PReD-Bench/PRed-Bench huggingface dataset:
Intermedin attenuates cardiomyocytes hypoxia‚Äêinjury through upregulating long noncoding RNA MALAT1
Authors: Long Liu
Haiming Xu
Jingze Zhang
Qini Zhao
Liquan Yin
Journal: Journal of Cellular Biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Retraction; Intermedin; Cardiomyocytes; Hypoxia-injury; Long noncoding RNA
Affiliations: Department of Cardiovascular Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China., Jilin Provincial Precision Medicine Key Laboratory for Cardiovascular Genetic Diagnosis, Changchun, Jilin, China., Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, Jilin, China., Department of Rehabilitation Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

Abstract:  Retraction: 'Intermedin attenuates cardiomyocytes hypoxia-injury through upregulating long noncoding RNA MALAT1', by Long Liu, Haiming Xu, Jingze Zhang, Liquan Yin, Qini Zhao, J Cell Biochem. 2020 (Online Version of Record before inclusion in an issue): The above article, published online on 6 January 2020 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcb.29642), has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The authors asked to retract this manuscript and stated that not all co-authors agree on the usage of the published data, initially, but were not available for further comments during the investigation. The retraction has been agreed following an investigation based on allegations raised by a third party and after the authors stated that not all co-authors agree on the usage of the published data, which could not be verified. 

Retracted: No

PubPeer comments:
 2009 retraction. https: www.cell.com immunity fulltext S1074-7613(09)00153-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761309001538%3Fshowall%3Dtrue The authors have agreed to retract this paper because of duplication of the flow cytometry dot plots in Figure 1C (labeled as WT and u0394355+8F) by the first author. This figure shows the reconstitution of mouse cells deficient in IL-2 receptor beta with various wild-type and mutant human IL-2 receptor beta chains. This data established the system used to test various properties of these receptor chains in the later work of the paper. This matter was investigated by the California Institute of Technology and the Office of Research Integrity at the United States Department of Human Services, which found the first author to be responsible for the scientific misconduct pertaining to the issue described here. The authors stand by the validity of the other figures and sincerely apologize for the inconvenience caused by this retraction. ,
GRAMD4 mimics p53 and mediates the apoptotic function of p73 at mitochondria
Authors: V Alla
K John
B M P√ºtzer
C Meier
Journal: Cell death and differentiation (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p73; apoptosis; mitochondria; GRAMD4; Bcl-2
Affiliations: Department of Vectorology and Experimental Gene Therapy, Biomedical Research Center, University of Rostock, Schillingallee 69, Rostock, Germany.

Abstract:  p73, a member of the p53 family, shares high sequence homology with p53 and shows many p53-like properties: it binds to p53-DNA target sites, transactivates p53-responsive genes and induces cell cycle arrest and apoptosis. Apart from this transcription-dependent effect, less is known about the downstream mechanism(s) by which p73 controls cell fate at the mitochondria. We have previously identified GRAMD4 (alias KIAA0767 or Death-Inducing-Protein) as a novel p53-independent pro-apoptotic target of E2F1, which localizes to mitochondria. In this study, we found that p73-induced apoptosis is mediated by GRAMD4 expression and translocation to the mitochondria. We showed that this protein physically interacts with Bcl-2, promotes Bax mitochondrial relocalization and oligomerization, and is highly efficient in inducing mitochondrial membrane permeabilization with release of cytochrome c and Smac. Overexpression of p73Œ± and p73Œ≤ isoforms, but not p53, leads to direct GRAMD4 promoter transactivation. In addition, GRAMD4 induces changes in Bcl-2 and Bax protein levels. GRAMD4 transcription is activated in response to cisplatin (cDDP) in a manner dependent on endogenous p73. Using solid tumor xenografts, ectopic expression of GRAMD4 together with cDDP resulted in enhanced cancer killing. Our findings demonstrate that p73 is able to trigger apoptosis via the mitochondrial pathway by a new mechanism using pro-apoptotic GRAMD4 as mediator, and strongly support its p53-like function. 

Retracted: No

PubPeer comments:
 2012 correction. https: www.nature.com articles cdd2011194 It has come to our attention that the wrong western blot results for actin in the bottom panel of Figure 3b and for COX4 in Figure 7c were inserted. The correct actin lane mislabeled as COX4 in the mitochondrial fraction (Ad.GRAMD4) of Figure 7c has been replaced. Appropriate figures are reproduced below. The authors apologize for any confusion this might have caused. ,
Improved Treatment of MT-3 Breast Cancer and Brain Metastases in a Mouse Xenograft by LRP-Targeted Oxaliplatin Liposomes
Authors: Ralf Axel Hilger
Iduna Fichtner
Andrea Orthmann
Lisa Peiker
Reiner Zeisig
Annika Hoffmann
Journal: Journal of Biomedical Nanotechnology (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Oxaliplatin; Liposomes; Breast carcinoma; Brain metastasis; Angiopep

