PReD-Bench/PRed-Bench huggingface dataset:
Association of Daily Wear of Eyeglasses With Susceptibility to Coronavirus Disease 2019 Infection
Authors: Yiping Wei
Xingting Qiu
Junyu Li
Pinhong Song
Xiaolin Wang
Jianjun Xu
Yong Yang
Weibiao Zeng
Journal: JAMA Ophthalmology (2020)
Discipline: CLINICAL MEDICINE
Keywords: eyeglasses; COVID-19 susceptibility; myopia; daily wear; hospitalization
Affiliations: Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China., Department of Critical Care Medicine, Suizhou Zengdu Hospital, Suizhou, China., Department of Radiotherapy, Jiangxi Cancer Hospital, Nanchang, China., Department of Computed Tomography and Magnetic Resonance Imaging, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.

Abstract:  Importance: The proportion of daily wearers of eyeglasses among patients with coronavirus disease 2019 (COVID-19) is small, and the association between daily wear of eyeglasses and COVID-19 susceptibility has not been reported. Objective: To study the association between the daily wearing of eyeglasses and the susceptibility to COVID-19. Design, setting, and participants: This cohort study enrolled all inpatients with COVID-19 in Suizhou Zengdu Hospital, Suizhou, China, a designated hospital for COVID-19 treatment in the area, from January 27 to March 13, 2020. COVID-19 was diagnosed according to the fifth edition of Chinese COVID-19 diagnostic guidelines. The proportion of persons with myopia who wore eyeglasses in Hubei province was based on data from a previous study. Exposures: Daily wearing of eyeglasses for more than 8 hours. Main outcomes and measures: The main outcomes were the proportions of daily wearers of eyeglasses among patients admitted to the hospital with COVID-19 and among the local population. Data on exposure history, clinical symptoms, underlying diseases, duration of wearing glasses, and myopia status and the proportion of people with myopia who wore eyeglasses in Hubei province were collected. People who wore glasses for more than 8 hours a day were defined as long-term wearers. Results: A total of 276 patients with COVID-19 were enrolled. Of these, 155 (56.2%) were male, and the median age was 51 (interquartile range, 41-58) years. All those who wore glasses for more than 8 hours a day had myopia and included 16 of 276 patients (5.8%; 95% CI, 3.04%-8.55%). The proportion of people with myopia in Hubei province, based on a previous study, was 31.5%, which was much higher than the proportion of patients with COVID-19 who had myopia in this sample. Conclusions and relevance: In this cohort study of patients hospitalized with COVID-19 in Suizhou, China, the proportion of inpatients with COVID-19 who wore glasses for extended daily periods (&gt;8 h/d) was smaller than that in the general population, suggesting that daily wearers of eyeglasses may be less susceptible to COVID-19. 

Retracted: No

PubPeer comments:
 https: twitter.com GidMK status 1307853460751040512 ,
Id3 and Bcl6 Promote the Development of Long-Term Immune Memory Induced by Tuberculosis Subunit Vaccine
Authors: Juan Wang
Jiangyuan Han
Lan Ma
Chunxiang Bai
Tao Xie
Wei Lv
Daquan Tan
Bingdong Zhu
Yanlin Ma
Hongxia Niu
Youjun Mi
Journal: Vaccines (2021)
Discipline: IMMUNOLOGY
Keywords: Bcl6; IL-7; Id3; immune memory; vaccine.
Affiliations: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China., Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China., Institute of Pathophysiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.

Abstract:  Long-lived memory cell formation and maintenance are usually regulated by cytokines and transcriptional factors. Adjuvant effects of IL-7 have been studied in the vaccines of influenza and other pathogens. However, few studies investigated the adjuvant effects of cytokines and transcriptional factors in prolonging the immune memory induced by a tuberculosis (TB) subunit vaccine. To address this research gap, mice were treated with the Mycobacterium tuberculosis (M. tuberculosis) subunit vaccine Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64&lt;190-198&gt;-Mtb8.4-Rv2626c (LT70), together with adeno-associated virus-mediated IL-7 or lentivirus-mediated transcriptional factor Id3, Bcl6, Bach2, and Blimp1 at 0, 2, and 4 weeks, respectively. Immune responses induced by the vaccine were examined at 25 weeks after last immunization. The results showed that adeno-associated virus-mediated IL-7 allowed the TB subunit vaccine to induce the formation of long-lived memory T cells. Meanwhile, IL-7 increased the expression of Id3, Bcl6, and bach2-the three key transcription factors for the generation of long-lived memory T cells. The adjuvant effects of transcriptional factors, together with TB fusion protein MH/LT70 vaccination, showed that both Bcl6 and Id3 increased the production of antigen-specific antibodies and long-lived memory T cells, characterized by high proliferative potential of antigen-specific CD4+ and CD8+ T cells, and IFN-γ secretion in CD4+ and CD8+ T cells, respectively, after re-exposure to the same antigen. Overall, our study suggests that IL-7 and transcriptional factors Id3 and Bcl6 help the TB subunit vaccine to induce long-term immune memory, which contributes to providing immune protection against M. tuberculosis infection. 

