PReD-Bench/PRed-Bench huggingface dataset:
In vitro effect of microRNA-107 targeting Dkk-1 by regulation of Wnt/β-catenin signaling pathway in osteosarcoma
Authors: Bai-Chuan Wang
Zeng-Wu Shao
Tong-Chuan He
Fei-Fei Pu
Shu-Hua Yang
Xian-Lin Zeng
Yu-Kun Zhang
Xiao-Dong Guo
Jian-Xiang Liu
Zhi-Cai Zhang
Qiang Wu
Journal: Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: miR-107; Dkk-1; osteosarcoma; Wnt/β-catenin signaling pathway; LRP5
Affiliations: aDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China bMolecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL.

Abstract:  Background: The aim of the study was to explore the effects of microRNA-107 (miR-107) by targeting Dkk-1 on osteosarcoma (OS) via the Wnt/β-catenin signaling pathway. Methods: OS and adjacent tissues were collected from 67 patients diagnosed with OS. Expressions of miR-107, Dkk-1, LRP5, β-catenin, and c-Myc were detected by the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The dual-luciferase reporter gene assay was performed to observe the relationship between miR-107 and Dkk-1.Transfected cells were divided into different investigating groups designated as Inhibitor, Mimic, siRNA, Inhibitor + siRNA, negative control (NC), and blank groups. qRT-PCR and Western blotting were used to detect expressions of miR-107, Dkk-1, β-catenin, Bcl-2, c-Myc, Caspase-3, and PARP. Cell counting kit-8 (CCK-8), flow cytometry (FCM), colony-formation efficiency (CFE), and subcutaneous tumorigenicity assays were all utilized for to determine cell proliferation, apoptosis, colony-forming, and tumorigenic abilities. Results: Dkk-1 is the target gene of miR-107. Decreased expressions of miR-107, LRP5, β-catenin, and c-Myc, and increased expressions of Dkk-1 were found in OS tissues. The Mimic and siRNA groups exhibited decreased proliferation rates, colony-forming abilities, and tumorigenicity and increased apoptosis rates, whereas the inhibitor group showed opposite trends when compared to the blank group. On the other hand, expressions of miR-107, LRP5, β-catenin, c-Myc, Caspase-3, and PARP were all elevated in the mimic group, whereas expressions of Dkk-1 and Bcl-2 were reduced; opposite trends were observed in the inhibitor group. Conclusion: We conclude that miR-107 is likely to inhibit the occurrence and development of OS by down-regulating Dkk-1 via the Wnt/β-catenin signaling pathway, providing us with a new therapeutic target for the treatment of OS. 

Retracted: No

PubPeer comments:
 Fig 9A.  Protein expressions shown as bands (A) and histograms (B) of Bcl2, cleavage PARP, and cleavage of Caspase 3 in different groups . Below, Fig 3B from [Wu et al (2018)] . No authors in common but the papers seem to be drawing on the same stock of protein blobs for their Western Blots. ![file] , 
 Fig 6A,  The cell cycle... of MG-63, U-2-OS, and HOS cells in 6 groups. Overhangs in the histograms of cell count against channel (and or in the fitted curve that sums the red-marked peaks and striped plateau). How does this happen? ![file] ,
Ku affects the CHK1-dependent G(2) checkpoint after ionizing radiation
Authors: Ya Wang
Gloria C Li
George Iliakis
Xiang Wang
Journal: Cancer research (2002)
Discipline: CLINICAL MEDICINE
Keywords: DNA double strand breaks; nonhomologous end joining; homologous recombination repair; Ku; ATM-dependent
Affiliations: Department of Radiation Oncology, Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Abstract:  There are two major pathways for repairing DNA double strand breaks in mammalian cells: nonhomologous end joining (NHEJ) and homologous recombination repair (HRR). The nonhomologous end joining repair is deficient in cells without Ku, whereas HRR is highly efficient in such cells compared with their wild-type counterparts. The mechanism remains unclear. We reported previously that Ku80(-/-) cells show a stronger ATM-dependent S-phase checkpoint response than Ku80(+/+) cells after ionizing radiation (IR; X-Y. Zhou et al., Oncogene, 21:6377-6381, 2002). We report in this study that Ku80(-/-) cells also show a much stronger G(2) accumulation than Ku80(+/+) cells after IR. The stronger G(2) checkpoint response in Ku80(-/-) cells is ATM independent but is accompanied with a higher activity of CHK1 kinase. Treatment with Chk1 antisense oligonucleotide abolishes the stronger G(2) checkpoint response and sensitizes Ku80(-/-) cells to IR. These data indicate that the stronger G(2) checkpoint response shown in Ku80(-/-) cells is CHK1 dependent and suggest that the CHK1-dependent checkpoint response contributes to the highly efficient HRR in such cells. 

Retracted: No

PubPeer comments:
 Figure 2. Much more similar than you would expect. https: imgur.com L0uJU80 , 
 #1 Figure 2 continued. Much more similar than you would expect. https: imgur.com dUvyO4r , 
 #2 Much more similar than you would expect. https: imgur.com irqPdsN , 
 Figure 3A. Much more similar than you would expect. https: imgur.com bX14jpb ,
A truncated fragment of Src protein kinase generated by calpain-mediated cleavage is a mediator of neuronal death in excitotoxicity
Authors: Andrew F Hill
Gregory J Dusting
Dominic C H Ng
M Aizuddin Kamaruddin
Donald J Fujita
Carli L Roulston
Percy W Y Chu
M Iqbal Hossain
Jeffrey D Bjorge
Steve N Cheung
Heung-Chin Cheng
Tung O Chan
Nicholas A Williamson
Journal: Journal of Biological Chemistry (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Excitotoxicity; Glutamate receptors; Neuronal death; Ischemic stroke; Calpains
Affiliations: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 30 Flemington Road, Parkville, Victoria 3010, Australia.

