study confirmed that intermittent fasting enhanced the tumor growth inhibition of 20(S)-PPD in H22 tumor-bearing mice without obvious side effects. Conclusion: Fasting significantly sensitized HCC cells to 20(S)-PPD in vivo and in vitro. These data indicated that dietary restriction can be one of the potential strategies of chinese medicine or its active metabolites against hepatocellular carcinoma. 

Retracted: No

PubPeer comments:
 Figure 3A. * Red, green, and yellow boxes highlight three sets of panels that appear to overlap with each other. ![file] , 
 #1 Thanks a million! We will check it carefully! ,
Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid
Authors: Feng Deng
Jingjing Li
Jingyuan Wan
Liangke Zhang
Tong Chen
Pei Yuan
Yalan Tang
Journal: International Journal of Nanomedicine (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: albumin; curcumin; glycyrrhetinic acid; nanoparticles; surface-functionalized.

Abstract:  We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 μg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity. 

Retracted: No

PubPeer comments:
 Figure 7B and 7C appear to have images which overlap. *** ![file] , 
 I note that the author list on PubPeer has slightly different (or garbled) names compared to the manuscript. I used the corresponding authoru2019s email address for the last author Liangke Zhang from the manuscript here: zlkdyx@126.com , 
 Figure 3C appears to have at least one area that seems to have been cut and pasted. *** ![file] , 
 #3 Similar issue with 3D. *** ![file] , 
 More in Figure 7. *** ![file] *** ![file] , 
 Received: 28 May 2021 Accepted: 28 May 2021 Published: 29 June 2021 The authors have advised Figure 7 on page 5482 is incorrect. The authors inadvertently included duplicate images for the panels shown in Before treatment A and C, After treatment B and C and For attachment D and E. The correct Figure 7 is as follows. ![file] *** The correction does not mention issues in the images in Figure 3. ,
Can education be personalised using pupils’ genetic data?
Authors: George Davey Smith
Tim T Morris
Neil M Davies
Journal: eLife (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ALSPAC; achievement; education; genetics; genomics
Affiliations: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom., Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

Abstract:  The increasing predictive power of polygenic scores for education has led to their promotion by some as a potential tool for genetically informed policy. How accurately polygenic scores predict an individual pupil's educational performance conditional on other phenotypic data is however not well understood. Using data from a UK cohort study with data linkage to national schooling records, we investigated how accurately polygenic scores for education predicted pupils' test score achievement. We also assessed the performance of polygenic scores over and above phenotypic data that are available to schools. Across our sample, there was high overlap between the polygenic score and achievement distributions, leading to poor predictive accuracy at the individual level. Prediction of educational outcomes from polygenic scores were inferior to those from parental socioeconomic factors. Conditional on prior achievement, polygenic scores failed to accurately predict later achievement. Our results suggest that while polygenic scores can be informative for identifying group level differences, they currently have limited use for accurately predicting individual educational performance or for personalised education. 

Retracted: No

PubPeer comments:
 https: elifesciences.org articles 55720 ,
Radiation-induced glioblastoma signaling cascade regulates viability, apoptosis and differentiation of neural stem cells (NSC)
Authors: Vladimir N Ivanov
Tom K Hei
Journal: APOPTOSIS (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ionizing radiation; chemotherapy; brain tumors; glioblastoma; neural stem cells
Affiliations: Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA, .

