PReD-Bench/PRed-Bench huggingface dataset:
Oral insulin enhances intestinal regrowth following massive small bowel resection in rat
Authors: Raanan Shamir
Jorge G Mogilner
Naim Shehadeh
Igor Sukhotnik
Jacob Bejar
Aleksander Bernshteyn
Journal: Digestive Diseases and Sciences (2005)
Discipline: CLINICAL MEDICINE
Keywords: insulin; small intestinal growth; structural intestinal adaptation; enterocyte proliferation; apoptosis
Affiliations: Rappaport Faculty of Medicine, Technion, Department of Pediatric Surgery B, Bnai Zion Medical Center, Haifa, Israel. 

Abstract:  Experimental studies have suggested that insulin (INS) plays an important role in small intestinal growth and development. In the present study we investigated the effect of oral INS on structural intestinal adaptation and enterocyte proliferation and loss via apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-INS rats underwent bowel resection and were treated with oral INS given in the drinking water from the 3rd to the 15th postoperative day. Parameters of intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villous height, and crypt depth), enterocyte proliferation, and apoptosis were determined on day 15. SBS-INS rats demonstrated a significant increase (vs SBS rats) in jejunal and ileal overall bowel and mucosal weight, ileal mucosal DNA and protein, ileal villous height, and crypt depth. SBS-INS rats also showed an increased cell proliferation index in jejunum and ileum and decreased apoptotic index in jejunum compared to SBS animals. In conclusion, in a rat model of SBS, oral INS strongly enhances intestinal adaptation. Possible mechanisms may include increased cell proliferation and decreased enterocyte loss via apoptosis. 

Retracted: No

PubPeer comments:
 Figure 4C: More similar than expected. ![file] , 
 Penultimate author [calling for] new research integrity office at Unicamp. ,
Evidence for a causal role by mouse mammary tumour-like virus in human breast cancer
Authors: Wendy K Glenn
James S Lawson
Journal: NPJ breast cancer (2019)
Discipline: CLINICAL MEDICINE
Keywords: Breast cancer; Cancer; Oncogenesis.
Affiliations: School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW Australia.

Abstract:  We have reviewed the evidence relevant to mouse mammary tumour viruses (MMTV) and human breast cancer. The prevalence of MMTV- like gene sequences is 15-fold higher in human breast cancer than in normal human breast tissue controls and is present in up to 40% of human breast cancers. MMTV-like gene sequences can be identified in benign breast tissues 1-11 years before the development of positive MMTV-like breast cancer in the same women. The prevalence of MMTV antibodies in sera from women with breast cancer is 5-fold higher than in normal women. MMTV can infect human breast epithelial cells and integrate at random into the human genome located in those cells. MMTV-like gene sequences are present in human milk from normal lactating women and with increased prevalence in milk from women at risk of breast cancer. MMTV-like virus associated human breast cancer has strikingly similar features to MMTV-associated mouse mammary tumours. These features include almost identical nucleotide sequences and structure of the MMTV genome, histology, superantigen expression, MMTV infection of B and T lymphocytes and hormone dependence. MMTV-like gene sequences have also been identified in dogs, cats, monkeys, mice and rats. Saliva has been identified as the most plausible means of transmission from human to human and possibly from dogs to humans. The evidence meets the classic causal criteria. A causal role for MMTV-like viruses in human breast cancer is highly likely. 

Retracted: No

PubPeer comments:
 This review neglected to point out the lack of evidence for integrated MMTV-like sequences found during whole genome sequencing of human breast cancer DNA. The only evidence of MMTV-like sequences in human breast samples is based on contamination-prone PCR experiments. ,
Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter
Authors: Jianguo Wu
Yan Hu
Elaine Pinder
Allen C Gao
Jae Yeon Chun
Fengzhi Li
Journal: Molecular Cancer Therapeutics (2007)
Discipline: CLINICAL MEDICINE
Keywords: Survivin; Selenium; Cancer; Chemopreventive agent; Drug resistance
Affiliations: Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