Abstract:  The anti-cancer drug oxaliplatin (OxP) has rarely been used to treat breast carcinoma, as it cannot cross the BBB to treat the frequently subsequent brain metastases. Here, we encapsulated OxP in liposomes prepared to reduce side effects and to simultaneously treat primary tumor and brain metastasis. The angiopep LRP-receptor ligand was bound to the vesicular surface for targeting. Targeted and non-targeted OxP liposomes were tested in vitro (binding, uptake, and transcytosis) and in vivo. Liposomes contained 0.65 mg OxP/mL, their mean diameter was 165 nm, and they released 50% of OxP within 8 days at 4 degrees C and within 22 h at 36 degrees C. MDCK cells were used for uptake and transcytosis quantification. Compared to non-targeted liposomes, targeted liposomes showed 12-fold greater uptake, and 2.25-fold higher transcytosis. In vivo efficacy was tested using human MT-3 breast cancer cells transplanted subcutaneously and intracerebrally into female nude mice, and tumor growth inhibition was measured. OxP was injected (6 mg OxP/kg) four times. The best results were obtained with targeted liposomes (T/C: 21% for subcutaneous and 50% for intracerebral). OxP liposomes with a fluid membrane all inhibited MT-3 tumors significantly better than free OxP, with no significant difference between targeted and non-targeted liposomes. The therapeutic effect was accompanied with strong leukopenia and mild thrombocytopenia with all formulations. The newly developed OxP liposomes significantly improved the treatment of subcutaneously and intracerebrally growing breast cancer, but the targeted angiopep-equipped liposomes showed no superior effect in vivo. 

Retracted: No

PubPeer comments:
 This paper makes use of the MT-3 cell line as a model of breast cancer. Unfortunatly it is a cell line contaminated by the colon adenocarcinoma cell line LS174T. This problem was not known when this paper was published, thus the authors are not responsible for using a wrong cell model for their study. But unfortunatly the use of MT-3 invalidates all the conclusions of this paper in the context of breast cancer. See the relevant [Cellosaurus entry] ,
Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors
Authors: W H Ng
S Wang
Y Zhao
C K Tham
J Lin
D H Lam
J Yang
Journal: Gene therapy (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Tumor-tropic neural stem cells; Trojan horse approach; targeted delivery; therapeutic agents; renewable source
Affiliations: Drug and Gene Delivery, Institute of Bioengineering and Nanotechnology, Singapore, Singapore.

Abstract:  Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirus-mediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: www.nature.com articles s41434-020-0135-y Retraction Note to: Gene Therapy https: doi.org 10.1038 gt.2011.82. The editor has retracted this article [1] following an investigation by Agency for Science, Technology and Research (A*STAR), Institute of Bioengineering and Nanotechnology, Singapore, which found evidence of fabricated animal survival data presented in Fig. 7C in the article to make the results statistically significant. DHL, JY, JL, CKT, WHN, and SW agree to this retraction. YZ has agreed to this retraction but not to the wording of this retraction notice. ,
Telomere length in early childhood is associated with sex and ethnicity
Authors: Emma Marks
Kien Ly
Russell Snell
Polly Atatoa-Carr
Sarah Berry
Zaneta Thayer
Susan Morton
Caroline Walker
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: Telomeres; Chromosomes; Telomere length; Children; Gender
Affiliations: Centre for Longitudinal Research - He Ara ki Mua and Growing Up in New Zealand, University of Auckland, Auckland, New Zealand. ., Centre for Longitudinal Research - He Ara ki Mua and Growing Up in New Zealand, University of Auckland, Auckland, New Zealand., School of Biological Sciences, Centre for Brain Research, University of Auckland, Auckland, New Zealand., Department of Anthropology, Dartmouth College, Hanover, New Hampshire, United States., National Institute of Demographic and Economic Analysis, Faculty of Arts and Social Sciences, University of Waikato, Hamilton, New Zealand.

Abstract:  Telomeres are repetitive DNA sequences at the end of chromosomes that function to protect chromosomes from degradation. Throughout the life course, telomere length decreases with age and is influenced by environmental factors and health conditions. This study aimed to determine the relative telomere lengths in a diverse cohort of about 4000 four-year-old children in New Zealand. Linear regression was used to investigate the relationship between telomere length, child gender, ethnicity, paternal age and deprivation. We observed substantial variation in telomere length according to sex and self-identified ethnicity. Telomere length was longer in females compared to males (coefficient of 0.042, 95% confidence interval (CI) 0.024-0.060). European children had shorter telomere than both the indigenous MƒÅori (coefficient of 0.03, CI 0.007-0.055) and Pacific children (coefficient of 0.15, CI 0.12-0.18). The data suggest that telomere lengths are highly variable and variability between individuals arise from early age, influenced partly by sex and ethnicity. Longer telomeres in indigenous MƒÅori and Pacific children may reflect the heritability of telomere length in genetically less complex populations. This study increases our understanding of telomere dynamics in young children since the majority of telomere studies are conducted in adults. 

Retracted: No

PubPeer comments:
 Abstract says,  Longer telomeres in indigenous Mu0101ori and Pacific children may reflect the heritability of telomere length in genetically less complex populations. However, this hypothesis about genetic complexity does not seem to be explained further in the body of the paper. Not sure what it means? ,
Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-Œ≤ Signaling Pathway to Facilitate the Virus Replication
Authors: Guowei Xu
Chaochao Shen
Xiangtao Liu
Ye Jin
Weijun Cao
Xuegang Zhang
Nannan Wei
Jing Hou
Minghao Yan
Keshan Zhang
Dajun Zhang
Junhong Hao
Haixue Zheng
Journal: Frontiers in Immunology (2021)
Discipline: IMMUNOLOGY
Keywords: foot-and-mouth disease virus; immune escape; interferon regulatory factor 3/interferon-Œ≤; tumor progression locus 2; viral protein 1.
Affiliations: State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute of Chinese Academy of Agriculture Science, Lanzhou, China.