Abstract:  Ionizing radiation alone or in combination with chemotherapy is the main treatment modality for brain tumors including glioblastoma. Adult neurons and astrocytes demonstrate substantial radioresistance; in contrast, human neural stem cells (NSC) are highly sensitive to radiation via induction of apoptosis. Irradiation of tumor cells has the potential risk of affecting the viability and function of NSC. In this study, we have evaluated the effects of irradiated glioblastoma cells on viability, proliferation and differentiation potential of non-irradiated (bystander) NSC through radiation-induced signaling cascades. Using media transfer experiments, we demonstrated significant effects of the U87MG glioblastoma secretome after gamma-irradiation on apoptosis in non-irradiated NSC. Addition of anti-TRAIL antibody to the transferred media partially suppressed apoptosis in NSC. Furthermore, we observed a dramatic increase in the production and secretion of IL8, TGFβ1 and IL6 by irradiated glioblastoma cells, which could promote glioblastoma cell survival and modify the effects of death factors in bystander NSC. While differentiation of NSC into neurons and astrocytes occurred efficiently with the corresponding differentiation media, pretreatment of NSC for 8 h with medium from irradiated glioblastoma cells selectively suppressed the differentiation of NSC into neurons, but not into astrocytes. Exogenous IL8 and TGFβ1 increased NSC/NPC survival, but also suppressed neuronal differentiation. On the other hand, IL6 was known to positively affect survival and differentiation of astrocyte progenitors. We established a U87MG neurosphere culture that was substantially enriched by SOX2(+) and CD133(+) glioma stem-like cells (GSC). Gamma-irradiation up-regulated apoptotic death in GSC via the FasL/Fas pathway. Media transfer experiments from irradiated GSC to non-targeted NSC again demonstrated induction of apoptosis and suppression of neuronal differentiation of NSC. In summary, intercellular communication between glioblastoma cells and bystander NSC/NPC could be involved in the amplification of cancer pathology in the brain. 

Retracted: No

PubPeer comments:
 Figure 6J and 7F. Brought to my attention by a reader. * Red arrows: The GAPDH panels in both figures look very similar. * Blue arrows: One band in the WIP panel in Figure 6J looks similar to a band in the Mst1 panel in Figure 7F, although it in mirror image and stretched differently. * Blots have very low resolution, show no background, and are cropped very closely to the bands. ![file] ,
Exosomal microRNA-503-3p derived from macrophages represses glycolysis and promotes mitochondrial oxidative phosphorylation in breast cancer cells by elevating DACT2
Authors: Shulin Huang
Xiaowen Gu
Zihua Chen
Jing Xie
Shanshan Lei
Zhongcheng Huang
Peizhi Fan
Chaojie Zhang
Journal: Cell Death Discovery (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MicroRNAs; miR-503-3p; breast cancer; macrophage-derived exosomes; DACT2
Affiliations: The Hunan Provincial Key Lab of Precision Diagnosis and Treatment for Gastrointestinal Tumor, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China., Department of Breast and Thyroid Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan, China., The Hunan Provincial Key Lab of Precision Diagnosis and Treatment for Gastrointestinal Tumor, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. ., Department of General Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan, China. .

Abstract:  MicroRNAs (miRNAs) are emerging drivers in tumor progression, while the role of miR-503-3p in breast cancer (BC) remains largely unknown. We aimed to explore the impact of macrophage-derived exosomal miR-503-3p in the development of BC by regulating disheveled-associated binding antagonist of beta-catenin 2 (DACT2). miR-503-3p and DACT2 expression in BC tissues and cells was assessed, and the expression of Wnt/β-catenin signaling pathway-related proteins in BC cells was also evaluated. Macrophages were induced and exosomes were extracted. The screened BC cell lines were, respectively, treated with exosomes, miR-503-3p inhibitor/mimic or upregulated/inhibited DACT2, and then the phenotypes, glucose intake, oxygen consumption rate, and adenosine-triphosphate (ATP) level of BC cells were determined. Cell growth in vivo was also observed. MiR-503-3p was elevated, DACT2 was reduced, and Wnt/β-catenin signaling pathway was activated in BC cells. Macrophage-derived exosomes, upregulated miR-503-3p or inhibited DACT2 promoted malignant behaviors of BC cells, glucose intake, and activity of the Wnt/β-catenin signaling pathway, while repressed oxygen consumption rate and ATP level in BC cells. Reversely, reduced miR-503-3p or upregulated DACT2 exerted opposite effects. This study revealed that reduction of macrophage-derived exosomal miR-503-3p repressed glycolysis and promoted mitochondrial oxidative phosphorylation in BC by elevating DACT2 and inactivating Wnt/β-catenin signaling pathway. Our research may provide novel targets for BC treatment. 