Abstract:  Excitotoxicity resulting from overstimulation of glutamate receptors is a major cause of neuronal death in cerebral ischemic stroke. The overstimulated ionotropic glutamate receptors exert their neurotoxic effects in part by overactivation of calpains, which induce neuronal death by catalyzing limited proteolysis of specific cellular proteins. Here, we report that in cultured cortical neurons and in vivo in a rat model of focal ischemic stroke, the tyrosine kinase Src is cleaved by calpains at a site in the N-terminal unique domain. This generates a truncated Src fragment of ~52 kDa, which we localized predominantly to the cytosol. A cell membrane-permeable fusion peptide derived from the unique domain of Src prevents calpain from cleaving Src in neurons and protects against excitotoxic neuronal death. To explore the role of the truncated Src fragment in neuronal death, we expressed a recombinant truncated Src fragment in cultured neurons and examined how it affects neuronal survival. Expression of this fragment, which lacks the myristoylation motif and unique domain, was sufficient to induce neuronal death. Furthermore, inactivation of the prosurvival kinase Akt is a key step in its neurotoxic signaling pathway. Because Src maintains neuronal survival, our results implicate calpain cleavage as a molecular switch converting Src from a promoter of cell survival to a mediator of neuronal death in excitotoxicity. Besides unveiling a new pathological action of Src, our discovery of the neurotoxic action of the truncated Src fragment suggests new therapeutic strategies with the potential to minimize brain damage in ischemic stroke. 

Retracted: No

PubPeer comments:
null, 
 #1 I agree with this concern, apparently unaddressed although reported 5 years ago. I added some author email addresses to this post. I would also like to bring attention to Figure 9C. It appears that the EthD-1 image for Myr-Akt is the same as the image for the overlay Myr-Akt+SrcN-GFP, albeit rotated or flipped horizontally and vertically (shown below with enhanced brightness). Possibly the SrcN-GFP and overlay image positions are reversed, and the flipping is inadvertent, but not sure that explains everything? Top: showing flip; Bottom: original Figure 9C *** ![file] *** ![file] ,
<p>Long Non-Coding RNA HOTAIR Modulates KLF12 to Regulate Gastric Cancer Progression via PI3K/ATK Signaling Pathway by Sponging miR-618</p>
Authors: Chunfeng Wang
Lianfeng Zhang
Bing Gao
Jianning Yao
Jin Xun
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: HOTAIR; KLF12; PI3K/ATK signaling pathway; gastric cancer; miR-618.
Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People's Republic of China.

Abstract:  Purpose: Long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) has been reported to dysregulate in many tumors. However, the mechanism of HOTAIR was rarely reported in GC. Methods: The levels of HOTAIR, microRNA-618 (miR-618) and Krueppel-like factor 12 (KLF12) in GC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptotic rate were assessed via cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The migrating and invading abilities were tested by Transwell assay. The protein levels of KLF12, p-PI3K, PI3K, p-ATK and ATK were measured by Western blot assay. These interactions between miR-618 and HOTAIR or KLF12 were predicted by DIANA tools, and then, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to validate these interactions. Besides, the xenograft tumor experiment was performed to further verify the roles of HOTAIR in GC. Results: The levels of HOTAIR and KLF12 were significantly upregulated and the level of miR-618 was strikingly downregulated in GC tissues and cells. miR-618 was verified as a direct target of HOTAIR or KLF12. HOTAIR silencing blocked GC progression and PI3K/ATK signaling pathway by sponging miR-618 and also restrained xenograft tumor growth in vivo. miR-618 inhibited GC progression and PI3K/ATK signaling pathway by targeting KLF12. Mechanistically, HOTAIR modulated KLF12 expression by sponging miR-618 in GC cells. Conclusion: These data unraveled that HOTAIR promoted GC progression through PI3K/ATK signaling pathway via miR-618/KLF12 axis. 

Retracted: No

PubPeer comments:
 All the Western immuno blots in this article look artificial. The bands are blurry and there is no background noise at all, even if you increase the contrast to the extreme. ![file] ,
MiR-106b-5p regulates the migration and invasion of colorectal cancer cells by targeting FAT4
Authors: Chunqiao Chen
Feifei Wei
Hui Huang
Guiyan Tang
Min Pan
Qiuqiu Chen
Yusong Lu
Journal: Bioscience Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Colorectal cancer; FAT4; MicroRNA-106b-5p.
Affiliations: Department of Oncology and Radiotherapy, Guilin People's Hospital, Guilin, China.

Abstract:  MicroRNA-106b-5p (miR-106b-5p) is involved in the development of many cancers including colorectal cancer (CRC), and FAT4 is correlated with regulation of growth and apoptosis of cancer cells. The present study aimed to investigate the relation between FAT4 and miR-106b-5p and the underlying mechanism of the two on the development of CRC. Quantitative real-time PCR (qRT-PCR) assay and Western blot (WB) analysis were performed to detect the expressions of messenger RNAs (mRNAs), microRNAs (miRNAs) and proteins. The viability of CRC cells was detected by cell counting kit-8 (CCK-8). Scratch test and transwell assay were performed to measure the migration and invasion of CRC cell. Tumor angiogenesis was simulated by in vitro angiogenesis experiment. Dual-luciferase reporter assay was performed to verify the targeting relation between miR-106b-5p and FAT4. The study found that the expression of FAT4 was down-regulated and that of miR-106b-5p was up-regulated in CRC tissues. Overexpression of FAT4 resulted in decreased proliferation, migration, invasion and angiogenesis of CRC cells, whereas silencing of FAT4 led to the opposite results. In rescue experiment, miR-106b-5p partially reversed the function of FAT4 in CRC cells, thus playing a carcinogenic role by targeting FAT4 in the CRC cells. 

