PReD-Bench/PRed-Bench huggingface dataset:
Heparin Increases Food Intake through AgRP Neurons
Authors: Qianyun Xi
Canjun Zhu
Tao Wang
Yongliang Zhang
Yanlin He
Lina Wang
Qingyan Jiang
Yong Xu
Junguo Wu
Liusong Yang
Lulu Yu
Pingwen Xu
Xiaotong Zhu
Songbo Wang
Ping Gao
Gang Shu
Yexian Yuan
Xingcai Cai
Journal: Cell Reports (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AgRP; food intake; heparin; insulin receptor.
Affiliations: Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510640, China., Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Ave., Room 8070, Houston, TX 77030, USA., Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Ave., Room 8070, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: ., Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510640, China. Electronic address: .

Abstract:  Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin treatment increases food intake and body weight gain. By using electrophysiological, pharmacological, molecular biological, and chemogenetic approaches, we provide evidence that heparin increases food intake by stimulating AgRP neurons and increasing AgRP release. Our results support a model whereby heparin competes with insulin for insulin receptor binding on AgRP neurons, and by doing so it inhibits FoxO1 activity to promote AgRP release and feeding. Heparin may be a potential drug target for food intake regulation and body weight control. 

Retracted: No

PubPeer comments:
 Interesting but weight gain in humans due to heparin is very rare:  68,064 people reported to have side effects when taking Heparin. Among them, 385 people (0.57%) have Weight gain. https: www.ehealthme.com ds heparin weight-gain , 
 #1 Hello, I am Canjun Zhu, the first author of this article. Your question is very good, we have received many similar questions in the process of research. In my opinion, it is usually accompanied by interference of other cardiovascular diseases in clinic. In addition, factors such as concentration and time of use may lead to inconsistent results with mice. ,
Hepatitis C virus single-stranded RNA induces innate immunity via Toll-like receptor 7
Authors: Ying-Jun Guo
Bin Li
Yi-Liang Zhang
Shu-Han Sun
Journal: Journal of Hepatology (2009)
Discipline: CLINICAL MEDICINE
Keywords: HCV infection; innate immune responses; interferons; virus recognition; IFN induction
Affiliations: Department of Medical Genetics, Second Military Medical University, 800 Xiang'Yin Road, 200433 Shanghai, China.

Abstract:  Background/aims: Innate immune responses to HCV infection are triggered through host recognition of pathogen-associated molecular patterns. Interferons are critical for the protection against HCV infection. However, the pathways linking virus recognition to IFN induction remain poorly understood. Methods: Immune cells and Huh-7 cells were infected with HCV cell culture (HCVcc) or transfected with HCV-derived immunostimulatory RNA oligonucleotides (ORNs), and immune activation was assessed. Results: We found that HCVcc suppressed immune responses because the HCVcc protein impaired the PBMC and pDC responses. However, HCVcc genomic RNA had an immunostimulatory effect. HCV encodes G/U-rich ssRNA TLR7 ligands that significantly activate innate immunity, and induced IFN-alpha production. Moreover, HCV-derived ORNs also activated IRF7 and NF-kappaB in Huh-7 cells. In particular, the HCV 3'-UTR strongly induced cytokine production. Different lengths of polyuridine tract in the 3'-UTR of different HCV strains induced IFN-alpha production. These data demonstrate that the HCV-specific G/U fragment is a motif sequence, and is recognized by TLR7 as a PAMP. The requirement for TLR7 to recognize HCV RNA was confirmed using specific inhibitors, RNAi and by TLR7overexpression. Conclusion: These results provide an insight into the development of immune adjuvant for vaccines and for the production of new antiviral drugs. 

Retracted: No

PubPeer comments:
 Figure 5 appears to show some repetitive areas. On the left is the unmarked, original Figure 5B. On the right, a version where boxes of the same color highlight areas that look similar. I am looking forward to the authors clarification. ![file] ,
Protein Kinase D1 regulates focal adhesion dynamics and cell adhesion through Phosphatidylinositol-4-phosphate 5-kinase type-l γ
Authors: Peter Storz
Jason Long
Kun Ling
Nisha Durand
Heike Döppler
Ligia I Bastea
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Focal adhesions; Protein Kinase D1; turnover; cell adhesion; integrin engagement
Affiliations: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida 32224, USA., Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.

Abstract:  Focal adhesions (FAs) are highly dynamic structures that are assembled and disassembled on a continuous basis. The balance between the two processes mediates various aspects of cell behavior, ranging from cell adhesion and spreading to directed cell migration. The turnover of FAs is regulated at multiple levels and involves a variety of signaling molecules and adaptor proteins. In the present study, we show that in response to integrin engagement, a subcellular pool of Protein Kinase D1 (PKD1) localizes to the FAs. PKD1 affects FAs by decreasing turnover and promoting maturation, resulting in enhanced cell adhesion. The effects of PKD1 are mediated through direct phosphorylation of FA-localized phosphatidylinositol-4-phosphate 5-kinase type-l γ (PIP5Klγ) at serine residue 448. This phosphorylation occurs in response to Fibronectin-RhoA signaling and leads to a decrease in PIP5Klγs' lipid kinase activity and binding affinity for Talin. Our data reveal a novel function for PKD1 as a regulator of FA dynamics and by identifying PIP5Klγ as a novel PKD1 substrate provide mechanistic insight into this process. 

