PReD-Bench/PRed-Bench huggingface dataset:
Nodal Promotes the Migration and Invasion of Bladder Cancer Cells via Regulation of Snail
Authors: Wenwei Chen
Houping Mao
Qin Chen
Hua Zhang
Tao Jiang
Yanfeng He
Rui Gao
Xingjian Gao
Journal: Journal of Cancer (2019)
Discipline: CLINICAL MEDICINE
Keywords: ATM; Nodal, Snail, bladder cancer, EMT; YY1.
Affiliations: Department of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.

Abstract:  Urinary bladder cancer is one of commonly diagnosed malignancies worldwide, especially in males. Understanding the mechanisms of advanced metastasis in bladder cell is important for therapy and drug development. Nodal, an important embryonic morphogen, has been reported to modulate tumorigenesis. We found that the expression of Nodal was upregulated in bladder cancer cells and tissues as compared to their corresponding controls. Knockdown of Nodal can suppress the migration, invasion, and epithelial-to-mesenchymal transition (EMT) of bladder cancer cells. Nodal can positively regulate the expression of Snail, one powerful EMT transcription factors, in bladder cancer cells. Overexpression of Snail can attenuate the si-Nodal suppressed cell migration and invasion. Nodal can increase the transcription and protein stability of Snail in bladder cancer cells. YY1, which can be activated by Nodal, is responsible for Nodal induced transcription of Snail. ATM, which can stabilize Snail by phosphorylation on Serine-100, was involved in Nodal upregulated protein stability of Snail. Collectively, our data showed that Nodal can trigger the malignancy of bladder cancer cells via increasing the transcription and protein stability of Snail. It indicated that Nodal might be a potential therapeutic target for bladder cancer treatment. 

Retracted: No

PubPeer comments:
 Published 2022-2-17 In our paper [1], the western blot band for GAPDH (Figure 6D) was used wrong. We reperformed this experiment and provided corrected Figure 6D. The correction made in this erratum does not affect the counting results and original conclusions. We apologize for the error and for any inconvenience that may cause to the readers and the editors of this journal. ![file] ,
Floating-bioadhesive microspheres containing acetohydroxamic acid for clearance of Helicobacter pylori
Authors: N K Jain
R B Umamaheswari
G P Agrawal
P K Tripathi
Subheet Jain
Journal: Drug Delivery (2002)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: gastric retention; Helicobacter pylori; floating microspheres; acetohydroxamic acid; bioadhesive system
Affiliations: Department of Pharmaceutical Science, Dr. H. S. Gour University, Sagar, India.

Abstract:  A new strategy based on gastric retention is proposed for the treatment of Helicobacter pylori. (H. pylori). A synergism between a floating and a bioadhesive system has been explored. Floating microspheres containing the antiurease drug acetohydroxamic acid (AHA) were prepared by a novel quasi-emulsion solvent diffusion method. The microballons were characterized for size distribution, morphology, drug content, drug release, and in vitro floating property. The microballons were coated with 2% w/v solution of polycarbophil by the air suspension coating method. The bioadhesive property of the microspheres was investigated by the detachment force measurement method. In vitro growth inhibition studies were performed in isolated H. pylori culture. The results suggest that AHA-loaded floating microspheres are superior as potent urease inhibitors whereas urease plays an important role in the colonization of H. pylori. We suggest that an oral dosage containing floating-bioadhesive microspheres may form a useful drug delivery system for the treatment of H. pylori. 

Retracted: No

PubPeer comments:
  FIG. 2. Optical photomicrographs of bioadhesive microspheres (45u00a3). ![file] Part of the image has been duplicated repeatedly (emphasised in lower version). I can think of any number of innocent explanations for this: the photomicrograph may have existed only as a printed copy, which became damaged before it could be scanned, inspiring someone to paper over the damage as being irrelevant to the purpose of the figure. In general, I think I would would prefer imperfect illustrations, with the imperfection explained if necessary. ,
Quercetin attenuates atherosclerotic inflammation and adhesion molecule expression by modulating TLR-NF-κB signaling pathway
Authors: Shobha Bhaskar
A Helen
P R Sudhakaran
Journal: Cellular Immunology (2016)
Discipline: IMMUNOLOGY
Keywords: Adhesion molecule; Atherosclerosis; Cytokine; Inflammation; Quercetin
Affiliations: Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India., Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India. Electronic address: .

Abstract:  Adhesion molecules expressed by activated endothelial cells play key role in regulating leukocyte trafficking to sites of inflammation. The present study attempted to explore whether the polyphenolic flavonoid quercetin influence leukocyte endothelial attraction and the involvement of TLR-NF-κB signaling pathway in the expression of adhesion molecules involved in the early development of atherosclerosis. Quercetin at 25μM concentration significantly reduced the HUVEC expression of VCAM-1 and ICAM-1 evidently enhanced by oxLDL. In addition, quercetin significantly downregulated the mRNA expression of MCP-1 and alleviated the nuclear translocation of NF-κB p65 subunit in oxLDL induced HUVECs. Western blot and PCR analyses revealed that quercetin significantly attenuated the expression of both protein and mRNA expression of TLR2 and TLR4. Quercetin supplementation significantly decreased the inflammatory mediators like COX, 5-LOX, MPO, NOS, CRP and the mRNA expression of the cytokine; IL-6 in hypercholesterolemic diet (HCD) fed atherosclerotic rats. The results demonstrate that quercetin is effective to regulate the atherosclerotic inflammatory process by inhibiting oxLDL induced endothelial leukocyte adhesion by attenuating the TLR-NF-κB signaling pathway in endothelial cells and decrease the inflammatory process induced by HCD in rats. Therefore, quercetin acts as anti-inflammatory and anti-atherogenic agent, which may have implications for strategies attenuating endothelial dysfunction-related atherosclerosis. 

