PReD-Bench/PRed-Bench huggingface dataset:
Inducible costimulator is essential for collagen-induced arthritis
Authors: Chen Dong
Roza I Nurieva
Richard A Flavell
Julie Duong
Piper Treuting
Journal: Journal of Clinical Investigation (2003)
Discipline: CLINICAL MEDICINE
Keywords: CD4(+) helper Th cells; rheumatoid arthritis; costimulatory molecules; Inducible costimulator (ICOS); Th2 cytokine expression
Affiliations: Department of Immunology, and. Department of Comparative Medicine, University of Washington School of Medicine, Seattle, Washington, USA.

Abstract:  CD4(+) helper Th cells play a major role in the pathogenesis of rheumatoid arthritis. Th cell activation, differentiation, and immune function are regulated by costimulatory molecules. Inducible costimulator (ICOS) is a novel costimulatory receptor expressed on activated T cells. We, as well as others, recently demonstrated its importance in Th2 cytokine expression and Ab class switching by B cells. In this study, we examined the role of ICOS in rheumatoid arthritis using a collagen-induced arthritis model. We found that ICOS knockout mice on the DBA/1 background were completely resistant to collagen-induced arthritis and exhibited absence of joint tissue inflammation. These mice, when immunized with collagen, exhibited reduced anti-collagen IgM Ab's in the initial stage and IgG2a Ab's at the effector phase of collagen-induced arthritis. Furthermore, ICOS regulates the in vitro and in vivo expression of IL-17, a proinflammatory cytokine implicated in rheumatoid arthritis. These data indicate that ICOS is essential for collagen-induced arthritis and may suggest novel means for treating patients with rheumatoid arthritis. 

Retracted: Yes

PubPeer comments:
null, 
 Original citation: J. Clin. Invest.111:701u2013706 (2003). doi:10.1172 JCI17321. Citation for this retraction: J. Clin. Invest. doi:10.1172 JCI17321R1. My colleagues and I performed collagen-induced arthritis experiments reported in the paper under the impression that this study had been approved by the Institutional Animal Care and Usage Committee (IACUC) of the University of Washington, but we were subsequently informed by this committee that such approval had not been granted. There were no scientific errors in the paper, and we stand by the validity, importance, and interest of the results. However, the paper is to be retracted according to the JCI s policy of publishing only studies that have been formally approved by an IACUC. We are sorry for any inconvenience this has caused. Chen Dong ,
RETRACTED: Resveratrol augments the canonical Wnt signaling pathway in promoting osteoblastic differentiation of multipotent mesenchymal cells
Authors: Xiyu Zhang
Haibin Zhou
Xi Li
Chenhong Guo
Changshun Shao
Qiji Liu
Bingxi Chen
Linshan Shang
Guimin Gao
Yaoqin Gong
Journal: Experimental Cell Research (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Retraction; Western blot analysis; ERK phosphorylation; Loading control; Authors
Affiliations: Institute of Molecular Medicine and Genetics, Shandong University, Shandong 250012, China.

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 authors. The authors were alerted about the loading control in a Western blot analysis of ERK phosphorylation shown in Figure 6B, and they were unable to locate the original scan. Although the authors stand by the conclusion based on this figure, and the conclusion of the entire article, they wish to retract this article. 

Retracted: No

PubPeer comments:
 An actin band in figures 6A and 6B has been resized and used to represent two conditions. Could the authors please post the original uncropped scans? It appears the last author is no longer at Rutgers. I input their apparent current email address at Soochow University. ***  *** Original showing location  , 
 July 1, 2021 This article has been retracted at the request of the authors. The authors were alerted about the loading control in a Western blot analysis of ERK phosphorylation shown in Figure 6B, and they were unable to locate the original scan. Although the authors stand by the conclusion based on this figure, and the conclusion of the entire article, they wish to retract this article. ,
Dioscin alleviates BDL- and DMN-induced hepatic fibrosis via Sirt1/Nrf2-mediated inhibition of p38 MAPK pathway
Authors: Xufeng Tao
Lina Xu
Yan Qi
Lina Gu
Jinyong Peng
Lianhong Yin
Xu Han
Youwei Xu
Journal: Toxicology and Applied Pharmacology (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Dioscin; Hepatic fibrosis; Nrf2; Oxidative stress; Sirt1
Affiliations: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China., College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Electronic address: .

Abstract:  Oxidative stress is involved in hepatic stellate cells (HSCs) activation and extracellular matrix overproduction. We previously reported the promising effects of dioscin against CCl4-induced liver fibrosis, but its effects and mechanisms on BDL- and DMN-induced liver fibrosis remain unknown. The results in the present study indicated that dioscin significantly inhibited HSCs activation and attenuated hepatic fibrosis in rats. Furthermore, dioscin markedly up-regulated the levels of sirtuin 1 (Sirt1), HO-1, GST, GCLC and GCLM via increasing the nuclear translocation of nuclear erythroid factor 2-related factor 2 (Nrf2), which in turn inhibited mitogen-activated protein kinase 14 (p38 MAPK) phosphorylation and reduced the levels of COL1A1, COL3A1, Œ±-SMA and fibronectin. These results were further validated by knockdown of Sirt1 and Nrf2 using siRNAs silencing, and abrogation of p38 MAPK using SB-203580 (a p38 MAPK inhibitor) in HSC-T6 and LX-2 cells. Collectively, our findings confirmed the potent effects of dioscin against liver fibrosis and also provided novel insights into the mechanisms of this compound as a candidate for the prevention of liver fibrosis in the future. 

