PReD-Bench/PRed-Bench huggingface dataset:
Imbalance of local bone metabolism in inflammatory arthritis and its reversal upon tumor necrosis factor blockade: direct analysis of bone turnover in murine arthritis
Authors: Birgit Tuerk
Josef S Smolen
Georg Schett
Kurt Redlich
Jochen Zwerina
Journal: Arthritis research & therapy (2006)
Discipline: CLINICAL MEDICINE
Keywords: Chronic arthritis; bone resorption; osteoclastogenesis; osteoblast function; inflammatory arthritis
Affiliations: Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. 

Abstract:  Chronic arthritis typically leads to loss of periarticular bone, which results from an imbalance between bone formation and bone resorption. Recent research has focused on the role of osteoclastogenesis and bone resorption in arthritis. Bone resorption cannot be observed isolated, however, since it is closely linked to bone formation and altered bone formation may also affect inflammatory bone loss. To simultaneously assess bone resorption and bone formation in inflammatory arthritis, we developed a histological technique that allows visualization of osteoblast function by in-situ hybridization for osteocalcin and osteoclast function by histochemistry for tartrate-resistant acid phosphatase. Paw sections from human tumor necrosis factor transgenic mice, which develop an erosive arthritis, were analyzed at three different skeletal sites: subchondral bone erosions, adjacent cortical bone channels, and endosteal regions distant from bone erosions. In subchondral bone erosions, osteoclasts were far more common than osteoblasts. In contrast, cortical bone channels underneath subchondral bone erosions showed an accumulation of osteoclasts but also of functional osteoblasts resembling a status of high bone turnover. In contrast, more distant skeletal sites showed only very low bone turnover with few scattered osteoclasts and osteoblasts. Within subchondral bone erosions, osteoclasts populated the subchondral as well as the inner wall, whereas osteoblasts were almost exclusively found along the cortical surface. Blockade of tumor necrosis factor reversed the negative balance of bone turnover, leading to a reduction of osteoclast numbers and enhanced osteoblast numbers, whereas the blockade of osteoclastogenesis by osteoprotegerin also abrogated the osteoblastic response. These data indicate that bone resorption dominates at skeletal sites close to synovial inflammatory tissue, whereas bone formation is induced at more distant sites attempting to counter-regulate bone resorption. 

Retracted: No

PubPeer comments:
 image duplication  Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway
Authors: Seong A Kang
Shomit S Sengupta
Anne E Carmack
Katherine L Madden
Thurl E Harris
David A Guertin
Timothy R Peterson
David M Sabatini
Brian N Finck
Eric Balderas
Anne E Carpenter
Journal: Cell (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mTORC1; SREBP; lipin 1; protein synthesis; autophagy
Affiliations: Whitehead Institute for Biomedical Research, Koch Center for Integrative Cancer Research at MIT, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Abstract:  The nutrient- and growth factor-responsive kinase mTOR complex 1 (mTORC1) regulates many processes that control growth, including protein synthesis, autophagy, and lipogenesis. Through unknown mechanisms, mTORC1 promotes the function of SREBP, a master regulator of lipo- and sterolgenic gene transcription. Here, we demonstrate that mTORC1 regulates SREBP by controlling the nuclear entry of lipin 1, a phosphatidic acid phosphatase. Dephosphorylated, nuclear, catalytically active lipin 1 promotes nuclear remodeling and mediates the effects of mTORC1 on SREBP target gene, SREBP promoter activity, and nuclear SREBP protein abundance. Inhibition of mTORC1 in the liver significantly impairs SREBP function and makes mice resistant, in a lipin 1-dependent fashion, to the hepatic steatosis and hypercholesterolemia induced by a high-fat and -cholesterol diet. These findings establish lipin 1 as a key component of the mTORC1-SREBP pathway. 

Retracted: No

PubPeer comments:
 Figure 4A: HMGCR and FDPS mRNA expression in DMSO and Torin1 seem to be exactly same u2013 even the error bars. Could the authors check please?  , 
 Hi there, I am the 1st author on this manuscript. Looking back at the original data it appears the SCD1 data wasnu2019t shown and instead the FDPS data was shown twice. The mistake appears to have happened when preparing the Illustrator file as the correct data appears similar such that I overlooked it. Iu2019ve attached a corrected Figure 4A. Thank you for finding this mistake. David will be following up shortly with the journal to correct it. Best regards, Tim Peterson  , 
 The rapa 24 bars are different. , 
 #2 Thanks to the author for honestly admitting that the SCD1 data were also wrong. Of note, the statistical significance for Rapa 24 is not there any more in the new SCD1 graph. Wouldn t that mean that the conclusions drawn for this gene are affected too? , 
 I agree with Curtobacterium Fangii. Moreover, in the new set of results, ACACA is no more statistical significant in 8h point. Supplemental Fig. 5A should represent an experiment with n=4, but no error bars are presented. Could authors check if this is a mistake?  , 
 Some results from Figure 4, don t match the results from the thesis https: dspace.mit.edu handle 1721.1 58293    ,
RETRACTED: Long non-coding RNA Mirt2 prevents TNF-Œ±-triggered inflammation via the repression of microRNA-101
Authors: Zhuan Zhong
Wei Quan
Chunyang Kang
Mingyang Kang
Yingying Han
Heming Gao
Journal: International Immunopharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: NF-Œ∫B; Parkinson's disease; TNF-Œ±; p38MAPK.
Affiliations: Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130000, Jilin, China., Department of Orthopaedics, The Second Hospital of Jilin University, Changchun 130000, Jilin, China., Department of General Medicine, Jilin Province People's Hospital, Changchun 130000, Jilin, China., Department of Orthopaedics, The Second Hospital of Jilin University, Changchun 130000, Jilin, China. Electronic address: .