Retracted: No

PubPeer comments:
 This paper is one of a small collection of papers which appears to include a typographical error in the spelling of an manufacturer. The company name is ACEA Biosciences headquartered in San Diego. In this paper and the others, the name is spelled ACEC. This suggests that the paper was written from a common template, although the author groups are mostly different. *** ![file] , 
 Many thanks for your pointing out the mistake. It should be ACEA. ,
Hispidulin attenuates bone resorption and osteoclastogenesis via the RANKL-induced NF-κB and NFATc1 pathways
Authors: Liang Li
Jung-Il Chae
Bo-Yun Choi
Moon-Shik Yang
Manoj Nepal
Yunjo Soh
Hwa Jung Choi
Journal: European Journal of Pharmacology (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Bone resorption; Hispidulin; Osteoclastogenesis; RANKL; μCT.
Affiliations: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University, Jeonju 561-756, Republic of Korea.

Abstract:  Hispidulin, a flavonoid that is known to have anti-inflammatory and anti-oxidant effects, attenuates osteoclastogenesis and bone resorption. To investigate the molecular mechanism of its inhibitory effect on osteoclastogenesis, we employed the receptor activator of the nuclear factor κB (NF-κB) ligand (RANKL)-induced murine monocyte/macrophage RAW 264.7 cells and bone marrow-derived macrophages (BMMs) for osteoclastic differentiation in vitro. The inhibitory effect on in vitro osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and by measuring the expression levels of osteoclast-specific genes such as matrix metalloproteinase 9 (MMP9), TRAP and cathepsin K. Similarly, hispidulin significantly inhibited osteoclast activity in RAW 264.7 cell as well as stimulated the ALP activity of MC3T3E1 cells. Furthermore, the in vivo suppressive effect on bone loss was assessed quantitatively in a lipopolysaccharide (LPS)-induced mouse model using microcomputational tomography (μCT) and histochemical analyses. Hispidulin was found to inhibit RANKL-induced activation of Jun N-terminal kinase (JNK) and p38, in addition to NF-κB in vitro experiment. Additionally, hispidulin decreased NFATc1 transcriptional activity in RANKL-induced osteoclastogenesis. This study identifies hispidulin as a potent inhibitor of osteoclastogenesis and bone resorption and provides evidence for its therapeutic potential to treat diseases involving abnormal bone lysis. 

Retracted: No

PubPeer comments:
 Figure 4B appears to have a vertical splice in the phospo-p65 and phospo-Iu03baB bands, but none appear in the others. Can the authors provide the full blots for analysis? *** ![file] ,
Abnormal Locus Coeruleus Sleep Activity Alters Sleep Signatures of Memory Consolidation and Impairs Place Cell Stability and Spatial Memory
Authors: Gary Aston-Jones
Michelle A Frazer
Brooks A Gross
Yong Li
Elena M Vazey
Susan J Sara
Gina R Poe
Anthony E Pickering
David S Bauer
Kevin M Swift
Kyle J D Clark
Journal: Current Biology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NREM; REM; hippocampus; locus coeruleus; optogenetic
Affiliations: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA., Integrative Biology and Physiology Department and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA., Department of Biology, University of Massachusetts, Amherst, MA 01003, USA., Brain Health Institute, Rutgers University, New Brunswick, NJ 08854, USA., School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol BS8 1TD, UK., Center for Interdisciplinary Research in Biology, College de France, Paris 75005, France; Child and Adolescent Psychiatry, New York University Medical School, New York, NY 10003, USA., Integrative Biology and Physiology Department and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: .

Abstract:  Sleep is critical for proper memory consolidation. The locus coeruleus (LC) releases norepinephrine throughout the brain except when the LC falls silent throughout rapid eye movement (REM) sleep and prior to each non-REM (NREM) sleep spindle. We hypothesize that these transient LC silences allow the synaptic plasticity that is necessary to incorporate new information into pre-existing memory circuits. We found that spontaneous LC activity within sleep spindles triggers a decrease in spindle power. By optogenetically stimulating norepinephrine-containing LC neurons at 2 Hz during sleep, we reduced sleep spindle occurrence, as well as NREM delta power and REM theta power, without causing arousals or changing sleep amounts. Stimulating the LC during sleep following a hippocampus-dependent food location learning task interfered with consolidation of newly learned locations and reconsolidation of previous locations, disrupting next-day place cell activity. The LC stimulation-induced reduction in NREM sleep spindles, delta, and REM theta and reduced ripple-spindle coupling all correlated with decreased hippocampus-dependent performance on the task. Thus, periods of LC silence during sleep following learning are essential for normal spindle generation, delta and theta power, and consolidation of spatial memories. 

Retracted: No

PubPeer comments:
 Figure 5C. * Orange boxes: In the +Frac CBX PHC panel the same area appears to be visible twice ![file] ,
TRIM56 suppresses the malignant development of hepatocellular carcinoma via targeting RBM24 and inactivating the Wnt signaling
Authors: W-X Guo
Y Yang
F-F Mao
L Guo
Journal: European review for medical and pharmacological sciences (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: TRIM56; Hepatocellular carcinoma; Prognosis; Molecular mechanisms; Clinical data
Affiliations: Department of Hepatic Surgery VI, Third Affiliated Hospital of Second Military Medical University, Shanghai, China. .