Retracted: No

PubPeer comments:
 The lane 1 is same in another publication stating different treatment condition. Could the authors clarify? ![file] ,
Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via respecification of lineage-restricted precursors
Authors: Peter G Kim
Irwin D Bernstein
Sergei Doulatov
Hu Li
Linda T Vo
Leonard I Zon
Stephanie S Chou
Natasha Arora
George Q Daley
James J Collins
Brandon K Hadland
Journal: Cell Stem Cell (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Human pluripotent stem cells; hPSCs; hematopoietic stem and progenitor cells; HSPCs; CD34
Affiliations: Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children's Hospital Boston and Dana Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.

Abstract:  Human pluripotent stem cells (hPSCs) represent a promising source of patient-specific cells for disease modeling, drug screens, and cellular therapies. However, the inability to derive engraftable human hematopoietic stem and progenitor cells (HSPCs) has limited their characterization to in vitro assays. We report a strategy to respecify lineage-restricted CD34(+)CD45(+) myeloid precursors derived from hPSCs into multilineage progenitors that can be expanded in vitro and engrafted in vivo. HOXA9, ERG, and RORA conferred self-renewal and multilineage potential in vitro and maintained primitive CD34(+)CD38(-) cells. Screening cells via transplantation revealed that two additional factors, SOX4 and MYB, conferred engraftment. Progenitors specified with all five factors gave rise to reproducible short-term engraftment with myeloid and erythroid lineages. Erythroid precursors underwent hemoglobin switching in vivo, silencing embryonic and activating adult globin expression. Our combinatorial screening approach establishes a strategy for obtaining transcription-factor-mediated engraftment of blood progenitors from human pluripotent cells. 

Retracted: No

PubPeer comments:
 Supplemental Figure 1D, SOX4 panel. The first 2 lanes look unexpectedly similar, and there is a sharp transition visible between them. Shown with red arrows. Image made darker to bring out details. Would the authors be so kind to explain if these 2 lanes were supposed to look similar? ![file] Here is a close-up to show the similarities. ![file] ,
Apelin-13 induces autophagy in hepatoma HepG2 cells through ERK1/2 signaling pathway-dependent upregulation of Beclin1
Authors: Dong Han
Deguan Lv
Junyue Lei
Linxi Chen
Zhongyu Li
Qiulin Huang
Chao Cao
Xuan Liu
Jia Yu
Guodong Chen
Journal: Oncology letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: expression levels; extracellular signal-regulated kinase 1/2; phosphorylation.
Affiliations: Department of General Surgery, First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China., Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan 421001, P.R. China., Department of Microbiology, School of Medicine, University of South China, Hengyang, Hunan 421001, P.R. China.

Abstract:  The aim of the present study was to investigate the effect of Apelin-13 on autophagy in hepatocellular carcinoma HepG2 cells and the underlying mechanism of the effect. The HepG2 cells were treated with Apelin-13 at a final concentration of 0.0001, 0.001, 0.01 and 0.1 µmol/l for 24 h. Cells were also treated with 10 µmol/l PD98059 for 24 h. The expression of the extracellular signal-regulated kinase (ERK)1/2, phosphorylated ERK1/2 (pERK1/2) and Beclin1 proteins were detected by western blot analysis. Beclin1 mRNA expression was also detected by reverse transcription-polymerase chain reaction. Autophagy was observed using fluorescence microscopy subsequent to monodansylcadaverine (MDC) staining. Following treatment with the various concentrations of Apelin-13, the expression of the ERK1/2 protein remained at a similar level, whereas the expression of pERK1/2 increased in a dose-dependent manner. Compared with the control group, the increase was significant (P&lt;0.05). Similarly, Beclin1 expression was upregulated at the protein and mRNA levels by Apelin-13 treatment in a dose-dependent manner and was significantly increased compared with the control group. However, following treatment with the Apelin-13 inhibitor PD98059, the expression of pERK1/2, Beclin1 protein and Beclin1 mRNA were significantly decreased (P&lt;0.05). In addition, Apelin-13 induced the autophagy of HepG2 cells in a dose-dependent manner, as revealed by MDC staining. PD98059 inhibited autophagy of HepG2 cells induced by Apelin-13. Therefore, Apelin-13 may promote autophagy in HepG2 cells by inducing the phosphorylation of ERK1/2 and upregulating the expression of Beclin1. 

Retracted: No

PubPeer comments:
 Fig 1, histopathological analysis of Kidney slices - Panel B and C look remarkably similar. Could the authors comment on this apparent repetition and detail the steps to rectify this. ![file] ,
Identification of the protein kinases Pyk3 and Phg2 as regulators of the STATc-mediated response to hyperosmolarity
Authors: Christoph S Clemen
Jianbo Na
Ludwig Eichinger
Linh Hai Vu
Tsuyoshi Araki
Jeffrey G Williams
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Cellular adaptation; environmental osmolarity; Dictyostelium; STATc; transcriptional response
Affiliations: Center for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany., College of Life Sciences, Wellcome Trust Building, University of Dundee, Dundee, United Kingdom.