Retracted: No

PubPeer comments:
 Iu2019ve seen a collection of odd looking Western Blots in recent papers at this journal. Because the journal suffered at the hands of what appears to be one or more papermills they instituted new measures including the requirement that the authors make original scans available. The corresponding author on this paper was kind enough to provide these for Figure 6B at my request (via email). Figure 6B as published ![file] *** Originals provided by author [link] ![file] *** My attempt to analyze found some repetitive background features, but they are difficult to see. The images on the right may be the easiest to see at this resolution. Can anyone do better? ![file] , 
 April 7, 2021 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. ,
IkappaB kinase is an essential component of the Tpl2 signaling pathway
Authors: Minying Zhang
Michael Waterfield
Shao-Cong Sun
William Reiley
Wei Jin
Journal: Molecular and Cellular Biology (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: IKK; immune response; inflammatory response; NF-kappaB; Tpl2 kinase
Affiliations: Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033, USA. 

Abstract:  IkappaB kinase (IKK), a key regulator of immune and inflammatory responses, is known as an effector kinase mediating activation of the transcription factor NF-kappaB. Whether IKK also participates in other signaling events is not known. Here we show that IKK serves as an essential component of a signaling pathway that involves activation of the Tpl2 kinase and its downstream targets, MEK1 and ERK. Inhibition of IKKbeta in macrophages eliminates Tpl2 activation and ERK phosphorylation induced by lipopolysaccharide and tumor necrosis factor alpha. Using IKK-deficient murine fibroblasts, we further demonstrate that IKKbeta, but not IKKalpha, is required for Tpl2 activation. Moreover, this novel function of IKKbeta appears to involve phosphorylation and degradation of the Tpl2 inhibitor NF-kappaB1/p105. These findings suggest that IKKbeta exerts its immune-regulatory functions by targeting different downstream signaling pathways. 

Retracted: No

PubPeer comments:
 Figure 1B. https: imgur.com MKMTCt2 ,
The anti-fibrotic effect of bone morphogenic protein-7(BMP-7) on liver fibrosis
Authors: Hengjun Gao
Changqing Yang
Xiaolin Wang
Li Yang
Shenglan Wang
Lan Zhong
Journal: International journal of medical sciences (2013)
Discipline: CLINICAL MEDICINE
Keywords: bone morphogenic protein-7; epithelial-to-mesenchymal transition; extracellular matrix.; hepatic stellate cell; hepatocytes
Affiliations: Division of Gastroenterology, East Hospital of Tongji University School of Medicine, Shanghai 200120, China.

Abstract:  Background/Aims : Transforming growth factor-β1 (TGF-β1) plays an important role in the pathogenesis of liver fibrosis and cirrhosis. Recombinant human bone morphogenic protein-7 (rhBMP-7) alleviates renal fibrosis and improves kidney function. However, the beneficial effect of BMP-7 on hepatic fibrosis and cirrhosis remains unknown. The purpose of this study was to investigate the prophylactic and therapeutic effects of rhBMP-7 on liver fibrosis and the underlying mechanisms. Methods : Liver fibrosis in the rat model was induced by peritoneal injection of porcine-serum (0.5ml/kg body weight) twice a week over 8 weeks. The effect of rhBMP-7 on hepatic fibrosis was monitored in rhBMP-7 pre-treated and non-treated rats. Pathologic changes were determined by immunohistolocial staining. TGF-β1 expression was investigated by immunohistolocial staining, western blotting, and real-time PCR. Collagen secretion was measured by enzyme-linked immunosorbent assay. Results : Liver fibrosis was significantly reduced by rhBMP-7. The secretion of collagen type-I and -III was decreased by rhBMP-7 in hepatic stellate cells (HSCs) but not in hepatocytes. The anti-fibrotic effect of rhBMP-7 on liver fibrosis was resulted by blocking the nuclear accumulation of Smad2/3 or by inhibiting TGF-β1 expression in HSCs or hepatocytes. Conclusions : The anti-fibrogenic mechanism of rhBMP-7 in the rat liver fibrosis was depended on the reduction of TGF-β1 overexpression and the inhibition of TGF-β1 triggered intracellular signalling in hepatic cells. 

Retracted: No

PubPeer comments:
 ![file] ![file] ![file] ,
Radiation-induced bystander signaling pathways in human fibroblasts: a role for interleukin-33 in the signal transmission
Authors: Benjamin Yaghoubian
Hongning Zhou
Thomas B Karasic
Vladimir N Ivanov
Tom K Hei
Sally A Amundson
Shanaz A Ghandhi
Journal: Cellular Signalling (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: signal transmission; radiation-induced bystander response; NF-kappaB; IL8; IL6
Affiliations: Center for Radiological Research, Department of Radiation Oncology, Columbia University, New York, NY 10032, USA. 