Abstract:  Objective: The aim of this study was to explore the expression pattern of TRIM56 in Hepatocellular carcinoma (HCC) patients and its influence on the prognosis, and to illustrate the molecular mechanisms of TRIM56 in regulating HCC cell behaviors. Patients and methods: TRIM56 levels in HCC specimens and paracancerous specimens were detected. Then, the influences of TRIM56 on clinical data and prognosis in HCC patients were assessed. Next, the regulatory effects of TRIM56 on proliferative potential in Huh7 and Bel-7402 cells were determined, and the role of TRIM56 on the Wnt signaling was examined. Finally, biological characteristics between TRIM56 and RBM24 in HCC development were illustrated by Luciferase assay and rescue experiments. Results: TRIM56 was lowly expressed in HCC tissues and cell lines. HCC patients expressing a low level of TRIM56 suffered advanced T stage and poor survival. Besides, overexpression of TRIM56 inhibited proliferative potential of Huh7 cells, while knockdown of TRIM56 in Bel-7402 yielded the opposite result. TRIM56 was able to negatively regulate key genes in the Wnt signaling. In addition, RBM24 was proven to be the downstream target of TRIM56, which was involved in TRIM56-influenced HCC development. Conclusions: Downregulated TRIM56 in HCC samples is closely linked to pathological staging and prognosis. TRIM56 alleviates the malignant development of HCC by inactivating the Wnt signaling and targeting RBM24. 

Retracted: No

PubPeer comments:
 The images in Figure 3 appear to have some repeated features. *** ![file] , 
 Figure 7 too. *** ![file] , 
 Middle panel of Figure 7, using false color. I suspect I have not identified them all. *** ![file] ,
Inhaled carbon monoxide confers antiinflammatory effects against ventilator-induced lung injury
Authors: Mária Szilasi
Augustine M K Choi
Mingyao Liu
Tamás Dolinay
Journal: American Journal of Respiratory and Critical Care Medicine (2004)
Discipline: CLINICAL MEDICINE
Keywords: Ventilator-induced lung injury; heme oxygenase-1; carbon monoxide; antiinflammatory effects; rat model
Affiliations: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

Abstract:  Ventilator-induced lung injury (VILI) is a major cause of morbidity and mortality in intensive care units. The stress-inducible gene product, heme oxygenase-1, and carbon monoxide (CO), a major by-product of heme oxygenase catalysis of heme, have been shown to confer potent antiinflammatory effects in models of tissue and cellular injury. In this study, we observed increased expression of heme oxygenase-1 mRNA and protein in a rat model of VILI. To assess the physiologic function of heme oxygenase-1 induction in VILI, we determined whether low concentration of inhaled CO could serve to protect the lung against VILI. Low concentration of inhaled CO significantly reduced tumor necrosis factor-alpha levels and total cell count in lavage fluid, while simultaneously elevating levels of antiinflammatory interleukin-10 levels. To better characterize the mechanism of CO-mediated antiinflammatory effects, we examined key signaling pathways, which may mediate CO-induced antiinflammatory effects. We demonstrate that inhaled CO exerts antiinflammatory effects in VILI via the p38 mitogen-activated protein kinase pathway but independent of activator protein-1 and nuclear factor-kappaB pathways. Our data lead to a tempting speculation that inhaled CO might be useful in minimizing VILI. 

Retracted: No

PubPeer comments:
 Figure 7. Many more similarities than differences. https: imgur.com CzwHFSz ,
Redefining the intraepithelial lymphocytes threshold to diagnose gluten sensitivity in patients with architecturally normal duodenal histology
Authors: V Villanacci
G Magazzù
S Pellegrino
G Vieni
G Tuccari
A Princiotta
C Sferlazzas
G Bassotti
N Sansotta
R Scarfì
Journal: Alimentary Pharmacology & Therapeutics (2011)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Intraepithelial lymphocytes; coeliac disease; diagnostic accuracy; HLA-DQ2/DQ8 alleles; sensitivity
Affiliations: Regional Celiac Center, Pad. NI, University Hospital G. Martino, via Consolare Valeria 1, Messina, Italy. 

Abstract:  Background: Accuracy of intraepithelial lymphocytes counts for diagnosing mild enteropathy coeliac disease in absence of villous atrophy can be limited by inappropriate controls included in the studies. Aim: To determine the diagnostic accuracy of intraepithelial lymphocytes counts utilising controls lacking HLA coeliac disease-associated alleles. Methods: Intraepithelial lymphocytes counting at villus tip and per 100 enterocytes was performed at haematoxylin and eosin (H&amp;E) and CD3-stainings in: 29 cases (21 with potential coeliac disease and 8 affected by latent coeliac disease) representing the patient population and 14 noncoeliac controls lacking HLA-DQ2/DQ8 alleles. Results: Threshold (mean+2 s.d.) of duodenal intraepithelial lymphocytes at villus tip and per 100 enterocytes in noncoeliac controls was respectively: 3.5 and 18 at H&amp;E, 3.2 and 17 following CD3-staining. Considering the whole patient population, the sensitivity of tip intraepithelial lymphocytes in detecting mild enteropathy coeliac disease was 90% (95% CI=72.6-97.8) both at H&amp;E and CD3-stainings. The sensitivity of intraepithelial lymphocytes per 100 enterocytes was 93% (95% CI=77.2-99.2) both at H&amp;E and CD3-staining. Specificity of both intraepithelial lymphocytes counts was 100% (95% CI=76.8-100). Using a threshold of 25 intraepithelial lymphocytes per 100 enterocytes could miss 59% of cases at H&amp;E and 48% following CD3-staining. Conclusions: Intraepithelial lymphocytes counts are diagnostic feasible tools to detect mild enteropathy coeliac disease. Threshold of duodenal intraepithelial lymphocytes may be lower than currently accepted. 

