PReD-Bench/PRed-Bench huggingface dataset:
MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS
Authors: Yi Xiao
Zhen Shang
Taoran Deng
Changliang Su
Journal: Oncology Letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: Kirsten rat sarcoma viral oncogene homolog; acute myeloid leukemia; apoptosis; chemosensitivity; microRNA-217.
Affiliations: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Abstract:  Acute myeloid leukemia (AML) is a heterogeneous malignant disorder derived from the myeloid hematopoietic cells that accounts for ~80% of all adult acute leukemia. Numerous studies have shown that drug resistance not only exists against conventional chemotherapeutic drugs, but also limits the efficacy of new biological agents. Therefore, it is important to identify the mechanisms behind chemoresistance and seek therapeutic strategies to enhance efficacy in AML chemotherapy. MicroRNA (miR)-217 has been recognized as a tumor suppressor that is downregulated in various types of cancer, however the mechanisms behind the expression and function of miR-217 in AML have not yet been recognized. The expression of miR-217 was determined by quantitative polymerase chain reaction (qPCR). Following transfection with miR-217 mimics, an MTT assay, chemosensitivity assay, cell apoptosis assay and western blot analysis were performed in AML cell lines. Functional assays were also performed to explore the effects of endogenous Kirsten rat sarcoma viral oncogene homolog (KRAS) in AML. The results revealed that miR-217 was downregulated in patients with AML. Overexpression of miR-217 inhibited cellular proliferation and enhanced cell chemosensitivity to doxorubicin by the cell apoptosis pathway in AML cells. A dual-luciferase reporter assay demonstrated that KRAS was a direct target gene of miR-217 in vitro. qPCR and western blot analysis revealed that miR-217 negatively regulated KRAS protein expression, but had no impact on KRAS mRNA expression. Knockdown of KRAS expression markedly suppressed AML cellular proliferation, and enhanced cell chemosensitivity to doxorubicin via the cell apoptosis pathway. These findings indicate that miR-217 functions as a tumor suppressor in AML by directly targeting KRAS. Therefore, miR-217-based therapeutic strategies may provide a novel strategy for the enhancement of efficacy in the treatment of AML. 

Retracted: No

PubPeer comments:
 Dear reader, please note that an updated version of the toolbox presented in the paper can be found [here](http: https: www.nitrc.org projects rshrf). with links to the matlab and python version. Thanks! ,
Knockdown of lncRNA AK139328 alleviates myocardial ischaemia/reperfusion injury in diabetic mice via modulating miR-204-3p and inhibiting autophagy
Authors: Xin-Qun Hu
Liang Tang
Bo Dong
Sheng-Hua Zhou
Si-Yang Yu
Zhen-Fei Fang
Journal: Journal of Cellular and Molecular Medicine (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MiR-204-3p; diabetes mellitus; lncRNA AK139328; myocardial ischaemia/reperfusion injury.
Affiliations: Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract:  This study was aimed at investigating the effects of lncRNA AK139328 on myocardial ischaemia/reperfusion injury (MIRI) in diabetic mice. Ischaemia/reperfusion (I/R) model was constructed in normal mice (NM) and diabetic mice (DM). Microarray analysis was utilized to identify lncRNA AK139328 overexpressed in DM after myocardial ischaemia/reperfusion (MI/R). RT-qPCR assay was utilized to investigate the expressions of lncRNA AK139328 and miR-204-3p in cardiomyocyte and tissues. Left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and fractioning shortening (FS) were obtained by transthoracic echocardiography. Haematoxylin-eosin (HE) staining and Masson staining were utilized to detect the damage of myocardial tissues degradation of myocardial fibres and integrity of myocardial collagen fibres. Evans Blue/TTC staining was used to determine the myocardial infarct size. TUNEL staining was utilized to investigate cardiomyocyte apoptosis. The targeted relationship between lncRNA AK139328 and miR-204-3p was confirmed by dual-luciferase reporter gene assay. MTT assay was used for analysis of cardiomyocyte proliferation. Western blot was utilized to investigate the expression of alpha smooth muscle actin (α-SMA), Atg7, Atg5, LC3-II/LC3-I and p62 marking autophagy. Knockdown of lncRNA AK139328 relieved myocardial ischaemia/reperfusion injury in DM and inhibited cardiomyocyte autophagy as well as apoptosis of DM. LncRNA AK139328 modulated miR-204-3p directly. MiR-204-3p and knockdown of lncRNA AK139328 relieved hypoxia/reoxygenation injury via inhibiting cardiomyocyte autophagy. Silencing lncRNA AK139328 significantly increased miR-204-3p expression and inhibited cardiomyocyte autophagy, thereby attenuating MIRI in DM. 

Retracted: No

PubPeer comments:
 In Fig 4A, normal mice and diabetic mice had an overlapped horizon, very interesting. ![file] ,
Late phase of the endoplasmic reticulum stress response pathway is regulated by Hog1 MAP kinase
Authors: Joel Tourtellotte
Alicia A Bicknell
Maho Niwa
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: unfolded proteins; endoplasmic reticulum; ER stress; unfolded protein response; UPR
Affiliations: Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA.