Abstract:  Survivin, an antiapoptotic protein highly expressed in cancer, regulates multiple cellular network associated with cancer cell viability and drug resistance. Inhibition of survivin expression has been pursued as a valid cancer therapeutic target. In this study, we showed that selenium, an effective chemopreventive agent for many types of cancers, down-regulated survivin expression. Selenium inhibited survivin expression in both mRNA and protein levels in a dose- and time-dependent manner. Using a series of survivin promoter-luciferase constructs, a 37-bp DNA element in the survivin core promoter region that mediates the ability of selenium to inhibit survivin transcription was identified. Gel mobility shift assays and chromatin immunoprecipitation analyses revealed that selenium prevents the binding of Sp1 or Sp1-like proteins to the 37-bp cis-acting DNA element in the survivin promoter. Furthermore, inhibition of survivin expression by small interfering RNA enhanced selenium's inhibitory effects on cell growth, whereas overexpression of survivin in LNCaP human prostate cancer cells desensitized cancer cells to selenium effect, suggesting that the expression of survivin plays an important role in determining the response of cancer cells to selenium. Taken together, these results suggest that selenium down-regulated survivin expression by preventing the binding of Sp1 or Sp1-like proteins to the promoter of survivin, which contributes at least in part to the inhibitory effect of selenium on survivin gene transcription. In addition, down-regulation of survivin expression may account for one of the molecular mechanisms of the anticancer effects of selenium. 

Retracted: No

PubPeer comments:
 Figure 1D. Much more similar than you would expect even though the conditions are different. https: imgur.com lYOgxpL ,
Discontinuation of smokeless tobacco and mortality risk after myocardial infarction
Authors: Lars Lind
Karl Michaëlsson
Johan Sundström
Gabriel Arefalk
Bertil Lindahl
Kristina Hambraeus
Journal: Circulation (2014)
Discipline: CLINICAL MEDICINE
Keywords: mortality; myocardial infarction; prognosis; risk factors; smokeless tobacco.
Affiliations: From the Department of Medical Sciences (G.A., L.L., B.L., J.S.) and Department of Surgical Sciences (K.M.), Uppsala University, Uppsala, Sweden; and the Department of Cardiology, Falu Hospital, Falu, Sweden (K.H.). ., From the Department of Medical Sciences (G.A., L.L., B.L., J.S.) and Department of Surgical Sciences (K.M.), Uppsala University, Uppsala, Sweden; and the Department of Cardiology, Falu Hospital, Falu, Sweden (K.H.).

Abstract:  Background: Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and results: All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were &lt;75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). Conclusions: In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged. 

Retracted: No

PubPeer comments:
 This study should be read carefully. Cardiovascular deaths are not significantly changed. Only after including non-cardiovascular death u2014 generally not attributed to snus u2014 is the correlation statistically significant. This implies that confounding variables influenced the outcome. Indeed, smoking intensity was not adjusted for, even though most subjects smoked. Moreover, snus cessation after a heart attack is likely correlated with following medical advice, including smoking cessation, which is not adjusted for in this study. It should be noted that subsequently a large study found no adverse effect of giving NRT to hospitalized cardiovascular patients. https: pubmed.ncbi.nlm.nih.gov 30371184 ,
Cardiac fibroblast-dependent extracellular matrix accumulation is associated with diastolic stiffness in type 2 diabetes
Authors: James A Stewart Jr
C Kevin Lord
Kirk R Hutchinson
T Aaron West
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Cardiovascular complications; Type 2 diabetes mellitus; Diastolic dysfunction; Left ventricular function; Stiffness
Affiliations: Department of Physiology, University of Arizona, Tucson, Arizona, United States of America.

Abstract:  Cardiovascular complications are a leading cause of death in patients with type 2 diabetes mellitus (T2DM). Diastolic dysfunction is one of the earliest manifestations of diabetes-induced changes in left ventricular (LV) function, and results from a reduced rate of relaxation and increased stiffness. The mechanisms responsible for increased stiffness are not completely understood. Chronic hyperglycemia, advanced glycation endproducts (AGEs), and increased levels of proinflammatory and profibrotic cytokines are molecular pathways known to be involved in regulating extracellular matrix (ECM) synthesis and accumulation resulting in increased LV diastolic stiffness. Experiments were conducted using a genetically-induced mouse model of T2DM generated by a point mutation in the leptin receptor resulting in nonfunctional leptin receptors (db/db murine model). This study correlated changes in LV ECM and stiffness with alterations in basal activation of signaling cascades and expression of profibrotic markers within primary cultures of cardiac fibroblasts from diabetic (db/db) mice with nondiabetic (db/wt) littermates as controls. Primary cultures of cardiac fibrobroblasts were maintained in 25 mM glucose (hyperglycemic-HG; diabetic db/db) media or 5 mM glucose (normoglycemic-NG, nondiabetic db/wt) media. The cells then underwent a 24-hour exposure to their opposite (NG; diabetic db/db) media or 5 mM glucose (HG, nondiabetic db/wt) media. Protein analysis demonstrated significantly increased expression of type I collagen, TIMP-2, TGF-β, PAI-1 and RAGE in diabetic db/db cells as compared to nondiabetic db/wt, independent of glucose media concentration. This pattern of protein expression was associated with increased LV collagen accumulation, myocardial stiffness and LV diastolic dysfunction. Isolated diabetic db/db fibroblasts were phenotypically distinct from nondiabetic db/wt fibroblasts and exhibited a profibrotic phenotype in normoglycemic conditions. 