Retracted: No

PubPeer comments:
 Can the authors check these images? The third image is clearly duplicated from the others two. ![file] , 
 Duplications in this paper and DOI: 10.3748 wjg.v21.i9.2593 by Bassotti G and Villanacci V. ![file] , 
 ![file] , 
 ![file] , 
 Same histopathology images but patients are from different casistic. ![file] ,
S. boulardii Fails to Hold Its Cell Wall Integrity against Nonpathogenic E. coli: Are Probiotic Yeasts Losing the Battle?
Authors: Anindita Gayen
Sandip Paul
Manabendra Chandra
Deepak Singh
Satyajit Lenka
Journal: ACS Infectious Diseases (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: cell wall damage; dark-field microscopy; drug-resistance and pathogenicity; lipopolysaccharides; live cell imaging.
Affiliations: Department of Chemistry Indian Institute of Technology Kanpur UP-208016, India

Abstract:  Probiotic yeast Saccharomyces boulardii exerts direct probiotic action on pathogenic E. coli by trapping them on surfaces and inactivating toxic lipopolysaccharides. Using optical dark-field microscopy, we show that nonpathogenic E. coli cells also readily bind probiotic S. boulardii. More importantly, the adhered nonpathogenic E. coli progressively damage S. boulardii cell walls and lyse them. Co-cultured methylene blue-supplemented agar-plate assay indicates that rough lipopolysaccharides might be playing a key role in S. boulardii cell wall damage. When experiments are repeated with lipopolysaccharide-depleted E. coli and also lipopolysaccharide-deficient E. coli, adhesion decreases substantially. The co-cultured assay further reveals that free lipopolysaccharides, released from E. coli, are also causing damage to S. boulardii walls like adhered E. coli. These new findings contradict the known S. boulardii-E. coli interaction mechanisms. We confirm that E. coli cells do not bind or damage human erythrocyte cell walls; therefore, they have not developed pathogenicity. The combined results demonstrate the first example of nonpathogenic E. coli being harmful to probiotic yeast S. boulardii. This finding is important because gut microbial flora contain large numbers of nonpathogenic E. coli. If they bind or damage probiotic S. boulardii cell walls, then the probiotic efficiency toward pathogenic E. coli will be compromised. 

Retracted: No

PubPeer comments:
 In SI video (see https: pubs.acs.org doi suppl 10.1021 acsinfecdis.0c00413 suppl_file id0c00413_si_003.mp4), authors claim to show that  Cytosol leaks out from S. boulardii that trap E. coli . I have to admit that I am not able to see such a leakage. Could the authors better explain how they concluded to a cytosol leakage from this video ? Fig S6 is supposed to support the efficiency of chemical LPS-depletion. If some LPS can be detected after treatment because it is released in the medium, I see no quantification of LPS remaining in E. coli cells so that no conclusion about the efficiency of treatment can be drawn. ![file] Could the authors bring evidence that cells are indeed LPS-depleted ? Also, DH-5a are used as  LPS-deficient cells, but they are not. Authors explanation stating that recA mutation causes cells to be longer so that LPS is  more diluted along the cell wall is absurd. Could the authors provide a more detailed explanation if I missed a point ? Thank you ,
miR-217 targeting Wnt5a in osteosarcoma functions as a potential tumor suppressor
Authors: Jiajia Su
Renxiong Wei
Zhouming Deng
Journal: Biomedicine & Pharmacotherapy (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Osteosarcoma; Tumor progression; Wnt5a; miR-217.
Affiliations: Department of Orthopaedic, Zhongnan Hospital of Wuhan University, 169, Donghu Road, Wuhan, Hubei 430071, China. Electronic address: ., Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, China., Department of Radiology, Hubei Cancer Hospital, Wuhan, Hubei, China.

Abstract:  Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults, however roles of microRNAs (miRNAs) in OS is still unclear. miR-217 is recently widely studied in various cancers, but not including OS. This study is aimed to investigate the expression and cellular function of miR-217 in OS. The data showed that miR-217 expression was consistently lower in OS tissues and cell lines than the normal controls. Restoration of miR-217 expression in MG-63 and U2OS cells could inhibit cell proliferation, migration and invasion, and induced apoptosis. Bioinformatic prediction suggested that Wnt5a is a target gene of miR-217. Using luciferase assay, mRNA and protein expression analysis, it was verified that Wnt5a was a target gene of miR-217 in OS cells. Restored expression of Wnt5a weakened miR-217-mediated suppression of tumor progression. Taken together, our data indicate that miR-217 functions as a tumor suppressor in OS by suppressing Wnt5a expression. 

Retracted: No

PubPeer comments:
 Fig 6C.  Cell apoptosis of MG-63 cells co-infected with miR-217 and LV-Wnt5a was detected by Annexin V-PE staining . ![file] All the points cells plotted in the right-hand panel are also present in the left-hand control panel. They appear to have been plotted from the same raw-data file. Here dramatised by color-reversing the miR-217+Wnt5a result and superimposing it on the Control result. Red points are unique to the latter. Any points unique to the former would be cyan. ![file] ,
AEG-1 induces gastric cancer metastasis by upregulation of eIF4E expression
Authors: Ping Li
Shengjie Wu
Xuerong Wang
Dandan Wu
Wenbin Huang
Zhongyuan Gao
Li Yang
Journal: Journal of Cellular and Molecular Medicine (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AEG-1; eIF4E; epithelial-mesenchymal transition; gastric cancer; metastasis.
Affiliations: Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China., Department of General Surgery, Medical Oncology and Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China., Department of Basic Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China., Department of Pathology, Nanjing Medical University Affiliated Nanjing Hospital (Nanjing First Hospital), Nanjing, Jiangsu, China.