Retracted: No

PubPeer comments:
 Fig 3G.  flow cytometry determined cell cycle distribution . Editors and peer-reviewers at Cell Death Discovery looked at these grotesqueries and thought  Yes! That s exactly what flow-cytometry histograms should look like! ![file] ,
Downregulation of microRNA‑221 decreases migration and invasion in fibroblast‑like synoviocytes in rheumatoid arthritis
Authors: Shuzhong Yang
Yougeng Yang
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miR-221; rheumatoid arthritis; autoimmune diseases; cell proliferation
Affiliations: Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

Abstract:  MicroRNAs (miRNAs/miRs) are a group of non-coding RNAs that regulate the activity of target mRNAs and cellular processes, and which have been implicated in the pathogenesis of autoimmune diseases. miR-221 is one of the miRNAs that regulate cell proliferation, invasion and apoptosis in tumors. However, the role of miR-221 in rheumatoid arthritis (RA) remains to be fully elucidated. Therefore, the present study was undertaken to identify the role of miR-221 in RA. The expression of miR-221 in serum and synovial tissues of patients with RA and healthy controls was confirmed by reverse transcription quantitative polymerase chain reaction analysis. The effects of miR-221 on pro-inflammatory cytokines and a chemokine were assessed by ELISA. The effects of miR-221 on cell apoptosis, migration and invasion in fibroblast-like synoviocytes (FLS) were also assessed in vitro. The results showed that miR-221 expression in serum and synovial tissues of patients with RA was higher than that in healthy controls. Downregulation of miR-221 significantly suppressed the expression of pro-inflammatory cytokines and the chemokine, and inhibited FLS cell migration and invasion via inhibiting vascular endothelial growth factor, matrix metalloproteinase (MMP)-3 and MMP-9 expression. In addition, downregulation of miR-221 significantly induced cell apoptosis and decreased survivin and X-linked inhibitor of apoptosis protein expression. These findings indicated that downregulation of miR-221 inhibited the expression of pro-inflammatory cytokines and the chemokine, suppressed FLS cell migration and invasion, and induced cell apoptosis. Therefore, miR-221 is likely to be implicated in RA pathogenesis via these mechanisms, and may be a target for the treatment of RA. 

Retracted: No

PubPeer comments:
 Fig 3B.  FLS cells were pre-treated with miR-221 inhibitor or corresponding NC for 24 h and exposed to LPS for 48 h, then survivin and XIAP expression were determined by ELISA. ![file] I have no idea why Western Blotting has been labeled as  ELISA . In addition, could the authors comment on the similarity of the loading control band to that of *[right]* Fig 5D from [Zhang et al (2014)] ? ![file] In Fig 4 from [Li et al (2015)] , it becomes a PI3K band. ![file] Other manifestations are linked in those threads. , 
 Fig 5B.  FLS were pre-treated with miR-221 inhibitor or corresponding NC for 24 h and exposed to human LPS for 48 h, then MMP-3 and MMP-9 protein expression were measured by western blot. ![file] Loading control seems to match that of *[left]* Fig 2C from [Liu et al (2014)] . ![file] Also AKT band in Fig 6 of [Zhang et al (2014)] . ![file] ,
Inhibition of histone deacetylase activity promotes invasion of human cancer cells through activation of urokinase plasminogen activator
Authors: Sai Murali Krishna Pulukuri
Jasti S Rao
Bharathi Gorantla
Journal: Journal of Biological Chemistry (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Histone acetylation; chromatin remodeling; gene expression; urokinase plasminogen activator (uPA); histone deacetylation
Affiliations: Department of Cancer Biology, University of Illinois College of Medicine, Peoria, Illinois 61656, USA.