Retracted: No

PubPeer comments:
  , 
 Figure 6A, the twobands are same but with different treatments. , 
 #1 Thank you for pointing our possible errors in the paper. Since there are large quantities of bands in Fig. 6, during the submission of this manuscript, the band of u03b2-Tubulin of DMN-induced rats were pasted repeatedly to that of Lamin B1 in Fig. 6A due to our carelessness. I am contacting the journal with the information and the raw data to publish an erratum. Thanks again for your comments. , 
  ,
Aqueous Extract of Moringa oleifera Exhibit Potential Anticancer Activity and can be Used as a Possible Cancer Therapeutic Agent: A Study Involving In Vitro and In Vivo Approach
Authors: Sweety Nath Barbhuiya
Puja Upadhaya
Dharmeswar Barhoi
Anirudha Giri
Sarbani Giri
Journal: Journal of the American College of Nutrition (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Moringa oleifera; Ehrlich ascites carcinoma; apoptosis; cytotoxicity; solid tumor.
Affiliations: Laboratory of Molecular and Cell Biology, Department of Life Science and Bioinformatics, Assam University, Silchar, India;, Laboratory of Environmental and Human Toxicology, Department of Life Science and Bioinformatics, Assam University, Silchar, India

Abstract:  Objectives: New cases of cancers are increasing at an alarming rate globally. It has been hypothesized that modern cancer treatment is associated with lots of side effects and thus evoking the need to develop safer treatment measures. Thus, the present study was undertaken to evaluate the anti-carcinogenic potential of a highly nutricious plant "Moringa oleifera" (MO) in vitro and in vivo. Methods: GC-MS analysis of aqueous extract of Moringa oleifera (AEMO) was employed to identify the bioactive compound present. Anti-tumor activity of AEMO was assessed in EAC (Ehrlich acites carcinoma) induced solid tumor bearing mice by analyzing tumor weight (TW) and Tumor volume (TV). To assess AEMO induced cytotoxicity, EAC and HEp-2 (Human laryngeal carcinoma) cells were treated with AEMO (0.05, 0.1, 0.25, 0.5 and 1 mg/ml) for both 48 h and 72 h and trypan blue, MTT and LDH released assay was done. Further, cell cycle assay and apoptosis assay was done in EAC cells to understand the mechanism of AEMO induced tumor regression. Results: GC-MS analysis revealed the presence of quinic acid, octadecanoic acid, hexadecanoic acid (palmitic acid), Œ±-tocopherol (Vitamin-E) and …£-sitosterol as major bioactive compounds. AEMO administration reduced the TV and TW of tumor-bearing mice and increases the life span. Side effect analysis showed that AEMO treatment did not induce significant alterations of liver and kidney function and hematological parameters. Further, in vitro cytotoxicity assays revealed that AEMO treatment induced dose and time-dependent toxicity in both the cell lines tested. Flow cytometric analysis confirmed significant induction of apoptotic cells by changing the mitochondrial membrane potential in EAC cell line. Conclusion: The results of the present study suggest that AEMO has immense potential to inhibit the tumor progression without affecting the normal physiology and functioning of the body and thus can be used as a cancer therapeutic agent. 

Retracted: No

PubPeer comments:
 https: imgur.com a 8lkUxe1 ,
Id4 dependent acetylation restores mutant-p53 transcriptional activity
Authors: Jaideep Chaudhary
Shanora Glymph
Divya Patel
Derrick J Morton
Pankaj Sharma
Ashley E Knowell
Journal: Molecular Cancer (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mutant p53; Id4; prostate cancer; transcriptional activity; apoptosis
Affiliations: Center for Cancer Research and Therapeutics Development, Clark Atlanta University, 223 James P, Brawley Dr, SW, Atlanta, GA 30314, USA. .