Abstract:  Parkinson's disease is normally accompanied by excessive inflammation. Myocardial infraction associated transcript 2 (Mirt2) has an activity to relieve inflammation in numerous cell types. Here, we aimed to investigate whether Mirt2 could elevate the resistance of SH-Sy5y cells to inflammation. Tumor necrosis factor alpha (TNF-Œ±) was used to induce inflammation in SH-Sy5y cells. Mirt2 overexpressed or silenced cells were established. MicroRNA-101 (miR-101) mimic was used to up-regulate miR-101. Viable and apoptotic cells as well as reactive oxidative species (ROS) were detected after staining. Proteins associated with apoptosis, interleukin (IL) and signaling regulators were evaluated by Western blot. IL secretion was assessed by ELISA. Mirt2 and miR-101 were determined by qRT-PCR. We discovered that TNF-Œ± weakened viability of SH-Sy5y cells and resulted in sensitivity to apoptosis with cleavage of PARP and caspase-3. Expression and secretion of IL-6 as well as generation of ROS were facilitated by TNF-Œ±. However, Mirt2 overexpression moderated TNF-Œ±-caused apoptosis associated with inflammation and oxidative stress. Mirt2 suppressed TNF-Œ±-induced accumulation of miR-101, and based on this Mirt2 exhibited anti-inflammatory roles. Additionally, TNF-Œ±-triggered phosphorylation of regulators was blocked by Mirt2 while restored by miR-101 mimic. In short Mirt2 overexpression exhibited anti-inflammatory properties through miR-101 suppression. Through down-regulating miR-101, Mirt2 blocked TNF-Œ±-triggered NF-Œ∫B/p38MAPK pathway. 

Retracted: Yes

PubPeer comments:
 Two images in Figure 5d appear to overlap. ***  ,
Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha
Authors: Anna Schinzel
Michael C Bassik
Claudio Hetz
Neal N Iwakoshi
Stanley J Korsmeyer
Laurie H Glimcher
Gabriel S Brandt
Ann-Hwee Lee
Paula Bernasconi
Jill Fisher
Bruno Antonsson
Journal: Science (2006)
Discipline: Multidisciplinary
Keywords: misfolded protein; endoplasmic reticulum; unfolded protein response; UPR; IRE1alpha
Affiliations: Howard Hughes Medical Institute, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA. 

Abstract:  Accumulation of misfolded protein in the endoplasmic reticulum (ER) triggers an adaptive stress response-termed the unfolded protein response (UPR)-mediated by the ER transmembrane protein kinase and endoribonuclease inositol-requiring enzyme-1alpha (IRE1alpha). We investigated UPR signaling events in mice in the absence of the proapoptotic BCL-2 family members BAX and BAK [double knockout (DKO)]. DKO mice responded abnormally to tunicamycin-induced ER stress in the liver, with extensive tissue damage and decreased expression of the IRE1 substrate X-box-binding protein 1 and its target genes. ER-stressed DKO cells showed deficient IRE1alpha signaling. BAX and BAK formed a protein complex with the cytosolic domain of IRE1alpha that was essential for IRE1alpha activation. Thus, BAX and BAK function at the ER membrane to activate IRE1alpha signaling and to provide a physical link between members of the core apoptotic pathway and the UPR. 

Retracted: No

PubPeer comments:
 Figure 8B contains a duplicated FACS plot  , 
 Thanks to the authors for the quick action. Correction submitted: CORRECTION ARTICLE Front. Immunol. | doi: 10.3389 fimmu.2021.672701  Corrigendum: Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer In the original article, there was a mistake a duplication of one dot plot in Figure 8B as published. The corrected Figure 8B appears below. 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. ,
Regulation of MYC expression and differential JQ1 sensitivity in cancer cells
Authors: Cheng-Ming Chiang
David H Price
Ronald Conaway
Joan Conaway
James E Bradner
Ali Shilatifard
Ananda L Roy
Trent Fowler
Payel Ghatak
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: MYC expression; JQ1; tumor cells; Burkitt's lymphoma; Brd4
Affiliations: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America., Biochemistry Department, University of Iowa, Iowa City, Iowa, United States of America., Stowers Institute for Medical Research, Kansas City, Missouri, United States of America., Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America., Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America., Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America ; Program in Genetics, Sackler School of Biomedical Science, Tufts University School of Medicine, Boston, Massachusetts, United States of America ; Program in Immunology, Sackler School of Biomedical Science, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

Abstract:  High level MYC expression is associated with almost all human cancers. JQ1, a chemical compound that inhibits MYC expression is therapeutically effective in preclinical animal models in midline carcinoma, and Burkitt's lymphoma (BL). Here we show that JQ1 does not inhibit MYC expression to a similar extent in all tumor cells. The BL cells showed a ‚à?0% decrease in MYC transcription upon treatment with JQ1, however, no corresponding reduction was seen in several non-BL cells. Molecularly, these differences appear due to requirements of Brd4, the most active version of the Positive Transcription Elongation Factor B (P-TEFb) within the Super Elongation Complex (SEC), and transcription factors such as Gdown1, and MED26 and also other unknown cell specific factors. Our study demonstrates that the regulation of high levels of MYC expression in different cancer cells is driven by unique regulatory mechanisms and that such exclusive regulatory signatures in each cancer cells could be employed for targeted therapeutics. 