Abstract:  Cellular adaptation to changes in environmental osmolarity is crucial for cell survival. In Dictyostelium, STATc is a key regulator of the transcriptional response to hyperosmotic stress. Its phosphorylation and consequent activation is controlled by two signaling branches, one cGMP- and the other Ca(2+)-dependent, of which many signaling components have yet to be identified. The STATc stress signalling pathway feeds back on itself by upregulating the expression of STATc and STATc-regulated genes. Based on microarray studies we chose two tyrosine-kinase like proteins, Pyk3 and Phg2, as possible modulators of STATc phosphorylation and generated single and double knock-out mutants to them. Transcriptional regulation of STATc and STATc dependent genes was disturbed in pyk3(-), phg2(-), and pyk3(-)/phg2(-) cells. The absence of Pyk3 and/or Phg2 resulted in diminished or completely abolished increased transcription of STATc dependent genes in response to sorbitol, 8-Br-cGMP and the Ca(2+) liberator BHQ. Also, phospho-STATc levels were significantly reduced in pyk3(-) and phg2(-) cells and even further decreased in pyk3(-)/phg2(-) cells. The reduced phosphorylation was mirrored by a significant delay in nuclear translocation of GFP-STATc. The protein tyrosine phosphatase 3 (PTP3), which dephosphorylates and inhibits STATc, is inhibited by stress-induced phosphorylation on S448 and S747. Use of phosphoserine specific antibodies showed that Phg2 but not Pyk3 is involved in the phosphorylation of PTP3 on S747. In pull-down assays Phg2 and PTP3 interact directly, suggesting that Phg2 phosphorylates PTP3 on S747 in vivo. Phosphorylation of S448 was unchanged in phg2(-) cells. We show that Phg2 and an, as yet unknown, S448 protein kinase are responsible for PTP3 phosphorylation and hence its inhibition, and that Pyk3 is involved in the regulation of STATc by either directly or indirectly activating it. Our results add further complexities to the regulation of STATc, which presumably ensure its optimal activation in response to different environmental cues. 

Retracted: No

PubPeer comments:
 Figure 3. * Red boxes: The total STATc panels in Figure 3A and 3B appear to look unexpectedly similar. Reported to the journal in October 2015, but no action taken as of today. ![file] ,
GATA2 regulates GATA1 expression through LSD1-mediated histone modification
Authors: Yongsen Wang
Bo Huo
Jing Sun
Lingyuan Meng
Zhizhuang Joe Zhao
Tian Hao
Yidi Guo
Xin Hu
Xueqi Fu
Journal: American journal of translational research (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: GATA1; GATA2; LSD1; histone modification.
Affiliations: School of Life Sciences, Jilin University Changchun 130012, China., School of Life Sciences, Jilin UniversityChangchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin UniversityChangchun 130012, China; National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin UniversityChangchun 130012, China.

Abstract:  The dynamic and reversed expression of GATA1 and GATA2 are essential for proper erythroid differentiation. Our previous work demonstrates that LSD1, a histone H3K4 demethylase, represses GATA2 expression at late stage of erythroid differentiation. K562 and MEL cells were used and cultured in Roswell Park Memorial Institute-1640 medium (RPMI) and Dulbecco's modified Eagle's medium (DMEM), respectively. Western blot assay was used to examine the GATA1, GATA2, TAL1, HDAC1, HDAC2, CoREST and β-actin protein. The immunoprecipitation assay and GST pull-down assay were employed to detect the precipitated protein complexes and investigate the interaction between the proteins. The small interfering RNA (siRNA) and nonspecific control siRNA were synthesized to silence the target genes. Double fluorescence immunostaining was used to observe the association of LSD1 with GATA2 in K562 cells. The results indicated that knockdown of LSD1 in K562 cell causes increased H3K4 di-methylation at GATA1 locus and activates GATA1 expression, demonstrating that LSD1 represses GATA1 expression through LSD1-mediated histone demethylation. Upon induced erythroid differentiation of K562 cells, the interaction between GATA2 and LSD1 is decreased, consistent with a de-repression of GATA1 expression. Meanwhile, the interaction between TAL1 and LSD1 is increased, which forms a complex that efficiently suppresses GATA2 expression. In conclusion, these observations reveal an elegant mechanism to modulate GATA1 and GATA2 expression during erythroid differentiation. While LSD1 mainly forms complex with GATA2 to repress GATA1 expression in hematopoietic progenitor cells, it mostly forms complex with TAL1 to repress GATA2 expression in differentiated cells. 

Retracted: No

PubPeer comments:
 The input band figure 1A was splicing! ![file] ,
RETRACTED: A universal Echosupport can fix a technique of ultrasound-guided continuous femoral nerve block
Authors: Hiroshi Otake
Motonori Nakagawa
Hironobu Ueshima
Journal: Journal of Clinical Anesthesia (2016)
Discipline: CLINICAL MEDICINE
Keywords: Continuous femoral nerve block; Device for probe fixation; Ultrasound-guided.
Affiliations: Department of Anesthesiology, Showa University Hospital, Tokyo, Japan. Electronic address: ., Department of Anesthesiology, Showa University Hospital, Tokyo, Japan.

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief for inappropriate authorship. The Editor-in-Chief decision was based on the investigation by the Japanese Society of Anesthesiologists which concluded that the corresponding author, Dr. Ueshima presented the names of the individuals not involved or only partially involved in research as lead authors, presented the names of the individuals not involved in research as co-authors and submitted papers without the agreement of the co-authors. The investigation report can be found here. 