Abstract:  Foot-and-mouth disease (FMD) is a severe, highly contagious viral disease of cloven-hoofed animals. In order to establish an infection, the FMD virus (FMDV) needs to counteract host antiviral responses. Tumor progression locus 2 (TPL2), a mitogen-activated protein kinase, can regulate innate and adaptive immunity; however, its exact mechanisms underlying TPL2-mediated regulation of the pathogenesis of FMDV infection remain unknown. In this study, we confirmed that TPL2 could inhibit FMDV replication in vitro and in vivo. The virus replication increased in Tpl2-deficient suckling mice in association with reduced expression of interferon-stimulated genes interferon-Œ± (IFN-Œ±) and myxovirus resistance (MX2) and significantly reduced expression of C-X-C motif chemokine ligand 10 (CXCL10), interferon regulatory factor 3 (IRF3), and IRF7, while the phosphorylation of IRF3 was not detected. Moreover, the interactions between TPL2 and VP1 were also confirmed. The overexpression of TPL2 promoted IRF3-mediated dose-dependent activation of the IFN-Œ≤ signaling pathway in association with interactions between IRF3 and TPL2. VP1 also inhibited phosphorylation of TPL2 at Thr290, while Thr290 resulted as the key functional site associated with the TPL2-mediated antiviral response. Taken together, this study indicated that FMDV capsid protein VP1 antagonizes TPL2-mediated activation of the IRF3/IFN-Œ≤ signaling pathway for immune escape and facilitated virus replication. 

Retracted: No

PubPeer comments:
 Fig.6A: Western Blot with 10 bands for myc-TLP2 and 12 bands for beta-actin control  , 
 **CORRECTION**  *In the original article, there was a mistake in FIGURE 6, FMDV VP1 inhibits TPL2 phosphorylation at the Thr290 site as published. We forgot to marker the two lanes of control plasmids(pCMV-3N-Myc) in the left Myc-TPL2 image in Fig.6A during prepare and proof stage of our paper. This mistake lead to the result that the actin control line includes 12 lanes, while the Myc-TPL2 line contains 10 lanes in Fig.6A. There was no description of the transfected empty plasmids in the legend of Fig.6A. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.* https: www.frontiersin.org articles 10.3389 fimmu.2021.686494 full , 
 #2 The mentioned mistake has been corrected in the updated paper. ,
Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA damage
Authors: Hiroshi Arakawa
Li Lan
Helfrid Hochegger
Esther Hou
Takashi Okada
Shunichi Takeda
Jean-Marie Buerstedde
Richard D Wood
Akira Yasui
Samuel H Wilson
Michio Yoshimura
Mineaki Seki
Masaoki Kohzaki
Kenjiro Asagoshi
Keizo Tano
Masahiro Hiraoka
Rajendra Prasad
Eiichiro Sonoda
Jun Nakamura
Journal: Molecular Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Base excision repair; POLQ; DNA polymerase; translesion DNA synthesis; oxidative stress
Affiliations: Department of Radiation Genetics, CREST, Japan Science and Technology Laboratory, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan.

Abstract:  Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLQ is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) past base damage. We disrupted POLQ, and its homologs HEL308 and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to oxidative base damage induced by H(2)O(2), but not to UV or cisplatin. Surprisingly, this phenotype was synergistically increased by concomitant deletion of the major BER polymerase, POLbeta. Moreover, extracts from a polq null mutant cell line show reduced BER activity, and POLQ, like POLbeta, accumulated rapidly at sites of base damage. Accordingly, POLQ and POLbeta share an overlapping function in the repair of oxidative base damage. Taken together, these results suggest a role for vertebrate POLQ in BER. 