Retracted: No

PubPeer comments:
 Reported to the journal in April 2014, corrected in April 2015. The correction can be found here: https: journals.plos.org plosone article?id=10.1371 journal.pone.0126328 and it reads:  *There is an error in Fig 2 that appears to have occurred during the preparation of files after the manuscript was accepted. In Fig 2B, the blot for Brd4 incorrectly appears as a duplicate of P-Brd4. The authors have provided a corrected version of Fig 2 here.* Here is the original Figure 2, with the duplication marked with red boxes. I thank the authors for correcting this error.  ,
Inhibition of multiple myeloma‚Äëderived exosomes uptake suppresses the functional response in bone marrow stromal cell
Authors: Yongjiang Zheng
Jinheng Wang
Chenggong Tu
Jingwen Zhang
Journal: International Journal of Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: exosomes; uptake; endocytosis; multiple myeloma; bone marrow stromal cell.
Affiliations: Department of Hematology, The Third Affiliated Hospital of Sun Yat‚ÄëSen University, Guangzhou, Guangdong 510630, P.R. China, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China

Abstract:  The communication between multiple myeloma (MM) cells and bone marrow stromal cells (BMSCs) serves a pivotal role in MM progression by supporting MM cell growth, proliferation and drug resistance. An exosomes‚Äëbased endogenous transport system has been determined as a novel mechanism of this communication by revealing the capacity for exchange of functional components between cells. An exosomes transfer‚Äëmediated biological response in recipient cells is strongly determined by the detailed routes and mechanisms of exosomes internalization, which are diverse and can depend on surface molecules on the membrane of the vesicle and the recipient cell. Understanding the routes of exosomes uptake during MM cell‚ÄëBMSC communication is of great importance for the development of blocking strategies beneficial for MM treatment. In the present study, fluorescently‚Äëlabeled exosomes and pharmacological inhibitors, which are known to interfere with different internalization pathways, were used to characterize the cellular mechanisms involved in the uptake of MM cell‚Äëderived exosomes by BMSCs. MM cell‚Äëderived exosomes can promote BMSC viability and induce changes in multiple pro‚Äësurvival and pro‚Äëproliferation pathways in BMSCs. As determined by flow cytometry and confocal microscopy, the uptake of MM cell‚Äëderived exosomes proceeded primarily through endocytosis, via special caveolin‚Äëdependent endocytosis, and partially through macropinocytosis and membrane fusion. Furthermore, treatment with endocytosis inhibitors suppressed the exosomes‚Äëinduced changes in pathways in BMSCs. Collectively, these results indicate that endocytosis is the primary route of internalization of MM cell‚Äëderived exosomes by BMSCs and indicate that inhibition of exosomes uptake can interrupt the communication between MM cells and BMSCs and thus serve as a potential adjunctive strategy for MM treatment. 

Retracted: No

PubPeer comments:
 Figure 2C Left 3 panels of MDA-MB-231 may have some unexpected very similar patterns, marked in green and blue ovals  The whole picture is as below:  ,
Nanotechnology for multimodality treatment of cancer
Authors: Pei-Ying Zhang
Xiao-Ying Zhang
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: cancer; nanocarriers; nanomedicine; nanotechnology.
Affiliations: Nanjing University of Chinese Medicine, Information Institute, Nanjing, Jiangsu 221009, P.R. China., Department of Cardiology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China.

Abstract:  Nanotechnology is the latest evolving field and its applications in medicine in recent decades has shown great potential. It has also given a new face to the therapeutics against cancer in recent years. The electronic databases of MEDLINE, EMBASE and PubMed were searched for recent studies, reporting the importance of nanomedicine. The concluding remarks of the above papers mostly confirmed the growing potential of nanomedicine, particularly in the field of cancer. Furthermore, nanomedicine has been observed to promote the therapeutic effect of agents by formulating them into nanocarriers. Delivery of the therapeutic agents via nanodelivery systems is dedicated to solving problems in traditional anticancer agents, including formulation in the physiological environment, their accumulation in tumor, and their adverse side effect in normal organs. The present review focused on the latest updates on nanotechnology in cancer. In conclusion, the future of any therapeutic option lies in the specific delivery of the particular drug. Additionally, this specific delivery may be achieved efficiently by nanodelivery systems and more studies should be conducted in this direction for the establishment of nanodelivery systems as gold standard delivery modules in clinical setting. 

Retracted: Yes

PubPeer comments:
 Two sets of images in Figure 2 appear to be repeated. In one case (red), the inset is different. ***  ,
Long noncoding RNA HOTAIR promotes the proliferation and metastasis of osteosarcoma cells through the AKT/mTOR signaling pathway
Authors: Baotong Ma
Zhe Zhao
Enqi Li
Jinli Zhang
Journal: Experimental and Therapeutic Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: Hox transcript antisense intergenic RNA; long non-coding RNAs; metastasis; osteosarcoma; proliferation.
Affiliations: Department of Orthopaedic Trauma, Tianjin Hospital, Tianjin 300211, P.R. China., Department of Surgery of Traditional Chinese Medicine, Tianjin Hospital, Tianjin 300211, P.R. China.