Retracted: Yes

PubPeer comments:
 **Retracted**, February 9, 2022: https: doi.org 10.1016 j.jclinane.2016.01.046  *This article has been retracted: please see Elsevier Policy on Article Withdrawal (http: www.elsevier.com locate withdrawalpolicy).* *This article has been retracted at the request of the Editor-in-Chief for inappropriate authorship.* *The Editor-in-Chief decision was based on the investigation by the Japanese Society of Anesthesiologists which concluded that the corresponding author, Dr. Ueshima presented the names of the individuals not involved or only partially involved in research as lead authors, presented the names of the individuals not involved in research as co-authors and submitted papers without the agreement of the co-authors. The investigation report can be found here.* The investigation report: https: anesth.or.jp img upload ckeditor files 2105_34_700_2.pdf See also: https: retractionwatch.com 2022 02 10 more-than-100-of-an-anesthesiologists-papers-retracted #more-124200 ,
Interferon-γ induces senescence in normal human melanocytes
Authors: Suiquan Wang
Liangjun Lu
Aie Xu
Yiping Zhu
Dongyin Liu
Fuquan Lin
Miaoni Zhou
Weisong Hong
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: IFN-γ; melanocytes; senescence; apoptosis; cell cycle
Affiliations: Department of Dermatology, Hangzhou Institute of Dermatology and Venereology, Third People's Hospital of Hangzhou, Hangzhou, Zhejiang Province, China., Department of Dermatology, Hangzhou Institute of Dermatology and Venereology, Third People's Hospital of Hangzhou, Hangzhou, Zhejiang Province, China; Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.

Abstract:  Background: Interferon-γ (IFN-γ) plays an important role in the proceedings of vitiligo through recruiting lymphocytes to the lesional skin. However, the potential effects of IFN-γ on skin melanocytes and the subsequent contribution to the vitiligo pathogenesis are still unclear. Objective: To investigate the effects of IFN-γ on viability and cellular functions of melanocytes. Methods: Primary human melanocytes were treated with IFN-γ. Cell viability, apoptosis, cell cycle melanin content and intracellular reactive oxygen species (ROS) level were measured. mRNA expression was examined by real-time PCR. The release of interleukin 6 (IL-6) and heat shock protein 70 (HSP-70) was monitored by ELISA. β-galactosidase staining was utilized to evaluate melanocyte senescence. Results: Persistent IFN-γ treatment induced viability loss, apoptosis, cell cycle arrest and senescence in melanocytes. Melanocyte senescence was characterized as the changes in pigmentation and morphology, as well as the increase of β-galactosidase activity. Increase of p21Cip1/Waf1 protein was evident in melanocytes after IFN-γ treatment. IFN-γ induction of senescence was attenuated by siRNAs against p21, Janus kinase 2 (JAK2) or signal transducer and activator of transcription 1 (STAT1), but not by JAK1 siRNA nor by p53 inhibitor pifithrin-α. IFN-γ treatment increased the accumulation of intracellular ROS in melanocytes, while ROS scavenger N-acetyl cysteine (NAC) effectively inhibited IFN-γ induced p21 expression and melanocyte senescence. IL-6 and HSP-70 release was significantly induced by IFN-γ treatment, which was largely inhibited by NAC. The increase of IL-6 and HSP-70 release could also be observed in senescent melanocytes. Conclusion: IFN-γ can induce senescence in melanocytes and consequently enhance their immuno-competency, leading to a vitiligo-prone milieu. 

Retracted: No

PubPeer comments:
 This article cites a work that has been already retracted since 2018: *Estruch R, Ros E, Salas-Salvadu00f3 J, et al. Primary prevention of cardiovascular disease with a Mediterranean Diet. N Engl J Med. 2013;368(14):1279u201390.* See for example: https: www.npr.org sections health-shots 2018 06 13 619619302 researchers-soften-claim-that-mediterranean-diet-prevents-heart-attacks?live=1 Could the authors please comment? ,
miR-135 regulated breast cancer proliferation and epithelial-mesenchymal transition acts by the Wnt/β-catenin signaling pathway
Authors: Daqiong Jiang
Bo Zhou
Yan Xiong
Hongbing Cai
Journal: International Journal of Molecular Medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: Breast cancer; microRNAs; miR-135; cell growth; migration
Affiliations: Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.

Abstract:  Breast cancer (BC) is the most common cancer in women around the world. microRNAs (miRNAs/miRs) have been proved to be associated with the development and progression of breast cancer. In the present study, to elucidate the effects of dysregulated miR‑135 on cells and underlying mechanisms in BC, in vitro and in vivo experiments were conducted. The biological functions of miR‑135 were studied using MTT, colony formation, wound healing, transwell assays as well as tumorigenicity analysis. Gain‑ and loss‑ of function of miR‑135 studies revealed that ectopic expression of miR‑135 in MDA‑MB‑468 and MCF‑7 cells significantly inhibited cell growth, migration, invasion and EMT, at least in part through inhibiting the activation of the Wnt/β‑catenin pathway. Moreover, this was reversed in cells which were transfected with miR‑135 inhibitors. Taken together, the results of the present study provided evidence that miR‑135 acted as a tumor suppressor in BC, which may represent a novel therapeutic strategy for the diagnosis and prognosis of BC. 