Abstract:  Gastric cancer is the third leading cause of cancer-related deaths worldwide, and patients with lymph node, peritoneal and distant metastasis have a poor prognosis. Overexpression of Astrocyte-elevated gene-1 (AEG-1) has been reported to be correlated with the progression and metastasis of gastric cancer. However, its mechanisms are quite unclear. In this study, we found that elevated expression of AEG-1 was correlated with metastasis in human gastric cancer tissues. Moreover, gain- or loss-of-function of AEG-1, respectively, promoted or suppressed epithelial-mesenchymal transition (EMT), migration and invasion of gastric cancer cells. AEG-1 positively regulated eIF4E, MMP-9 and Twist expression. Manipulating eIF4E expression by transfection of overexpression constructs or siRNAs partially eliminated AEG-1-regulated EMT, cell migration and invasion. In addition, overexpression or knockdown of eIF4E promoted or suppressed EMT, cell migration and invasion in parallel with upregulation of MMP-9 and Twist expression, while manipulating eIF4E expression partially abrogated AEG-1-induced MMP-9 and Twist. Finally, silencing of AEG-1 expression not only inhibited tumour growth in parallel with downregulation of eIF4E, MMP-9 and Twist expression in a xenograft nude mouse model, but also suppressed lymph node and peritoneal metastasis of gastric cancer in an orthotopic nude mouse model. These findings suggest that AEG-1 promotes gastric cancer metastasis through upregulation of eIF4E-mediated MMP-9 and Twist, which provides new diagnostic markers and therapeutic targets for cancer metastasis. 

Retracted: No

PubPeer comments:
 Figure 5 appears to have an image overlap. B is a migration assay and C is an invasion assay so they should not be the same. ![file] ,
Peroxisomal and microsomal lipid pathways associated with resistance to hepatic steatosis and reduced pro-inflammatory state
Authors: Jacques S Beckmann
Bernard Thorens
Christophe Empsen
Carine Poussin
Mark Ibberson
Matej Oresic
Albert E Geerts
Magali Joffraud
Diana Hall
Yann Ravussin
Vidya R Velagapudi
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: liver fat accumulation; genetic susceptibility; hepatosteatosis; obesity; transcriptomic analysis
Affiliations: Department of Physiology and Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.

Abstract:  Accumulation of fat in the liver increases the risk to develop fibrosis and cirrhosis and is associated with development of the metabolic syndrome. Here, to identify genes or gene pathways that may underlie the genetic susceptibility to fat accumulation in liver, we studied A/J and C57Bl/6 mice that are resistant and sensitive to diet-induced hepatosteatosis and obesity, respectively. We performed comparative transcriptomic and lipidomic analysis of the livers of both strains of mice fed a high fat diet for 2, 10, and 30 days. We found that resistance to steatosis in A/J mice was associated with the following: (i) a coordinated up-regulation of 10 genes controlling peroxisome biogenesis and β-oxidation; (ii) an increased expression of the elongase Elovl5 and desaturases Fads1 and Fads2. In agreement with these observations, peroxisomal β-oxidation was increased in livers of A/J mice, and lipidomic analysis showed increased concentrations of long chain fatty acid-containing triglycerides, arachidonic acid-containing lysophosphatidylcholine, and 2-arachidonylglycerol, a cannabinoid receptor agonist. We found that the anti-inflammatory CB2 receptor was the main hepatic cannabinoid receptor, which was highly expressed in Kupffer cells. We further found that A/J mice had a lower pro-inflammatory state as determined by lower plasma levels and IL-1β and granulocyte-CSF and reduced hepatic expression of their mRNAs, which were found only in Kupffer cells. This suggests that increased 2-arachidonylglycerol production may limit Kupffer cell activity. Collectively, our data suggest that genetic variations in the expression of peroxisomal β-oxidation genes and of genes controlling the production of an anti-inflammatory lipid may underlie the differential susceptibility to diet-induced hepatic steatosis and pro-inflammatory state. 

Retracted: No

PubPeer comments:
 2020 correction. https: www.jbc.org content 295 22 7813.short An incorrect version of Fig. 4B was inadvertently used in the version of this article that was published on October 1, 2010. This error has now been corrected. ,
Increasing miR-150 and lowering HMGA2 inhibit proliferation and cycle progression of colon cancer in SW480 cells
Authors: L-M Yin
L-L Wu
Z-C Zhang
G-P Wang
M Li
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HMGA2; miR-150; colorectal cancer; cell proliferation; cell cycle
Affiliations: Department of Gastroenterology, The First People's Hospital of Wenling, Wenling, Zhejiang Province, China. .

Abstract:  Objective: High mobility group protein A2 (HMGA2) is a kind of oncogene that regulates cell proliferation and cycle. HMGA2 up-regulation is related to the occurrence of multiple tumors including colorectal cancer. MiR-150 is found down-regulated in colorectal cancer tissue. Bioinformatics analysis shows the complementary targeted relationship between miR-150 and the 3'-UTR of HMGA2. This study explores the role of microRNA-150 (miR-150) in regulating HMGA2 expression, colorectal cancer cell proliferation, and cycle. Patients and methods: Colorectal cancer patients were enrolled to collect cancer and para-carcinoma tissues. MiR-150 and HMGA2 expressions were tested in tissue. MiR-150, HMGA2, and Cyclin A levels in colorectal cancer cell line SW480, and normal colorectal epithelial cell line FHC were compared. The targeted relationship between miR-150 and the 3'-UTR of HMGA2 was evaluated by dual luciferase reporter gene assay. SW480 cells were divided into five groups, including miR-control, miR-150 mimic, small interfere normal control (si-NC), si-HMGA2, and miR-150 mimic + si-HMGA2. Cell cycle was determined by using flow cytometry. The cell proliferation was detected by using the cell counting kit 8 (CCK-8) test. Results: HMGA2 expression was significantly increased, while miR-150 levels were significantly declined in colorectal cancer tissue compared with that in para-carcinoma tissue (p&lt;0.05). HMGA2 and Cyclin A levels were higher significantly, whereas miR-150 expression was lower significantly in SW480 cells compared to that in FHC cells (p&lt;0.05). MiR-150 targeted band to the 3'-UTR of HMGA. MiR-150 mimic and/or si-HMGA2 significantly reduced HMGA2 and Cyclin A expressions, blocked cell cycle in the G0/G1 phase, and attenuated cell proliferation. Conclusions: We observed that miR-150 down-regulated Cyclin A expression to block colorectal cancer cell cycle and inhibit proliferation through targeted inhibiting HMGA2. 