Abstract:  When unfolded proteins accumulate in the endoplasmic reticulum (ER) causing ER stress, the unfolded protein response (UPR) responds rapidly to induce a transcriptional program that functions to alleviate the stress. However, under extreme conditions, when UPR activation is not sufficient to alleviate ER stress, the stress may persist long term. Very little is known about how the cell responds to persistent ER stress that is not resolved by the immediate activation of the UPR. We show that Hog1 MAP kinase becomes phosphorylated during the late stage of ER stress and helps the ER regain homeostasis. Although Hog1 is well known to function in osmotic stress and cell wall integrity pathways, we show that the activation mechanism for Hog1 during ER stress is distinct from both of these pathways. During late stage ER stress, upon phosphorylation, Hog1 translocates into the nucleus and regulates gene expression. Subsequently, Hog1 returns to the cytoplasm, where its phosphorylation levels remain high. From its cytoplasmic location, Hog1 contributes to the activation of autophagy by enhancing the stability of Atg8, a critical autophagy protein. Thus, Hog1 coordinates a multifaceted response to persistent ER stress. 

Retracted: No

PubPeer comments:
 Duplication of flow cytometry data in Figure 1 B. In the two feft panels the authors present flow cytometry histograms that apparently is based on cells that have been under normoxia (Nor) in the mid panel and hypoxia (Hyp) in the right panel. There are no difference between the panels = duplication. In addition, the histograms do not match the quantifications shown in the left panel. In normoxia the histogram top is centered over a fluorescence intensity of 10000, while the average in the left panel is 4000 with a very small SEM. The x and y axis are not defined, but I guess that y-aksis is number of cells and the x-axis is median fluorescence intensity of ecto-CD47. As the intergrity of data in science is of outmost importance, the authors needs to disclose raw flow cytometry data for each experiment (all three) as ther are several pubpeer based issue reports from this group. ![file] , 
 Note: This article has been corrected. Please see the link below: https: www.oncotarget.com article 26474 ,
Low daunomycin concentrations protect colorectal cancer cells from hypoxia-induced apoptosis
Authors: Valérie Benoît
Valérie Deregowski
Roland Greimers
Chantal Lechanteur
Marie-Paule Merville
Vincent Bours
Nathalie Jacobs
Alain Chariot
Journal: Oncogene (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hypoxia; apoptosis; drug diffusion; cancer cells; daunomycin
Affiliations: Laboratory of Medical Chemistry and Human Genetics, Center for Biomedical Integrated Genoproteomics, University of Liège, Belgium.

Abstract:  Hypoxia, a common feature of solid tumors, is a direct stress that triggers apoptosis in many cell types. Poor or irregular tumor vascularization also leads to a decreased drug diffusion and cancer cells distant from blood vessels (hypoxic cells) are exposed to low drug concentrations. In this report, we show that low daunomycin concentrations protect HCT116 colorectal cancer cells from hypoxia-induced apoptosis. While hypoxia induced p53 accumulation without expression of its responsive genes (bax and p21), daunomycin treatment restored p53 transactivation activity and cell cycle progression. We also demonstrated a role for Akt activation in daunomycin-induced protection through phosphorylation and inactivation of the Bcl-2 family proapoptotic factor Bad. Our data therefore suggest that chemotherapy could possibly, because of low concentrations in poorly vascularized tumors, protect cancer cells from hypoxia-induced cytotoxicity. 

Retracted: No

PubPeer comments:
 Figure 2. https: imgur.com C59QOFB ,
miR-503-5p inhibits colon cancer tumorigenesis, angiogenesis, and lymphangiogenesis by directly downregulating VEGF-A
Authors: Yaotian Zhang
Ning Han
Shichen Sun
Chaonan Sun
Linlin Wei
Journal: Gene Therapy (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MicroRNAs; miR-503-5p; colon cancer; pathogenesis; downregulation
Affiliations: Department of Radiotherapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, China. ., Department of Radiotherapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, China.

Abstract:  MicroRNAs (miRNAs) are considered important in the pathogenesis of colon cancer. But the mechanism of their role in colon cancer is still largely unknown. Here, we aimed to explore the function of miR-503-5p in the pathogenesis of colon cancer. This study analyzed miRNA microarray of colon cancer. Then, we performed EdU, CCK-8, flow cytometry, Transwell invasion assays and in vivo assays to explore the exact role of miR-503-5p in colon cancer. We observed considerable downregulation of miR-503-5p expression in colon cancer cells and tissues and significant correlation with the TNM stage, differentiation grade and lymph node metastasis of colon cancer. Overexpression of miR-503-5p promoted the apoptosis and G1 arrest of colon cancer cells, and inhibited migration, proliferation, invasion and colony formation. Interestingly, ectopic miR-503-5p overexpression could significantly inhibit vascular endothelial growth factor (VEGF)-A expression and reduce the activity of a luciferase reporter containing the VEGF-A 3'-untranslated region. Furthermore, overexpressed miR-503-5p in human umbilical vein endothelial cells (HUVECs) and colon cancer cells resulted in lower expression levels of VEGFR-2, and subsequently inhibited AKT signaling pathway. Additionally, overexpression of miR-503-5p suppressed both lymphangiogenesis and angiogenesis in vivo and significantly inhibited the tumorigenicity of HT-29 cells in nude mice. In summary, our study shows downregulation of miR-503-5p at least partially contributes to the tumorigenesis of colon cancer through modulating the angiogenesis and lymphangiogenesis by targeting VEGF-A while stimulating AKT signaling pathways. Therapeutic strategies to restore miR-503-5p in colon cancer could be useful to inhibit tumor progression. 