Retracted: No

PubPeer comments:
 Could the authors comment on these images - are they intended to overlap? Other readers on social media suggest that a clarification would be helpful as these appear to be different treatment groups. ***  ***  ,
Gene rearrangements in the molecular pathogenesis of acute promyelocytic leukemia
Authors: L Delva
H Zhang
M Giorgio
Z G Wang
M Gaboli
D Gandini
D Peruzzi
R Rivi
S Kalantry
L Z He
C Tribioli
P P Pandolfi
N Hawe
Journal: Journal of Cellular Physiology (1997)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Acute Promyelocytic Leukemia; APL; Translocations; Retinoic Acid Receptor alpha; RAR alpha
Affiliations: Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Abstract:  Acute Promyelocytic Leukemia (APL) is a distinct subtype of myeloid leukemia that in the USA alone affects more than 3,000 individuals every year. APL is characterized by three distinct and unique features: i) the accumulation in the bone marrow of tumor cells with promyelocytic features; ii) the invariable association with specific translocations which always involve chromosome 17 and the Retinoic Acid Receptor alpha (RAR alpha) locus; iii) the exquisite sensitivity of APL blasts to the differentiating action of Retinoic Acid (RA). These features have led APL to become the paradigm for therapeutic approaches utilizing differentiating agents. The last 5 years have provided crucial insights into the molecular basis of APL. RAR alpha translocates in 99% of cases to a gene located on chromosome 15 that we initially named myl and subsequently has been called PML. In a few cases, RAR alpha variably translocates to chromosome 11 where it fuses to the PLZF gene or to a newly described partner, NuMA. In addition, RAR alpha is also found translocated to chromosome 5 where it fuses to the NPM gene. The cloning of variant translocations in APL and the comparative analysis of their associated products is crucial for the understanding of the molecular etiopathogenesis of the disease. The generation of animal models, i.e., transgenic mice expressing the fusion genes, will be instrumental in determining the precise contribution of these fusion genes to leukemogenesis. In fact, mice harboring a PML/RAR alpha transgene whose expression is specifically targeted to the myeloid-promyelocytic lineage develop acute myeloid leukemia with promyelocytic features. Moreover, the functional analysis of the various fusion proteins, as well as RAR alpha partners, is revealing striking common features beneath a misleading structural heterogeneity which unravels a possible unifying molecular mechanism towards APL leukemogenesis. 

Retracted: No

PubPeer comments:
 Figure 3B. Much more similar than you would expect. https: imgur.com oxAlv1i , 
 Figure 3A. Much more similar than you would expect. https: imgur.com KDtWc4u ,
Glioma cells escaped from cytotoxicity of temozolomide and vincristine by communicating with human astrocytes
Authors: Anjing Chen
Bin Huang
Ying He
Chao Ma
Xun Qu
Songyu Chen
Peng Zhao
Weiliang Chen
Donghai Wang
Xinwen Du
Qianqian Shao
Xingang Li
Journal: Medical Oncology (2015)
Discipline: CLINICAL MEDICINE
Keywords: chemoresistance; gliomas; astrocytes; tumor microenvironment; apoptosis
Affiliations: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, China.

Abstract:  Resistance to chemotherapeutic drugs remains a great obstacle to successful treatment of gliomas. Understanding the mechanism of glioma chemoresistance is conducive to develop effective strategies to overcome resistance. Astrocytes are the major stromal cells in the brain and have been demonstrated to play a key role in the malignant phenotype of gliomas. However, little is known regarding its role in glioma chemoresistance. In our study, we established a co-culture system of human astrocytes and glioma in vitro to simulate tumor microenvironment. Our results showed that astrocytes significantly reduced glioma cell apoptosis induced by the chemotherapeutic drugs temozolomide and vincristine. This protective effect was dependent on direct contact between astrocytes and glioma cells through Cx43-GJC. Moreover, in human glioma specimens, we found astrocytes infiltrating around the tumor, with a reactive appearance, suggesting that these astrocytes would play the same chemoprotective effect on gliomas in vivo. Our results expand the understanding of the interaction between astrocytes and glioma cells and provide a possible explanation for unsatisfactory clinical outcomes of chemotherapeutic drugs. Cx43-GJC between astrocytes and glioma cells may be a potential target for overcoming chemoresistance in gliomas clinically. 

Retracted: No

PubPeer comments:
 Ref [2] is Li, Z, Vetro, M:  Levinu2019s type boundary behaviors for functions harmonic and admitting certain lower bounds . Bound. Value Probl. 2015, 159 (2015). [Since retracted for plagiarism and fictitious authorship] . Ref [5] is Yan, Z, Ychussie, B:  Normal families and asymptotic behaviors for solutions of certain Laplace equations . Adv. Differ. Equ. 2015, 226 (2015). [Since retracted] for [overlap with another manuscript] and for fictitious authorship. Ref [8] is Wang, J, Pu, J, Zama, A:  Solutions of the Dirichlet-Schru00f6dinger problems with continuous data admitting arbitrary growth property in the boundary . Adv. Differ. Equ. 2016, 33 (2016). [Since retracted for the usual reasons] . Note that the current paper overlaps significantly with the text of  Some new results on the boundary behaviors of harmonic functions with integral boundary conditions (Xie Viouonu, 2016), that overlap being one reason for the [recent retraction of that latter paper] , along with non-existent authorship. Given this intellectual tradition, I hope I can be forgiven for asking for evidence that the third (and corresponding) author does exist, and is affiliated to the Departamento de Matemu00e1tica, Universidade Federal do Rio de Janeiro. ,
RETRACTED ARTICLE: The value of FGF9 as a novel biomarker in the diagnosis of prostate cancer
Authors: Shiqing Zhang
Hongbo Guo
Jianlei Lu
Hongbin Ma
Xingzhou Gu
Genggang Cui
Mingming Shao
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Fibroblast growth factor 9; diagnosis; prostate cancer.
Affiliations: a Department of Urology Surgery, The First People's Hospital of Jining , Jining , Shandong , China., b Department of Urology Surgery, Yanzhou Branch of Jining Medical University , Jining , Shandong , China.