Retracted: No

PubPeer comments:
 Two images in figure 2A appear to be the same, but are described as something different. *** ![file] , 
 In addition to the concern above, Figures 8B and 8D appear to be the same. *** Enhanced brightness ![file] *** Original brightness ![file] , 
 Corrected [20 June 2022] . After the publication of the above article, an interested reader drew to the authors attention that, in Fig. 2A on p. 1626, the data panels showing the results for the u2018Bright Blank controlu2019 and u2018Bright miu2011135 inhibitorsu2019 experiments appeared to be identical; furthermore, in Fig. 8 on p. 1632, Figs. 8B and D appeared to contain identical data, even though the contrast settings for the two sets of panels were a little different. The authors have reu2011examined their original data, and regret that Figs. 2 and 8 were inadvertently both assembled incorrectly, as identified by the external reader. However, the authors retained their original data, and were able to reassemble both these figures correctly. The revised versions of Figs. 2 and 8 are shown on the next two pages, now including the correct data for the u2018Bright Blank controlu2019 experiment in Fig. 2A and the correct immunofluorescence data in Fig. 8B. Note that the revised data shown for these figures do not affect the overall conclusions reported in the paper. The authors express their gratitude to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. ,
Pivotal Role of gp91 phox -Containing NADH Oxidase in Lipopolysaccharide-Induced Tumor Necrosis Factor-α Expression and Myocardial Depression
Authors: Qingping Feng
Xiangru Lu
Tianqing Peng
Journal: Circulation (2005)
Discipline: CLINICAL MEDICINE
Keywords: Lipopolysaccharide; TNF-alpha; gp91phox-containing NADH oxidase; cardiomyocyte; myocardial dysfunction
Affiliations: Cardiology Research Laboratory, Centre for Critical Illness Research, Lawson Health Research Institute, Department of Medicine, University of Western Ontario, London, Ontario, Canada., From the Cardiology Research Laboratory, Centre for Critical Illness Research, Lawson Health Research Institute, London Health Sciences Centre, Departments of Medicine, Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.

Abstract:  Background: Lipopolysaccharide (LPS) induces cardiomyocyte tumor necrosis factor-alpha (TNF-alpha) production, which is responsible for myocardial depression during sepsis. The aim of this study was to investigate the role of gp91phox-containing NADH oxidase signaling in cardiomyocyte TNF-alpha expression and myocardial dysfunction induced by LPS. Methods and results: In cultured mouse neonatal cardiomyocytes, LPS increased NADH oxidase (gp91phox subunit) expression and superoxide generation. Deficiency of gp91phox or inhibition of NADH oxidase blocked TNF-alpha expression stimulated by LPS. TNF-alpha induction was also inhibited by tempol, N-acetylcysteine, or 1,3-dimethyl-2-thiourea. NADH oxidase activation by LPS increased ERK1/2 and p38 phosphorylation, and inhibition of ERK1/2 and p38 phosphorylation blocked the effect of NADH oxidase on TNF-alpha expression. Isolated mouse hearts were perfused with LPS (5 microg/mL) alone or in the presence of apocynin for 1 hour. Myocardial TNF-alpha production was decreased in gp91phox-deficient or apocynin-treated hearts compared with those of wild type (P&lt;0.05). To investigate the role of gp91phox-containing NADH oxidase in endotoxemia, mice were treated with LPS (4 mg/kg IP) for 4 and 24 hours, and their heart function was measured with a Langendorff system. Deficiency of gp91phox significantly attenuated LPS-induced myocardial depression (P&lt;0.05). Conclusions: gp91phox-Containing NADH oxidase is pivotal in LPS-induced TNF-alpha expression and cardiac depression. Effects of NADH oxidase activation are mediated by ERK1/2 and p38 MAPK pathway. The present results suggest that gp91phox-containing NADH oxidase may represent a potential therapeutic target for myocardial dysfunction in sepsis. 

Retracted: No

PubPeer comments:
 Also see the two control TNFu03b1 bands in Fig 3A (lane 1 and 2) ![file] , 
 ![file] ,
Preventive effect of caffeine and curcumin on hepato-carcinogenesis in diethylnitrosamine-induced rats
Authors: Takakazu Nagahara
Yuki Fujise
Ryu Imamoto
Ryo Abe
Jun-Ichi Okano
Yoshikazu Murawaki
Journal: International Journal of Oncology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Chemopreventive effects; caffeine; curcumin; diethylnitrosamine; hepatocarcinogenic rat model
Affiliations: Second Department of Internal Medicine, Tottori University School                     of Medicine, Tottori 683-8504, Japan.

Abstract:  Chemopreventive effects of caffeine and curcumin were evaluated in the diethylnitrosamine (DEN)-induced hepatocarcinogenic rat model. Animals injected with DEN for 10 weeks (G2-10w) and 14 weeks (G2-14w) were hepato-carcinogenic rats. Animals injected with DEN and treated with curcumin and caffeine for 10 weeks (G3-10w, G4-10w) and 14 weeks (G3-14w, G4-14w) were compared with those in G2. Macroscopic and microscopic features suggested that treatment with caffeine, but not curcumin, for 10 and 14 weeks was effective in inhibiting DEN-induced hepatocarcinogenesis. Immunohistochemical and western blot analysis with proliferating cell nuclear antigen and glutathione S-transferase-P antibodies also showed that expression levels of these hepato-carcinogenic markers were more efficiently reduced by treatment with caffeine than curcumin. Our data demonstrate that caffeine could be a more potent compound than curcumin for prevention of hepatocarcinogenesis in DEN-induced rats. 