Retracted: No

PubPeer comments:
 Fig. 3 The cells in the upper and lower rows are different, and they are not the same field of view. ![file] ,
Bioluminescence in vivo imaging of autoimmune encephalomyelitis predicts disease
Authors: Jian Luo
Lawrence Steinman
Tony Wyss-Coray
Peggy Ho
Journal: Journal of Neuroinflammation (2008)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Experimental autoimmune encephalomyelitis; bioluminescence imaging; neuroinflammation; drug screening; immunological studies
Affiliations: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA. 

Abstract:  Background: Experimental autoimmune encephalomyelitis is a widely used animal model to understand not only multiple sclerosis but also basic principles of immunity. The disease is scored typically by observing signs of paralysis, which do not always correspond with pathological changes. Methods: Experimental autoimmune encephalomyelitis was induced in transgenic mice expressing an injury responsive luciferase reporter in astrocytes (GFAP-luc). Bioluminescence in the brain and spinal cord was measured non-invasively in living mice. Mice were sacrificed at different time points to evaluate clinical and pathological changes. The correlation between bioluminescence and clinical and pathological EAE was statistically analyzed by Pearson correlation analysis. Results: Bioluminescence from the brain and spinal cord correlates strongly with severity of clinical disease and a number of pathological changes in the brain in EAE. Bioluminescence at early time points also predicts severity of disease. Conclusion: These results highlight the potential use of bioluminescence imaging to monitor neuroinflammation for rapid drug screening and immunological studies in EAE and suggest that similar approaches could be applied to other animal models of autoimmune and inflammatory disorders. 

Retracted: No

PubPeer comments:
 Figure 1C appears to have a repeated image. This work was supported by grants from the NIH (AG23708, AG20603) and the John Douglas French Alzheimer s Foundation (T.W-C). *** ![file] , 
 Dear Actinopolyspora, Thank you for alerting us about the mistake. Figure 1C of GFAP staining indeed has a repeated image. The representative image of day 35 was a mistake. Attached corrected Figure 1 here. Weu2019re sorry for the mistake and will work with the editorial office to fix it if possible. Best wishes, Jian ![file] ,
Simian virus 40 is present in human lymphomas and normal blood
Authors: C W Miller
H David
S Mendoza
T Konishi
Journal: Cancer Letters (2001)
Discipline: CLINICAL MEDICINE
Keywords: Simian virus 40 (SV40); normal tissues; neoplastic tissues; thyroid tumors; bone tumors

Abstract:  Many independent studies have demonstrated Simian virus 40 (SV40) in normal and neoplastic human tissues. Clonal integration of virus in the DNA of several thyroid and bone tumors suggests a direct role for SV40 in some cancers. However, in most cases the role of SV40 remains unclear. This study determined the presence of SV40, by amplification followed by hybridization, in 266 normal and neoplastic blood and lymphoid samples. Amplification detected SV40 in 14% of non-autoimmune deficiency syndrome (AIDS) lymphomas, 28% of AIDS related lymphoma and 16% of peripheral blood lymphocytes from non-cancerous patients. No SV40 was detected in leukemia samples. Direct Southern blotting of SV40+ samples detected no virus, consistent with less than one viral genome in ten cells. Sequence analysis of SV40 in blood and lymphoid samples found sequences distinct from laboratory strains of SV40. The presence of limited quantities of SV40 in a small proportion of both normal and neoplastic tissues is suggestive of an adventitious presence with no apparent direct role in blood and lymphoid cancers. 

Retracted: No

PubPeer comments:
 Another example of overlapping primer - probe  detection , cf. https: pubpeer.com publications EB6C29B7D49B52A465DA962C974D0B ![file] , 
 #1 From the PubPeer FAQs:  What makes a comment effective? Context, explanation and accuracy. Although it is good to be concise, **a minimum of context and explanation** can be very helpful to readers, so please consider providing this even if it does require extra work. ,
Charcot's paradox
Authors: Alex Tiburtino Meira
Olivier Walusinski
Hélio Afonso Ghizoni Teive
Maren de Moraes E Silva
Carlos Henrique Ferreira de Camargo
Journal: Arquivos de Neuro-Psiquiatria (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Jean-Martin Charcot; modern neurology; pathology; anatomical findings; anatomo-clinical method
Affiliations: Hospital da Cruz Vermelha Brasileira Filial do Paraná,  Brasil, Universidade Federal do Paraná,  Brasil, ,  France, Universidade Estadual de Ponta Grossa,  Brasil

Abstract:  Jean-Martin Charcot (1825-1893), considered the father of modern neurology, had a particular interest in pathology and learned to value anatomical findings. Among his main contributions is the use of the anatomo-clinical method in neurology. Although described as cold and impatient in his interpersonal relations, Charcot had a great affection for animals. He had two dogs in his home, which he called Carlo and Sigurd, and a little monkey, Rosalie. Despite his fascination with neuropathology and anatomo-clinical correlations, Charcot disapproved of studies using animal species other than humans, a seemingly paradoxical attitude. As a result, Charcot's human studies resulted in important advances in neurology as, prior to his research, anatomical observations of animals were extrapolated to humans, leading to conceptual errors. 

Retracted: No

PubPeer comments:
 I read with interest this paper and found that the dog presented on figure 1 is called by the authors Sigurd ![file] Obviously this dog is a Labrador and thus this dog is Carlo and not Sigurd , 
 #1 Thanks a lot! There was a technical error. ,
Effect of normal-fat diets, either medium or high in protein, on body weight in overweight subjects: a randomised 1-year trial
Authors: A Due
S Toubro
A Astrup
A R Skov
Journal: International Journal of Obesity (2004)
Discipline: CLINICAL MEDICINE
Keywords: fat-reduced diet; high-protein; weight loss; body composition; blood parameters
Affiliations: Department of Human Nutrition, Centre for Advanced Food Studies, The Royal Veterinary and Agricultural University, 1958 Frederiksberg C, Denmark.