Retracted: No

PubPeer comments:
 Figures 2 and 4. Reported to the journal in October 2015. The PonceauS panels in Figures 2A, 2C, and 4B all appear to look very similar. The ones in 2A and 2C represent the same experiment so even though one is upside down, this might be ok. However, the panel in Figure 3B is in mirror image, so now the lanes represent the wrong samples. ![file] ,
PAR-2 promotes cell proliferation, migration, and invasion through activating PI3K/AKT signaling pathway in oral squamous cell carcinoma
Authors: Kai-Liang Tang
Shi-Jiang Xiong
Yi Du
Tian Tian
Han-Ying Tang
Journal: Bioscience Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cell proliferation; Invasion; Migration; Oral squamous cell carcinoma; PAR-2
Affiliations: Department of VIP Center and Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, Jinan 250012, Shandong, China., Department of Endodontics, Jinan Stomatological Hospital, Jinan 250001, Shandong, China., Department of Oral Prosthology, Jinan Stomatological Hospital, Jinan 250001, Shandong, China., Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong, China., Department of VIP Center and Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, Jinan 250012, Shandong, China .

Abstract:  Objective: This research aimed to explore the function of protease activated receptor 2 (PAR-2) in oral squamous cell carcinoma (OSCC) development and progression, as well as underlying molecular mechanism.Methods: Tissue samples were collected from 115 OSCC patients. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of PAR-2 mRNA in OSCC tissues and cells. MTT and Transwell assays were used to detect the proliferation, migration, and invasion of OSCC cells, respectively. Western blot was performed to determine protein expression.Results: The expression of PAR-2 mRNA was up-regulated in OSCC tissue and cells (P&lt;0.01), and its mRNA level was obviously correlated to tumor differentiation and TNM stage in OSCC (P&lt;0.05 for both). The activation of PAR-2 with PAR-2AP (PAR-2 agonist) significantly promoted the proliferation, migration, and invasion of OSCC cells, while its knockout could inhibit malignant behaviors of OSCC cells (P&lt;0.05). Excessive activation of PAR-2 enhanced phosphorylation level of PI3K, AKT, and mTOR revealing the activation of PI3K/AKT pathway. Moreover, LY294002, the inhibitor of PI3K/AKT pathway, could reverse oncogenic action caused by PAR-2 activation.Conclusion:PAR-2 can promote OSCC growth and progression via activating PI3K/AKT signaling pathway. 