Abstract:  Background: The mechanisms that can restore biological activity of mutant p53 are an area of high interest given that mutant p53 expression is observed in one third of prostate cancer. Here we demonstrate that Id4, an HLH transcriptional regulator and a tumor suppressor, can restore the mutant p53 transcriptional activity in prostate cancer cells. Methods: Id4 was over-expressed in prostate cancer cell line DU145 harboring mutant p53 (P223L and V274F) and silenced in LNCaP cells with wild type p53. The cells were used to quantitate apoptosis, p53 localization, p53 DNA binding and transcriptional activity. Immuno-precipitation/-blot studies were performed to demonstrate interactions between Id4, p53 and CBP/p300 and acetylation of specific lysine residues within p53. Results: Ectopic expression of Id4 in DU145 cells resulted in increased apoptosis and expression of BAX, PUMA and p21, the transcriptional targets of p53. Mutant p53 gained DNA binding and transcriptional activity in the presence of Id4 in DU145 cells. Conversely, loss of Id4 in LNCaP cells abrogated wild type p53 DNA binding and transactivation potential. Gain of Id4 resulted in increased acetylation of mutant p53 whereas loss of Id4 lead to decreased acetylation in DU145 and LNCaP cells respectively. Id4 dependent acetylation of p53 was in part due to a physical interaction between Id4, p53 and acetyl-transferase CBP/p300. Conclusions: Taken together, our results suggest that Id4 regulates the activity of wild type and mutant p53. Id4 promoted the assembly of a macromolecular complex involving CBP/P300 that resulted in acetylation of p53 at K373, a critical post-translational modification required for its biological activity. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: Lane  L+mt looks unexpectedly similar to lane  D . A sharp vertical transition line appears to be visible between the first and second lanes.  ,
Increased bone formation in osteocalcin-deficient mice
Authors: A Bradley
B Story
C Desbois
G Karsenty
E Smith
G Pinero
C Gundberg
C Dunstan
P Ducy
B Boyce
J Bonadio
S Goldstein
Journal: Nature (1996)
Discipline: Multidisciplinary
Keywords: Vertebrates; bone remodeling; osteoclasts; osteoblasts; molecular determinants
Affiliations: Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

Abstract:  Vertebrates constantly remodel bone. The resorption of preexisting bone by osteoclasts and the formation of new bone by osteoblasts is strictly coordinated to maintain bone mass within defined limits. A few molecular determinants of bone remodelling that affect osteoclast activity have been characterized, but the molecular determinants of osteoblast activity are unknown. To investigate the role of osteocalcin, the most abundant osteoblast-specific non-collagenous protein, we have generated osteocalcin-deficient mice. These mice develop a phenotype marked by higher bone mass and bones of improved functional quality. Histomorphometric studies done before and after ovariectomy showed that the absence of osteocalcin leads to an increase in bone formation without impairing bone resorption. To our knowledge, this study provides the first evidence that osteocalcin is a determinant of bone formation. 

Retracted: No

PubPeer comments:
 Two new studies question the validity of findings in this paper and others on metabolic roles of osteocalcin mostly authored by same group. An osteocalcin-deficient mouse strain without endocrine abnormalities. Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass https: doi.org 10.1371 journal.pgen.1008361 https: doi.org 10.1371 journal.pgen.1008586 Excellent perspective about above studies, https: doi.org 10.1371 journal.pgen.1008714 ,
STING directly activates autophagy to tune the innate immune response
Authors: Huabin Tian
Xiaohui Wang
Hao Wu
Quan Chen
Jun Wang
Chenguang Wang
Zhengfan Jiang
Dong Liu
Yingli Shang
Lei Liu
Yanjun Li
Sami Siraj
Sheikh Arslan Sehgal
Journal: Cell Death and Differentiation (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: STING; autophagy; LC3; cGAS; innate immunity
Affiliations: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China., University of Chinese Academy of Sciences, Beijing, China., College of Life Sciences, Peking University, Beijing, China., Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China., Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Veterinary Medicine, Shandong Agricultural University, Tai'an, China., State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. ., University of Chinese Academy of Sciences, Beijing, China. ., College of Life Sciences, Nankai University, Tianjin, China. .

Abstract:  STING (stimulator of interferon genes) is a central molecule that binds to cyclic dinucleotides produced by the cyclic GMP-AMP synthase (cGAS) to activate innate immunity against microbial infection. Here we report that STING harbors classic LC-3 interacting regions (LIRs) and mediates autophagy through its direct interaction with LC3. We observed that poly(dA:dT), cGAMP, and HSV-1 induced STING-dependent autophagy and degradation of STING immediately after TBK1 activation. STING induces non-canonical autophagy that is dependent on ATG5, whereas other autophagy regulators such as Beclin1, Atg9a, ULK1, and p62 are dispensable. LIR mutants of STING abolished its interaction with LC3 and its activation of autophagy. Also, mutants that abolish STING dimerization and cGAMP-binding diminished the STING-LC3 interaction and subsequent autophagy, suggesting that STING activation is indispensable for autophagy induction. Our results thus uncover dual functions of STING in activating the immune response and autophagy, and suggest that STING is involved in ensuring a measured innate immune response. 

Retracted: No

PubPeer comments:
 Is this image recycling?  , 
 Authors have published an erratum for the same. https: onlinelibrary.wiley.com doi full 10.1002 jcp.29257 ,
USP22 down-regulation facilitates human retinoblastoma cell aging and apoptosis via inhibiting TERT/P53 pathway
Authors: S-M Peng
Z-J Chen
D-W Sun
P Liu
Y-L Liu
J Hu
D Zhou
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Retinoblastoma; telomerase; USP22; TERT; P53
Affiliations: Department of Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. .