Abstract:  The main goal of this study is to elucidate the mechanisms of the signal transmission for radiation-induced bystander response. The NF-kappaB-dependent gene expression of IL8, IL6, PTGS2/COX2, TNF and IL33 in directly irradiated human skin fibroblasts produced the cytokines and prostaglandin E2 (PGE2) with autocrine/paracrine functions, which further activated signaling pathways and induced NF-kappaB-dependent gene expression in bystander cells. As a result, bystander cells also started expression and production of interleukin-8, interleukin-6, COX-2-generated PGE2 and interleukin-33 (IL-33) followed by autocrine/paracrine stimulation of the NF-kappaB and MAPK pathways. A blockage of IL-33 transmitting functions with anti-IL-33 monoclonal antibody added into the culture media decreased NF-kappaB activation in directly irradiated and bystander cells. On the other hand, the IGF-1-Receptor kinase regulated the PI3K-AKT pathway in both directly irradiated and bystander fibroblasts. A pronounced and prolonged increase in AKT activity after irradiation was a characteristic feature of bystander cells. AKT positively regulated IL-33 protein expression levels. Suppression of the IGF-R1-AKT-IL-33 pathway substantially increased radiation-induced or TRAIL-induced apoptosis in fibroblasts. Taken together, our results demonstrated the early activation of NF-kappaB-dependent gene expression first in directly irradiated and then bystander fibroblasts, the further modulation of critical proteins, including IL-33, by AKT in bystander cells and late drastic changes in cell survival and in enhanced sensitivity to TRAIL-induced apoptosis after suppression of the IGF-1R-AKT-IL-33 signaling cascade in both directly irradiated and bystander cells. 

Retracted: No

PubPeer comments:
 ![file] , 
 ![file] , 
 The presence or the absence of splices are dependent of protein concentration of the corresponding polypeptide: beta-actin western (with high concentration of beta-actin in total protein extracts) are quite often without splice. Total GSK3-beta could also present without splices in western. , 
 #1 The correction has been made. A dividing line in the AKT-P scan Fig. 4C (Cell. Signal. 2010, 22: 1076-1087) indicates the boundary after removing unnecessary lane. ![file] , 
 #3 The correction was made. Two central lanes (after treatment modality, which was not used in this paper) were removed from the IL33 scan in Fig. 5A (Cell. Signal. 2010, 22: 1076-1087). A dividing line indicates the boundary between two parts of this scan. ![file] ,
Actinidia chinensis Planch root extract (acRoots) inhibits hepatocellular carcinoma progression by inhibiting EP3 expression
Authors: Minghuan Zheng
Jiayun Hou
Lingyan Wang
Mingyan He
Tingting Fang
Jinglin Xia
Xiangdong Wang
Journal: Cell Biology and Toxicology (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Actinidia chinensis; Hepatocellular carcinoma; Immunity; Prostaglandin E receptor 3.
Affiliations: Liver Cancer Institute, Zhongshan Hospital, Shanghai, China., Clinical Science Institute, Zhongshan Hospital, Shanghai, China., Clinical Science Institute, Zhongshan Hospital, Shanghai, China. ., Liver Cancer Institute, Zhongshan Hospital, Shanghai, China. ., Minhang Hospital, Shanghai Medical School of Fudan University, Shanghai, 201100, China. .

Abstract:  A wide range of studies has demonstrated the potent anticancer activity of Chinese herbs. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis root extract (acRoots) on hepatocellular carcinoma (HCC). HepG2 HCC cells were treated with various concentrations of acRoots for 72 h and examined by mRNA expression profiling, revealing alterations in cellular immunity, inflammation, proliferation, cell cycle, and metabolic signaling responses. Further analysis of the altered genes in cellular immunity and inflammation gene clusters identified prostaglandin E receptor 3 (EP3) as a key regulator of gene expression in response to acRoots. Further analysis revealed inhibition of cell growth, migration, and invasion in HCC in response to acRoots, along with increased apoptosis due to downregulation of EP3 expression. Treatment with acRoots and EP3 antagonist L-798106 led to decreases in VEGF, EGFR, MMP2, and MMP9 expression in HCC cells, along with significant effects on growth, migration, invasion, and apoptosis; the effects were reversed/blocked by the EP3 agonist sulprostone. Taken together, these data clearly demonstrated that acRoots inhibit HCC cell invasion and metastasis via inhibition of EP3 expression, resulting in decreased activation of VEGF, EGFR, MMP2, and MMP9. 

Retracted: No

PubPeer comments:
 Fig 6B has at least 4 pairs of overlaps ![] ,
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
Authors: Michael P Franczyk
Jun Yoshino
Bruce W Patterson
Terri Pietka
Shin-Ichiro Imai
Miriam Sindelar
Mihoko Yoshino
Brandon D Kayser
Kathryn F Mills
Gary J Patti
Samuel Klein
Journal: Science (2021)
Discipline: Multidisciplinary
Keywords: obesity; aging; nicotinamide adenine dinucleotide (NAD+); biosynthesis; nicotinamide mononucleotide (NMN)
Affiliations: Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA., Department of Chemistry, Washington University School of Medicine, St. Louis, MO, USA., Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA., Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA. .

Abstract:  In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239). 