Retracted: No

PubPeer comments:
 Some bands in Figure 6 share unexpected similarities although they have different dimensions. Could the authors please share the original uncropped scan? I would note that the email address for the corresponding author on this paper has little resemblance to their name, and they were already a registered user here on PubPeer prior to this post. The only other paper I see authored by this author is not yet posted on PubPeer and in that paper the non institutional email address used is different. Curious. *** Inverse ![file] *** Original ![file] , 
 April 6, 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. ,
Berberine attenuates axonal transport impairment and axonopathy induced by Calyculin A in N2a cells
Authors: Zuohua Feng
Limin Wan
Huanhuan Yan
Morad Dirhem Naji Abid
Hao Huang
Jie Zhou
Xiaofeng Liu
Juan Chen
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Berberine; Alzheimer's disease; axonal transport; neuroblastoma-2a cells; tau hyperphosphorylation
Affiliations: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract:  Berberine is a primary component of the most functional extracts of Coptidis rhizome used in traditional Chinese medicine for centuries. Recent reports indicate that Berberine has the potential to prevent and treat Alzheimer's disease (AD). The previous studies reported that Calyculin A (CA) impaired the axonal transport in neuroblastoma-2a (N2a) cells. Berberine attenuated tau hyperphosphorylation and cytotoxicity induced by CA. Our study aimed at investigating the effects of Berberine on the axonal transport impairment induced by CA in N2a cells. The results showed that Berberine could protect the cell from CA -induced toxicity in metabolism and viability, as well as hyperphosphorylation of tau and neurofilaments (NFs). Furthermore, Berberine could reverse CA-induced axonal transport impairment significantly. Berberine also partially reversed the phosphorylation of the catalytic subunit of PP-2A at Tyrosine 307, a crucial site negatively regulating the activity of PP-2A, and reduced the levels of malondialdehyde and the activity of superoxide dismutase, markers of oxidative stress, induced by CA. The present work for the first time demonstrates that Berberine may play a role in protecting against CA-induced axonal transport impairment by modulating the activity of PP-2A and oxidative stress. Our findings also suggest that Berberine may be a potential therapeutic drug for AD. 

Retracted: No

PubPeer comments:
 March 2016 correction, which reads:  The authors would like to correct Fig 5, as errors were introduced in preparation of this figure for publication. In panel A, the SF 12h panel and the SF 12h+CA 12h panel are erroneously derived from the same image. The authors have provided a corrected version of Fig 5 here that includes a new image for the SF 12h+CA 12h panel. The raw images used to create the revised panel can be viewed as Supporting Information. The authors confirm that this change does not alter their findings. Here is the original Figure 5 as reported to the journal in April 2014: ![file] ,
miR-29a inhibits human retinoblastoma progression by targeting STAT3
Authors: Chunling Xu
Xiaomeng Zhang
Yingxue Wang
Shu Liu
Chunmei Hu
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Retinoblastoma; microRNAs; miR-29a; cell proliferation; migration
Affiliations: Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China., Department of Tumor and Hematology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China., Department of Electrical Diagnosis, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

Abstract:  Retinoblastoma (RB) is the most common malignancy that occurs during childhood. Growing evidence supports a crucial role for microRNAs (miRNAs) in regulating the initiation and progression of RB. Aberrant expression of microRNA‑29a (miR‑29a) has been found in many types of cancers, but not including RB. Therefore, the aims of the present study were to evaluate the regulatory role and underlying mechanism of miR‑29a in human RB. In the present study, we found that miR‑29a expression was significantly downregulated in RB tissues and cell lines. Overexpression of miR‑29a in RB cells significantly inhibited cell proliferation, migration, and invasion and promoted cell apoptosis in vitro. Additionally, signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR‑29a in RB cells. miR‑29a overexpression in RB cells not only inhibited STAT3 expression but also altered expression of its downstream genes, including, Bcl2, cyclin D1 and matrix metalloproteinase 2 (MMP‑2). STAT3 mRNA expression was upregulated in RB tissues and negatively correlated with miR‑29a expression. Reintroduction of STAT3 without 3'‑untranslated region (3'UTR) reversed the inhibitory effects of miR‑29a on cell proliferation, migration and invasion. In vivo study confirmed that overexpression of miR‑29a also inhibited tumor formation of RB in a nude mouse model by repressing STAT3. Collectively, these data suggest that miR‑29a exerts a tumor suppressor effect on RB by repressing STAT3, supporting the targeting of miR‑29a as a potentially effective therapeutic method for RB. 

Retracted: No

PubPeer comments:
 Some bands in Figure 4D may be repeated. Could the authors please post the original uncropped scans? *** ![file] *** False color ![file] , 
 Corrected. [28 June 2021] . --------------------------------------- Following the publication of this article, an interested reader drew to the authors attention that some western blotting data bands had apparently been duplicated in Fig. 4D. The authors have reu2011examined their original data, and realized that this figure was assembled incorrectly. The corrected version of Fig. 4 is shown below. The authors sincerely apologize for the errors that were introduced during the preparation of this figure, and thank the Editor for allowing them the opportunity to publish a Corrigendum. Furthermore, they regret any inconvenience caused to the readership. ,
Glutamyl‐tRNA mediates a switch in RNA polymerase use during chloroplast biogenesis
Authors: Kengo Kanamaru
Mitsumasa Hanaoka
Hideo Takahashi
Makoto Fujiwara
Kan Tanaka
Journal: EMBO reports (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Chloroplast genes; RNA polymerase; NEP; PEP; transfer RNA
Affiliations: Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan., Institute of Molecular and Cellular Biosciences, The University of Tokyo  1‐1‐1 Yayoi Bunkyo‐ku Tokyo 113‐0032 Japan, Faculty of Agriculture, Kobe University  1‐1 Rokkodai‐cho Nada‐ku Kobe 657‐8501 Japan