Retracted: No

PubPeer comments:
 Would the authors be so kind as to share the original uncropped scans for Figure 1b. Iu2019m concerned about the apparent lack of background features in one lane. *** Original ![file] *** Inverse, contrast enhanced ![file] , 
 Here is a scan of the original autorad. It is the last two lanes of the IP. The immunoprecipitation with IgG is a control and should not does not immunoprecipitate PKD1. Therefore there is no signal (lack of background). Best, P. ![file] , 
 Would you please show the original FAk autorad also for comparing the background of PKD1? Thanks. ![file] , 
 ![file] ,
Total lymphocyte count, neutrophil&ndash;lymphocyte ratio, and platelet&ndash;lymphocyte ratio as prognostic factors in advanced non&ndash;small cell lung cancer with chemoradiotherapy
Authors: Zhehai Wang
Dawei Chen
Haiyong Wang
Xinyu Song
Ma Yuan
Journal: Cancer Management and Research (2018)
Discipline: CLINICAL MEDICINE
Keywords: NLR; PLR; TLC; advanced NSCLC; chemoradiotherapy.
Affiliations: Department of Medical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China, ; ., School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, China., Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, Shandong, China., Department of Medical Oncology, Weihai Central Hospital, Weihai, Shandong, China.

Abstract:  Objective: The objective of this study was to investigate the prognostic significance and the efficacy evaluation of total lymphocyte count (TLC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in advanced non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy. Patients and methods: A total of 389 advanced NSCLC patients who received chemoradiotherapy from 2011 to 2016 were enrolled in this retrospective study. TLC, NLR, and PLR were analyzed with overall survival (OS). Survival data were identified with the Kaplan-Meier method and optimal cutoff values with receiver operating characteristic curves. Results: The median OS for all patients was 18.37 months. Pretreatment and median baseline TLC was 2.47×103/μL (±0.78); NLR, 3.15 (±3.96); and PLR, 143.82 (±91.77); corresponding cutoffs were 2.4, 3.4, and 136.1. Higher TLC was associated with superior median OS (21.78 vs 15.66 months, P&lt;0.001), and higher NLR and PLR with worse median OS (NLR: 14.13 vs 23.8 months, P&lt;0.001; PLR: 15.49 vs 22.04 months, P&lt;0.001). Conclusion: The lymphopenia indicators (TLC, NLR, and PLR) were significant prognostic indicators of survival in advanced NSCLC patients treated with chemoradiotherapy. 

Retracted: No

PubPeer comments:
 ![file] Fig.3A: As indidated, could the authors provide the original uncropped images for all the samples (n = 3)? , 
 Thank you for informing us about this figure. Because some of the Western blot bands were detected separately by the age of mice, we pieced together the images from the results of 3-, 6- and 10- month old mice without any intentional and deliberate manipulation. So we have re-integrated Figure 3, but the editor didnu2018t adopt this format. The attachment is the response to the editor of Aging and the figures which were not adopted by the editor.![] ![file] ![file] ,
The relationship between Aquaporin-2 protein levels in amniotic fluid and the fetal kidney in humans
Authors: Jinjin Feng
Xi Guo
Lu Wen
Shaohua Yan
Yan Chen
Yibo Wen
Jian Guo Wen
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Amniotic fluid; Fetus; Human; Kidney; aquaporin2.
Affiliations: Department of Pediatric Urodynamic Center& Henan Joint International Pediatric Urodynamic Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China., Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China., Department of Pediatric Urodynamic Center& Henan Joint International Pediatric Urodynamic Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address: .

Abstract:  Objectives: Aquaporin-2 (AQP2) is an important water channel protein that is expressed in the renal collecting duct and plays a key role in urine concentration and body water homeostasis. It has been demonstrated that the urinary excretion of AQP2 correlates strongly with its expression in the kidney in adult humans and rats. However, there have been no studies on the urinary excretion of AQP2 in human fetuses during development. Fetal urine is the main source of the amniotic fluid; we speculate that the level of AQP2 in the amniotic fluid could reflect the expression level of the AQP2 protein in the fetal kidney. The purpose of the present study was to explore the relationship between AQP2 in the amniotic fluid and that in the fetal kidney. Methods: In the present study, the concentration of the AQP2 protein in human amniotic fluid was measured by Enzyme-linked immunosorbent assay (ELISA) and its expression level in human fetal kidneys were examined by wastern blot and immunohistochemistry. Results: Both the expression level of AQP2 in the fetal kidney (F = 195.9, P &lt; 0.001) and the concentration of AQP2 in the amniotic fluid increased with gestational age (F = 1098, P &lt; 0.001). Moreover, the concentration of AQP2 in the amniotic fluid was positively correlated with its expression level in the fetal kidney (r = 0.872, P &lt; 0.0001). Conclusions: Our research indicates that AQP2 levels in the amniotic fluid may be used as a marker for AQP2 expression in the fetal kidney. 