Abstract:  Background: Fibroblast growth factor 9 (FGF9) is reported to be associated with the pathogenesis of cancers. However, its clinic significance in prostate cancer (PCa) had not yet to be elucidated. The aim of this study was to investigate the diagnostic value of FGF9 in PCa. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were used to detect the expression of serum FGF9 at mRNA and protein level in 90 PCa patients, 48 prostatic benign diseases (PBD) patients and 30 normal individuals. The association between FGF9 and clinicopathological features was determined by Chi-square test. Receiver-operator characteristic (ROC) was established to evaluate the diagnostic performance of FGF9 and PSA. Results: Serum FGF9 expression was significantly elevated in PCa patients (p &lt; .001) and was obviously decreased after surgery (p &lt; .001). FGF9 expression was also associated with lymph node metastasis (p = .010). The diagnostic value of FGF9 was higher than the conventional tumor marker PSA with a AUC of 0.846 combined with a sensitivity of 83.3% and a specificity of 81.1%. Conclusions: Serum FGF9 may be employed as a potential diagnostic biomarker of PCa. 

Retracted: Yes

PubPeer comments:
 Standard deviations are incorrect for the following variables in Table 4: parent arrested, urban, south, prior violent delinquency. Because it is based on a logistic regression the relationship shown in Figure 1 should be non-linear. ,
Nicotine stimulates human lung cancer cell growth by inducing fibronectin expression
Authors: ShouWei Han
Jeffrey D Ritzenthaler
Ying Zheng
Jesse Roman
Journal: American journal of respiratory cell and molecular biology (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: tobacco; lung cancer; nicotine; NSCLC cells; fibronectin
Affiliations: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Abstract:  The mechanisms by which tobacco promotes lung cancer remain incompletely understood. Herein, we report that nicotine, a major component of tobacco, promotes the proliferation of cultured non-small cell lung carcinoma (NSCLC) cells; this effect was most noticeable at 5 days. However, nicotine had no effect on apoptosis of NSCLC cells. In experiments designed to unveil the mechanisms for this effect, we found that nicotine also stimulated mRNA and protein expression of fibronectin. Fibronectin is a matrix glycoprotein that regulates important cellular processes (e.g., adhesion, proliferation, and differentiation) and is highly expressed in tobacco-related lung disorders. Of note, reagents against the integrin alpha5beta1 (antibodies, RGD peptides, alpha5 shRNA) blocked the mitogenic effects of nicotine. Thus, nicotine stimulated NSCLC cell proliferation indirectly via fibronectin induction. We then focused on the mechanisms responsible for nicotine-induced fibronectin expression in NSCLC cells and found that nicotine stimulated the surface expression of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR), and that alpha-bungarotoxin, an inhibitor of alpha7 nAChR, abolished the nicotine-induced fibronectin response. The fibronectin-inducing effects of nicotine were associated with activation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3-K)/mammalian target of rapamycin (mTOR) signaling pathways, and were abrogated by inhibitors of ERK (PD98059), PI3-K (LY294002), and mTOR (rapamycin), but not by inhibitors of protein kinase (PK)C (calphostin C) and PKA (H89). These observations suggest that nicotine stimulates NSCLC proliferation through induction of fibronectin, and that these events are mediated through nAChR-mediated signals that include ERK and PI3-K/mTOR pathways. This work highlights the role of fibronectin and alpha5beta1 integrins as potential targets for anti-lung cancer therapies. 

Retracted: No

PubPeer comments:
 Figure 5. Much more similar than you would expect. https: imgur.com PcRwlrA ,
Identification of protein biomarkers and signaling pathways associated with prostate cancer radioresistance using label-free LC-MS/MS proteomic approach
Authors: Valerie C Wasinger
Lei Chang
Yong Li
Jingli Hao
David Malouf
Julia Beretov
Jie Ni
David Gillatt
Peter H Graham
Joseph Bucci
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Biomarkers; Signaling pathways; Prostate cancer; Radioresistance; LC-MS/MS proteomics
Affiliations: Cancer Care Centre, St George Hospital, Kogarah, NSW 2217, Australia., St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Kensington, NSW 2052, Australia., Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China., SEALS, Anatomical Pathology, St George Hospital, Kogarah, NSW 2217, Australia., Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, UNSW, Kensington, NSW 2052, Australia., School of Medical Science, UNSW, Kensington, NSW 2052, Australia., Department of Urology, St George Hospital, Kogarah, NSW 2217, Australia., Australian School of Advanced Medicine, Macquarie University, NSW 2109, Australia.