Retracted: No

PubPeer comments:
 Figure 1A. * Red boxes. Panels a (ethanol vehicle) and c (ethanol 1nM TPA) appear to show an area of overlap with a different zoom factor. ![file] , 
 Figure 6A. * Blue boxes: Three panels, Ethanol -1nmTPA, Ethanol +1nmTPA, and 10 nmDHT -1nmTPA all appear to show an area of overlap, albeit with different zoom and rotation factors. ![file] ,
Development and validation of a model to predict the risk of exacerbations in chronic obstructive pulmonary disease
Authors: Johannes B Reitsma
Karel G M Moons
Berna D L Broekhuizen
Jan Willem J Lammers
Loes C M Bertens
Frans H Rutten
Arno W Hoes
Yvonne van Mourik
Journal: International Journal of Chronic Obstructive Pulmonary Disease (2013)
Discipline: CLINICAL MEDICINE
Keywords: exacerbation of COPD; external validation; risk prediction; vascular disease.
Affiliations: Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands.

Abstract:  Purpose: Prediction models for exacerbations in patients with chronic obstructive pulmonary disease (COPD) are scarce. Our aim was to develop and validate a new model to predict exacerbations in patients with COPD. Patients and methods: The derivation cohort consisted of patients aged 65 years or over, with a COPD diagnosis, who were followed up over 24 months. The external validation cohort consisted of another cohort of COPD patients, aged 50 years or over. Exacerbations of COPD were defined as symptomatic deterioration requiring pulsed oral steroid use or hospitalization. Logistic regression analysis including backward selection and shrinkage were used to develop the final model and to adjust for overfitting. The adjusted regression coefficients were applied in the validation cohort to assess calibration of the predictions and calculate changes in discrimination applying C-statistics. Results: The derivation and validation cohort consisted of 240 and 793 patients with COPD, of whom 29% and 28%, respectively, experienced an exacerbation during follow-up. The final model included four easily assessable variables: exacerbations in the previous year, pack years of smoking, level of obstruction, and history of vascular disease, with a C-statistic of 0.75 (95% confidence interval [CI]: 0.69-0.82). Predictions were well calibrated in the validation cohort, with a small loss in discrimination potential (C-statistic 0.66 [95% CI 0.61-0.71]). Conclusion: Our newly developed prediction model can help clinicians to predict the risk of future exacerbations in individual patients with COPD, including those with mild disease. 

Retracted: No

PubPeer comments:
 I have some concerns about the caption of Table 3 in the main text of the paper. The example calculation does not seem to be right. The result of the calculation should be 1 (1 + exp( - (-1.33 + 1.62 - 0.05 * (32.9 5) +1.091 + 0.65))) = 0.84 which is different from the reported 0.79% in the caption. In the second example, calculating the natural logarithm of 0 seems very odd. Even if we replace that term with 0, we will get 1 (1 + exp( - (-1.33 + 0 - 0.05 * (77.7 5) + 0.15 * 2*0 + 0))) = 0.1084 which is different from the 0.09 reported. I hope the authors can clarify this. Thank you. ,
Dietary Restriction Extends Lifespan through Metabolic Regulation of Innate Immunity
Authors: Meltem Isik
Ziyun Wu
Peng Zhang
T Keith Blackwell
Natalie Moroz
Michael J Steinbaugh
Journal: Cell Metabolism (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ATF-7; C. elegans; aging; dietary restriction; food intake
Affiliations: Research Division, Joslin Diabetes Center, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA., Research Division, Joslin Diabetes Center, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: .

Abstract:  Chronic inflammation predisposes to aging-associated disease, but it is unknown whether immunity regulation might be important for extending healthy lifespan. Here we show that in C. elegans, dietary restriction (DR) extends lifespan by modulating a conserved innate immunity pathway that is regulated by p38 signaling and the transcription factor ATF-7. Longevity from DR depends upon p38-ATF-7 immunity being intact but downregulated to a basal level. p38-ATF-7 immunity accelerates aging when hyperactive, influences lifespan independently of pathogen exposure, and is activated by nutrients independently of mTORC1, a major DR mediator. Longevity from reduced insulin/IGF-1 signaling (rIIS) also involves p38-ATF-7 downregulation, with signals from DAF-16/FOXO reducing food intake. We conclude that p38-ATF-7 is an immunometabolic pathway that senses bacterial and nutrient signals, that immunity modulation is critical for DR, and that DAF-16/FOXO couples appetite to growth regulation. These conserved mechanisms may influence aging in more complex organisms. 

Retracted: No

PubPeer comments:
 Figure 3G: More similar than expected, could authors check it please? ![file] , 
 Thank you for pointing this out - we will check our original images. , 
 These images of a fluorescent reporter gene were exhibited as representative depictions of the indicated samples, for which quantification is shown in a different figure panel. The first author Ziyun Wu has determined that the panels in question are actually two different photographic images of the same sample (daf-2(RNAi) DR day 7), with one shown mistakenly as being representative of EV(RNAi) DR day 7. I have attached correct images of these samples and apologize for this inadvertent mistake. We thank you for pointing out this mistake and will notify the journal. ![file] ,
Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β -Cell Mass in Middle-Aged Obese Diabetic Mice
Authors: Ryan McMillan
Zhenquan Jia
Kyung-Shin Suh
William Moore
Mostafa Ali
Dongmin Liu
Aihua Wang
Wei Zhen
Matthew Hulver
Zhiyong Cheng
Hana Alkhalidy
Yanling Zhang
Journal: Journal of diabetes research (2015)
Discipline: CLINICAL MEDICINE
Keywords: Insulin resistance; β-cell mass; type 2 diabetes; kaempferol; hyperglycemia
Affiliations: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA., Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA ; The Metabolic Phenotyping Core, Virginia Tech, Blacksburg, VA 24061, USA., Department of Biology, The University of North Carolina at Greensboro, Greensboro, NC 27412, USA.