Retracted: No

PubPeer comments:
 Figure 3a appears to have some repeated elements. Could the authors please post the original uncropped scans? Original and marked-up versions below. *** ![file] ,
Tyrosine phosphatase inhibitors combined with retinoic acid can enhance differentiation of neuroblastoma cells and trigger ERK- and AKT-dependent, p53-independent senescence
Authors: Andrew W Stoker
Shruti Daga
Owen Clark
Journal: Cancer Letters (2013)
Discipline: CLINICAL MEDICINE
Keywords: Retinoic acid; differentiation therapy; neuroblastoma; vanadium-based PTP inhibitors; senescence
Affiliations: Neural Development Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom.

Abstract:  Retinoic acid (RA)-induced differentiation therapy is partially successful in neuroblastoma treatment. We found that a novel combination of vanadium-based PTP inhibitors with RA induced extensive differentiation in neuroblastoma cells. In contrast to RA alone, this led to either permanent differentiation or senescence after 14days of combined treatment followed by chemical removal. Senescence was dependent in part on synergistic AKT and ERK activation. p21 was also strongly induced, but in contrast to oncogene-induced senescence, p53 was not activated. Vanadium-based inhibitors thus serve strongly to enhance RA's ability to drive differentiation and a novel form of senescence in neuroblastoma cells. 

Retracted: No

PubPeer comments:
 Figure 6C. Splicing p53 and actin panels, but no splicing p21 panel. ![file] , 
 2021 expression of concern. https: www.sciencedirect.com science article pii S030438352100433X?via%3Dihub Owen Clark, Shruti Daga, Andrew W.Stoker. This is a note of an expression of concern related to the above-mentioned publication. The concern is about an image construction brought to our attention by a concerned reader and investigated by our Editor-in-Chief. Splicing of bands in two panels but not in the other panel of Figure 3C means that it is difficult to compare the spliced and un-spliced panels. The journal has been presented with an explanation (below) and raw data by the corresponding author and at this time does not feel there is cause to take further action. However, the Editor-in-Chief feels that an Expression of Concern is appropriate. The concern and this note will remain appended to the above-mentioned article, unless further investigation requires other action. Author explanation: u201cThe use of uneven splicing was not what had been planned, or preferred, but resulted from the accidental loading of several gels in a slightly different loading order. This needed to be corrected in order to simply make the figure internally consistent. The paramount point to make here is that nothing is u201cmissingu201d from the gels - where the splicing is present it is simply due to the horizontal flipping of those two middle lanes to make the loading order correct. I agree that uneven splicing is not ideal, but our use of it here was not intended to mislead.u201d ,
Epidermal growth factor receptor inhibitors enhance susceptibility to Fas-mediated apoptosis in oral squamous cell carcinoma cells
Authors: Masaru Ohashi
Masao Nagumo
Hitoshi Watanabe
Makiko Uchida
Masayasu Iwase
Sayaka Takaoka
Gen Kondo
Sayaka Yoshiba
Journal: Oral Oncology (2008)
Discipline: CLINICAL MEDICINE
Keywords: EGFR signaling; oral squamous cell carcinoma; apoptosis; Fas-mediated; inhibitors
Affiliations: Department of Oral and Maxillofacial Surgery, Showa University School of Dentistry, 2-1-1, Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan. 

Abstract:  Molecular inhibition of epidermal growth factor receptor (EGFR) signaling is a promising cancer treatment strategy. We examined whether inhibition of EGFR signaling would affect the susceptibility of oral squamous cell carcinoma (OSCC) cells to Fas-mediated apoptosis. Treatment of OSCC cells with an anti-EGFR monoclonal antibody, C225, and an EGFR tyrosine kinase inhibitor, AG1478, which target the extracellular and intracellular domains of the receptor, respectively, inhibited phosphorylation of EGFR and its downstream effector molecule Akt and amplified the induction of Fas-mediated apoptosis. In OSCC cells treated with EGFR inhibitors, Fas-mediated apoptosis was accompanied by caspase-8 activation but not Bid cleavage. Caspase-3 and -8 inhibitors reduced the effect of EGFR inhibitors on Fas-mediated apoptosis in OSCC cells, but a caspase-9 inhibitor did not. These results indicate that the pro-apoptotic activity of EGFR inhibitors in OSCC cells depends on the extrinsic pathway of the caspase cascade. Although EGFR inhibitors did not affect the expression of Fas, the Fas-associated death domain protein, or procaspase-8 in OSCC cells, the inhibition downregulated cellular FLICE-inhibitory protein (c-FLIP). Moreover, knockdown of c-FLIP in HSC-2 cells with a small interfering RNA strongly enhanced Fas-mediated apoptosis. These results suggest that the EGFR signaling pathway may, in part, regulate Fas-mediated apoptosis in OSCC cells through c-FLIP expression. 