Abstract:  Identifying biomarkers and signaling pathways are important for the management of prostate cancer (CaP) radioresistance. In this study, we identified differential proteins and signaling pathways from parental CaP cell lines and CaP radioresistant (RR) sublines using a label-free LC-MS/MS proteomics approach. A total of 309 signaling pathway proteins were identified to be significantly altered between CaP and CaP-RR cells (p ‚â?0.05, fold differences &gt;1.5, ‚â?0% power). Among these proteins, nineteen are common among three paired CaP cell lines and associated with metastasis, progression and radioresistance. The PI3K/Akt, VEGF and glucose metabolism pathways were identified as the main pathways associated with CaP radioresistance. In addition, the identified potential protein markers were further validated in CaP-RR cell lines and subcutaneous (s.c) animal xenografts by western blotting and immunohistochemistry, respectively and protein aldolase A (ALDOA) was selected for a radiosensitivity study. We found the depletion of ALDOA combined with radiotherapy effectively reduced colony formation, induced more apoptosis and increased radiosensitivity in CaP-RR cells. Our findings indicate that CaP radioresistance is caused by multifactorial traits and downregulation of ALDOA increases radiosensitivity in CaP-RR cells, suggesting that controlling these identified proteins or signaling pathways in combination with radiotherapy may hold promise to overcome CaP radioresistance. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 7A: * Blue boxes: The left p-Akt and p-mTOR panels look very similar. * Red boxes: The left CD147 panel and the right VEG VG-1 panel look very similar.  , 
 Brought to my attention by the same reader. Figure 9B. * Green boxes: The two panels on the right (top and bottom) look very similar to each other.  ,
Vitexin induces apoptosis through mitochondrial pathway and PI3K/Akt/mTOR signaling in human non-small cell lung cancer A549 cells
Authors: Suxia Luo
Qingfeng Jiang
Huaimin Liu
Xiaoli Liu
Journal: Biological research (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Mitochondrial dysfunction; Non-small cell lung cancer; PI3K/Akt/mTOR signaling; Vitexin.

Abstract:  Background: Currently, the prognosis of patients with non-small cell lung cancer (NSCLC) remains dismal; hence, it is critical to identify effective anti-NSCLC agents with limited side effects. This study aimed to evaluate the therapeutic potential of flavonoid compound vitexin in human NSCLC cells and the underlying mechanisms. Results: The experimental results indicated that vitexin reduced the viability of A549 cells in a dose-dependent manner with nearly no toxicity against normal human bronchial epithelial 16HBE cells. Vitexin also dose-dependently increased A549 cell apoptosis, accompanied by the decreased Bcl-2/Bax ratio and the increased expression of cleaved caspase-3. Moreover, the in vivo anticancer activity of vitexin was further determined in nude mice bearing A549 cells. In addition, vitexin induced the release of cytochrome c from the mitochondria to the cytosol and the loss of mitochondrial membrane potential. Vitexin also significantly reduced the levels of p-PI3K, p-Akt and p-mTOR, and the pro-apoptotic effect of vitexin on A549 cells was partly blocked by SC79, an Akt activator. Conclusions: Accordingly, we believed that vitexin could be used as a potential therapeutic agent for the treatment of NSCLC in the future. 

Retracted: No

PubPeer comments:
 Fig. 5b - patterns more similar than expected. Could the authors check the raw data?  ,
MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs
Authors: Prabhakar Tiwari
Ramandeep Singh
Saqib Kidwai
Garima Arora
Om Prakash Narayan
Mamta Singh
Journal: Nature Communications (2015)
Discipline: Multidisciplinary
Keywords: Toxin-antitoxin systems; Mycobacterium tuberculosis complex; mazEF family; MazF toxin; MazE antitoxin
Affiliations: Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, 496 Udyog Vihar Phase III, Gurgaon, Haryana 122016, India.

Abstract:  Toxin-antitoxin (TA) systems are highly conserved in members of the Mycobacterium tuberculosis (Mtb) complex and have been proposed to play an important role in physiology and virulence. Nine of these TA systems belong to the mazEF family, encoding the intracellular MazF toxin and its antitoxin, MazE. By overexpressing each of the nine putative MazF homologues in Mycobacterium bovis BCG, here we show that Rv1102c (MazF3), Rv1991c (MazF6) and Rv2801c (MazF9) induce bacteriostasis. The construction of various single-, double- and triple-mutant Mtb strains reveals that these MazF ribonucleases contribute synergistically to the ability of Mtb to adapt to conditions such as oxidative stress, nutrient depletion and drug exposure. Moreover, guinea pigs infected with the triple-mutant strain exhibits significantly reduced bacterial loads and pathological damage in infected tissues in comparison with parental strain-infected guinea pigs. The present study highlights the importance of MazF ribonucleases in Mtb stress adaptation, drug tolerance and virulence. 