Abstract:  It has been proven that long non-coding (lnc)RNAs serve an important role in the tumorigenesis and development of several types of human malignancy. Previous studies have demonstrated that the lncRNA Hox transcript antisense intergenic RNA (HOTAIR) is involved in the development various types of cancer, including osteosarcoma (OS). However, the underlying mechanisms by which it has an affect are still largely unknown. In the present study, it was observed that the expression of HOTAIR was significantly upregulated in OS tissues compared to matched adjacent normal tissues, using reverse transcription-quantitative polymerase chain reaction analysis. HOTAIR was silenced using specific small interfering RNA (siRNA/siR), siR-HOTAIR, in order to investigate its role in regulating OS cell proliferation, apoptosis, migration and invasion. siR-HOTAIR inhibited the proliferation of MG-63 cells due to the induction of G1 phase arrest. In addition, the results of in vitro assays demonstrated that the suppression of HOTAIR in MG-63 OS cells significantly reduced migration and invasion. The silencing of HOTAIR also significantly decreased the expression of matrix metalloproteinase (MMP) 2 and MMP9, but increased E-cadherin expression through regulating the RAC Œ± serine/threonine protein kinase-mammalian target of rapamycin signaling pathway. The results indicated that siR-HOTAIR may be a potential OS therapy. 

Retracted: No

PubPeer comments:
  Figure 4. HOTAIR silencing significantly reduces the migration and invasion of MGu201163 cells. (A) MGu201163 cells were transfected with siRu2011HOTAIR or siRu2011NC for 48 h and images were taken using a light microscope. Magnification, x200. A Transwell assay was performed for 48 h .  Red, orange and yellow-framed Invasion panels can also be found in Figure 5A of [Guo et al (2018)] .  The impact of lncRNA NEAT1 siRNA on HeLa cell invasion .  They can also be found in Fig 6 (TPC-1 section) of [Zhao et al (2016)] ,  The invasion ability of TPC-1 ... cells in each group by transwell assay after transfection (u00d7200). (A) blank group; (B) negative control (NC) group; (C) si-ANRIL group; (D) si-TGF-u03b21 group; (E) si-ANRIL + si-TGF-u03b21 group .  The unframed *Migration* panels appear in Fig 5 of Zhao et al.  The earliest appearance of these images appears to be Figs 7 and 12 from Li et al (2015) - below, shown at right.  ,
Effects of anti-VEGF agents on rat retinal M√ºller glial cells
Authors: Xinguang Yang
Yingli Wang
Qinhua Fan
Yannian Hui
Bin Guo
Journal: Molecular vision (2010)
Discipline: CLINICAL MEDICINE
Keywords: anti-rat vascular endothelial growth factor antibody; bevacizumab; rat retinal M√ºller glial cells; in vivo; in vitro
Affiliations: Bayi hospital, Department of ophthalmology, Yang Gongjin, Nanjing, Jiangsu, China. 

Abstract:  Purpose: To evaluate the effects of an anti-rat vascular endothelial growth factor antibody (ARVA) and bevacizumab (Avastin) on rat retinal M√ºller glial cells (RMGCs) in vivo and in vitro. Methods: Rat RMGCs were identified and cultivated, and were then treated with bevacizumab (0.1, 0.25, and 1 mg/ml), ARVA (0.1, 0.5, and 1 microg/ml), or 1 mg/ml of rat immunoglobulin G (IgG) for 12, 24, 48, and 72 h. The numbers of viable RMGCs were determined using a trypan blue dye exclusion assay and a methyl thiazolyl tetrazolium colorimetric assay. In the in vivo study, the rats received intravitreal injections of 5 microl bevacizumab (3.75 mg/ml), ARVA (15 microg/ml), and rat IgG (1 mg/ml). The electroretinogram was recorded. Seven days after the injections, histopathologic changes and glial fibrillary acidic protein expression of RMGCs in the retina were analyzed by immunohistochemistry with hematoxylin-eosin and fluorescent staining. Results: After exposure to bevacizumab at various concentrations for various periods of time, the stained cell numbers and optical density values of mitochondrial dehydrogenase activity of RMGCs had no significant differences (p&gt;0.05) from those of the control group and IgG medium. In the stained cells, ARVA demonstrated a dose-dependent increase. Compared with those treated for 12 and 24 h, the increase of stained cells treated with 0.5 and 1 microg/ml ARVA at 48 and 72 h was very significant (p&lt;0.01). The optical densities of RMGCs exposed to 0.5 and 1 microg/ml of ARVA at 48 and 72 h were significantly lower than cells exposed to a fresh culture medium (p&lt;0.01). The histology of both treated and control eyes after intravitreal injection was similar and showed no anatomic signs of toxicity. There were no obvious glial fibrillary acidic protein upregulations of RMGCs in all groups. The scotopic electroretinogram responses to flashes of light in the control and treated eyes had similar b-wave amplitudes. Conclusions: Intravitreal bevacizumab and ARVA had no short-term, direct retinal toxicity in rats. Bevacizumab exerts no inhibition on rat RMGCs, while ARVA at higher doses (over 0.5 microg/ml) may be harmful to the growth of RMGCs. 