Retracted: No

PubPeer comments:
 This article shows the effect of EGFR inhibitors on phosphorylation of EGFR and Akt in HSC-2 cells (Figure 1), effect of caspase-8 activation and Bid cleavage on Fas-mediated apoptosis in EGFR inhibitor-treated HSC-2 cells (Figure 4), and Effect of EGFR inhibitors on FADD, procaspase-8, and c-FLIP expression in HSC-2 cells (Figure 6). Several panels are duplicated among figures of this article or among figures from other articles published by the same group ([Iwase_et_al_2007](http: pubpeer.com publications 56517E5C7524BB1F6739010AD6CDCD), [Uchida_et_al_2007](http: pubpeer.com publications F5D53B6DE714FE0D8FBA554824458A#3) and [Takaoka_et_al_2007](http: pubpeer.com publications 43A433F2F37FCAAE0A10BD6DDC28A1#1)), where experiments, conditions and cell types were different. ![file] ,
miR-263b Controls Circadian Behavior and the Structural Plasticity of Pacemaker Neurons by Regulating the LIM-Only Protein Beadex
Authors: Xiaoge Nian
Wenfeng Chen
Weiwei Bai
Yong Zhang
Zhangwu Zhao
Journal: Cells (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Beadex; Drosophila; circadian rhythms; microRNA; structural plasticity.
Affiliations: Department of Entomology and MOA Key Lab of Pest Monitoring and Green Management, College of Plant Protection, China Agricultural University, Beijing 100193, China., Department of Biology, University of Nevada Reno, Reno, NV 89557, USA., Institute of Life Sciences, Fuzhou University, Fuzhou 350108, China., Department of Entomology and MOA Key Lab of Pest Monitoring and Green Management, College of Plant Protection, China Agricultural University, Beijing 100193, China. ., Department of Biology, University of Nevada Reno, Reno, NV 89557, USA. .

Abstract:  : Circadian clocks drive rhythmic physiology and behavior to allow adaption to daily environmental changes. In Drosophila, the small ventral lateral neurons (sLNvs) are primary pacemakers that control circadian rhythms. Circadian changes are observed in the dorsal axonal projections of the sLNvs, but their physiological importance and the underlying mechanism are unclear. Here, we identified miR-263b as an important regulator of circadian rhythms and structural plasticity of sLNvs in Drosophila. Depletion of miR-263b (miR-263bKO) in flies dramatically impaired locomotor rhythms under constant darkness. Indeed, miR-263b is required for the structural plasticity of sLNvs. miR-263b regulates circadian rhythms through inhibition of expression of the LIM-only protein Beadex(Bx). Consistently, overexpression of Bx or loss-of-function mutation (BxhdpR26) phenocopied miR-263bKO and miR-263b overexpression in behavior and molecular characteristics. In addition, mutating the miR-263b binding sites in the Bx 3' UTR using CRISPR/Cas9 recapitulated the circadian phenotypes of miR-263bKO flies. Together, these results establish miR-263b as an important regulator of circadian locomotor behavior and structural plasticity. 

Retracted: No

PubPeer comments:
 A critique of  depth cue combination in general, including comments on this article in particular, may be found here: https: psyarxiv.com 3ky4p ,
MicroRNA-708 is downregulated in hepatocellular carcinoma and suppresses tumor invasion and migration
Authors: Jingjing Liu
Fang Yang
Hongwei Xu
Guangjun Li
Xiangjie Fang
Zhongyi Yue
Journal: Biomedicine & Pharmacotherapy (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cancer progression; Hepatocellular carcinoma; Invasion; Migration; microRNA-708.
Affiliations: The First Department of General Surgery, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China., Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China. Electronic address: ., The Second Department of General Surgery, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China.

Abstract:  Background: MicroRNA-708 (miR-708) has been identified as one of down-regulated miRNAs in hepatocellular carcinoma (HCC) tissues by Taqman miRNAs array and confirmed quantitatively by reverse transcription polymerase chain reaction (qRT-PCR). However, its involvement in HCC remains unclear. The aim of this study was to investigate the roles of miR-708 in carcinogenesis and cancer progression of HCC. Materials and methods: QRT-PCR was performed to detect the expression of miR-708 in 100 pairs of HCC and adjacent non cancerous tissues. Then, its associations with various clinicopathological features of HCC patients were statistically evaluated. After that, we also observed the effects of enforced miR-708 expression on migration and invasion of HCC cells in vitro. Result: Our data confirmed that the expression level of miR-708 in HCC tissues was significantly lower than those in adjacent non-cancerous tissues (P=0.001). In addition, low miR-708 expression was found to be closely correlated with high Edmondson-Steiner grading (P=0.02) and advanced Tumor Node Metastasis (TNM) stage (P=0.01). Furthermore, the enforced expression of miR-708 could suppress the migration and invasion of HCC cell lines in vitro. Conclusion: Our findings support that miR-708, which is frequently down-regulated in HCC, may contribute to the aggressive progression of HCC and inhibit HCC cell mobility. Further studies on the identification of its target genes are required to be performed. 