Retracted: No

PubPeer comments:
 A corrigendum was published for this paper : In Fig. 5b in this Article, the photomicrograph of a lung section of the u0394mazF3u03949u03946 strain in the right hand panel was inadvertently duplicated from the photomicrograph of a lung section of the wild-type strain in the left hand panel. The correct version of Fig. 5b appears below. , 
 In Tiwari et al., 2015, the wild type well is rigorously identical to the wt well from Arora et al., 2018 while the mazF396 well is rigorously identical to the ppx1 well from Tiwari et al., 2019  , 
 Thank you for bringing this to our attention. We have discussed and resolved this matter with the Editorial Office of the Journal as per their recommendation. , 
 #3 Could the authors share what that recommendation was? ,
Retracted: Long-term outcomes of 530 esophageal squamous cell carcinoma patients with minimally invasive Ivor Lewis esophagectomy
Authors: Zhan Tianwei
Wu Ming
Shen Gang
Wu Zixiang
Fang Shuai
Wang Qi
Zhang Sai
Journal: Journal of surgical oncology (2018)
Discipline: CLINICAL MEDICINE
Keywords: Ivor Lewis; esophageal squamous cell carcinoma; minimally invasive esophagectomy; quality of life; survival.
Affiliations: Department of Thoracic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Abstract:  Background and objectives: The short-term benefits of minimally invasive esophagectomy (MIE) Ivor Lewis were proved, but 6-year outcomes in esophageal squamous cell carcinoma (ESCC) patients remain unclear. We sought to investigate perioperative outcomes, quality of life (QOL), survival and impact of adjuvant therapy in ESCC patients who underwent MIE Ivor Lewis. Methods: We conducted a retrospective review of 530 ESCC patients treated with MIE Ivor Lewis from 2011 to 2016. Relevant variables were collected and assessed. Overall survival (OS) and disease-free survival (DFS) was analyzed by Kaplan-Meier or Cox proportional hazards modeling. Results: Median operation duration was 266 min. The median number of lymph nodes was 28. The 30-day postoperative mortality was 1.7%. At a median follow-up of 41 months, the 6-year OS and DFS were 44.7% and 46.1%. Adjuvant chemoradiotherapy offered survival advantages in advanced stage patients. Pathological tumor-node-metastasis stage, postoperative complications, and recurrent laryngeal nerve lymphadenectomy were independent prognostic factors based on multivariate analysis. Generalized estimating equation analysis showed a rapid postoperative QOL improvement. Conclusions: MIE Ivor Lewis is a safe and feasible procedure in ESCC patients. It offers satisfactory perioperative outcomes, rapid QOL improvement, and acceptable long-term oncologic survival. Adjuvant chemoradiotherapy may improve OS and DFS in advanced stage patients. 

Retracted: No

PubPeer comments:
  The manuscript u201cCovid-19 And Vit-D: Disease Mortality Negatively Correlates with Sunlight Exposureu201d (Lansiaux et al., 2020) held our attention as we found fatal shortcomings that invalidate the analyses and conclusions. https: www.sciencedirect.com science article pii S1877584520300514 , 
 #1  We are extremely disappointed that our correspondents can t read and can t interpret correctly a Pearson Spearman coefficient Here is the response to Naudet et al. (what a shame for statisticians, working at INSERM or HSCP, not to know how to read the sign of a correlation) https: www.sciencedirect.com science article pii S1877584520300666 ,
Long noncoding RNA RBMS3-AS3 acts as a microRNA-4534 sponge to inhibit the progression of prostate cancer by upregulating VASH1
Authors: Yuxi Zhang
Zhenming Jiang
Pingeng Wu
Xi Chen
Dong Chen
Journal: Gene Therapy (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: lncRNAs; prostate cancer; RBMS3-AS3; miR-4534; VASH1
Affiliations: Department of Urology, The First Hospital of China Medical University, 110001, Shenyang, PR China., Department of Urology, The First Hospital of China Medical University, 110001, Shenyang, PR China. ., Department of Urology, People's Hospital of Datong Hui and Tu Autonomous County, 810100, Xining, PR China. ., Department of Pharmacy, The First Hospital of China Medical University, 110001, Shenyang, PR China., Central Lab, The First Hospital of China Medical University, 110001, Shenyang, PR China.

Abstract:  Long noncoding RNAs (lncRNAs) have been demonstrated to participate in the progression of many malignancies, including prostate cancer by serving as sponges of microRNAs (miRNAs). Initial microarray-based analysis screened out the poorly expressed lncRNA RBMS3-AS3 in prostate cancer, followed by the identification of putative binding sites with miR-4534 and its target VASH1. Therefore, the present study set out to investigate the potential role of RBMS3-AS3/miR-4534/VASH1 axis in the development of prostate cancer. The biological functions of RBMS3-AS3, miR-4534, and VASH1 on cell proliferation, migration, invasion, and angiogenesis of prostate cancer were evaluated via gain- and loss-of-function experiments. Furthermore, tumor xenograft in nude mice was performed to examine tumorigenesis in vivo. The obtained results indicated that RBMS3-AS3 was poorly expressed in prostate cancer tissues and cells. Of note, overexpression of RBMS3-AS3 was found to suppress cell proliferation, migration, invasion, and angiogenesis as well as the tumorigenic ability of prostate cancer. VASH1 was verified as a target gene of miR-4534. VASH1 expression was found to be downregulated in prostate cancer tissues and cells. Interestingly, RBMS3-AS3 was observed to competitively bind to miR-4534 to upregulate VASH1 expression, resulting in a suppressive role in prostate cancer development. Also, in vitro findings were reproduced in vivo on tumor xenograft in nude mice. Taken together, the present study provides evidence suggesting that RBMS3-AS3 acts as a miR-4534 sponge to inhibit the development of prostate cancer by upregulating VASH1, highlighting a theoretical target for prostate cancer treatment. 