Retracted: No

PubPeer comments:
 This paper has features suggestive of [what has elsewhere been labeled as  Papermill #2 ] , characterised by stylised geometrical WBs that are reduced to sharp-edged black ovals on a featureless grey background, reminiscent of a Miro painting: ![file] ![file] Other examples are listed in a Google document. https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit?usp=sharing ,
Human embryonic stem cells and derived contractile embryoid bodies are susceptible to Coxsakievirus B infection and respond to interferon Iβ treatment
Authors: Carolina Jaquenod de Giusti
María Questa
Ricardo M Gómez
María E Scassa
Gabriela Pretre
María F Ferrer
Santiago G Miriuka
Guillermo A Videla Richardson
Gustavo E Sevlever
Leonardo Romorini
Carolina Bluguermann
Journal: Stem Cell Research (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: human embryonic stem cells; Coxsackievirus B; infection; cardiac phenotype; receptors
Affiliations: Laboratorio de Biología del Desarrollo Celular, FLENI, Buenos Aires, Argentina.

Abstract:  We studied the susceptibility of human embryonic stem cells and derived contractile embryoid bodies from WAO9, HUES-5 and HUES-16 cell lines to Coxsackievirus B infection. After validating stem cell-like properties and cardiac phenotype, Coxsackievirus B receptors CAR and DAF, as well as type I interferon receptors were detected in all cell lines and differentiation stages studied. Real-time PCR analysis showed that CAR mRNA levels were 3.4-fold higher in undifferentiated cells, while DAF transcript levels were 2.78-fold more abundant in differentiated cultures (P&lt;0.05). All cell lines were susceptible to Coxsackievirus serotypes B1-5 infection as shown by RT-PCR detection of viral RNA, immunofluorescence detection of viral protein and infectivity titration of cell culture supernatants resulting in cell death. Supernatants infectivity titers 24-48 h post-infection ranged from 10⁵-10⁶ plaque forming units (PFU)/ml, the highest titers were detected in undifferentiated cells. Cell viability detected by a colorimetric assay, showed inverse correlation with infectivity titers of cell culture supernatants. Treatment with 100 U of interferon Iβ significantly reduced viral replication and associated cell death during a 24-48 h observation period, as detected by reduced infectivity titers in the supernatants and increased cell viability by a colorimetric assay, respectively. We propose human embryonic stem cell and derived contractile embryoid bodies as a valid model to study cardiac Coxsackievirus B infection. 

Retracted: No

PubPeer comments:
 Figure 4: More similar than expected. Could authors check it please? ![file] ,
Aqueous Fraction of Huogu Formula Promotes Osteogenic Differentiation of Bone Marrow Stromal Cells Through the BMP and Wnt Signaling Pathways
Authors: Xiangying Kong
Weiheng Chen
Liuluan Zhu
Hongye Wan
Cuiling Liu
Xiaomin Li
Hongchang Su
Qingxia Qin
Jia Zhu
Na Lin
Cun Zhang
Journal: Rejuvenation research (2016)
Discipline: CLINICAL MEDICINE
Keywords: BMP; Wnt; aqueous fraction of HG.
Affiliations: 1 Institute of Chinese Materia Medica , China Academy of Chinese Medical Sciences, Beijing, China ., 2 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University , Beijing, China ., 3 Beijing Key Laboratory of Emerging Infectious Diseases , Beijing, China ., 4 Wangjing Hospital , China Academy of Chinese Medical Sciences, Beijing, China .

Abstract:  Our recent studies have shown that Huogu (HG) formula was effective both in clinic experience and in experimental osteonecrosis of the femoral head (ONFH). Given that defective of bone marrow stromal cells (MSCs) contribute to the development of osteonecrosis and MSCs show enormous potential in the treatment of ONFH, especially to aging people. How HG impacts the differentiation of MSCs and what is the underlying cellular and molecular mechanism remains largely unknown. Here, we found that an aqueous fraction of HG (HGA) significantly increased the alkaline phosphatase (ALP) activity, mineralized nodules, and migration of MSCs in a dose-dependent manner. Meanwhile, HGA could enhance the mRNA and protein expression of Runt-related transcription factor 2 (Runx2), Alp, Bmp2, osteocalcin (Ocn), and Osterix (Osx). Further investigation of the molecular mechanisms revealed that HGA treatment obviously increased expression, secretion, and activation of bone morphogenetic protein (BMP) 2 and β-catenin, two key regulators of the BMP or Wnt signaling pathway. Furthermore, osteogenic differentiation of MSCs could be blocked by using pharmacological inhibitors for these signaling pathways such as Noggin and Dkk-1. Besides, HGA could inhibit adipogenic differentiation of MSCs. Our study reveals that HGA promotes the osteogenesis of MSCs via the BMP and Wnt signaling pathways. Our findings provide mechanistic insights into the role of HG in treating ONFH. 