Retracted: No

PubPeer comments:
 Fig 4A.  Enforced expression of microRNA (miR)-708 suppresses the invasion of hepatocellular carcinoma (HCC) cell lines in vitro. (A) Representative images showing HepG2 and SMMC-7721 cells transfected with miR-708 or negative control miRNA (miR-NC) that invaded through the Matrigel. I have marked some of the repeated areas. ![file] ,
Euxanthone suppresses tumor growth and metastasis in colorectal cancer via targeting CIP2A/PP2A pathway
Authors: Shanshui Luo
Fang Zhou
Jingjing Cao
Ning Wang
Jinhui Guo
Huaiyuan Zhu
Journal: Life sciences (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CIP2A; Colorectal cancer; Euxanthone.
Affiliations: The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China. Electronic address: ., The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China., People's Hospital of Henan, Henan, China.

Abstract:  Aim: Colorectal cancer (CRC) accounts for over 600,000 deaths annually worldwide. Euxanthone is a flavonoid compound extracted from Polygala caudata, with documented anti-neoplastic actions. The current study aimed to determine the therapeutic potential of euxanthone in CRC. Methods and materials: Cell Counting Kit-8 (CCK-8) assay was used to analyze the effect of euxanthone on the cell viability, and apoptosis was detected by the TUNEL assay. The in vitro migratory capacity was determined by wound healing and the invasiveness was assessed by Transwell assay. Western blotting was used to determine the level of relevant proteins. Furthermore, a CRC xenograft murine model was used to analyze the therapeutic efficacy of euxanthone in vivo. Isobaric tags for relative and absolute quantification (iTRAQ) was then performed to identify the potential targets of euxanthone. To validate the role of cancerous inhibitor of PP2A (CIP2A) in the anti-cancer effects of euxanthone, plasmid overexpressing CIP2A and shRNA targeting CIP2A were used in in vitro assays. Key findings: Euxanthone decreased cell viability and increased apoptosis in CRC cells, in addition to restraining migration, invasion and EMT. Similarly, euxanthone also effectively suppressed tumor growth and pulmonary metastasis in vivo. iTRAQ analysis identified CIP2A as the primary target responsible for the anticancer effects of euxanthone. The mediatory role of CIP2A was validated when the anticancer activity of euxanthone was significantly blocked by CIP2A overexpression, while CIP2A knockdown sensitized the CRC cells to euxanthone. Significance: Euxanthone exerts anti-cancer effects in vitro and in vivo in CRC by targeting CIP2A/PP2A signaling. 

Retracted: No

PubPeer comments:
 Dear Authors, in Supplemental Figure 1B, when increasing the contrast of the figure, the background of the gel stays pitch black. Whereas the background artifacts of the bands vanish at a sharp near-rectangular line. This could be interpreted as residues of pasting bands on a black background, yet i don t want to exclude other technical issues that lead to such a picture. I highlighted this in the attached picture. Would the authors to comment on this? ![file] ,
Allogeneic human mesenchymal stem cells restore epithelial protein permeability in cultured human alveolar type II cells by secretion of angiopoietin-1
Authors: Xiaohui Fang
Arne P Neyrinck
Michael A Matthay
Jae W Lee
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Acute lung injury; lung epithelium; pulmonary edema; protein-rich edema fluid; inflammatory cells
Affiliations: The Cardiovascular Research Institute, San Francisco, California, USA.