Retracted: No

PubPeer comments:
 image duplication  Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Upregulation of long noncoding RNA RP4 exacerbates hypoxia injury in cardiomyocytes through regulating miR-939/Bnip3/Wnt/Œ≤-catenin pathway
Authors: Hua Zhou
Honglin Guo
Qian Liu
Jijie Xu
Hao Chi
Yaoyao Wu
Jingfeng Rong
Ting Mu
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bnip3; Hypoxia-induced myocardial injury; RP4; Wnt/Œ≤-catenin pathway; long noncoding RNA
Affiliations: a Department of Medicine Cardiovascular, Luoyang Central Hospital Affiliated to Zhengzhou University , Luoyang , Henan , China., b Institute of Cardiovascular Research, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine , Shanghai , China., c Department of Cardiovascular, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine , Shanghai , China., d Department of Cardio-Thoracic Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine , Shanghai , China.

Abstract:  This research planned to dig the impacts and potential principles of long noncoding RNA RP4 onH9c2 cell injury induced by hypoxia. The H9c2 cardiac muscle cells were cultured under 3% O2 concentration to induce hypoxia injury, followed by detection of RP4 expression. RP4 was then overexpressed and silenced to investigate its effects on cell injury induced by hypoxia. The potential correlation between RP4 and miR-939, between miR-939 and Bnip3, and between RP4/miR-939/Bnip3 axis and Wnt/Œ≤-catenin pathway activation were explored. Biological processes (suppressed cell viability, migration and invasion, but enhanced cell apoptosis) were changed by hypoxia. Upregulation of RP4 enhanced hypoxia-produced damage in H9c2 cells. Additionally, miR-939 expression was opposite regulated by RP4, and miR-939 mimic abrogated the influences of pc-RP4 on enhanced hypoxia damage in H9c2 cells. Moreover, Bnip3 was targeted by miR-939 and their correlation is negative. Furthermore, upregulation of RP4 exacerbated hypoxia-produced injury in H9c2 cells by sensitizing Wnt/Œ≤-catenin signals in H9c2 cells, which was regulated by miR-939/Bnip3 axis. Our findings reveal that RP4 is highly expressed in the hypoxia-resulted H9c2 cells. Enhanced expression of RP4 may exacerbate hypoxia injury in cardiomyocytes through regulating miR-939/Bnip3 axis-mediated briskness of Wnt/Œ≤-catenin signals. Our study will offer a fresh theoretical basis for the treatment of ischemic myocardial injury. 

Retracted: No

PubPeer comments:
 Fig 2:  These stylised WBs and flow-cytometry plots are hallmarks of the [ tadpole papermill ] . ,
A novel herbometallic nanodrug has the potential for antibacterial and anticancer activity through oxidative damage
Authors: Kunal Pal
Sutapa Som Chaudhury
Chitrangada Das Mukhopadhyay
Prashanta Kumar Sarkar
Bhuban Ruidas
Journal: Nanomedicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: antimicrobial activity; apoptosis; cellular redox balance; herbometallic drug; peptidoglycan layer.
Affiliations: Centre for Healthcare Science &amp; Technology, Indian Institute of Engineering Science &amp; Technology, Shibpur, Howrah 711103, West Bengal, India, Department of Life Science &amp; Bio-technology, Jadavpur University, Kolkata 700032, West Bengal, India, Department of Pharmacy, J. B. Roy State Ayurvedic Medical College &amp; Hospital, Kolkata 700004, West Bengal, India

Abstract:  Aim: Preparation of a herbometallic nano-drug, Rasa Manikya nanoparticle (RMNP) and investigation of its antimicrobial, and anticancer activity. Materials &amp; methods: Physicochemical characterizations of RMNP were performed using different analytical methods. The antimicrobial and anticancer potential of RMNPs were assessed by an in vitro cellular assay. Bacterial cell wall lysis was observed by field emission scanning electron microscopy and mitochondrial metabolism alteration factor was measured via standard method. Results: Physicochemical analysis confirmed that RMNP was rich in mineral constituents. Synergistic effect of RMNPs enhanced lysis of bacterial peptidoglycan layers and impaired cellular redox balance, GSH/NADPH level followed by induction of cell apoptosis. Conclusion: The present study confirms that RMNP can be used as a dual therapeutic option for combating drug-resistant microbial strains and breast cancer. 

Retracted: No

PubPeer comments:
  The publication  A novel herbometallic nanodrug has the potential for antibacterial and anticancer activity through oxidative damage (10.2217 nnm-2018-0187) has some images replicated from  An In Vivo Study for Targeted Delivery of Curcumin in Human Triple Negative Breast Carcinoma Cells Using Biocompatible PLGA Microspheres Conjugated with Folic Acid (10.1166 jnn.2019.16292). **Fig. 5C MDA-MB-468 20u00b5g ml**, **Fig. 5D MDA-MB-468 40u00b5g ml**, of **DOI 10.2217 nnm-2018-0187** are similar to images **Fig. 5 MDA-MB-468 CCM**, **Fig. 5 MDA-MB-468 FA** of **DOI 10.1166 jnn.2019.16292** respectively. **Fig. 7E and 7F** of **DOI 10.2217 nnm-2018-0187** are supposed to be similar but are clearly not. ,
Synergistic effect of celecoxib on TRAIL-induced apoptosis in hepatocellular carcinoma cells
Authors: Guoyue Lu
Bai Ji
Guangyi Wang
Chunhai Hao
Feng Wei
Yahui Liu
Journal: Cancer Investigation (2010)
Discipline: CLINICAL MEDICINE
Keywords: TRAIL; cancer therapeutics; hepatocellular carcinomas; celecoxib; camptothecin
Affiliations: Department of General Surgery, The First Clinical Hospital, Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, People's Republic of China.