Abstract:  Objective: Retinoblastoma is the most common malignant intraocular tumor in childhood, and still lacks effective treatment. The immortality of tumor cell can be attributed to elevated telomerase activity, which has been considered as tumor marker and treatment target. USP22 is one of the important targets for inhibiting tumor growth, but clear illustration regarding its effects of telomerase, tumor cell immortality and retinoblastoma cell aging or apoptosis via suppressing TERT/P53 signal pathway remains to be elusive. Materials and methods: MTT was used for describing cell proliferation, and Western blot was used to test protein expression level of USP22, TERT and P53. RT-qPCR was used to test USP22 mRNA level, followed by TRAP method to detect telomerase activity. Flow cytometry and comet assay were used to quantify cell apoptosis and DNA damage. Cell aging was measured by Œ≤-galactosidase. Results: The overexpression of USP22 significantly enhanced cell proliferation potency and telomerase activity, elevated TERT expression level, inhibited p53 expression and cell aging, as well as decreased cell apoptosis or DNA damage. Down-regulation of USP22 contributed to opposite effects. Conclusions: USP22 played an important role in retinoblastoma cell proliferation/aging and apoptosis. The reduction of USP22 expression facilitated human retinoblastoma cell aging or apoptosis via suppressing TERT/P53 signal pathway. USP22, thus, may work as a target for treating retinoblastoma. 

Retracted: No

PubPeer comments:
 Figure 5A. This figure appears to contain parts visible multiple times within or across panels. One would hope that researchers at an eye hospital would have seen this. Also, given the topic of the paper, the involvement of researchers from the department of colorectal surgery is a bit bewildering.  , 
 #1 Came here to make the same observation, 8 months too late.  ,
Both the sequence and length of the C terminus of PEN-2 are critical for intermolecular interactions and function of presenilin complexes
Authors: Nobuo Sanjo
Hiroshi Hasegawa
Paul M Mathews
Stephen D Schmidt
Fusheng Chen
Taiichi Katayama
Paul E Fraser
Toshitaka Kawarai
Gerold Schmitt-Ulms
Peter St George-Hyslop
Yong-Jun Gu
Cortney Shier
Agnes Petit
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Presenilin 1; presenilin 2; nicastrin; APH-1; PEN-2
Affiliations: Centre for Research in Neurodegenerative Diseases, University of Toronto, West Toronto, Ontario M5S 3H2, Canada.

Abstract:  Presenilin 1 or presenilin 2, nicastrin, APH-1, and PEN-2 form high molecular weight complexes that play a pivotal role in the cleavage of various Type I transmembrane proteins, including the beta-amyloid precursor protein. The specific function of PEN-2 is unclear. To explore its function and intermolecular interactions, we conducted deletion and mutagenesis studies on a series of conserved residues at the C terminus of PEN-2. These studies suggest that: 1) both the presence and amino acid sequence of the conserved DYLSF domain at the C terminus of PEN-2 (residues 90-94) is critical for binding PEN-2 to other components in the presenilin complex and 2) the overall length of the exposed C terminus is critical for functional gamma-secretase activity. 

Retracted: No

PubPeer comments:
  , 
 Figure 7. Vertical splices in the A beta40 and A beta42 panel, but not in the other panels.  , 
 Figure 3. Vertical discontinuities some panels, but not others.  ,
Fluoxetine and Riluzole Mitigates Manganese-Induced Disruption of Glutamate Transporters and Excitotoxicity via Ephrin-A3/GLAST-GLT-1/Glu Signaling Pathway in Striatum of Mice
Authors: Bin Xu
Yu Deng
Zhipeng Qi
Jinghai Zhu
Miao He
Jiashuo Li
Xinxin Yang
Wei Liu
Yanqi Sang
Yanan Liu
Zhaofa Xu
Journal: Neurotoxicity Research (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Ephrin-A3; Excitotoxicity; Fluoxetine; GLAST; GLT-1
Affiliations: Department of Environmental Health, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China., Department of Environmental Health, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China. .

Abstract:  Manganese (Mn) is an essential element required for many biological processes and systems in the human body. Mn intoxication increases brain glutamate (Glu) levels causing neuronal damage. Recent studies have reported that ephrin-A3 regulates this glutamate transporter. However, none has explored the role of this crucial molecule in Mn-induced excitotoxicity. The present study investigated whether ephrin-A3/GLAST-GLT-1/Glu signaling pathway participates in Mn-induced excitotoxicity using astrocytes and Kunming mice. The mechanisms were explored using fluoxetine (ephrin-A3 inhibitor) and riluzole (a Glu release inhibitor). Firstly, we demonstrated that Mn exposure (500 ŒºM or 50 mg/kg MnCl2) significantly increased Mn, ephrin-A3, and Glu levels, and inhibited Na+-K+ ATPase activity, as well as mRNA and protein levels of GLAST and GLT-1. Secondly, we found that astrocytes and mice pretreated with fluoxetine (100 ŒºM or 15 mg/kg) and riluzole (100 ŒºM or 32 Œºmol/kg) prior to Mn exposure had lower ephrin-A3 and Glu levels, but higher Na+-K+ ATPase activity, expression levels of GLAST and GLT-1 than those exposed to 500 ŒºM or 50 mg/kg MnCl2. Moreover, the morphology of cells and the histomorphology of mice striatum were injured. Results showed that pretreatment with fluoxetine and riluzole attenuated the Mn-induced motor dysfunctions. Together, these results suggest that the ephrin-A3/GLAST-GLT-1/Glu signaling pathway participates in Mn-induced excitotoxicity, and fluoxetine and riluzole can mitigate the Mn-induced excitotoxicity in mice brain. 