Abstract:  Background: We have previously reported that a fat-reduced high-protein diet had more favourable effects on body weight loss over 6 months than a medium-protein diet. Objective: To extend this observation by a further 6-12 months less stringent intervention and a 24 months follow-up. Design: A randomised 6 months strictly controlled dietary intervention followed by 6-12 months dietary counselling period, and a subsequent 24 months follow-up, comparing an ad libitum, fat-reduced diet (30% of energy) either high in protein (25% of energy, HP) or medium in protein (12% of energy, MP). Subjects: A total of 50 overweight and obese subjects (age: 19-55 y; BMI: 26-34 kg/m(2)). Measurements: Change in body weight, body composition and blood parameters. Results: After 6 months, the HP group (n=23) achieved a greater weight loss than the MP group (n=23) (9.4 vs 5.9 kg) (P&lt;0.01). After 12 months, 8% had dropped out in the HP vs 28% in the MP group (P&lt;0.07). After 12 months, the weight loss was not significantly greater among the subjects in the HP group (6.2 and 4.3 kg), but they had a 10% greater reduction in intra-abdominal adipose tissue and more in the HP group (17%) lost &gt;10 kg than in the MP (P&lt;0.09). At 24 months, both groups tended to maintain their 12 months weight loss, but more than 50% were lost to follow-up. Conclusion: A fat-reduced diet high in protein seems to enhance weight loss and provide a better long-term maintenance of reduced intra-abdominal fat stores. 

Retracted: No

PubPeer comments:
 Did the authors mean u2018skewedu2019? ![file] ,
Myasthenic sera recognize the human acetylcholine receptor bound to thymopoietin
Authors: E Morel
B Vernet-der Garabedian
T K Audhya
F Raimond
G Goldstein
J F Bach
Journal: European Journal of Immunology (1987)
Discipline: IMMUNOLOGY
Keywords: thymopoietin; acetylcholine receptor; myasthenia gravis; neuromuscular conduction; antibodies

Abstract:  The thymic hormone, thymopoietin (Tpo), from human (HTpo), bovine (BTpo) and from synthetic (sHTpo) origins bound to the acetylcholine receptor (AChR) solubilized by Triton 1.5% from human muscle. This binding was demonstrated either by inhibition of formation of radiolabeled alpha bungarotoxin (alpha Bgt)-AChR complexes measured after precipitation by ammonium sulfate or by a myasthenic serum containing a high concentration of anti-AChR antibodies, or directly by incubating the human AChR with radiolabeled sHTpo or BTpo. The 125I-labeled alpha Bgt-AChR complexes were totally inhibited by 10(-6) M sHTpo or BTpo. The complexes formed by AChR and the radiolabeled Tpo were recognized specifically by sera containing anti-AChR antibodies from myasthenic patients. The active pentapeptide derivative of Tpo, thymopentin, another thymic hormone, thymulin, as well as bovine insulin did not interfere with the specific binding of alpha Bgt to human AChR. Tpo and anti-AChR antibodies could participate together in the inhibition of neuromuscular conduction with Tpo modulating the depressive effect of the antibodies on the neuromuscular junction in myasthenia gravis. 

Retracted: Yes

PubPeer comments:
 See retraction notice: https: doi.org 10.1002 eji.1830231150 The decision to retract a paper when a suspicion arises regarding the experimental material used is to be recommended! ,
c-Myc induced upregulation of long non-coding RNA SNHG16 enhances progression and carcinogenesis in oral squamous cell carcinoma
Authors: Shengkai Zhang
Shangfeng Li
Jie Chen
Journal: Cancer gene therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: SNHG16; c-Myc; oral squamous cell carcinoma; pathogenesis; regulatory mechanism
Affiliations: Department of Stomatology, The First People's Hospital of Shangqiu, Shangqiu, 476100, Henan, China. ., Department of Stomatology, The First People's Hospital of Shangqiu, Shangqiu, 476100, Henan, China., Department of Head and Neck Surgery, Hunan Cancer Hospital, Changsha, 410006, Hunan, China.

Abstract:  Small nucleolar RNA host gene 16 (SNHG16) has been documented to be involved in the pathogenesis of human cancers. Here, we elucidated the biological roles and regulatory mechanism of SNHG16 in the pathogenesis of oral squamous cell carcinoma (OSCC). In this paper, we found that c-Myc and SNHG16 were overexpressed in OSCC tissues and cell lines compared with normal tissues and normal human oral keratinocytes cells. There was a notable positive correlation between SNHG16 and c-Myc expression in OSCC tissues. c-Myc silencing by either shRNA c-Myc or by 10058-F4 (c-Myc inhibitor) resulted in a dose-dependent reduction in SNHG16 levels in CAL-27 and TSCCA cells; conversely, upregulation of c-Myc by pcDNA c-Myc markedly increased SNHG16 expression. Depletion of SNHG16 in CAL-27 cells strikingly inhibited cell proliferation, migration and invasion, as indicated by downregulation of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)-2 and MMP-9. Moreover, depletion of SNHG16 induced cell apoptosis and inhibited epithelial-to-mesenchymal transition as indicated by induction of cleaved caspase-3 and epithelial cadherin (E-cadherin) along with reduction of N-cadherin and Snail. Intriguingly, c-Myc knockdown led to the similar functional effects as that of SNHG16 knockdown in TSCCA cells. However, these changes caused by c-Myc knockdown were abrogated by SNHG16 overexpression. Knockdown of SNHG16 conspicuously repressed tumor growth in nude mice. Similarly, silencing of c-Myc markedly inhibited tumor growth and reduced SNHG16 expression in nude mice. Moreover, overexpression of SNHG16 blocked the inhibitory effect of c-Myc silencing on tumor growth in vivo. Thus, we conclude that c-Myc-induced upregulation of SNHG16 enhances progression and carcinogenesis in OSCC. 