Abstract:  Chloroplast genes of higher plants are transcribed by two types of RNA polymerase that are encoded by nuclear (NEP (nuclear-encoded plastid RNA polymerase)) or plastid (PEP (plastid-encoded plastid RNA polymerase)) genomes. NEP is largely responsible for the transcription of housekeeping genes during early chloroplast development. Subsequent light-dependent chloroplast maturation is accompanied by repression of NEP activity and activation of PEP. Here, we show that the plastid-encoded transfer RNA for glutamate, the expression of which is dependent on PEP, directly binds to and inhibits the transcriptional activity of NEP in vitro. The plastid tRNA(Glu) thus seems to mediate the switch in RNA polymerase usage from NEP to PEP during chloroplast development. 

Retracted: No

PubPeer comments:
 Figure 3B: much more similar than expected (red boxes). Could the authors please check? ![file] ,
Chemoprevention of skin cancer by the flavonoid fraction of Saraca asoka
Authors: Annie Abraham
D Gayathri Devi
T R Cibin
Journal: Phytotherapy Research (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Saraca asoka; flavonoids; chemopreventive property; skin cancer; mice models
Affiliations: Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India.

Abstract:  Saraca asoka (Family - Caesalpiniaceae) has been widely used in the Ayurvedic (traditional Indian) system of medicine especially due to its wound healing property. The present study investigated the chemopreventive property of flavonoids from the flowers of Saraca asoka on 7,12 dimethyl benz(a)anthracene (DMBA) induced skin cancer in mice models. A single topical application of DMBA (100 microg/50 microL of acetone) followed after 2 weeks by three times a week treatment with croton oil (1% in acetone), for 20 weeks resulted in tumor induction. The topical application of the flavonoid fraction of S. asoka (FF S. asoka), 30 min prior to the application of croton oil thrice weekly for 20 weeks, caused a significant reduction in the number of tumors per mouse and the percentage of tumor-bearing mice. Also the latency period for the appearance of the first tumor was delayed by S. asoka pretreatment. In the flavonoid fraction (5 mg and 10 mg/kg body weight) treated animals, the levels of biochemical markers - rhodanese, myeloperoxidase, beta-D-glucuronidase, sialic acid, hexokinase and caspase 3 were significantly restored to near normal levels. These findings suggest the chemopreventive activity of flavonoids from S. asoka on two stage skin carcinogenesis. Histological data also support the chemopreventive potential of S. asoka. 

Retracted: No

PubPeer comments:
 Two mice in Figure 1 of this paper look remarkably similar to two mice in Figure 2 in a 2008 by some of the same author, i.e. D. Gayathri Devi et al., Journal of Photochemistry and Photobiology B: Biology 92 (2008), DOI: 10.1016 j.jphotobiol.2008.06.002 - https: pubpeer.com publications 690163138AEB6E218717463D20E7A6 * Blue boxes: Tumor induced mouse in 2008 paper; tumor-induced mouse in 2010 paper * Red boxes: Squaraine + light treatment mouse in 2008 paper; Flavonoid treated mouse in 2010 paper (minus the yellow dye). Could the authors please clarify the confusion? ![file] , 
 Figure 11 panels from this paper also share a remarkable similarity to panels in Figure 2 of another paper by this group, published in 2013, i.e. D. Gayathri Devi et al., Photodiagnosis and Photodynamic Therapy (2013), DOI: 10.1016 j.pdpdt.2013.04.005 - https: pubpeer.com publications 68D61DD74B99086DF92570BFC1F0FE There they represent the controls of a different experiment. Could the authors please clarify the similarities, which I have marked with blue and green boxes? ![file] ,
Mechanistic target of rapamycin complex 1 (mTORC1)-mediated phosphorylation is governed by competition between substrates for interaction with raptor
Authors: Michael D Dennis
Leonard S Jefferson
Scot R Kimball
Journal: Journal of Biological Chemistry (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: mTORC1; p70S6K1; 4E-BP1; 4E-BP2; phosphorylation
Affiliations: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.