Retracted: No

PubPeer comments:
 Figure 2A * Green boxes: In the bottom row, the HGA 25ng mL panel looks similar to the HGA 100ng mL panel * Red boxes: In the bottom row, the HGA 50ng mL panel looks similar to the E2 panel ![file] , 
 #1 Here comparing Fig 2A (below) with (above) Fig 4A from [Kong et al (2017)] . ![file] The same panel illustrates the Control condition in the two studies, which is not unreasonable. I am more concerned with the overlap (shown in brown boxes) between the present E2 condition, and the HGE 100ng mL condition in the other paper. ,
Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders
Authors: Hong-Kun Wu
Yan Zhang
Ping Jiang
Chun-Mei Cao
Fenghua Liu
Peng Jiang
Rui-Ping Xiao
Fengxiang Lv
Mao Zhang
Ruisheng Song
Li Jin
Xiuqin Zhang
Shaoshuai Meng
Xin Zhang
Yanbin Pi
Wei Peng
Yongxing Cao
Jiaojiao Guo
Journal: Nature (2013)
Discipline: Multidisciplinary
Keywords: Insulin resistance; skeletal muscle; MG53; TRIM72; metabolic syndrome
Affiliations: Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871, China.

Abstract:  Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes. Although skeletal muscle accounts for 70-90% of insulin-stimulated glucose disposal, the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1), and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications. 

Retracted: No

PubPeer comments:
 Readers should become aware of a recent preprint entitled  MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle that calls into question part of the conclusions of Song et al., study https: www.biorxiv.org content 10.1101 2020.12.24.424288v1 From the Discussion:  Our results failed to confirm the role of MG53 as a critical regulator of insulin signaling pathway in vitro and of glucose homeostasis in vivo in contrast to earlier reports [7,8]. While we cannot exclude the possibility that different reagents may lead to different results, our data raise significant doubts about the involvement of MG53 in the regulation of insulin signaling. ,
The pivotal role of SUMO-1-JNK-Tau axis in an in vitro model of oxidative stress counteracted by the protective effect of curcumin
Authors: Jessica Dragotto
Federico Iorio
Kambiz Hassanzadeh
Marco Feligioni
Massimo Corbo
Lucia Buccarello
Journal: Biochemical Pharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Curcumin; JNK; Oxidative Stress; SUMO-1; Tau protein.
Affiliations: Laboratory of Neuropharmacology, EBRI Rita Levi-Montalcini Foundation, Rome, Italy., Laboratory of Neuropharmacology, EBRI Rita Levi-Montalcini Foundation, Rome, Italy; Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran., Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Milan, Italy., Laboratory of Neuropharmacology, EBRI Rita Levi-Montalcini Foundation, Rome, Italy; Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Milan, Italy. Electronic address: .

Abstract:  Oxidative stress is a toxic cellular condition, strictly related to inflammation and known to be a common feature of many neurodegenerative diseases. The imbalanced redox state modifies several molecular processes including protein SUMOylation, JNK and Tau protein activation, important actors in Alzheimer's disease. In this study, we showed a strong interaction among SUMO-1-JNK-Tau proteins and their molecular targets in an in vitro model (SHSY5Y cell line) of oxidative stress in which a significant reduction of cell viability and an augmented cell death was induced by increased doses of H2O2. The evoked oxidative stress led to a deficiency in the degradation system showing altered levels of Caspase-3, LC3BII/I and Ubiquitin. Curcumin, a natural compound with anti-oxidant and anti-inflammatory effects, demonstrated to tackle oxidative stress re-equilibrating SUMO-1, JNK and Tau functions. Importantly, 5 μM of curcumin induced an efficient recovery of cell viability, a reduction of cell death and a normalization of altered protein degradation marker levels. Interestingly, we found that H2O2 treatment induced a strong co-localization of SUMO-1-p-JNK-Tau proteins in nuclear bodies (NBs) and that curcumin was able to reduce these nuclear aggregates. These results highlight the SUMO-1-JNK-Tau axis key role in oxidative stress and the protective effect of curcumin against this pathological event, focusing on the importance of SUMO/deSUMOylation balance to regulate essential cellular processes. 

Retracted: No

PubPeer comments:
 Actin bands are identical in Fig. 1D and 5C (from different experimental groups!): ![file] Actin bands of Fig. 2A and 4A are identical, Fig. 2A is supposed to show different H2O2 concentrations, while Fig. 4A is supposed to show different curcumin concentrations: ![file] Actin bands of Fig. 3A and 6A are also highly similar although showing different experimental groups: ![file] ,
Targeting BAX ubiquitin‐binding sites reveals that BAX activation is essential for its ubiquitin‐dependent degradation
Authors: Rui Peng
Fangdong Zou
Jialin Zhu
Hongjuan Wu
Shujin Deng
Hui Shi
Shutao Xu
Journal: Journal of Cellular Biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BAX; activation; apoptotic ability; ubiquitination.
Affiliations: College of Life SciencesSichuan University Chengdu Sichuan China

Abstract:  BAX is an important proapoptotic protein of the BCL-2 family, and its stability is essential for the regulation of the mitochondrial apoptotic pathway. A previous study revealed that BAX could undergo degradation through the ubiquitin-proteasome pathway. In this study, we identified two lysine sites, K21 and K123, that were critical ubiquitin-binding sites in BAX. Mutation of these two sites prolonged the half-life of BAX and also affected its proapoptotic ability. Intriguingly, we found that ABT-737, a BCL-2 inhibitor, significantly enhanced TRAIL-induced BAX degradation in HCT116 cells and increased TRAIL-induced apoptosis in the HCT116 only with the BAX K21R/K123R mutant, not other BAX mutants. In addition, overexpression of PARKIN, an E3 ubiquitin ligase targeting BAX, dramatically decreased BAX protein level when only treated with ABT-737 in HCT116 cells. Therefore, we speculated that BAX activation is essential for its ubiquitin-dependent degradation. 