Retracted: No

PubPeer comments:
 Readers should become aware of a commentary recent made by Dr. Charles Brenner about this article: https: science.sciencemag.org content 373 6554 eabj1696 Abstract: Yoshino et al. (Reports, 11 June 2021, p. 1224) have reported that nicotinamide mononucleotide (NMN) increases muscle insulin sensitivity in prediabetic women. However, the 13 women who received NMN had hepatic lipid content of 6.3 u00b1 1.2%, whereas the 12 in the placebo group had 14.8 u00b1 2.0% (P = 0.003). Given that a target of NMN is liver fat clearance, this was not an effectively randomized trial. You can find author s reply on Response to Comment on u201cNicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women https: science.sciencemag.org content 373 6554 eabj7375 Abstract In evaluating any randomized clinical trial, it is important to determine whether baseline differences between groups could have affected the primary outcome. In our study, muscle insulin sensitivity, which was identical in both groups at baseline, improved after nicotinamide mononucleotide (NMN), not placebo, therapy. Differences in baseline intrahepatic triglyceride content between groups do not negate the effects of NMN observed in muscle. ,
MHC universal cells survive in an allogeneic environment after incompatible transplantation
Authors: Axel Seltsam
Stefanie Vahlsing
Dirk Wedekind
Rainer Blasczyk
Peter A Horn
Thomas Müller
Constança Figueiredo
Journal: BioMed Research International (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell transplantation; MHC diversity; Histocompatibility barrier; MHC class I-silenced cells; Allogeneic transplantation
Affiliations: Institute for Transfusion Medicine, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany., Institute for Laboratory Animal Science, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany., Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Nordrhein-Westfalen, Germany., Institute for Transfusion Medicine, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany ; German Red Cross, Blood Services NSTOB, Institute Springe, Lower Saxony, 31832 Springe, Germany.

Abstract:  Cell, tissue, and organ transplants are commonly performed for the treatment of different diseases. However, major histocompatibility complex (MHC) diversity often prevents complete donor-recipient matching, resulting in graft rejection. This study evaluates in a preclinical model the capacity of MHC class I-silenced cells to engraft and grow upon allogeneic transplantation. Short hairpin RNA targeting β2-microglobulin (RN_shβ2m) was delivered into fibroblasts derived from LEW/Ztm (RT1(l)) (RT1-A(l)) rats using a lentiviral-based vector. MHC class I (RT1-A-) expressing and -silenced cells were injected subcutaneously in LEW rats (RT1(l)) and MHC-congenic LEW.1W rats (RT1(u)), respectively. Cell engraftment and the status of the immune response were monitored for eight weeks after transplantation. In contrast to RT1-A-expressing cells, RT1-A-silenced fibroblasts became engrafted and were still detectable eight weeks after allogeneic transplantation. Plasma levels of proinflammatory cytokines IL-1 α , IL-1 β , IL-6, TNF- α , and IFN- γ were significantly higher in animals transplanted with RT1-A-expressing cells than in those receiving RT1-A-silenced cells. Furthermore, alloantigen-specific T-cell proliferation rates derived from rats receiving RT1-A-expressing cells were higher than those in rats transplanted with RT1-A-silenced cells. These data suggest that silencing MHC class I expression might overcome the histocompatibility barrier, potentially opening up new avenues in the field of cell transplantation and regenerative medicine. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
The DNA intercalators ethidium bromide and propidium iodide also bind to core histones
Authors: Chandrima Das
Jasdeep Singh
Kuladip Jana
Sulagna Sanyal
Amrita Banerjee
Parijat Majumder
Dipak Dasgupta
Journal: FEBS Open Bio (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chromatin compaction; DLS, dynamic light scattering; DNA release; EB, ethidium bromide; HAT, histone acetyl transferase
Affiliations: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhan Nagar, Kolkata 700064, West Bengal, India., Division of Molecular Medicine, Centre for Translational Animal Research, Bose Institute, P-1/12 C.I.T. Scheme VIIM, Kolkata 700054, West Bengal, India.

Abstract:  Eukaryotic DNA is compacted in the form of chromatin, in a complex with histones and other non-histone proteins. The intimate association of DNA and histones in chromatin raises the possibility that DNA-interactive small molecules may bind to chromatin-associated proteins such as histones. Employing biophysical and biochemical techniques we have characterized the interaction of a classical intercalator, ethidium bromide (EB) and its structural analogue propidium iodide (PI) with hierarchical genomic components: long chromatin, chromatosome, core octamer and chromosomal DNA. Our studies show that EB and PI affect both chromatin structure and function, inducing chromatin compaction and disruption of the integrity of the chromatosome. Calorimetric studies and fluorescence measurements of the ligands demonstrated and characterized the association of these ligands with core histones and the intact octamer in absence of DNA. The ligands affect acetylation of histone H3 at lysine 9 and acetylation of histone H4 at lysine 5 and lysine 8 ex vivo. PI alters the post-translational modifications to a greater extent than EB. This is the first report showing the dual binding (chromosomal DNA and core histones) property of a classical intercalator, EB, and its longer analogue, PI, in the context of chromatin. 

Retracted: No

PubPeer comments:
 Figure 3: Much more similar than expected ![file] , 
 Please see the corrigendum here: https: doi.org 10.1002 2211-5463.13397 ,
Retracted : Long noncoding RNA THRIL contributes in lipopolysaccharide‐induced HK‐2 cells injury by sponging miR‐34a
Authors: Ying Xiao
Qi Zhang
Sen Luan
Yao Deng
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: lipopolysaccharide; lncRNA THRIL; miR-34a; monocyte chemoattractant protein-1; systemic lupus erythematosus.
Affiliations: Department of Rheumatology and Immunology, Shengli Oilfield Central Hospital, Dongying, China., Department of Nephrology, Shengli Oilfield Central Hospital, Dongying, China.