Abstract:  In this study, the interaction of mTORC1 with its downstream targets p70S6K1 and 4E-BP1 was evaluated in both mouse liver and mouse embryonic fibroblasts following combined disruption of the genes encoding 4E-BP1 and 4E-BP2. Phosphorylation of p70S6K1 was dramatically elevated in the livers of mice lacking 4E-BP1 and 4E-BP2 following feeding-induced activation of mTORC1. Immunoprecipitation of mTORC1 suggested that elevated phosphorylation was the result of enhanced interaction of p70S6K1 with raptor. These findings were extended to a cell culture system wherein loss of 4E-BP1 and 4E-BP2 resulted in elevated interaction of p70S6K1 with IGF1-induced activation of mTORC1 in conjunction with an enhanced rate of p70S6K1 phosphorylation at Thr-389. Furthermore, cotransfecting HA-p70S6K1 with 4E-BP1, but not 4E-BP1(F114A), reduced recovery of mTORC1 in HA-p70S6K1 immunoprecipitates. Together, these findings support the conclusion that, in the absence of 4E-BP proteins, mTORC1-mediated phosphorylation of p70S6K1 is elevated by a reduction in competition between the two substrates for interaction with raptor. 

Retracted: No

PubPeer comments:
 Fig. 4A u2013 more similar than expected. Could authors check it please? ![file] , 
 Thank you for identifying this error in the manuscript. The original blot for mTOR in whole cell lysate (WCL) of wild-type MEF cells in Fig 4A is incorrect. More specifically, the mTOR blot is an unintentional duplication of the raptor blot for those same samples. The attached image includes both the uncropped original blots, as well as an amended assembly with the corrected mTOR blot for wild-type MEF WCL. The amended mTOR blot is consistent with the prior suggestion that mTOR protein expression in wild-type WCL was not altered after exposure to IGF. I sincerely apologize for any confusion caused by my error in assembly of this figure and have contacted JBC to provide a corrected version of Figure 4. -Michael Dennis ![file] ,
Ulinastatin reduces cancer recurrence after resection of hepatic metastases from colon cancer by inhibiting MMP-9 activation via the antifibrinolytic pathway
Authors: Huan-Qing Xiao
Kun-Ping Li
Jiang-Lin Li
Bo Xu
Fei Shen
Qi-Cai Liu
Wen-Song Cai
Lin Jia
Journal: BioMed Research International (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: colon cancer; liver metastasis; ulinastatin; recurrence; hepatectomy
Affiliations: Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical College, 1 Panfu Road, Yuexiu District, Guangzhou 510180, China., Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical College, 1 Panfu Road, Yuexiu District, Guangzhou 510180, China, Experimental Medical Research Center, Guangzhou Medical College, 195 Dongfengxi Road, Yuexiu District, Guangzhou 510182, China

Abstract:  High recurrence of colon cancer liver metastasis is observed in patients after hepatic surgery, and the cause is believed to be mostly due to the growth of residual microscopic metastatic lesions within the residual liver. Therefore, triggering the progression of occult metastatic foci may be a novel strategy for improving survival from colon cancer liver metastases. In the present study, we identified an anti-recurrence effect of ulinastatin on colon cancer liver metastasis in mice after hepatectomy. Transwell cell invasion assays demonstrated that ulinastatin significantly inhibited the in vitro invasive ability of colon cancer HCT116 cells. Moreover, gelatin zymography and ELISA analysis showed that MMP-9 activity and plasmin activity of colon cancer HCT116 cells were inhibited by ulinastatin, respectively. Furthermore, in vivo BALB/C nu/nu mice model indicated that ulinastatin effectively reduced recurrence after resection of hepatic metastases from colon cancer. The optimum timing for ulinastatin administration was one week after hepatectomy. Taken together, our findings point to the potential of ulinastatin as an effective approach in controlling recurrence of hepatic metastases from colon cancer after hepatectomy via its anti-plasmin activity. 