Retracted: No

PubPeer comments:
 Figure 5C. Two panels appear to be identical Could the authors please check? ![file] , 
 Figure 5C. Two panels appear to be identical Could the authors please check? ![file] , 
 Figure 5C. Two panels appear to be identical. Marked with red boxes. Could the authors please check? ![file] , 
 Apologies for multiple identical posts. The  Something went wrong button appeared after I hit submit, so I submitted multiple times without realizing that it was actually posting my text. I guess duplication is sort of my thing. :-) ,
Development of a single dose tetanus toxoid formulation based on polymeric microspheres: a comparative study of poly(D,L-lactic-co-glycolic acid) versus chitosan microspheres
Authors: D Prabakaran
Anubhav Jain
Suresh P Vyas
Swati Gupta
Y U B Rao
K S Jaganathan
Paramjit Singh
Journal: International journal of pharmaceutics (2005)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: polymeric microspheres; controlled release; tetanus toxoid; PLGA; chitosan
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, Madhya Pradesh 470003 India.

Abstract:  Stable polymeric microspheres capable of controlled release of tetanus toxoid (TT) for periods ranging from days to over months were developed. TT was stabilized, encapsulated in microspheres prepared from poly(D,L)-lactide-co-glycolide (PLGA) and chitosan by using protein stabilizer (trehalose) and its immune response was compared. The influence of co-encapsulated protein stabilizer on tetanus toxoid's stability and release from the microspheres was studied. The protein stabilizer (trehalose) prevented structural losses and aggregation of microencapsulated TT. To neutralize the acids liberated by the biodegradable lactic/glycolic acid-based polymer, we also co-incorporated into the polymer an antacid, (Mg(OH)2), which neutralized the acidity during degradation of the polymer and also prevented TT structural losses and aggregation. The in vitro release experiments with PLGA and chitosan microspheres were performed and the release of TT was increased up to 80-90%. The antigen integrity was investigated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by coomassie brilliant blue staining. The SDS-PAGE analysis confirmed that antigen integrity was not affected by the encapsulation procedure. In addition, the immunogenicity of PLGA and chitosan microspheres based single dose vaccine was evaluated in guinea pigs and compared with multiple doses of alum adsorbed TT. Results indicated that a single injection of PLGA and chitosan microspheres containing TT could maintain the antibody response at a level comparable to the booster injections of conventional alum adsorbed vaccines. The both PLGA and chitosan based stable vaccine formulations produced an equal immune response. Hence chitosan can be used to replace the expensive polymer PLGA. This approach should have potential application in the field of vaccine delivery. 

Retracted: No

PubPeer comments:
 Fig. 5.  SDS-PAGE analysis of TT; lane 1: standard TT antigen; lane 2: TT antigen extracted from PLGA microspheres; lane 3: TT antigen extracted from chitosan microspheres; lane 4: TT antigen extracted from microspheres containing no trehalose. ![file] Fig. 3 from [Mishra et al (2006)] .  SDSu2013PAGE analysis of tetanus toxoid in various formulations; lane 1: standard TTx antigen; lane 2: Alum adsorbed TTx antigen; lane 3: TTx antigen in plain lipsomoes; lane 4: TTx antigen in cationic liposomes; lane 5: TTx antigen in fusogenic vesosomes. ![file] Unexpected similarities. ,
Carvacrol suppresses the expression of inflammatory marker genes in D-galactosamine-hepatotoxic rats
Authors: Balakrishnan Aristatile
Kodukkur Viswanathan Pugalendi
Abdullah H Al-Assaf
Journal: Asian Pacific Journal of Tropical Medicine (2013)
Discipline: CLINICAL MEDICINE
Keywords: anti-inflammatory activity; carvacrol; D-galactosamine; hepatotoxic rats; TNF-α

Abstract:  Objective: To unravel the mechanism of anti-inflammatory activity of carvacrol in D-galactosamine (D-GalN)-induced hepatotoxic rats. Methods: The mRNA and protein expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor kappa-B (NF-κB) were assayed by semi-quantitative reverse transcriptase polymerase chain reaction (RTPCR) and western blot analysis. Results: We found that the mRNA and protein expressions of TNF-α, IL-6, iNOS, COX-2 and NF-κB were significantly up-regulated in D-galactosamine induced hepatotoxic rats and treatment with carvacrol significantly down-regulated the expressions of these genes showing the mechanism behind the anti-inflammatory activity of carvacrol. Conclusions: All above results reveal that the carvacrol well known anti-inflammatory activities in D-galactosamine induced hepatotoxic rats. 

Retracted: No

PubPeer comments:
 Figure 2, 3, and 5 all appear to show the same image, that of iNOS expression. According to the legend, they should show 3 different protein expressions. Could the authors please check? ![file] ,