Abstract:  Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown etiology. Nowadays, several long noncoding RNAs (lncRNAs) have been reported as molecular alterations involved in SLE. This study aimed to reveal the function of TNF-related and HNRNPL-related immunoregulatory lncRNA (THRIL) in SLE. Human epithelial HK-2 cells were exposed to lipopolysaccharide (LPS) to mimic an in vitro SLE model. Then, the functions of THRIL, miR-34a, and monocyte chemoattractant protein-1 (MCP-1), as well as their correlations were detected. LncRNA THRIL was highly expressed in the LPS-stimulated cells, and THRIL overexpression aggravated LPS-induced cell damage as cell viability was decreased, and apoptosis and the release of proinflammatory cytokines were increased. THRIL worked as a sponge of microRNA-34a (miR-34a) and it could directly target MCP-1. Furthermore, MCP-1-activated JNK and Wnt/β-catenin signaling pathways. In conclusion, this study suggested that lncRNA THRIL might be a key regulator participating in LPS-induced injury in HK-2 cells. THRIL overexpression aggravated LPS-induced injury possibly via sponging miR-34a, and thus preventing MCP-1 from degradation by miR-34a. The THRIL/miR-34a/MCP-1 axis might play critical roles in SLE. 

Retracted: Yes

PubPeer comments:
 Retracted [19 July 2021] . ---------------------------------------------- The above article, published online on 9 November 2018 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. As several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. --------------------------------- The paper appears to be another product of the Tadpole Papermill that had previously escaped the attention of Pubpeer contributors. ![file] ,
LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN 2 as a regulator of effector functions
Authors: Jerôme Garin
Bernard Malissen
Carine Froment
Manuel Martinez
Laura Girard
Daiki Mori
Anne Gonzalez de Peredo
Marisa Goncalves Menoita
Marie Malissen
Claude Gregoire
Odile Burlet-Schiltz
Romain Roncagalli
Marie Locard-Paulet
Youcef Ounoughene
Hervé Luche
Guillaume Voisinne
Journal: Molecular Systems Biology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ITSN2; LymphoAtlas; TCR signaling network; dynamic biological processes; phosphoproteomics.
Affiliations: Institut de Pharmacologie et de Biologie Structurale (IPBS) Université de Toulouse, CNRS, UPS Toulouse France, Centre d'Immunologie de Marseille‐Luminy INSERM, CNRS Aix Marseille Université Marseille France, Centre d'Immunophénomique INSERM, CNRS UMR Aix Marseille Université Marseille France, CEA, BIG, Biologie à Grande Echelle, INSERM, U1038 Université Grenoble‐Alpes Grenoble France

Abstract:  T-cell receptor (TCR) ligation-mediated protein phosphorylation regulates the activation, cellular responses, and fates of T cells. Here, we used time-resolved high-resolution phosphoproteomics to identify, quantify, and characterize the phosphorylation dynamics of thousands of phosphorylation sites in primary T cells during the first 10 min after TCR stimulation. Bioinformatic analysis of the data revealed a coherent orchestration of biological processes underlying T-cell activation. In particular, functional modules associated with cytoskeletal remodeling, transcription, translation, and metabolic processes were mobilized within seconds after TCR engagement. Among proteins whose phosphorylation was regulated by TCR stimulation, we demonstrated, using a fast-track gene inactivation approach in primary lymphocytes, that the ITSN2 adaptor protein regulated T-cell effector functions. This resource, called LymphoAtlas, represents an integrated pipeline to further decipher the organization of the signaling network encoding T-cell activation. LymphoAtlas is accessible to the community at: https://bmm-lab.github.io/LymphoAtlas. 

Retracted: No

PubPeer comments:
 This SSRN preprint appears to be computer-generated with [SCIgen] . It claims u201cForthcoming: Proceedings of the USENIX Technical Conference CSET u201815u201d but there is no such title in the [program of CSET 15] . ![file] --- ![file] --- ![file] --- ![file] --- This comment was written by Guillaume Cabanac and Cyril Labbu00e9. Contact: [SeekAndBlastn-Operators@univ-grenoble-alpes.fr](mailto:SeekAndBlastn-Operators@univ-grenoble-alpes.fr). ,
Staurosporine-induced apoptosis is independent of p16 and p21 and achieved via arrest at G2/M and at G1 in U251MG human glioma cell line
Authors: Fumiyuki Yamasaki
Kaita Yahara
Seiji Hama
Yoshinori Kajiwara
Kazuhiko Sugiyama
Kazunori Arita
Kaoru Kurisu
Yuji Heike
Hiroyuki Yoshioka
Journal: Cancer Chemotherapy and Pharmacology (2003)
Discipline: CLINICAL MEDICINE
Keywords: cell cycle; cell death; staurosporine; G1 arrest; G2/M arrest
Affiliations: Department of Neurosurgery, Faculty of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. 

Abstract:  Objective: The mechanisms involved in the cell cycle and cell death remain unresolved despite much investigation. Staurosporine induces cell death and G1 or G2/M arrest in a dose-dependent manner, but the mechanisms remain unknown. Methods: In the present study an adenovirus vector expressing p16 or p21 genes in human glioma cell lines was used to examine cell cycle regulation and cell death induced by staurosporine. Results: A low concentration (&lt;/=10 n M) of staurosporine induced G1 arrest of U251MG cells, whereas a high concentration (&gt;/=30 n M) induced G2/M arrest and finally induced apoptosis via a caspase-3-activated pathway from both the G2/M and G1 phases. However, pRb was dephosphorylated and cdc2 was inhibited at both the low and the high concentrations of staurosporine, indicating that the mechanisms of cell cycle regulation are not simply p53-Rb- or cdc2-dependent pathways. Conclusions: Forced G1 arrest by transfection with p16 or p21 genes did not alter the rate of staurosporine-induced cell death. This implies that an unknown pathway of apoptosis occurs from the G1 phase. 