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. ,
Mitochondrial substrate availability and its role in lipid-induced insulin resistance and proinflammatory signaling in skeletal muscle
Authors: Tamara Suhm
Katherine Macrae
Marcin Baranowski
Christopher Lipina
Cora Weigert
Harinder S Hundal
Agnieszka Blachnio-Zabielska
Karl Burgess
Jan Gorski
Journal: Diabetes (2013)
Discipline: CLINICAL MEDICINE
Keywords: glucose; lipid metabolism; insulin resistance; skeletal muscle; palmitate

Abstract:  The relationship between glucose and lipid metabolism has been of significant interest in understanding the pathogenesis of obesity-induced insulin resistance. To gain insight into this metabolic paradigm, we explored the potential interplay between cellular glucose flux and lipid-induced metabolic dysfunction within skeletal muscle. Here, we show that palmitate (PA)-induced insulin resistance and proinflammation in muscle cells, which is associated with reduced mitochondrial integrity and oxidative capacity, can be attenuated under conditions of glucose withdrawal or glycolytic inhibition using 2-deoxyglucose (2DG). Importantly, these glucopenic-driven improvements coincide with the preservation of mitochondrial function and are dependent on PA oxidation, which becomes markedly enhanced in the absence of glucose. Intriguingly, despite its ability to upregulate mitochondrial PA oxidation, glucose withdrawal did not attenuate PA-induced increases in total intramyocellular diacylglycerol and ceramide. Furthermore, consistent with our findings in cultured muscle cells, we also report enhanced insulin sensitivity and reduced proinflammatory tone in soleus muscle from obese Zucker rats fed a 2DG-supplemented diet. Notably, this improved metabolic status after 2DG dietary intervention is associated with markedly reduced plasma free fatty acids. Collectively, our data highlight the key role that mitochondrial substrate availability plays in lipid-induced metabolic dysregulation both in vitro and in vivo. 

Retracted: Yes

PubPeer comments:
 2021 retraction. https: diabetes.diabetesjournals.org content early 2021 07 07 db21-rt08b ![file] ,
Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization
Authors: Xiaoyong Li
Wenhai Xie
Ji Wu
Lin Hou
Dali Li
Qifeng Lyu
Geng G Tian
Huacheng Luo
Austin J Cooney
Hu Wang
Xiaodong Zhao
Yunze Yang
Xinbao Ding
Ji Xiong
Changliang Hou
Journal: Journal of Advanced Research (2021)
Discipline: Multidisciplinary
Keywords: 3D cell culture; Chromatin reorganization; Defined factors; Induced germline stem cells; Offspring production

Abstract:  Introduction: Fate determination of germline stem cells remains poorly understood at the chromatin structure level. Objectives: Our research hopes to develop successful offspring production of ovarian organoids derived from spermatogonial stem cells (SSCs) by defined factors. Methods: The offspring production from oocytes transdifferentiated from mouse SSCs with tracking of transplanted SSCs in vivo, single cell whole exome sequencing, and in 3D cell culture reconstitution of the process of oogenesis derived from SSCs. The defined factors were screened with ovarian organoids. We uncovered extensive chromatin reorganization during SSC conversion into induced germline stem cells (iGSCs) using high throughput chromosome conformation. Results: We demonstrate successful production of offspring from oocytes transdifferentiated from mouse spermatogonial stem cells (SSCs). Furthermore, we demonstrate direct induction of germline stem cells (iGSCs) differentiated into functional oocytes by transduction of H19, Stella, and Zfp57 and inactivation of Plzf in SSCs after screening with ovarian organoids. We uncovered extensive chromatin reorganization during SSC conversion into iGSCs, which was highly similar to female germline stem cells. We observed that although topologically associating domains were stable during SSC conversion, chromatin interactions changed in a striking manner, altering 35% of inactive and active chromosomal compartments throughout the genome. Conclusion: We demonstrate successful offspring production of ovarian organoids derived from SSCs by defined factors with chromatin reorganization. These findings have important implications in various areas including mammalian gametogenesis, genetic and epigenetic reprogramming, biotechnology, and medicine. 