Retracted: No

PubPeer comments:
  , 
  ,
RETRACTED ARTICLE: Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer
Authors: Yuanjie Yu
Xiaohong Lu
Shiyun Tan
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Colon cancer; XIAP-AS1; long non-coding RNAs; p63.
Affiliations: a Department of Gastroenterology , Renmin Hospital of Wuhan University, Hubei Key Laboratory of Digestive System Disease , Wuhan , Hubei , China.

Abstract:  Colon cancer is one of the most commonly diagnosed and deadly cancers worldwide. Further understanding of the biological mechanisms is important for exploring the molecular biomarkers and therapeutic targets of this disease. Dysregulation of long non-coding RNAs (lncRNAs) has been reported to be associated with the development and progression of various cancers. XIAP-AS1 is a novel lncRNA, which can regulate apoptosis in gastric cancer cells. However, the role of XIAP-AS1 in colorectal cancer (CRC) remains unclear. In this study, we found that XIAP-AS1 expression was significantly increased in CRC tissues and its expression showed a positive correlation with TNM stage and cumulative survival rate of CRC. To investigate whether XIAP-AS1 regulates the progression of CRC, we knocked down its expression in several CRC cell lines. CCK-8 assays showed that XIAP-AS1 knockdown remarkably suppressed CRC cell growth and arrested the cell cycle at the G0/G1 phase (flow cytometric analysis). Furthermore, XIAP-AS1 knockdown also remarkably blocked cell invasion of colon cancer cells by regulating the expression of EMT markers, such as E-cadherin, ZO-1, vimentin, and N-cadherin. Importantly, we found that XIAP-AS1 knockdown significantly reduced STAT3 phosphorylation. Overall, this study suggests that lncRNA XIAP-AS1 might serve as a potential oncogene for colon cancer. 

Retracted: Yes

PubPeer comments:
 Retracted [11 January 2021] . -------------------------------------------- We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article:u202f Xiaohong Lu, Yuanjie Yu Shiyun Tan (2019) Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer. Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 767u2013775, DOI: https: doi.org 10.1080 21691401.2019.1577880 It has come to our attention that the full authorship list and affiliations for this manuscript were changed after the article was submitted. We have contacted the author for an explanation, but we have not received a satisfactory explanation. As determining authorship is core to the integrity of published work, we are therefore retracting the article. The authors listed in this publication have been informed and do not agree with the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.u202f The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u2018Retractedu2019.u202f ,
Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome
Authors: Fawaz Haj
Beverley Adams-Huet
Sridevi Devaraj
Ishwarlal Jialal
Ahmed Bettaieb
Journal: Atherosclerosis (2015)
Discipline: CLINICAL MEDICINE
Keywords: Adipose tissue; Fetuin A; Lipopolysaccharide binding protein; Metabolic syndrome; TLR.
Affiliations: Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, Division of Endocrinology, Diabetes and Metabolism, University of California Davis Medical Center, Sacramento, CA, USA; Medical Services, VA Medical Center, Mather, CA, USA. Electronic address: ., Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA., Department of Nutrition, University of California Davis, Davis, CA, USA., Department of Clinical Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Abstract:  Objective: Adipose Tissue (AT) dysregulation contributes to the pro-inflammatory state and insulin resistance of Metabolic Syndrome (MetS). We examined AT secretion of the hepatokine, Fetuin-A, LBP, sCD14 and HMGB-1, and toll-like receptor 2 and 4 protein levels in MetS and controls. Design and methods: Secreted levels of Fetuin-A, LBP, HMGB-1 and sCD14 and TLR2 and TLR4 protein in AT of controls and MetS patients were assayed. Also mRNA and protein for Fetuin-A, LBP, sCD14 and HMGB-1 were studied in subcutaneous fat depot of mice and during adipocyte differentiation. Results: Secretion of Fetuin-A, LBP and HMGB-1 from AT were significantly increased in MetS (n = 28) compared to controls (n = 25), even after adjustment for adiposity. There were no significant differences in sCD14. Both LBP and Fetuin-A correlated significantly with HOMA-IR and increased significantly with increasing features of MetS. There was a significant increase in AT TLR2 and TLR4 protein in MetS compared to controls. Expression of Fetuin-A and LBP were significantly higher in subcutaneous white adipose tissue of HFD fed mice as well as in ob/ob mice compared to C57BL6/J control mice (n = 6 per group). Additionally mRNA and protein levels of FetA, LBP and HMGB-1 increased during differentiation of 3T3-L1 adipocytes. Conclusions: We make the novel observation of increased secretion of Fetuin A, LBP and HMGB-1 from AT and hypothesize that these engage TLRs in AT and other tissues contributing to the pro-inflammatory state and insulin resistance of MetS. 