Retracted: No

PubPeer comments:
 Figure 5C is falsified. This is clearly shown by the repetitive patterns. In addition, the Western immuno blots (Figure 5E and Figure 6) look artificial. They have poor resolultion and difficult to conclude. ![file] ,
FITC-Dextran entrapped and silica coated gadolinium oxide nanoparticles for synchronous optical and magnetic resonance imaging applications
Authors: Shailja Kumar
Puja Panwar Hazari
Virendra Kumar Meena
Rakesh Kumar Sharma
Journal: International Journal of Pharmaceutics (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Contrast agent; FITC-dextran; Gadolinium oxide nanoparticles; Optical imaging.
Affiliations: Nanotechnology and Drug Delivery Research Lab, Department of Chemistry, University of Delhi, Delhi 110007, India., Nanotechnology and Drug Delivery Research Lab, Department of Chemistry, University of Delhi, Delhi 110007, India; Institute of Nuclear Medicine and Allied Sciences, DRDO, Ministry of Defence, Lucknow Road, Timarpur, Delhi 110054, India., Institute of Nuclear Medicine and Allied Sciences, DRDO, Ministry of Defence, Lucknow Road, Timarpur, Delhi 110054, India. Electronic address: ., Nanotechnology and Drug Delivery Research Lab, Department of Chemistry, University of Delhi, Delhi 110007, India. Electronic address: .

Abstract:  We report, microemulsion mediated synthesis of FITC-dextran dye entrapped and silica coated Gd2O3 nanoparticles (NPs) for dual purpose of optical and magnetic resonance imaging, in the present study. TEM image revealed that the average size of the NPs is 18nm and hydrodynamic diameter of the particles as measured by DLS comes out to be about 16nm. Gd2O3 core show paramagnetism which is affirmed by the NMR line broadening effect on neighboring water proton spectrum and also by magnetization curve obtained in VSM analysis. The fluorescence of the entrapped dye is confirmed by the UV-vis and fluorescence spectroscopy. Nanoencapsulation of FITC-dextran fluorophore was found to increase its optical activity and provided a blanket against quenching. Moreover, TGA data revealed that entrapment of dye imparts thermal stability to it and enhances its fluorescence in comparison to bare dye. The release kinetic pattern (at pH 7.4) of the entrapped dye revealed that these particles behave as non-releasing system. The in-vitro cell viability (SRB) assay of the particles done on normal cell line (HEK-293) as well as cancerous cell line (A-549) indicated non-cytotoxic nature of the particles. In a nut-shell, these particles have the potential to be efficiently used for optical and magnetic resonance imaging. We anticipate that further optimization of these particles can be done by either conjugating or entrapping a drug for targeted drug delivery which would open more prospective options in biomedical field. 

Retracted: No

PubPeer comments:
 The paper doesnu2019t have a section for the statistics and even not a single word the u201cstatisticsu201d in whole the paper, therefore, the error bars in figure 12b create confusion. 1.tWhat do these error bars indicate? S.D, S.E.M, or something else? please mention 2.tWhy the same length of all error bars in figure-12b. Any reason? ![file] ,
miR-508-5p acts as an anti-oncogene by targeting MESDC1 in hepatocellular carcinoma
Authors: L M Wu
Z H Li
X Y Wang
B J Chen
W Chen
B Bao
J Dong
S G Wu
L Wang
Y J Huang
X H Liu
Journal: Neoplasma (2017)
Discipline: CLINICAL MEDICINE
Keywords: MESDC1 hepatocellular carcinoma.; miR-508-5p.

Abstract:  Hepatocellular carcinoma (HCC) is the third leading cause of cancer associated mortality. Accumulating evidence has shown that microRNAs (miRNAs) act as critical factors for tumor recurrence and metastasis. MiR-508-5p has been reported as a down-regulated miRNA in the primary gastric cancer tissues. However, the role of miR-508-5p on HCC has not been well elucidated. In this study, we observed that miR-508-5p was downregulated in HCC tissues when compared to the non-tumorous tissues. We then demonstrated that overexpression of miR-508-5p attenuated HepG2 cells proliferation and invasion and induced cell apoptosis in vitro. Furthermore, our further investigations revealed that mesoderm development candidate 1 (MESDC1) is a potential target of miR-508-5p, as well as miR-508-5p overexpression downregulated MESDC1 expression. Overexpression of MESDC1 promoted HepG2 cells migration, invasion and proliferation in vitro. In addition, miR-508-5p markedly suppressed the tumor growth in xenograft model, while MESDC1 promoted the tumor growth in xenograft model. This study provides new insight into molecular mechanisms that miR-508-5p acts as a tumor suppressor by targeting MESDC1 in HCC progression. 