Abstract:  Acute lung injury is characterized by injury to the lung epithelium that leads to impaired resolution of pulmonary edema and also facilitates accumulation of protein-rich edema fluid and inflammatory cells in the distal airspaces of the lung. Recent in vivo and in vitro studies suggest that mesenchymal stem cells (MSC) may have therapeutic value for the treatment of acute lung injury. Here we tested the ability of human allogeneic mesenchymal stem cells to restore epithelial permeability to protein across primary cultures of polarized human alveolar epithelial type II cells after an inflammatory insult. Alveolar epithelial type II cells were grown on a Transwell plate with an air-liquid interface and injured by cytomix, a combination of IL-1beta, TNFalpha, and IFNgamma. Protein permeability measured by (131)I-labeled albumin flux was increased by 5-fold over 24 h after cytokine-induced injury. Co-culture of human MSC restored type II cell epithelial permeability to protein to control levels. Using siRNA knockdown of potential paracrine soluble factors, we found that angiopoietin-1 secretion was responsible for this beneficial effect in part by preventing actin stress fiber formation and claudin 18 disorganization through suppression of NFkappaB activity. This study provides novel evidence for a beneficial effect of MSC on alveolar epithelial permeability to protein. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 I agree with the overlap shown in Figure 11B above and also note that 11A seems to have a similar issue. TAM. *** ![file] , 
 ![file] , 
 Two images in Figure 12A appear to overlap, after rotation and change in aspect ratio. They seem to be described as having been treated differently. *** ![file] ,
Long non-coding RNA LINC00978 promotes cell proliferation and tumorigenesis via regulating microRNA-497/NTRK3 axis in gastric cancer
Authors: Yi-Feng Liao
Ju-Yuan Bu
Bao-Jun Lv
Xiao-Yu Xiao
Wei-Ze Lv
Journal: International Journal of Biological Macromolecules (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Gastric cancer; LINC00978; microRNA-497.
Affiliations: Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, China., Department of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, China., Department of Tumor Chemotherapy, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, China., Department of Anesthesiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, China., Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, China. Electronic address: .

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editors-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article “…the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated”, the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editors-in-Chief decided to retract the article. 

Retracted: Yes

PubPeer comments:
 Figure 1B. MCF-7 beta-actin panel and SUM103 RAD51L1 panels do not look like they come from the same blot as the other panels for those cell lines. ![file] ,
Hepatoprotective and antifibrotic effect of a new silybin–phosphatidylcholine–Vitamin E complex in rats
Authors: A Di Sario
M Marzioni
S De Minicis
A Benedetti
E Bendia
S Taffetani
C Candelaresi
A Omenetti
Journal: Digestive and Liver Disease (2005)
Discipline: CLINICAL MEDICINE
Keywords: Silybin; Vitamin E; hepatoprotective; antifibrotic; hepatic fibrosis
Affiliations: Gastrointestinal Unit, University of Ancona, III Piano, Via Tronto 10, 60020 Torrette, Ancona, Italy. 

Abstract:  Background: Silybin, the main active component of silymarin, has been reported to reduce hepatic fibrosis by 30% in bile duct ligated rats, whereas Vitamin E alone does not significantly modify liver damage and collagen deposition in chronic liver injury. Aim: The aim of the present study was to evaluate the hepatoprotective and the antifibrotic properties of a new silybin-phosphatidylcholine-Vitamin E complex, characterised by elevated oral bioavailability and lipophilicity, on rat hepatic fibrosis induced by dimethylnitrosamine administration and by bile duct ligation. Methods/results: The complex was administered by gastric gavage at a dose of 250 and 75 mg/kg (as silybin and Vitamin E, respectively). Treatment with the complex was able to prevent the dimethylnitrosamine-induced loss in body and liver weight, as well as to reduce the degree of liver injury, as determined by alanine aminotransferase values and necroinflammatory score. This was associated with reduced hepatic stellate cells proliferation both after 1 and 5 weeks of treatment. Treatment with the complex reduced also hepatic stellate cells activation and collagen deposition. Treatment with dimethylnitrosamine induced an increase in alpha1(I) procollagen, TGF(beta1), tissue inhibitor of metalloproteinase 1 and metalloproteinase 2 mRNA expression, which were significantly reduced by administration of the complex. In the bile duct ligation model, the administration of the complex was able to reduce hepatic stellate cells proliferation and activation, as well as collagen deposition and alpha1(I) procollagen mRNA expression. Conclusions: These results suggest that this new silybin-phosphatidylcholine-Vitamin E complex could be an interesting drug to be tested in patients with chronic liver disease. 

Retracted: No

PubPeer comments:
 Figure 4. A duplicated image [green square] has been published twice in this paper and Hepatology 2003:37;256-66 (Figure 8). However indicated treatments are different (red circles). The quantitative data derived from this image [yellow square] are obviously NOT supported.![file] , 
 Figure 1 and Figure 2. The same image showing unusually similarities seems to have been resued in these two figures to represent exposure to different treatments. The quantitative data are NOT supported by these images.![file] , 
 Figure 1 and 3. Same image used twice to illustarte dirfferent treatments. ![file] , 
 The same loading control in four different panels. ![file] , 
 A similar image in Figure 1 and 2. Could the authors provide the original uncropped scans of these figures?. This will easily solve the issue. Thanks. ![file] ,
Oxidation of a critical thiol residue of the adenine nucleotide translocator enforces Bcl-2-independent permeability transition pore opening and apoptosis
Authors: H L Vieira
A S Belzacq
P Costantini
N Larochette
S A Susin
C Brenner
M A de Pablo
G Kroemer
N Zamzami
Journal: Oncogene (2000)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Mitochondrial membrane permeabilization; permeability transition pore complex (PTPC); thiol crosslinking agents; adenine nucleotide translocator (ANT); cysteine residue
Affiliations: Centre National de la Recherche Scientifique, ERS 1984, 19 rue Guy Môquet, F-94801 Villejuif, France.