Abstract:  Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is currently under clinical development as a cancer therapeutic because it can induce apoptosis selectively in cancer cells. The vast majority of hepatocellular carcinomas (HCC), however, are resistant to TRAIL. In search of cancer therapeutics that can overcome TRAIL resistance, we show here that celecoxib and camptothecin can sensitize TRAIL-resistant HCC cell lines, HepG2 and Hep3B, to TRAIL-induced apoptosis through downregulation of cellular Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (c-FLIP) and cleavage of caspase-8 and caspase-3 in the HCC cells. The study suggests a framework for TRAIL-based combination treatment of HCC. 

Retracted: No

PubPeer comments:
 Figure 3. * Green boxes: Two ERK1 2 panels appear to look more similar than expected. Reported to the journal in October 2015, with a reminder in September 2017.  ,
miR-539 inhibits human colorectal cancer progression by targeting RUNX2
Authors: Jingjing Liu
Weidong Jiang
Shutao Zhao
Songhe Li
Jiaming Zhu
Dacheng Wen
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Colorectal cancer; Invasion; MicroRNAs; Proliferation; RUNX2
Affiliations: Department of Gastrointestinal nutrition and hernia surgery, the Second Hospital of Jilin University, Nanguan District, Changchun 130041, China., Department of Ophthalmology, the First Hospital of Jilin University, Chaoyang District, Changchun 130021, China. Electronic address: ., Department of Hepatobiliary and Pancreatic Surgery, the Second Hospital of Jilin University, Nanguan District, Changchun 130041, China.

Abstract:  Emerging evidence has shown that microRNAs (miRNAs) such as miR-539 play critical roles in carcinogenesis and progression in many types of cancer, including human colorectal cancer (CRC). However, the roles and underlying mechanism of miR-539 in CRC have not been well identified. The aims of this study were, therefore, to investigate the regulatory role and potential mechanism of miR-539 in human CRC. Here, we show that miR-539 expression is downregulated in CRC tissues and cell lines. The expression level of miR-539 is inversely associated with advanced clinical stage and lymph node metastasis. In vitro studies reveal that overexpression of miR-539 inhibits CRC cell proliferation and colony formation as well as migration and invasion; in vivo results demonstrate that overexpression of miR-539 dramatically reduces CRC xenograft tumor growth. Moreover, runt-related transcription factor 2 (RUNX2), a known oncogene, was identified as a target transcript of miR-539 in CRC by bioinformatic analysis, luciferase reporter assay, qPCR, and western blotting. RUNX2 expression levels were upregulated and inversely correlated with miR-539 expression in CRC tissues. Importantly, overexpression of RUNX2 without the 3'-untranslated region that is targeted by miR-539 partially reversed the inhibitory effect of miR-539 on CRC cell proliferation, migration, and invasion. Collectively, these findings demonstrate that miR-539 functions as a tumor suppressor in CRC, at least in part, by targeting RUNX2, supporting the targeting of the novel miR-539 as a potentially effective therapeutic approach for treatment of CRC. 

Retracted: No

PubPeer comments:
 Fig 6D.  The RUNX2 protein expression was determined in CRC xenograft tumors .  An error here, I think: 6D is a second copy of FIg 4D,  Restoration of miR-539 reduced the RUNX2 mRNA and RUNX2 protein expression levels in SW480 cells . The lane labels make more sense in that context. ,
The functional influences of common ABCB1 genetic variants on the inhibition of P-glycoprotein by Antrodia cinnamomea extracts
Authors: Ying-Yi Chen
Yu-Ning Teng
Chin-Chuan Hung
Ming-Jyh Sheu
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Antrodia cinnamomea; ethanolic extract; P-glycoprotein; ABCB1 genetic variants; efflux function
Affiliations: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan., Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan ; Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan.

Abstract:  Antrodia cinnamomea is a traditional healthy food that has been demonstrated to possess anti-inflammatory, antioxidative, and anticacer effects. The purpose of this study was to evaluate whether the ethanolic extract of A. cinnamomea (EEAC) can affect the efflux function of P-glycoprotein (P-gp) and the effect of ABCB1 genetic variants on the interaction between EEAC and P-gp. To investigate the mechanism of this interaction, Flp-In‚Ñ?293 cells stably transfected with various genotypes of human P-gp were established and the expression of P-gp was confirmed by Western blot. The results of the rhodamine 123 efflux assay demonstrated that EEAC efficiently inhibited wild-type P-gp function at an IC50 concentration of 1.51 ¬± 0.08 ¬µg/mL through non-competitive inhibition. The IC50 concentrations for variant-type 1236T-2677T-3435T P-gp and variant-type 1236T-2677A-3435T P-gp were 5.56 ¬± 0.49 ¬µg/mL and 3.33¬±0.67 ¬µg/mL, respectively. In addition, the inhibition kinetics of EEAC also changed to uncompetitive inhibition in variant-type 1236T-2677A-3435T P-gp. The ATPase assay revealed that EEAC was an ATPase stimulator and was capable of reducing verapamil-induced ATPase levels. These results indicate that EEAC may be a potent P-gp inhibitor and higher dosages may be required in subjects carrying variant-types P-gp. Further studies are required to translate this basic knowledge into clinical applications. 