Retracted: No

PubPeer comments:
 Figure 2. * Blue arrows: In the TLR2 blot, the left two bands look very similar, and their spacing is different than that between the other bands. In addition, a sharp vertical background transition appears to be visible to the right of the leftmost band (pink arrow). * Red arrows: In the TLR4 blot, the left two bands look very similar. To take away any concerns, could the authors share the uncropped blots for each of these three panels, please?  ,
K+ channel regulator KCR1 suppresses heart rhythm by modulating the pacemaker current If
Authors: Guido Michels
Jeannette Endres-Becker
Natig Gassanov
Fikret Er
Mathias C Brandt
Uta C Hoppe
David C Johns
Ismail F Khan
Journal: PLoS ONE (2008)
Discipline: Multidisciplinary
Keywords: HCN channels; pacemaker current; I(f); regulatory proteins; protein-protein interaction
Affiliations: Department of Internal Medicine III, University of Cologne, Cologne, Germany.

Abstract:  Hyperpolarization-activated, cyclic nucleotide sensitive (HCN) channels underlie the pacemaker current I(f), which plays an essential role in spontaneous cardiac activity. HCN channel subunits (HCN1-4) are believed to be modulated by additional regulatory proteins, which still have to be identified. Using biochemistry, molecularbiology and electrophysiology methods we demonstrate a protein-protein interaction between HCN2 and the K(+) channel regulator protein 1, named KCR1. In coimmunoprecipitation experiments we show that KCR1 and HCN2 proteins are able to associate. Heterologously expressed HCN2 whole-cell current density was significantly decreased by KCR1. KCR1 profoundly suppressed I(HCN2) single-channel activity, indicating a functional interaction between KCR1 and the HCN2 channel subunit. Endogenous KCR1 expression could be detected in adult and neonatal rat ventriculocytes. Adenoviral-mediated overexpression of KCR1 in rat cardiomyocytes (i) reduced I(f) whole-cell currents, (ii) suppressed most single-channel gating parameters, (iii) altered the activation kinetics, (iv) suppressed spontaneous action potential activity, and (v) the beating rate. More importantly, siRNA-based knock-down of endogenous KCR1 increased the native I(f) current size and single-channel activity and accelerated spontaneous beating rate, supporting an inhibitory action of endogenous KCR1 on native I(f). Our observations demonstrate for the first time that KCR1 modulates I(HCN2)/I(f) channel gating and indicate that KCR1 serves as a regulator of cardiac automaticity. 

Retracted: No

PubPeer comments:
 Figure 5A suffers from similar issues to several papers of this group of authors. Some regions of overlap indicated. ***   ,
Progress of ethylene action mechanism and its application on plant type formation in crops
Authors: Jihui Wei
Jian Liu
Hongjian Zheng
Pingdong Sun
Yingxiong Hu
Lifeng Wu
Hui Wang
Weiqiang Zhang
Journal: Saudi Journal of Biological Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Action mechanism; Ethylene; Maize; Plant type formation; Rice.
Affiliations: CIMMYT-China Specialty Maize Research Center, Crop Breeding and Cultivation Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China., Farmland Irrigation Research Institute, Chinese Academy of Agricultural Sciences, Xinxiang 453003, China., School of Hydraulic and Ecological Engineering, Nanchang Institute of Technology, Nanchang 330099, China.

Abstract:  The plant hormone ethylene exerts a huge influence in the whole life cycle of plants, especially stress-resistance responses. With the development of functional genomics, that the action mechanism of ethylene takes part in mediated plant architecture has been clarified gradually, such as plant roots, stems, leaves, fiber elongation and so on. Accordingly, the application of ethylene on crops chemical control and genetic improvement is greatly expanded. From the view of ethylene mediated plant architecture in crops, here reviewed advances in ethylene biosynthesis and signal transduction pathway, stress-resistance responses and the yield potential enhance of crops in recently 20 years. On these grounds, the objectives of this paper were to provide scientific reference and a useful clue for the crop creation of ideal plant type. 

Retracted: No

PubPeer comments:
 References from Int. J. Electrochem Sci. seem to have stumbled in from some other paper,  For example, ethylene-based plant growth regulators such as ethephon, EDAH (the compound of ethephon and DA-6) and phosphonates (e.g. DHEAP), could be applied to control the plant height and ear position of maize so as to establish related agronomic traits to enhance lodging resistance and increase yield potential (Rajala and Peltonen-Sainio, 2002, Zhang et al., 2017, Wang et al., 2017, Wang et al., 2018, Amirian et al., 2019, Zhang et al., 2019). - K. Wang, L. Li, W. Xue, S. Zhou, Y. Lan, H. Zhang, Z. Sui **Electrodeposition Synthesis of PANI MnO2 Graphene Composite Materials and its Electrochemical Performance** Int. J. Electrochem. Sci., 12 (2017), pp. 8306-8314 - K. Wang, S. Zhou, Y. Zhou, J. Ren, L. Li, Y. Lan **Synthesis of Porous Carbon by Activation Method and its Electrochemical Performance** Int. J. Electrochem. Sci., 13 (2018), pp. 10766-10773 ,
Functional Analysis of Four Bile Salt Hydrolase and Penicillin Acylase Family Members in Lactobacillus plantarum WCFS1
Authors: Michiel Kleerebezem
Roger S Bongers
Jolanda M Lambert
Willem M de Vos
Journal: Applied and Environmental Microbiology (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bile salts; digestion; lipids; vertebrates; glycine
Affiliations: TI Food &amp; Nutrition, P.O. Box 557, 6700 AN Wageningen, The Netherlands, NIZO food research, P.O. Box 20, 6710 BA Ede, The Netherlands, Wageningen University, Laboratory of Microbiology, P.O. Box 8033, 6700 EJ Wageningen, The Netherlands