Retracted: No

PubPeer comments:
 Figure 2. * Boxes of the same color highlight parts of blots that look more similar than expected. Part of a set of 29 papers reported to the journal in the summer of 2015 with a friendly reminder in April 2017, but no answer. With the exception of one paper, the journal did not correct or retract a single paper from this set. ![file] ,
c-Jun-deficient cells undergo premature senescence as a result of spontaneous DNA damage accumulation
Authors: William Clark
David A F Gillespie
Elizabeth J Black
Ann MacLaren
Journal: Molecular and Cellular Biology (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: c-Jun proto-oncogene; premature senescence; DNA damage; oxygen; p53
Affiliations: Beatson Institute for Cancer Research, Bearsden, UK. , Beatson Institute for Cancer Research, Bearsden

Abstract:  Mouse embryo fibroblasts deficient for the c-Jun proto-oncogene (c-Jun-/- MEF) undergo p53-dependent premature senescence in conventional culture. This phenotype becomes evident only after several cell divisions, suggesting that senescence may result from exposure to unknown environmental factors. Here, we show that c-Jun-/- MEF can proliferate successfully in low oxygen (3% O2), indicating that premature senescence under conventional culture conditions is a consequence of hyperoxic stress. c-Jun-/- MEF exhibit higher basal levels of DNA damage compared to normal fibroblasts in high but not low oxygen, implying that senescence results from chronic accumulation of spontaneous DNA damage. This accumulation may be attributable, at least in part, to inefficient repair, since DNA damage induced by gamma ionizing radiation and H2O2 persists for longer in c-Jun-/- MEF than in wild-type MEF. Unexpectedly, p53 expression, phosphorylation, and transcriptional activity are largely unaffected by oxygen exposure, indicating that the accumulation of spontaneous DNA damage does not result in chronic activation of p53 as judged by conventional criteria. Finally, we find that c-Jun associates with nuclear foci containing gammaH2AX and ATM following irradiation, suggesting a potential role for c-Jun in DNA repair processes per se. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than expected. ![file] ,
STAT3 Decoy Oligodeoxynucleotides-Loaded Solid Lipid Nanoparticles Induce Cell Death and Inhibit Invasion in Ovarian Cancer Cells
Authors: Yao Yao
Yanhui Ma
Ziyan Yang
Xiaoxuan Xu
Liang Shen
Xiaolei Zhang
Peishu Liu
Journal: PLoS ONE (2015)
Discipline: Multidisciplinary
Keywords: nanoparticles; solid lipid nanoparticles; STAT3 decoy ODN; gene delivery; cancer therapy
Affiliations: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China., Department of Obstetrics and Gynecology, Provincial Hospital Affiliated with Shandong University, Jinan, Shandong, China., Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.

Abstract:  Recent advances in the synthesis of multi-functional nanoparticles have opened up tremendous opportunities for the targeted delivery of genes of interest. Cationic solid lipid nanoparticles (SLN) can efficiently bind nucleic acid molecules and transfect genes in vitro. Few reports have combined SLN with therapy using decoy oligodeoxynucleotides (ODN). In the present study, we prepared SLN to encapsulate STAT3 decoy ODN; then, the properties and in vitro behavior of SLN-STAT3 decoy ODN complexes were investigated. SLN-STAT3 decoy ODN complexes were efficiently taken up by human ovarian cancer cells and significantly suppressed cell growth. Blockage of the STAT3 pathway by SLN-STAT3 decoy ODN complexes resulted in an evident induction of cell death, including apoptotic and autophagic death. The mechanism involved the increased expression of cleaved caspase 3, Bax, Beclin-1 and LC3-II and reduced expression of Bcl-2, pro-caspase 3, Survivin, p-Akt and p-mTOR. In addition, SLN-STAT3 decoy ODN complexes inhibited cell invasion by up-regulating E-cadherin expression and down-regulating Snail and MMP-9 expression. These findings confirmed that SLN as STAT3 decoy ODN carriers can induce cell death and inhibit invasion of ovarian cancer cells. We propose that SLN represent a potential approach for targeted gene delivery in cancer therapy. 

Retracted: No

PubPeer comments:
 Figure 6A. * Yellow boxes: In the 0h row, the NC and SLN-Decoy ODN panels appear to show an overlap * Red boxes: In the 24h row, the SLN-Decoy ODN and Lipo-Decoy ODN panels appear to show an overlap ![file] ,
The myristoylation of TRIF-related adaptor molecule is essential for Toll-like receptor 4 signal transduction
Authors: Masahiro Yamamoto
Nicholas J Gay
Daniel C Rowe
Luke A O&#x27;Neill
Douglas T Golenbock
Eicke Latz
Brian G Monks
Shizuo Akira
Katherine A Fitzgerald
Anne F McGettrick
Journal: Proceedings of the National Academy of Sciences of the United States of America (2006)
Discipline: Multidisciplinary
Keywords: TRAM; Toll-like receptor signaling; myristoylation; plasma membrane; Golgi apparatus
Affiliations: Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract:  TRIF-related adaptor molecule (TRAM) is the fourth Toll/IL-1 resistance domain-containing adaptor to be described that participates in Toll-like receptor (TLR) signaling. TRAM functions exclusively in the TLR4 pathway. Here we show by confocal microscopy that TRAM is localized in the plasma membrane and the Golgi apparatus, where it colocalizes with TLR4. Membrane localization of TRAM is the result of myristoylation because mutation of a predicted myristoylation site in TRAM (TRAM-G2A) brought about dissociation of TRAM from the membrane and its relocation to the cytosol. Further, TRAM, but not TRAM-G2A, was radiolabeled with [3H]myristate in vivo. Unlike wild-type TRAM, overexpression of TRAM-G2A failed to elicit either IFN regulatory factor 3 or NF-kappaB signaling. Moreover, TRAM-G2A was unable to reconstitute LPS responses in bone marrow-derived macrophages from TRAM-deficient mice. These observations provide clear evidence that the myristoylation of TRAM targets it to the plasma membrane, where it is essential for LPS responses through the TLR4 signal transduction pathway, and suggest a hitherto unappreciated manner in which LPS responses can be regulated. 