Abstract:  Mitochondrial membrane permeabilization is a critical event in the process leading to physiological or chemotherapy-induced apoptosis. This permeabilization event is at least in part under the control of the permeability transition pore complex (PTPC), which interacts with oncoproteins from the Bcl-2 family as well as with tumor suppressor proteins from the Bax family, which inhibit or facilitate membrane permeabilization, respectively. Here we show that thiol crosslinking agents including diazenedicarboxylic acid bis 5N, N-dimethylamide (diamide), dithiodipyridine (DTDP), or bis-maleimido-hexane (BMH) can act on the adenine nucleotide translocator (ANT), one of the proteins within the PTPC. ANT alone reconstituted into artificial lipid bilayers suffices to confer a membrane permeabilization response to thiol crosslinking agents. Diamide, DTDP, and BMH but not tert-butylhydroperoxide or arsenite cause the oxidation of a critical cysteine residue (Cys 56) of ANT. Thiol modification within ANT is observed in intact cells, isolated mitochondria, and purified ANT. Recombinant Bcl-2 fails to prevent thiol modification of ANT. Concomitantly, a series of different thiol crosslinking agents (diamide, DTDP, and BMH, phenylarsine oxide) but not tert-butylhydroperoxide or arsenite induce mitochondrial membrane permeabilization and cell death irrespective of the expression level of Bcl-2. These data indicate that thiol crosslinkers cause a covalent modification of ANT which, beyond any control by Bcl-2, leads to mitochondrial membrane permeabilization and cell death. 

Retracted: No

PubPeer comments:
 Figure 5A. Much more similar than expected. https: imgur.com x4X5uSf ,
Healing potential of nanohydroxyapatite, gelatin, and fibrin-platelet glue combination as tissue engineered scaffolds in radial bone defects of rats
Authors: Ahmad Oryan
Hojjat Gholipour
Abdolhamid Meimandi-Parizi
Journal: Connective Tissue Research (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Nanohydroxyapatite; bone healing; fibrin-platelet glue; gelatin; radius
Affiliations: Division of Surgery, Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran, Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

Abstract:  Different biomaterials have been used in orthopedic surgery. Evaluation of biomaterials for bone healing promotion has been a wide area of research of the orthopedic field. Sixty critical size defects of 5 mm long were bilaterally created in the radial diaphysis of 30 rats. The animals were randomly divided into six equal groups as empty defect, autograft, nanohydroxyapatite (nHA), Gelatin (Gel)-nHA, fibrin-platelet glue (FPG)-nHA, and Gel-FPG-nHA groups (n = 10 in each group). Radiographs of each forelimb were taken postoperatively on the 1st day and then at the 28th and 56th days post injury. After 56 days, the rats were euthanized and their harvested healing bone samples were evaluated by histopathology, scanning electron microscopy, and biomechanical testing. All the treated defects demonstrated significantly superior new bone formation, remodeling, and bone tissue volume. Moreover, the defects treated with FPG-nHA showed significantly higher ultimate load, yield load, and stiffness. The Gel-FPG-nHA moderately improved bone regeneration that was not close to the autograft in some parameters, whereas FPG-nHA significantly improved bone healing closely comparable with the autograft group in most parameters. In conclusion, although all the nHA-containing scaffolds had some beneficial effects on bone regeneration, the FPG-nHA scaffold was more effective in improving the structural and functional properties of the newly formed bone and was more osteoinductive than the Gel and was comparable to the autograft. Therefore, the FPG can be regarded as a promising option to be used in conjunction with mineral scaffolds for bone tissue engineering. 

Retracted: No

PubPeer comments:
 Figure 3A. * Green boxes: Panels  Wild and  Mock appear to overlap, but are stretched differently, suggesting it is not a simple duplication error. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. I would love to hear from the authors if the journal ever contacted them in the past five years. ![file] ,
Molecular and biochemical characterization of benzalacetone synthase and chalcone synthase genes and their proteins from raspberry (Rubus idaeus L.)
Authors: Desen Zheng
Geza Hrazdina
Journal: Archives of biochemistry and biophysics (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: polyketide synthase; raspberry fruits; RiPKS4; RiPKS5; enzyme products
Affiliations: Department of Food Science and Technology, Cornell University, NYSAES, 630 W. North Street, Geneva, NY 14456, USA.