Abstract:  Histone acetylation plays an important role in chromatin remodeling and gene expression. The molecular mechanisms involved in differential regulation of urokinase plasminogen activator (uPA) gene expression are not fully understood. In this study, we investigated whether histone deacetylation was involved in repression of uPA expression in human cancer cells. Induction of uPA expression by histone deacetylase (HDAC) inhibitors trichostatin A (TSA), sodium butyrate, and scriptaid was observed in all three different types of human cancer cells examined. Chromatin immunoprecipitation assays showed that the induction of uPA expression by TSA was accompanied by a remarkable increase of acetylation of histones H3 and H4, which are associated with the uPA promoter region in human cancer cells. These results were further substantiated by the findings of a restriction enzyme accessibility assay and TSA-stimulated uPA promoter activity through the inhibition of HDAC activity. In vitro Matrigel invasion assays showed that induction of uPA expression by HDAC inhibitors in human cancer cells resulted in a significant increase of cancer cell invasion. Furthermore, HDAC1 knockdown by small interference RNA stimulated uPA expression and cancer cell invasion. In conclusion, this study demonstrates the important role of histone modifications in regulating uPA gene expression and raises a possibility that the use of HDAC inhibitors in patients as cancer therapy may paradoxically establish metastasis through up-regulation or reactivation of uPA. 

Retracted: Yes

PubPeer comments:
 Figure 6A. The HDAC5 and HDAC7 panels look remarkably similar. Image made darker to bring out the background details. Note how the background of the other panels looks different. ![file] , 
 2020 retraction. https: www.jbc.org content 295 38 13407.short This article has been retracted by the publisher. None of the authors could be reached for comment. The last three lanes of the actin panel from SK-N-AS cells in Fig. 2B were reused in the first three lanes of the HDAC1 panel in Fig. 7A. In Fig. 6A, the HDAC5 and HDAC7 immunoblots are the same. A portion of the input panel from Fig. 6B was reused in the input panel for siHDAC1 in Fig. 7B. ,
EGFR/HER2 inhibitors effectively reduce the malignant potential of MDR breast cancer evoked by P-gp substrates in vitro and in vivo
Authors: Qiang Zou
Yiting Jin
Chengyu Chu
Wei Zhang
Xiuping Liu
Hongying Wang
Zijing Zhang
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Multidrug resistance; chemotherapy; breast cancer; EGFR; HER2
Affiliations: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200240, P.R. China., Department of Pathology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, P.R. China.

Abstract:  Multidrug resistance (MDR) induced by chemotherapy in breast cancer frequently leads to tumor invasion, metastasis and poor clinical outcome. We preliminarily found that the epidermal growth factor receptor (EGFR) is involved in enhancing the malignant potential of MDR breast cancer cells, but the mechanism remains unclear. In the present study, we demonstrated in vitro and in vivo that EGFR/HER2 promote the invasive and metastatic abilities of MDR breast cancer. More importantly, a new function of EGFR/HER2 inhibitors was revealed for the first time, which could improve the treatment efficacy of breast cancer by reversing the MDR process rather than by inhibiting tumor growth. Firstly, using quantitative real‑time PCR and western blot analysis, we found that overexpression of EGFR/HER2 in MCF7/Adr cells upregulated CD147 and MMP2/9 at both the transcription and protein expression levels, which promoted tumor cell migration, as determined using an in vitro invasion assay. Secondly, the upregulated levels of CD147 and MMP2/9 were decreased when EGFR/HER2 activity was inhibited, and therefore tumor invasion was also significantly inhibited. These phenomena were also demonstrated in nude mouse assays. Additionally, in MDR breast cancer patients, we found that overexpression of EGFR and P‑gp levels led to shorter overall survival (OS) and disease‑free survival (DFS) by IHC assays and Kaplan‑Meier survival analysis. In conclusion, EGFR/HER2 play a crucial role in enhancing CD147 and MMP expression to establish favorable conditions for invasion/metastasis in MDR breast cancer. The scope of application of EGFR/HER2 inhibitors may be expanded in EGFR/HER2‑positive patients. We suggest that MDR breast cancer patients may benefit from novel therapies targeting EGFR/HER2. 