Abstract:  Bile salts play an important role in the digestion of lipids in vertebrates and are synthesized and conjugated to either glycine or taurine in the liver. Following secretion of bile salts into the small intestine, intestinal microbes are capable of deconjugating the glycine or taurine from the bile salts, using an enzyme called bile salt hydrolase (Bsh). Intestinal lactobacilli are regarded as major contributors to bile salt hydrolysis in vivo. Since the bile salt-hydrolyzing strain Lactobacillus plantarum WCFS1 was predicted to carry four bsh genes (bsh1, bsh2, bsh3, and bsh4), the functionality of these bsh genes was explored using Lactococcus lactis heterologous overexpression and multiple bsh deletion strains. Thus, Bsh1 was shown to be responsible for the majority of Bsh activity in L. plantarum WCFS1. In addition, bsh1 of L. plantarum WCFS1 was shown to be involved in conferring tolerance to specific bile salts (i.e., glycocholic acid). Northern blot analysis established that bsh1, bsh2, bsh3, and bsh4 are all expressed in L. plantarum WCFS1 during the exponential growth phase. Following biodiversity analysis, bsh1 appeared to be the only bsh homologue that was variable among L. plantarum strains; furthermore, the presence of bsh1 correlated with the presence of Bsh activity, suggesting that Bsh1 is commonly responsible for Bsh activity in L. plantarum strains. The fact that bsh2, bsh3, and bsh4 genes appeared to be conserved among L. plantarum strains suggests an important role of these genes in the physiology and lifestyle of the species L. plantarum. Analysis of these additional bsh-like genes in L. plantarum WCFS1 suggests that they might encode penicillin acylase rather than Bsh activity, indicating their implication in the conversion of substrates other than bile acids in the natural habitat. 

Retracted: No

PubPeer comments:
 I am wondering why have the authors not disclosed the accession numbers of the genes that they have characterized in this study. This could have greatly helped other researchers in the field. Even the original article that they are citing (by the same authors, doi: 10.1073 pnas.0337704100) for the presence of these bile salt hydrolase in L. plantarum WCFS1 genome does not contain any description or accession numbers of these genes. ,
Supplemental Oxygen Protects Heart Against Acute Myocardial Infarction
Authors: Brian K Rivera
Anjali M Prabhat
Sarath Meduru
Periannan Kuppusamy
Abishai Dominic
Mahmood Khan
Shan K Naidu
M Lakshmi Kuppusamy
Praneeth T Reddy
Journal: Frontiers in Cardiovascular Medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: ischemia-reperfusion injury; myocardial infarction; oximetry; oxygen cycling; supplemental oxygen.

Abstract:  Myocardial infarction (MI), which occurs often due to acute ischemia followed by reflow, is associated with irreversible loss (death) of cardiomyocytes. If left untreated, MI will lead to progressive loss of viable cardiomyocytes, deterioration of cardiac function, and congestive heart failure. While supplemental oxygen therapy has long been in practice to treat acute MI, there has not been a clear scientific basis for the observed beneficial effects. Further, there is no rationale for the amount or duration of administration of supplemental oxygenation for effective therapy. The goal of the present study was to determine an optimum oxygenation protocol that can be clinically applicable for treating acute MI. Using EPR oximetry, we studied the effect of exposure to supplemental oxygen cycling (OxCy) administered by inhalation of 21-100% oxygen for brief periods (15-90 min), daily for 5 days, using a rat model of acute MI. Myocardial oxygen tension (pO2), cardiac function and pro-survival/apoptotic signaling molecules were used as markers of treatment outcome. OxCy resulted in a significant reduction of infarct size and improvement of cardiac function. An optimal condition of 30-min OxCy with 95% oxygen + 5% CO2 under normobaric conditions was found to be effective for cardioprotection. 

Retracted: No

PubPeer comments:
 Would the authors be able to provide the uncropped original scan of this image from Figure 6? The published photo shows possible signs that the bands were processed differently, especially the p53 band, suggesting perhaps that they did not originate on the same gel. *** Enhanced color  *** Level sweep  ,
Exosomes Secreted from Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Prevent Osteonecrosis of the Femoral Head by Promoting Angiogenesis
Authors: Yang Wang
Bin Hu
Shengbao Chen
Wenqi Song
Xiaolin Liu
Qing Li
Changqing Zhang
Jian Ding
Xin Niu
Journal: International Journal of Biological Sciences (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Angiogenesis.; Exosomes; Femoral head; Osteonecrosis; induced pluripotent stem cells (iPSCs).
Affiliations: Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China., Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China.