Retracted: No

PubPeer comments:
 Figure 3F: Overlap between different experimental conditions. Would the authors please comment?  ,
Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach
Authors: J E Angell
E R Hofmann
D V Kalvakolanu
P S Shapiro
D J Lindner
Journal: Journal of Biological Chemistry (2000)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: interferon-beta; all-trans-retinoic acid; tumor cells; growth-suppressive action; gene products

Abstract:  We show here that the combination of interferon-beta (IFN-beta) and all-trans-retinoic acid (RA) induces the death of tumor cells. To understand the molecular basis for synergistic growth-suppressive action and to identify the gene products that participate in this process, we have employed an antisense knock-out technique. This approach permits the isolation of cell death-associated genes based on their selective inactivation by overexpression of antisense cDNAs. Because the antisense mRNA inactivates gene expression of death-specific genes, transfected cells survive in the presence death inducers. Several Genes associated with Retinoid-IFN-induced Mortality (GRIM) were identified using this approach. Here we report the isolation of a novel GRIM gene, GRIM-19. This 552-base pair cDNA encodes a 16-kDa protein. Antisense expression of GRIM-19 confers a strong resistance against IFN/RA-induced death by reducing the intracellular levels of GRIM-19 protein. Overexpression of GRIM-19 enhances cell death in response to IFN/RA. GRIM-19 is primarily a nuclear protein whose expression is induced by the IFN/RA combination. Together, our studies identify a novel cell death-regulatory molecule. 

Retracted: No

PubPeer comments:
 Figure 12. Much more similar than expected. https: imgur.com gqVbDPM ,
The left ventral premotor cortex is involved in hand shaping for intransitive gestures: evidence from a two-person imitation experiment
Authors: Arran T Reader
Nicholas P Holmes
Journal: Royal Society Open Science (2018)
Discipline: Multidisciplinary
Keywords: motion-tracking; motor control; social interaction.
Affiliations: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden, School of Psychology, University of Nottingham, Nottingham, UK

Abstract:  The ventral premotor cortex (PMv) is involved in grasping and object manipulation, while the dorsal premotor cortex (PMd) has been suggested to play a role in reaching and action selection. These areas have also been associated with action imitation, but their relative roles in different types of action imitation are unclear. We examined the role of the left PMv and PMd in meaningful and meaningless action imitation by using repetitive transcranial magnetic stimulation (rTMS). Participants imitated meaningful and meaningless actions performed by a confederate actor while both individuals were motion-tracked. rTMS was applied over the left PMv, left PMd or a vertex control site during action observation or imitation. Digit velocity was significantly greater following stimulation over the PMv during imitation compared with stimulation over the PMv during observation, regardless of action meaning. Similar effects were not observed over the PMd or vertex. In addition, stimulation over the PMv increased finger movement speed in a (non-imitative) finger-thumb opposition task. We suggest that claims regarding the role of the PMv in object-directed hand shaping may stem from the prevalence of object-directed designs in motor control research. Our results indicate that the PMv may have a broader role in 'target-directed' hand shaping, whereby different areas of the hand are considered targets to act upon during intransitive gesturing. 

Retracted: No

PubPeer comments:
 This paper was criticised as part of a self-reflection posted on Twitter on 2nd-3rd April, 2021 (twitter TheHandLab status 1377760796130869248) Criticism: This experiment should have worked better. TMS is wrongly labelled a virtual lesion method, but even repetitive TMS over premotor cortex during a movement task can not work so well. We should also have done more with the EMG data in my opinion. ,
Urinary Amino-Terminal Pro‚ÄìC-Type Natriuretic Peptide: A Novel Marker of Chronic Kidney Disease in Diabetes
Authors: Eric A Espiner
Helen F Heenan
Helen Lunt
Timothy C R Prickett
Julie Warwick
Journal: Clinical Chemistry (2019)
Discipline: CLINICAL MEDICINE
Keywords: Chronic renal inflammation; fibrosis; diabetes mellitus; NPPC expression; C-type natriuretic peptide
Affiliations: Department of Medicine, University of Otago, Christchurch, New Zealand, Diabetes Outpatients, Canterbury District Health Board, Christchurch, New Zealand

Abstract:  Background: Chronic renal inflammation and fibrosis are common sequelae in diabetes mellitus (DM) and are major causes of premature mortality. Although upregulation of NPPC expression occurs in response to renal inflammation in experimental animals, nothing is known of the molecular forms of C-type natriuretic peptide (CNP) products in urine of people with DM or links with renal function. Methods: ProCNP products in urine were characterized with HPLC and a range of antisera directed to specific epitopes of amino-terminal proCNP (NTproCNP). The 5-kDa intact peptide was quantified in spot urine samples from healthy adults and 202 participants with DM selected to provide a broad range of renal function. Results: The predominant products of proCNP in urine were consistent with the 2-kDa fragment (proCNP 3-20) and a smaller peak of intact (5-kDa) fragment (proCNP 1-50, NTproCNP). No peaks consistent with bioactive forms (proCNP 82-103, 50-103) were identified. The urine NTproCNP to creatinine ratio (NCR) was more reproducible than the albumin to creatinine ratio (ACR) and strongly associated with the presence of chronic kidney disease. In models predicting independence, among 10 variables associated with renal function in DM, including plasma NTproCNP, only 3 (sex, ACR, and plasma creatinine) contributed to NCR. Conclusions: Characterization of the products of proCNP in urine confirmed the presence of NTproCNP. In spot random urine from study participants with DM, NCR is inversely associated with estimated glomerular filtration rate. In contrast to ACR, NCR reflects nonvascular factors that likely include renal inflammation and fibrosis. 

Retracted: No

PubPeer comments:
 As the silent killer, it remains a big challenge for the clinic lab to detect chronic kidney disease at the early stage. New markers are used to evaluate the GFR, and hopefully we can test GFR actually. ,