Retracted: No

PubPeer comments:
 In Figure 4B, a micrograph has been duplicated and presented as something else. ![file] , 
 After careful examination, we are very sorry that we uploaded a wrong photo when we contributed. We didn t do it on purpose. Our results were authentic and there was no fraud. If necessary, we can provide the correct picture again. Thank you for pointing it out. We will try our best to avoid this kind of mistakes in future contributions. Once again, I apologize for this oversight. ,
Calpain activity is generally elevated during transformation but has oncogene-specific biological functions
Authors: N O Carragher
B D Fonseca
M C Frame
Journal: Neoplasia (2004)
Discipline: CLINICAL MEDICINE
Keywords: oncogene; calpain; transformation; v-Src; v-Jun
Affiliations: The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Glasgow G61 1BD, Scotland, UK. 

Abstract:  Several oncogene and tumor-suppressor gene products are known substrates for the calpain family of cysteine proteases, and calpain is required for transformation by v-src and tumor invasion. Thus, we have now addressed whether calpain is generally associated with transformation and how calpain contributes to oncogene function. Our results demonstrate that calpain activity is enhanced upon transformation induced by the v-Src, v-Jun, v-Myc, k-Ras, and v-Fos oncoproteins. Furthermore, elevated calpain activity commonly promotes focal adhesion remodelling, disruption of actin cytoskeleton, morphological transformation, and cell migration, although proteolysis of target substrates (such as focal adhesion kinase, talin, and spectrin) is differently specified by individual oncoproteins. Interestingly, v-Fos differs from other common oncoproteins in not requiring calpain activity for actin/adhesion remodelling or migration of v-Fos transformed cells. However, anchorage-independent growth of all transformed cells is sensitive to calpain inhibition. In addition, elevated calpain activity contributes to oncogene-induced apoptosis associated with transformation by v-Myc. Taken together, these studies demonstrate that calpain activity is necessary for full cellular transformation induced by common oncoproteins, but has distinct roles in oncogenic events induced by individual transforming proteins. Thus, targeting calpain activity may represent a useful general strategy for interfering with activated proto-oncogenes in cancer cells. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than expected. ![file] , 
 ![file] , 
 Figure 7B. Much more similar than expected. ![file] , 
 #3 Thank you for highlighting these errors. We will contact the journal to discuss next steps and a potential note correction. ,
Pathogenic mechanism of miR-21 in autoimmune lymphoid hyperplasia syndrome
Authors: Yonglong Yan
Fang Li
Xiaoran Ning
Xinna Deng
Jingjing Cao
Journal: Oncology Letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: B cells at the germinal center; Fas; autoimmune lymphoid hyperplasia syndrome; homeostatic proliferation; miR-21.
Affiliations: Department of Rheumatology, Hebei Province General Hospital, Shijiazhuang, Hebei 050051, P.R. China., Department of Medical Oncology, Hebei Province General Hospital, Shijiazhuang, Hebei 050051, P.R. China.

Abstract:  miR-21 plays an important role in immune responses and inflammatory diseases, but the mechanism of action of miR-21 in autoimmune lymphoid hyperplasia syndrome still remains unclear. The aim of the present study was to assess the mechanism of miR-21 in autoimmune disease, particularly, the autoimmune lymphoid hyperplasia syndrome. The pathology and immunity-related phenotypes of miR-21 transgenic mice, and the lymphocyte subsets were analyzed. The related T cell subsets and germinal center B (GCB) cells generated at the germinal center were detected with flow cytometry. The target genes of miR-21 were evaluated with the luciferase reporter gene method. The homeostatic proliferation of the lymphocytes was detected with the EdU incorporation assay. Inflammatory infiltration occurred to the lung and liver of the transgenic mice at 8 weeks. The frequency of the regulatory helper T cells decreased slightly. Significantly increased double negative T cells were observed in the spleen of the transgenic mice (P&lt;0.05). The immunoglobulins IgG1, IgG2a, IgG2b, and IgG3 in the serum of the transgenic mice aged 8 weeks were significantly higher than those in the wild-type mice aged 8 weeks (P&lt;0.05). The percentages of the GCB cells in the peripheral lymphoid organs such as lymph nodes, mesenteric lymph nodes, PP and spleen in the transgenic mice aged 8-52 weeks increased significantly (P&lt;0.05). The percentage (26.32%) of the newly-formed GCB cells derived from transgenic mice was significantly higher than that (3.87%) of the GCB cells derived from the wild-type mice. miR-21 played a role of negative feedback regulation by inhibiting the NF-κB signal pathway. The highly-expressed miR-21 B cells promoted homeostatic proliferation of the T cells. miR-21 can promote homeostatic proliferation of lymphocytes by inhibiting the NF-κB signal pathway. 

Retracted: No

PubPeer comments:
  Figure 4. - miR-21 downregulates the Fas protein expression in GCB cells. (A) Fas protein was highly expressed in wild-type mice. Overexpression of miR-21 significantly reduced Fas protein expression in GCB cells . It is not a big deal, but two panels appear to be duplicates. ![file] ,
Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis
Authors: Olivier Chazouillères
Chantal Housset
Saint-Antoine IBD Network
Christophe Corpechot
Harry Sokol
Marjolène Straube
Sarah Jegou
Astrid Kemgang
Sara Lemoinne
Karima Ben Belkacem
Journal: Gut (2020)
Discipline: CLINICAL MEDICINE
Keywords: fungi; gut microbiota; inflammatory bowel disease; primary sclerosing cholangitis.
Affiliations: Centre de Recherche Saint-Antoine (CRSA), Sorbonne Université, INSERM, Paris, France.