Abstract:  Background: Local ischemia is the main pathological performance in osteonecrosis of the femoral head (ONFH). There is currently no effective therapy to promote angiogenesis in the femoral head. Recent studies revealed that exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSC-Exos) have great therapeutic potential in ischemic tissues, but whether they could promote angiogenesis in ONFH has not been reported, and little is known regarding the underlying mechanism. Methods: iPS-MSC-Exos were intravenously injected to a steroid-induced rat osteonecrosis model. Samples of the femoral head were obtained 3 weeks after all the injections. The effects were assessed by measuring local angiogenesis and bone loss through histological and immunohistochemical (IHC) staining, micro-CT and three-dimensional microangiography. The effects of exosomes on endothelial cells were studied through evaluations of proliferation, migration and tube-forming analyses. The expression levels of angiogenic related PI3K/Akt signaling pathway of endothelial cells were evaluated following stimulation of iPS-MSC-Exos. The promoting effects of exosomes were re-evaluated following blockade of PI3K/Akt. Results: The in vivo study revealed that administration of iPS-MSC-Exos significantly prevented bone loss, and increased microvessel density in the femoral head compared with control group. We found that iPS-MSC-Exos significantly enhanced the proliferation, migration and tube-forming capacities of endothelial cells in vitro. iPS-MSC-Exos could activate PI3K/Akt signaling pathway in endothelial cells. Moreover, the promoting effects of iPS-MSC-Exos were abolished after blockade of PI3K/Akt on endothelial cells. Conclusions: Our findings suggest that transplantation of iPS-MSC-Exos exerts a preventative effect on ONFH by promoting local angiogenesis and preventing bone loss. The promoting effect might be attributed to activation of the PI3K/Akt signaling pathway on endothelial cells. The data provide the first evidence for the potential of iPS-MSC-Exos in treating ONFH. 

Retracted: No

PubPeer comments:
 Figure 6F appears to have two images which are unexpectedly similar. Could the authors please comment? ***  ,
5-Aza-2‚Ä?deoxycytidine induces p21WAF expression by demethylation of p73 leading to p53-independent apoptosis in myeloid leukemia
Authors: Mandy Wagner
Bernd D√∂rken
Karin Schmelz
Ingo Tamm
Journal: International Journal of Cancer (2005)
Discipline: CLINICAL MEDICINE
Keywords: DNA methylation inhibitor; 5-Aza-2'-deoxycytidine; therapeutic value; myelodysplastic syndrome; acute myeloid leukemia
Affiliations: Department of Hematology and Oncology, Universit√§tsmedizin Berlin, Charit√©, Campus Virchow, Berlin, Germany.

Abstract:  The DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) has significant therapeutic value for the treatment of patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The demethylating effect of 5-Aza-CdR has been well characterized. In contrast, less is known about the molecular events downstream of the methylation inhibition. Here, 5-Aza-CdR induced apoptosis in AML cells (both p53 mutant and wild-type) but not in epithelial or normal PBMCs. Cell death was accompanied by activation of the mitochondrial apoptosis pathway, as shown by release of cytochrome c and AIF and loss of mitochondrial membrane potential (DeltaPsim). Activation of caspase-3 (but not -6 and -8) was detectable using Western blot analysis and measurement of caspase enzymatic activity. 5-Aza-CdR treatment resulted in the induction of p21, which correlated with the arrest of AML cells in the G1 cell cycle phase. Induction of p21 expression was independent of its promoter methylation status but mediated by 5-Aza-CdR-induced reexpression of the tumor-suppressor p73, a known upstream regulator of p21. The p73 promoter was hypermethylated in AML cell lines and in primary AML cells but not in epithelial cells, which were resistant toward 5-Aza-CdR. Therefore, 5-Aza-CdR-mediated specific killing of myeloid cells might be dependent on its ability to revert p73 promoter methylation and to reexpress p73 mRNA. In addition, exogenous expression of p73 rendered epithelial cells sensitive to apoptosis induced by 5-Aza-CdR or other cytostatic drugs. We therefore conclude that p73 is a relevant target for methylation-dependent efficacy of 5-Aza-CdR in AML cells. 

Retracted: No

PubPeer comments:
 Figure 6. Much more similar than you would expect.  ,
Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis
Authors: Huafeng Wei
Jian Zhao
Huaqing Wang
Bo Zhang
Jianxin Dai
Yajun Guo
Kexing Fan
Journal: Biochemical and Biophysical Research Communications (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bone resorption; Osteoclast survival; Osteopontin; Osteoporosis.
Affiliations: International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, People's Republic of China; PLA General Hospital Cancer Center & PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing, People's Republic of China., International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, People's Republic of China; PLA General Hospital Cancer Center & PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing, People's Republic of China; National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203, People's Republic of China., International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, People's Republic of China., International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, People's Republic of China; National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203, People's Republic of China., International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, People's Republic of China; PLA General Hospital Cancer Center & PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing, People's Republic of China; National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203, People's Republic of China. Electronic address: .

Abstract:  Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorption through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases. 

Retracted: No

PubPeer comments:
 Concerns about Figure 2. * Green boxes: Two panels in B appear to look identical * Red boxes: Two panels in C appear to overlap  ,