Abstract:  Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction. 

Retracted: Yes

PubPeer comments:
 the western blot results were obviously modified. 4a ![file] 4d ![file] , 
 the blot of AMPKu03b1 in 4d has a different number of samples is and not shown in other blots in the same place (blue arrow). ![file] , 
 Dear Streptomyces, I appreciate your comments on this paper. I do see that Glut 4 blots were problematic and looks like that the control and HF+K1 (K2) from different blots. This experiment was performed by a visiting student and she sent to me all figures and images, which were to small to see this issue. She did this experiment in 2011 and left, so I will contact her right now to ask her explanation, and to determine if the images were unethically modified. Thank you again for spotting this issue. All the best, Dongmin ,
Bone morphogenetic protein and activin membrane‑bound inhibitor suppress bone cancer progression in MG63 and SAOS cells via regulation of the TGF‑β‑induced EMT signaling pathway
Authors: Fengsong Liu
Ya-Lin Yang
Liang Zhang
Kai Wang
Journal: Oncology Letters (2018)
Discipline: CLINICAL MEDICINE
Keywords: bone morphogenetic protein and activin membrane-bound inhibitor; growth; invasion; osteosarcoma; transforming growth factor-β/epithelial-to-mesenchymal transition.
Affiliations: Department of Orthopedics, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.

Abstract:  Bone cancer is one of the most common tumor types that occurs in bones and their affiliated tissues. The prognosis remains poor due to the limited number of effective therapeutic targets. Downregulation of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) has been observed in human cancer cells and BAMBI reconstitution can inhibit growth and metastasis of human cancer cells. In the present study, a potential mechanism mediated by BAMBI in osteosarcoma cells was investigated. The data demonstrated that BAMBI reconstitution suppressed the cell growth, migration and invasion of the osteosarcoma cell lines SAOS2 and MG63. Alterations to the epithelial-to-mesenchymal transition (EMT) marker expression were observed in BAMBI-treated osteosarcoma SAOS2 and MG63 cells. The apoptosis rate of SAOS2 and MG63 cells induced by cisplatin were increased in BAMBI-treated osteosarcoma SAOS2 and MG63 cells via downregulation of the anti-apoptosis genes P16, P21 and B-cell lymphoma 2. The potential mechanism investigated indicated that BAMBI administration downregulated the transforming growth factor-β (TGF-β) signaling pathway, whilst knockdown of BAMBI upregulated the TGF-β signaling pathway in SAOS2 and MG63 cells. Reconstitution of BAMBI in SAOS2 and MG63 cells resulted in a notable reduction of TGF-β-induced EMT, cell growth, migration and invasion in vitro. In conclusion, the results demonstrated that BAMBI reconstitution inhibited growth and invasiveness of osteosarcoma, as well as promoted the apoptotic sensibility, which indicated that the TGF-β-induced EMT signaling pathway may be regarded as a potential target for osteosarcoma therapy. 

Retracted: No

PubPeer comments:
 Figure 2 shows a bunch of prepared plasma beads. However all the beads in A and B look very similar to each other (light dot in the middle, little blob at the top) while the beads in C also look similar to each other (darker spot and slanted stripe at the top). Could the authors please explain how all beads look so identical to each other? Table 1 appears to suggest the beads are a bit more variable in diameter than shown in Figure 2. ![file] ,
Angelica sinensis polysaccharide inhibits proliferation, migration, and invasion by downregulating microRNA-675 in human neuroblastoma cell line SH-SY5Y
Authors: Jian Jiang
Lingzhen Wang
Lirong Sun
Yan Sun
Xiaojun Shao
Jing Yang
Journal: Cell Biology International (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Angelica sinensis polysaccharide; PI3K/AKT/JAK/STAT; anti-tumor activity; microRNA-675; neuroblastoma.
Affiliations: Department of Pediatric Hematology; The Affiliated Hospital of Qingdao University; Qingdao 266000 China, Department of Neurology; The Affiliated Hospital of Qingdao University; Qingdao 266000 China

Abstract:  Neuroblastoma is the most common tumor diagnosed in children and infants, with high recurrence and poor prognosis. Angelica sinensis polysaccharide (AP) whose average molecular weight is 72,900 Da possesses various bioactivities. We aimed to explore the effects of AP on neuroblastoma SH-SY5Y cells as well as the underlying mechanisms. Effects of AP on cell viability, proliferation, apoptosis, migration, invasion, and expressions of long noncoding RNA H19 (lncRNA-H19), microRNA (miR)-675, and CD44 were assessed. Then, effects of miR-675 overexpression on AP-treated cells were analyzed. Next, expression of key kinases in the PI3K/AKT and JAK/ STAT pathways was detected. The possible target gene of miR-675 was finally explored. Cell viability was reduced by 200-500 µg/mL AP. Meanwhile, AP repressed cell proliferation, migration, and invasion, but induced apoptosis. Expressions of lncRNA-H19 and miR-675 were upregulated in neuroblastoma cells, and were downregulated by AP. AP was also identified to upregulate CD44. We next found AP affected SH-SY5Y cells through downregulating miR-675. Key kinases in the PI3K/AKT and JAK/STAT pathways were downregulated by AP stimulation, while these downregulations were abrogated by miR-675 overexpression. KIF1B isoform β (KIF1Bβ) is proved to be a target of miR-675. In conclusion, AP was first identified to inhibit proliferation, migration, and invasion but induce apoptosis. Furthermore, AP might repress tumorigenesis of SH-SY5Y cells through miR-675-mediated inactivation of the PI3K/AKT and JAK/STAT pathways. Besides, KIF1Bβ might be a target of miR-675. 