Retracted: No

PubPeer comments:
 This paper has a 2014 correction due  to the release of confidential or copyrighted information . But a problem in Figure 1A appears to remain: Figure 1A. * Red boxes: several lanes within the P-gp panel appear to look similar to each other. * Blue boxes: several lanes within the b-actin panel appear to look similar to each other. Image made darker to bring out more details.  Reported to the journal in October 2015. , 
 Dear Professor: we appreciate your comments. Verification will be carried out and we will report to the journal as fast we can. , 
 Dear Professor: we appreciate your comments. Verification will be carried out and we will report to the journal as fast we can. ,
PHD inhibition mitigates and protects against radiation-induced gastrointestinal toxicity via HIF2
Authors: Cullen M Taniguchi
Todd F Atwood
Amato J Giaccia
Lei Xing
Yu Rebecca Miao
Erinn B Rankin
Anh N Diep
Colleen Wu
Journal: Science Translational Medicine (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Radiation-induced gastrointestinal toxicity; morbidity; mortality; diarrhea; water loss
Affiliations: Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA., Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA. .

Abstract:  Radiation-induced gastrointestinal (GI) toxicity can be a major source of morbidity and mortality after radiation exposure. There is an unmet need for effective preventative or mitigative treatments against the potentially fatal diarrhea and water loss induced by radiation damage to the GI tract. We report that prolyl hydroxylase inhibition by genetic knockout or pharmacologic inhibition of all PHD (prolyl hydroxylase domain) isoforms by the small-molecule dimethyloxallyl glycine (DMOG) increases hypoxia-inducible factor (HIF) expression, improves epithelial integrity, reduces apoptosis, and increases intestinal angiogenesis, all of which are essential for radioprotection. HIF2, but not HIF1, is both necessary and sufficient to prevent radiation-induced GI toxicity and death. Increased vascular endothelial growth factor (VEGF) expression contributes to the protective effects of HIF2, because inhibition of VEGF function reversed the radioprotection and radiomitigation afforded by DMOG. Additionally, mortality from abdominal or total body irradiation was reduced even when DMOG was given 24 hours after exposure. Thus, prolyl hydroxylase inhibition represents a treatment strategy to protect against and mitigate GI toxicity from both therapeutic radiation and potentially lethal radiation exposures. 

Retracted: No

PubPeer comments:
  ,
Preclinical antileukemia activity of JNJ-26481585, a potent second-generation histone deacetylase inhibitor
Authors: Zhihong Fang
William Stevenson
Janine Arts
Guillermo Garcia-Manero
Wei-Gang Tong
Yue Wei
Ming Zhang
Shao-Qing Kuang
Journal: Leukemia research (2010)
Discipline: CLINICAL MEDICINE
Keywords: Histone deacetylase inhibitors; cell cycle arrest; terminal differentiation; apoptosis; JNJ-26481585
Affiliations: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States.

Abstract:  Histone deacetylase (HDAC) inhibitors have been shown to induce cell cycle arrest, terminal differentiation, and apoptosis in a broad spectrum of human tumors and animal xenograft models. JNJ-26481585 is a hydroxamic acid derivative, second-generation pan-HDAC inhibitor that has demonstrated high potency in preclinical studies. In the current study, we demonstrated that JNJ-26481585 has antileukemia and molecular activity in leukemia cell lines and primary human leukemia cells. We also observed a synergistic effect between treatment with decitabine and JNJ-26481585. In conclusion, JNJ-26481585 is a potent second-generation pan-HDAC inhibitor with activity in human leukemia, and it is currently in clinical development. 

Retracted: No

PubPeer comments:
 In Figure 2, two of the western blots presented in this figure look surprisingly similar despite the samples are from different cell lines (U937 vs MOLT4 and THP1 vs HL60).  , 
 I don t think the images are identical, but they look like 2 different exposures of the same western blot. Here s a link to the high res image from the journal: https: ars.els-cdn.com content image 1-s2.0-S0145212609003713-gr2_lrg.jpg You can see that the shape of the bands is remarkably similar. In lane #3 of the U937 and MOLT4 there s a spot in exactly the same location for both samples, although it looks like one of images might have been stretched a bit. In both cases the lower panel looks like a longer exposure of the upper panel. ,
Enhanced magnetocaloric effect in Ni-Mn-Sn-Co alloys with two successive magnetostructural transformations
Authors: Mingfang Qian
Hehe Zhang
Lin Geng
Xuexi Zhang
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: magnetocaloric refrigeration; Co-doping; martensite transformation; magnetic properties; magnetocaloric effects
Affiliations: School of Materials Science and Engineering, Harbin Institute of Technology, Harbin, 150001, China. ., School of Materials Science and Engineering, Harbin Institute of Technology, Harbin, 150001, China.