Abstract:  Objective: Patients with primary sclerosing cholangitis (PSC) were previously shown to display a bacterial gut dysbiosis but fungal microbiota has never been examined in these patients. The aim of this study was to assess the fungal gut microbiota in patients with PSC. Design: We analysed the faecal microbiota of patients with PSC and concomitant IBD (n=27), patients with PSC and no IBD (n=22), patients with IBD and no PSC (n=33) and healthy subjects (n=30). Bacterial and fungal composition of the faecal microbiota was determined using 16S and ITS2 sequencing, respectively. Results: We found that patients with PSC harboured bacterial dysbiosis characterised by a decreased biodiversity, an altered composition and a decreased correlation network density. These alterations of the microbiota were associated with PSC, independently of IBD status. For the first time, we showed that patients with PSC displayed a fungal gut dysbiosis, characterised by a relative increase in biodiversity and an altered composition. Notably, we observed an increased proportion of Exophiala and a decreased proportion of Saccharomyces cerevisiae. Compared with patients with IBD and healthy subjects, the gut microbiota of patients with PSC exhibited a strong disruption in bacteria-fungi correlation network, suggesting an alteration in the interkingdom crosstalk. Conclusion: This study demonstrates that bacteria and fungi contribute to gut dysbiosis in PSC. 

Retracted: No

PubPeer comments:
 There are medium indications of contamination in this publication. The bacterial section show Rhizobia, which are most likely contaminants, but otherwise the profile looks like to be expected for gut content. The fungal section shows Alternaria (major plant pathogen), Davidiella (plant pathogen), Monographella (plant pathogen), Fusarium (plant pathogen) and Cordycipitaceae (plant pathogen), but the majority ( 50%) of the data looks likely for gut content. The fungal section is more likely to be affected by contamination, since the fungal part of the gut microbiota is only minor. ,
S100A7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formation
Authors: Hari K Bhat
Kevin McHugh
Kornelia Polyak
Vikram Paruchuri
Anil Prasad
Ramesh K Ganju
Journal: PloS one (2008)
Discipline: Multidisciplinary
Keywords: S100A7; EGF; tumorigenic effects; HER+ high-grade tumors; molecular mechanisms
Affiliations: Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Abstract:  S100A7 is a small calcium binding protein, which has been shown to be differentially expressed in psoriatic skin lesions, as well as in squamous cell tumors of the skin, lung and breast. Although its expression has been correlated to HER+ high-grade tumors and to a high risk of progression, the molecular mechanisms of these S100A7-mediated tumorigenic effects are not well known. Here, we showed for the first time that epidermal growth factor (EGF) induces S100A7 expression in both MCF-7 and MDA-MB-468 cell lines. We also observed a decrease in EGF-directed migration in shRNA-downregulated MDA-MB-468 cell lines. Furthermore, our signaling studies revealed that EGF induced simultaneous EGF receptor phosphorylation at Tyr1173 and HER2 phosphorylation at Tyr1248 in S100A7-downregulated cell lines as compared to the vector-transfected controls. In addition, reduced phosphorylation of Src at tyrosine 416 and p-SHP2 at tyrosine 542 was observed in these downregulated cell lines. Further studies revealed that S100A7-downregulated cells had reduced angiogenesis in vivo based on matrigel plug assays. Our results also showed decreased tumor-induced osteoclastic resorption in an intra-tibial bone injection model involving SCID mice. S100A7-downregulated cells had decreased osteoclast number and size as compared to the vector controls, and this decrease was associated with variations in IL-8 expression in in vitro cell cultures. This is a novel report on the role of S100A7 in EGF-induced signaling in breast cancer cells and in osteoclast formation. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than you would expect. https: imgur.com 8UKKOAq ,
Regulation of DNA methylation in human breast cancer. Effect on the urokinase-type plasminogen activator gene production and tumor invasion
Authors: Moshe Szyf
Yongjing Guo
Julienne Gladu
Shafaat A Rabbani
Pouya Pakneshan
Andrew Slack
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: uPA; DNA methylation; breast cancer; gene expression; CpG dinucleotides
Affiliations: Departments of Medicine and Pharmacology, McGill University Health Center, Montreal, Quebec H3A 1A1, Canada.

Abstract:  Urokinase-type plasminogen activator (uPA) is a member of the serine protease family and can break down various components of the extracellular matrix to promote growth, invasion, and metastasis of several malignancies including breast cancer. In the current study we examined the role that the DNA methylation machinery might be playing in regulating differential uPA gene expression in breast cancer cell lines. uPA mRNA is expressed in the highly invasive, hormone-insensitive human breast cancer cell line MDA-MB-231 but not in hormone-responsive cell line MCF-7. Using methylation-sensitive PCR, we show that 90% of CpG dinucleotides in the uPA promoter are methylated in MCF-7 cells, whereas fully demethylated CpGs were detected in MDA-MB-231 cells. uPA promoter activity, which is directly regulated by the Ets-1 transcription factor, is inhibited by methylation as determined by uPA promoter-luciferase reporter assays. We then tested whether the state of expression and methylation of the uPA promoter correlates with the global level of DNA methyltransferase and demethylase activities in these cell lines. We show that maintenance DNA methyltransferase activity is significantly higher in MCF-7 cells than in MDA-MB-231 cells, whereas demethylase activity is higher in MDA-MB-231 cells. We suggest that the combination of increased DNA methyltransferase activity with reduced demethylase activity contributes to the methylation and silencing of uPA expression in MCF-7 cells. The converse is true in MDA-MB-231 cells, which represents a late stage highly invasive breast cancer. The histone deacetylase inhibitor, Trichostatin A, induces the expression of the uPA gene in MDA-MB-231 cells but not in MCF-7 cells. This supports the hypothesis that DNA methylation is the dominant mechanism involved in the silencing of uPA gene expression. Taken together, these results provide insight into the mechanism regulating the transcription of the uPA gene in the complex multistep process of breast cancer progression. 