Abstract:  Two new members of the polyketide synthase (PKS) gene family (RiPKS4 and RiPKS5) were cloned from raspberry fruits (Rubus idaeus L., cv Royalty) and expressed in Escherichia coli. Characterization of the recombinant enzyme products indicated that RiPKS4 is a bifunctional polyketide synthase producing both 4-hydroxybenzalacetone and naringenin chalcone. The recombinant RiPKS4 protein, like the native protein from raspberry fruits [W. Borejsza-Wysocki, G. Hrazdina, Plant Physiol. 1996;110: 791-799] accepted p-coumaryl-CoA and ferulyl-CoA as starter substrates and catalyzed the formation of both naringenin chalcone, 4-hydroxy-benzalacetone and 3-methoxy-4-hydroxy-benzalacetone. Although activity of RiPKS4 was higher with ferulyl-CoA than with p-coumaryl-CoA, the corresponding product, 3-methoxy-4-hydroxy phenylbutanone could not be detected in raspberries to date. Sequence analysis of the genes and proteins suggested that this feature of RiPKS4 was created by variation in the C-terminus due to DNA recombination at the 3' region of its coding sequence. RiPKS5 is a typical chalcone synthase (CHS) that uses p-coumaryl-CoA only as starter substrate and produces naringenin chalcone exclusively as the reaction product. 

Retracted: No

PubPeer comments:
 Figure 4 https: imgur.com a GSf79ou ,
3‐Acetyl‐11‐keto‐β‐boswellic acid attenuated oxidative glutamate toxicity in neuron‐like cell lines by apoptosis inhibition
Authors: Hamid Reza Sadeghnia
Arezoo Rajabian
Azar Hosseini
Mohammad Taher Boroushaki
Seyed Hadi Mousavi
Journal: Journal of Cellular Biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: 3-acetyl-11-keto-β-boswellic acid (AKBA); DNA injury; cytotoxicity; glutamate; neuroprotection
Affiliations: Pharmacological Research Center of Medicinal Plants, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract:  3-Acetyl-11-keto-β-boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 µM) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P &lt; .001). However, AKBA (2.5-10 µM) enhanced the cell viability in both treatment regimens (P &lt; .001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P &lt; .05 and P &lt; .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P &lt; .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate-induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl-2 and cleaved-caspase-3 proteins, concentration-dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate-induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death. 

Retracted: No

PubPeer comments:
 Figure 5: Two panels representing different experiments appear to share similar constellations of dots. Could the authors please explain? ![file] ,
Ginsenoside metabolite compound K promotes recovery of dextran sulfate sodium-induced colitis and inhibits inflammatory responses by suppressing NF-κB activation
Authors: Shaoping Hu
Tianhui Hu
Jiahui Yuan
Wei Zhong
Juan Li
Bing Zhang
Gang Song
Weiwei Wang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Phytogenic compounds; ginsenoside metabolite compound K; berberine; cancer; inflammation
Affiliations: Cancer Research Center, Medical College of Xiamen University, Xiamen, China., Department of Basic Medicine, Medical College of Xiamen University, Xiamen, China.

Abstract:  Phytogenic compounds with anti-oxidant and anti-inflammatory properties, such as ginsenoside metabolite compound K (CK) or berberine (BBR), are currently discussed as promising complementary agents in the prevention and treatment of cancer and inflammation. The latest study showed that ginsenoside Rb1 and its metabolites could inhibit TNBS-induced colitis injury. However, the functional mechanisms of anti-inflammation effects of ginsenoside, particularly its metabolite CK are still not clear. Here, using dextran sulfate sodium (DSS)-induced colitis in mice, clinical parameters, intestinal integrity, pro-inflammatory cytokines production, and signaling pathways in colonic tissues were determined. In mild and sever colitis mice, CK and BBR (as a positive agent) alleviated colitis histopathology injury, ameliorated myeloperoxidase (MPO) activity, reduced pro-inflammatory cytokines production, such as, IL-6, IL-1β, TNF-α, and increased anti-inflammatory cytokine IL-10 production in both mice colon tissues and blood. Nevertheless, the results revealed that CK and BBR inhibited NF-κB p65 nuclear translocation, downregulated p-IκBα and upregulated IκBα, indicating that CK, as well as BBR, suppressed the activation of the NF-κB pathway in the progression of colitis with immunofluorescence, immunohistochemical and western blotting analysis. Furthermore, CK inhibited pro-inflammatory cytokines production in LPS-activated macrophages via down-regulation of NF-κB signaling pathway. Taken together, our results not only reveal that CK promotes the recovery of the progression of colitis and inhibits the inflammatory responses by suppressing NF-κB activation, but also suggest that CK downregulates intestinal inflammation through regulating the activation of macrophages and pro-inflammatory cytokines production. 

Retracted: No

PubPeer comments:
 Figure 7F G * Red boxes: The b-tublin (sic) panel of Figure 7F appears to look very similar to the Lamin B panel in Figure 7G. Contrast enhanced to bring out details. Reported to the journal in April 2014, but no action taken as of today. ![file] , 
 #1 Thank you very much for pointing out the problem in the paper. As for the problem of Fig7F,G sharing a blank strip, I have found it in 2016uff0cand conducted repeated tests for this problemuff0cand the conclusion is basically the same as before. The original data of repeated experiments are attached. ![file] ![file] ,