Retracted: No

PubPeer comments:
 Figure 2E. * Red boxes: Two panels appear to show an overlap * Blue boxes: Two panels appear to show an overlap ![file] ,
CRISPR-Mediated Gene Activation (CRISPRa) of pp38/pp24 Orchestrates Events Triggering Lytic Infection in Marek’s Disease Virus-Transformed Cell Lines
Authors: Venugopal Nair
Poornima Roy
Katy Moffat
Yongxiu Yao
Journal: Microorganisms (2021)
Discipline: MICROBIOLOGY
Keywords: CRISPRa; apoptosis; latent/lytic switch; pp38.
Affiliations: Viral Oncogenesis Group, The Pirbright Institute, Pirbright, Surrey GU24 0NF, UK.

Abstract:  Marek's disease (MD) is an immunosuppressive and highly contagious lymphoproliferative disease caused by Marek's disease virus (MDV) in poultry. Lymphoblastoid cell lines (LCLs) generated ex vivo from MD lymphomas are considered excellent models to study virus-host molecular interactions. LCLs mostly have latently infected MDV genome, but many of them also have varying populations of lytically-infected cells, thus making them very suitable to examine the molecular events associated with the switch from latent to lytic infection. MDV-encoded phosphoprotein 38 (pp38) is readily detectable in lytically-infected LCLs and hence considered as a biomarker for lytic infection. Whilst previous studies have suggested that pp38 is essential for the early cytolytic infection of B-cells, its role in the switch from latent to lytic infection of LCLs is still unclear. pp24, another phosphorylated protein in the same protein complex, shares the same promoter and N-terminal 65 amino acids as pp38. In this study we employed CRISPR activation (CRISPRa) technology for targeted activation of pp38/pp24 in LCLs to investigate their role in inducing lytic infection. Our results show that enforced expression of pp38/pp24 through CRISPRa induces orchestrated upregulation of other MDV genes including ICP4, gB, Meq and pp14 as well as differential expression of host genes thereby facilitating lytic infection. Our results also show that pp38/pp24 expression induces the lytic switch through inhibiting apoptosis. 

Retracted: No

PubPeer comments:
 ![file] The authors did not acknowledge the Plasmid maker ![file] ,
Tumor endothelial marker 1–specific DNA vaccination targets tumor vasculature
Authors: Stefano Ugel
Chunsheng Li
Andrea Facciabene
Arjun Raj
John G Facciponte
Efthymia Matthaiou
Francesco De Sanctis
Liping Wang
Gautham Nair
George Coukos
Sandy Sehgal
Journal: Journal of Clinical Investigation (2014)
Discipline: CLINICAL MEDICINE
Keywords: TEM1; cancer immunotherapy; vaccination; tumor vasculature; CD8+ T cells

Abstract:  Tumor endothelial marker 1 (TEM1; also known as endosialin or CD248) is a protein found on tumor vasculature and in tumor stroma. Here, we tested whether TEM1 has potential as a therapeutic target for cancer immunotherapy by immunizing immunocompetent mice with Tem1 cDNA fused to the minimal domain of the C fragment of tetanus toxoid (referred to herein as Tem1-TT vaccine). Tem1-TT vaccination elicited CD8+ and/or CD4+ T cell responses against immunodominant TEM1 protein sequences. Prophylactic immunization of animals with Tem1-TT prevented or delayed tumor formation in several murine tumor models. Therapeutic vaccination of tumor-bearing mice reduced tumor vascularity, increased infiltration of CD3+ T cells into the tumor, and controlled progression of established tumors. Tem1-TT vaccination also elicited CD8+ cytotoxic T cell responses against murine tumor-specific antigens. Effective Tem1-TT vaccination did not affect angiogenesis-dependent physiological processes, including wound healing and reproduction. Based on these data and the widespread expression of TEM1 on the vasculature of different tumor types, we conclude that targeting TEM1 has therapeutic potential in cancer immunotherapy. 

Retracted: No

PubPeer comments:
 Embryo section images marked with red and green frames are for different treatment groups but identical. It is extremely difficult to embed embryos in an identical orientation. The four numbered panels (1 -4) appear to show different levels of sections obtained from the same embryo. ![file] , 
 #1 The embryo pictures are from Figure 7B. In Figure 7C, 3 out of 4 spleen panels are taken from a single section. ![file] , 
 Figure 7C uterus looks like exocervix. ,