Retracted: No

PubPeer comments:
 Fig 4C.  Flow cytometry by Annexin V propidium iodide staining was conducted to assess the effect of HOXA-AS2 on the apoptosis of CCRF-CEM, Jurkat and CEM C1 cells in the presence of dexamethasone. ![file] Two of the CEM C1 panels are very similar in their left-hand quadrants. Here emphasised by superimposing one on the other, with one panel color-reversed so that identical points cancel out. ![file] All three Jurkat panels are remarkably similar, though I have only superimposed two of them. ![file] ,
The expression of TP53 pathway-related proteins in ovarian carcinoma transplanted subcutaneously in nude mice
Authors: D-B Li
J-W Xue
S-R Zhang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: TP53 pathway; ovarian carcinoma; p53 inhibitor; nude mice; tumor growth
Affiliations: Department of Obstetrics and Gynecology, Yantaishan Hospital, Yantai, Shandong Province, China. .

Abstract:  Objective: Given the important functions of TP53 pathway in various biological processes, this study aimed to investigate the expression of TP53 pathway-related proteins in ovarian carcinoma transplanted subcutaneously in nude mice with and without the presence of p53 inhibitor and to explore possible roles of p53 in the development of ovarian cancer. Materials and methods: Thirty BALB/c-nu female nude mice were randomly divided into model group, control group and p53 inhibitor group (Pftα group). There were 10 rats in each group. The nude mice were subcutaneously inoculated with human ovarian cancer cell line SKOV3, and the tumor growth was observed. Morphological changes of tumor tissue were observed by hematoxylin and eosin (HE) staining. The mRNA and protein levels of TP53 pathway related factors-p53, p21 and mouse double minute 2 homolog (MDM2) were detected by RT-PCR and Western blot. Results: p53 inhibitor can increase the growth rate of subcutaneously transplanted tumor in nude mice. p53 inhibitor could decrease the expression of p53 and p21 at both mRNA and protein levels and increase the expression of MDM2 at both mRNA and protein levels in ovarian carcinoma transplanted subcutaneously in nude mice. Conclusions: TP53 pathway may play pivotal roles in the development of ovarian cancer and TP53 pathway may be a new target for the treatment of ovarian cancer. 

Retracted: No

PubPeer comments:
  Figure 2. HE staining of the subcutaneous tumor tissue sections (u00d7100). A, model group; B, solvent group; C, Pfta group. ![file] ,
STAT1 signaling modulates HIV-1–induced inflammatory responses and leukocyte transmigration across the blood-brain barrier
Authors: Anathbandhu Chaudhuri
Bo Yang
Yuri Persidsky
Howard E Gendelman
Georgette D Kanmogne
Journal: Blood (2008)
Discipline: CLINICAL MEDICINE
Keywords: neuroinflammation; blood-brain barrier; HIV-1 infection; neuroAIDS; signal transducers and activators of transcription (STATs) pathways
Affiliations: Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5215, USA., Center for Neurovirology and Neurodegenerative Disorders,, Departments ofPharmacology and Experimental Neuroscience,, Internal Medicine,, Pathology and Microbiology, University of Nebraska Medical Center, Omaha

Abstract:  The relationship among neuroinflammation, blood-brain barrier (BBB) dysfunction, and progressive HIV-1 infection as they affect the onset and development of neuroAIDS is incompletely understood. One possible link is signal transducers and activators of transcription (STATs) pathways. These respond to proinflammatory and regulatory factors and could affect neuroinflammatory responses induced from infected cells and disease-affected brain tissue. Our previous works demonstrated that HIV-1 activates pro-inflammatory and interferon-alpha-inducible genes in human brain microvascular endothelial cells (HBMECs) and that these genes are linked to the Janus kinase (JAK)/STAT pathway. We now demonstrate that HIV-1 activates STAT1, induces IL-6 expression, and diminishes expression of claudin-5, ZO-1, and ZO-2 in HBMECs. The STAT1 inhibitor, fludarabine, blocked HIV-1-induced IL-6, diminished HIV-1-induced claudin-5 and ZO-1 down-regulation, and blocked HIV-1- and IL-6-induced monocyte migration across a BBB model. Enhanced expression and activation of STAT1 and decreased claudin-5 were observed in microvessels from autopsied brains of patients with HIV-1-associated dementia. These data support the notion that STAT1 plays an integral role in HIV-1-induced BBB damage and is relevant to viral neuropathogenesis. Inhibition of STAT1 activation could provide a unique therapeutic strategy to attenuate HIV-1-induced BBB compromise and as such improve clinical outcomes. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,