Retracted: No

PubPeer comments:
 All the Western immunoblots in this articles are falsified, where all the blots share identical background. This is seen by increasing the contrast. An example is shown from Figure 5. Please note that this article is part of what we called Papermill 1, which has been described in more details here: https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers So far more than 550 papers have been identified as papermill 1 products. ![file] ,
Protein Kinase Cθ Via Activating Transcription Factor 2-Mediated CD36 Expression and Foam Cell Formation of Ly6C hi Cells Contributes to Atherosclerosis
Authors: Nikhlesh K Singh
Gadiparthi N Rao
Somasundaram Raghavan
Arul M Mani
Sivaiah Gali
Journal: Circulation (2018)
Discipline: CLINICAL MEDICINE
Keywords: CD36; G protein-coupled receptor signaling; PKCθ; atherosclerosis; foam cell
Affiliations: Department of Physiology, University of Tennessee Health Science Center, Memphis.

Abstract:  Background: Although the role of thrombin in atherothrombosis is well studied, its role in the pathogenesis of diet-induced atherosclerosis is not known. Methods: Using a mouse model of diet-induced atherosclerosis and molecular biological approaches, here we have explored the role of thrombin and its G protein-coupled receptor signaling in diet-induced atherosclerosis. Results: In exploring the role of G protein-coupled receptor signaling in atherogenesis, we found that thrombin triggers foam cell formation via inducing CD36 expression, and these events require Par1-mediated Gα12-Pyk2-Gab1-protein kinase C (PKC)θ-dependent ATF2 activation. Genetic deletion of PKCθ in apolipoprotein E (ApoE)-/- mice reduced Western diet-induced plaque formation. Furthermore, thrombin induced Pyk2, Gab1, PKCθ, and ATF2 phosphorylation, CD36 expression, and foam cell formation in peritoneal macrophages of ApoE-/- mice. In contrast, thrombin only stimulated Pyk2 and Gab1 but not ATF2 phosphorylation or its target gene CD36 expression in the peritoneal macrophages of ApoE-/-:PKCθ-/- mice, and it had no effect on foam cell formation. In addition, the aortic root cross-sections of Western diet-fed ApoE-/- mice showed increased Pyk2, Gab1, PKCθ, and ATF2 phosphorylation and CD36 expression as compared with ApoE-/-:PKCθ-/- mice. Furthermore, although the monocytes from peripheral blood and the aorta of Western diet-fed ApoE-/- mice were found to contain more of Ly6Chi cells than Ly6Clo cells, the monocytes from Western diet-fed ApoE-/-:PKCθ-/- mice were found to contain more Ly6Clo cells than Ly6Chi cells. It is interesting to note that the Ly6Chi cells showed higher CD36 expression with enhanced capacity to form foam cells as compared with Ly6Clo cells. Conclusions: These findings reveal for the first time that thrombin-mediated Par1-Gα12 signaling via targeting Pyk2-Gab1-PKCθ-ATF2-dependent CD36 expression might be playing a crucial role in diet-induced atherogenesis. 

Retracted: No

PubPeer comments:
 Figure 1F and 3G: * Blue boxes: The siPar1 panel in Figure 1F appears to significantly overlap with the siRhoA panel in Figure 3G. ![file] ,
Cross talk between DevS sensor kinase homologue, Rv2027c, and DevR response regulator of Mycobacterium tuberculosis
Authors: Vandana Malhotra
Deepak Kumar Saini
Jaya Sivaswami Tyagi
Journal: FEBS Letters (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Rv2027c; histidine sensor kinase; DevS; hypoxia-responsive; autophosphorylation
Affiliations: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.

Abstract:  Rv2027c is a putative orphan histidine sensor kinase that bears strong homology to DevS of the hypoxia-responsive DevR-DevS two-component system in M. tuberculosis. The cytosolic C-terminal domain of Rv2027c protein (Rv2027c(194)) was overexpressed in E. coli and biochemically characterized. Rv2027c(194) underwent autophosphorylation at a conserved His(392) residue and engaged in phosphotransfer with DevR response regulator. The rates of autophosphorylation and the stabilities of the phosphorylated species were broadly similar in Rv2027c and DevS. However, unlike DevS, Rv2027c utilized Ca(2+) as an alternative divalent ion during autophosphorylation. In contrast to DevS which completed phosphotransfer to DevR in 5-10 min, phosphotransfer from Rv2027c approximately P was only partial at 30 min. Unlike devS transcription that was hypoxia-responsive, Rv2027c transcript levels were not upregulated from basal levels during hypoxia. The differential regulation of devS and Rv2027c genes, the ability of Rv2027c to utilize Ca(2+) as a divalent cation in autophosphorylation at physiological concentrations and to engage in phosphotransfer with DevR suggests that the DevR regulon could be modulated by more than one environmental cue relayed through DevS and Rv2027c. 

Retracted: No

PubPeer comments:
 ![file] ,