Abstract:  High magnetocaloric refrigeration performance requires large magnetic entropy change ŒîS M and broad working temperature span ŒîT FWHM . A fourth element doping of Co in ternary Ni-Mn-Sn alloy may significantly enhance the saturation magnetization of the alloy and thus enhance the ŒîS M . Here, the effects of Co-doping on the martensite transformation, magnetic properties and magnetocaloric effects (MCE) of quaternary Ni47-xMn43Sn10Cox (x = 0, 6, 11) alloys were investigated. The martensite transformation temperatures decrease while austenite Curie point increases with Co content increasing to x = 6 and 11, thus broadening the temperature window for a high magnetization austenite (13.5, 91.7 and 109.1 A¬∑m2/kg for x = 0, 6 and 11, respectively). Two successive magnetostructural transformations (A ‚Ü?10 M and A ‚Ü?10 M + 6 M) occur in the alloy x = 6, which are responsible for the giant magnetic entropy change ŒîS M = 29.5 J/kg¬∑K, wide working temperature span ŒîT FWHM = 14 K and large effective refrigeration capacity RC eff = 232 J/kg under a magnetic field of 5.0 T. These results suggest that Ni40.6Mn43.3Sn10.0Co6.1 alloy may act as a potential solid-state magnetic refrigerant working at room temperature. 

Retracted: No

PubPeer comments:
 Figure 4 Two identical XRD patterns  ,
Thymosin beta4 induces angiogenesis through Notch signaling in endothelial cells
Authors: Geng Xu
Gang Cheng
Ying Zhou
Shumin Lv
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Thymosin beta4; Notch signaling pathway; angiogenesis; endothelial cells; VEGF
Affiliations: Department of Cardiology, The Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China.

Abstract:  Thymosin beta4 (TŒ≤4) has multi-functional roles in angiogenesis and arteriogenesis, but little is known about its mechanism. The Notch signaling pathway is important in regulation of angiogenic behavior of endothelial cells, in addition to vascular endothelial growth factor (VEGF). Whether, TŒ≤4 regulates angiogenesis through Notch signaling pathway is not clear. In this article, we evaluated the effect of Notch signaling in TŒ≤4-induced angiogenesis in human umbilical vein endothelial cell (HUVEC). Our results revealed that TŒ≤4 increased Notch1 and Notch4 expression in a dose and time-dependent manner. The inhibition of Notch1 or Notch4 with siRNA or the Notch receptor inhibitor DAPT significantly prevented TŒ≤4-induced HUVEC tube formation and lymphocyte transendothelial migration. The inhibition of Notch1 or Notch4 also blocked TŒ≤4-induced VEGF and HIF-1Œ± expression. VE-cadherin is the major endothelial adhesion molecule in the control of angiogenesis. TŒ≤4 significantly reduced VE-cadherin expression levels in HUVEC, while the inhibition of Notch signaling prevented TŒ≤4-induced VE-cadherin down-regulation. The results of this study suggest that TŒ≤4 induces HUVEC angiogenesis through Notch signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: The actin panel in Figure 2B looks similar to that in Figure 2C, if rotated 180 degrees. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today.  ,
Enhanced reversible redox activity of hemin on cellulose microfiber integrated reduced graphene oxide for H2O2 biosensor applications
Authors: Craig E Banks
Vijayalakshmi Velusamy
Sridharan Balu
Shih-Wen Chen
Thomas C K Yang
Selvakumar Palanisamy
Journal: Carbohydrate Polymers (2019)
Discipline: CHEMISTRY
Keywords: Cellulose microfibers; H(2)O(2) biosensor; Hemin; Peroxidase mimic; Redox electrochemistry
Affiliations: Division of Electrical and Electronic Engineering, School of Engineering, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, United Kingdom; Department of Chemical Engineering, National Taipei University of Technology, No. 1, Section 3, Chung-Hsiao East Road, Taipei City, Taiwan, ROC. Electronic address: ., Division of Electrical and Electronic Engineering, School of Engineering, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, United Kingdom. Electronic address: ., Department of Chemical Engineering, National Taipei University of Technology, No. 1, Section 3, Chung-Hsiao East Road, Taipei City, Taiwan, ROC., Department of Chemical Engineering, National Taipei University of Technology, No. 1, Section 3, Chung-Hsiao East Road, Taipei City, Taiwan, ROC. Electronic address: ., School of Science and the Environment, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, United Kingdom.

Abstract:  In recent years, the carbohydrate polymers incorporated composite materials have shown significant interest in the bioanalytical chemistry due to their enhanced catalytic performances of various enzymes or mimics. This paper reports the fabrication of novel H2O2 biosensor using a hemin immobilized reduced graphene oxide-cellulose microfiber composite (hemin/RGO-CMF). The RGO-CMF composite was prepared by the reduction of GO-CMF composite using vitamin C as a reducing agent. Various physio-chemical methods have applied for the characterization of RGO-CMF composite. Cyclic voltammetry results revealed that the hemin/RGO-CMF composite shows a better redox electrochemical behavior than hemin/RGO and hemin/GO-CMF. Under optimized conditions, the hemin/RGO-CMF composite exhibit a linear response to H2O2 in the concentration range from 0.06 to 540.6 ŒºM with the lower detection limit of 16 nM. The sensor also can able to detect the H2O2 in commercial contact lens solution and milk samples with functional recovery, which authenticates the potential ability in practical sensors. 

Retracted: No

PubPeer comments:
 Figure 1  (B) Raman spectra of GO, GO-CMF, RGO, and RGO-CMF . RGO and RGO-CMF spectra appear to be the same, with identical noise, differing only in vertical scale. Could the authors check?  Here s the RGO spectrum, compressed to 80% vertical scale and superimposed on RGO-CMF.  ,