Retracted: No

PubPeer comments:
 Figure 1. Much more similar than expected. ![file] ,
Mammalian PRP4 kinase copurifies and interacts with components of both the U5 snRNP and the N-CoR deacetylase complexes
Authors: Dasa Longman
Joseph Torchia
Wendy A Bickmore
Reinhard Lührmann
Heidi G E Sutherland
Evgeny M Makarov
Jeff J M Cowger
Graham Dellaire
Journal: Molecular and Cellular Biology (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: pre-mRNA processing; transcriptional regulation; PRP4 kinase; splicing; PRP4K
Affiliations: MRC-Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK., Department of Cellular Biochemistry, Max-Planck-Institute for Biophysical Chemistry, Gottingen, Germany, Department of Pharmacology and Toxicology and Oncology, Cancer Research Laboratories, London Regional Cancer Centre, The University of Western Ontario, London, Ontario, Canada, MRC-Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom

Abstract:  A growing body of evidence supports the coordination of pre-mRNA processing and transcriptional regulation. We demonstrate here that mammalian PRP4 kinase (PRP4K) is associated with complexes involved in both of these processes. PRP4K is implicated in pre-mRNA splicing as the homologue of the Schizosaccharomyces pombe pre-mRNA splicing kinase Prp4p, and it is enriched in SC35-containing nuclear splicing speckles. RNA interference of Caenorhabditis elegans PRP4K indicates that it is essential in metazoans. In support of a role for PRP4K in pre-mRNA splicing, we identified PRP6, SWAP, and pinin as interacting proteins and demonstrated that PRP4K is a U5 snRNP-associated kinase. In addition, BRG1 and N-CoR, components of nuclear hormone coactivator and corepressor complexes, also interact with PRP4K. PRP4K coimmunoprecipitates with N-CoR, BRG1, pinin, and PRP6, and we present data suggesting that PRP6 and BRG1 are substrates of this kinase. Lastly, PRP4K, BRG1, and PRP6 can be purified as components of the N-CoR-2 complex, and affinity-purified PRP4K/N-CoR complexes exhibit deacetylase activity. We suggest that PRP4K is an essential kinase that, in association with the both U5 snRNP and N-CoR deacetylase complexes, demonstrates a possible coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation. 

Retracted: No

PubPeer comments:
 duplication ![file] , 
 Thanks for you note. We will look into this and prepare an erratum if needed. , 
 2021 correction. https: www.atsjournals.org doi full 10.1165 rcmb.v64erratum9 The authors of an article published in 2016 (1) were notified of an anomaly in the figures. In the published article, the phase contrast images of room airu2013exposed SIRT1-siRNAu2013 and NRF2-siRNAu2013transfected cells in Figure 3C and Figure 4C contain an area of duplication. The authors were unable to locate the original figures, but they have now provided a corrected version of Figure 3C and Figure 4C after repeating the experiments. The authors state that this correction does not change the scientific interpretation or conclusions reached in the article, and they apologize for this error. ,
Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion
Authors: Bin Xu
Yu Deng
Chang Liu
Can Wang
Zhao-Fa Xu
Wei Liu
Zhuo Ma
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Manganese; SNARE complex; Calpains; SNAP-25; Neurotransmitter release
Affiliations: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, People's Republic of China., Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, People's Republic of China. .

Abstract:  Overexposure to manganese (Mn) could disrupt neurotransmitter release via influencing the formation of SNARE complex, but the underlying mechanisms are still unclear. A previous study demonstrated that SNAP-25 is one of substrate of calpains. The current study investigated whether calpains were involved in Mn-induced disorder of SNARE complex. After mice were treated with Mn for 24 days, Mn deposition increased significantly in basal nuclei in Mn-treated and calpeptin pre-treated groups. Behaviorally, less time spent in the center of the area and decreased average velocity significantly in an open field test after 24 days of Mn exposure. With the increase in MnCl2 dosage, intracellular Ca2+ increased significantly, but pretreatment with calpeptin caused a dose-dependent decrease in calpains activity. There were fragments of N-terminal of SNAP-25 protein appearance in Mn-treated groups, but it is decreased with pretreatment of calpeptin. FM1-43-labeled synaptic vesicles also provided evidence that the treatment with Mn resulted in increasing first and then decreasing, which was consistent with Glu release and the 80 kDa protein levels of SNARE complexes. In summary, Mn induced the disorder of neurotransmitter release through influencing the formation of SNARE complex via cleaving SNAP-25 by overactivation of calpains in vivo. 

Retracted: No

PubPeer comments:
 I m confused about Figure 2. Several images appear to overlap after rotation and resizing. Scale bars and legend seem to indicate the same magnification was used for all. *** ![file] ![file] ,