Retracted: No

PubPeer comments:
 ![file] ,
MicroRNA-143 inhibits cell growth by targeting ERK5 and MAP3K7 in breast cancer
Authors: J L Dong
G Huang
J Wu
Z L Sun
L L Zhou
Journal: Brazilian Journal of Medical and Biological Research (2017)
Discipline: CLINICAL MEDICINE
Keywords: microRNA-143; breast cancer; ERK5; MAP3K7; cell growth
Affiliations: Henan University,  China

Abstract:  This study aimed to investigate the function and mechanism of microRNA-143 (miR-143) in the occurrence and development of breast cancer (BC). A total of 30 BC tissues, 30 corresponding noncancerous tissues, and 10 normal control (NC) breast tissues were obtained to detect the levels of miR-143, extracellular signal-regulated kinase 5 (ERK5) and mitogen-activated protein 3 kinase 7 (MAP3K7) using RT-qPCR, western blotting or immunohistochemistry. The correlation of miR-143 with ERK5 or MAP3K7 was evaluated using Pearson correlation analysis. MCF-7 cells were transiently transfected with miR-143 mimic, miR-143 inhibitor, miR-143 mimic/inhibitor + si-ERK5, si-MAP3K7 or si-cyclin D1. Then, cell growth was evaluated by MTT assay and the expressions of phospho-ERK5 (p-ERK5), ERK5, p-MAP3K7, MAP3K7 and cyclin D1 were detected by western blotting. Results showed that, compared with noncancerous tissues or NC breast tissues, miR-143 level was decreased, while p-ERK5, ERK5, p-MAP3K7 and MAP3K7 expressions were increased in BC tissues (all P&lt;0.01). The miR-143 level was negatively correlated with the mRNA level of ERK5 or MAP3K7 (r=-4.231 or r=-4.280, P&lt;0.01). In addition, up-regulated miR-143 significantly decreased the expressions of p-ERK5, ERK5, p-MAP3K7, MAP3K7 and cyclin D1 (all P&lt;0.01), as well as cell viability in MCF-7 cells (all P&lt;0.05) while the effect of down-regulated miR-143 was the opposite. In conclusion, both ERK5 and MAP3K7 may be the target genes of miR-143. Increased expression of miR-143 can inhibit cell growth, which may be associated with ERK5 and MAP3K7 expressions in BC. 

Retracted: No

PubPeer comments:
 Fig 1B Week 2 and 4 overlap for Control group ![file] ,
LncRNA MALAT1 promotes migration and invasion of non-small-cell lung cancer by targeting miR-206 and activating Akt/mTOR signaling
Authors: Yu Deng
YueJun Chen
GaoMing Xiao
Yi Tang
Journal: Anti-Cancer Drugs (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; MALAT1; metastasis; lung cancer; NSCLC
Affiliations: 1st Department of Thoracic Surgery., Department of Thoracic Radiation, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.

Abstract:  Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) functions as a crucial regulator of metastasis in lung cancer. The aim of this study is to unravel the underlying mechanisms of lncRNA MALAT1 in non-small-cell lung cancer (NSCLC). A cohort of 36 NSCLC tumor tissues and adjacent normal tissues was collected postoperatively from patients with NSCLC. qRT-PCR was performed to detect the expression of MALAT1 in both NSCLC tissues and cell lines. Cell migration and invasion were monitored by wound healing assay and transwell invasion assay. Western blot was used to detect the expression levels of epithelial-mesenchymal transition proteins and Akt/mTOR key components after treatment. Dual luciferase reporter assay coupled with qRT-PCR was used to verify the direct interaction between MALAT1 and miR-206. MALAT1 was significantly up-regulated in both NSCLC tissues and cell lines. High expression of MALAT1 correlated positively with tumor size and lymphatic metastasis in NSCLC, whereas no correlation was found between MALAT1 expression and sex, age, clinical stage, and histological grade. We also showed that MALAT1 promoted epithelial-mesenchymal transition, cell migration, and invasion by activating Akt/mTOR signaling in A549 and H1299 cells. miR-206 was a direct downstream target of MALAT1 in NSCLC. MALAT1 promoted cell migration and invasion by sponging miR-206 in NSCLC cells. In addition, miR-206 inhibited MALAT1-mediated activation of Akt/mTOR signaling in A549 and H1299 cells. lncRNA MALAT1 promotes migration and invasion of NSCLC by targeting miR-206 and activating Akt/mTOR signaling. 

Retracted: No

PubPeer comments:
 Figure 6e appears to have an image overlap ![file] ,
Long non-coding RNA LINC00160 functions as a decoy of microRNA-132 to mediate autophagy and drug resistance in hepatocellular carcinoma via inhibition of PIK3R3
Authors: Kai Liu
Wei Han
Yu Deng
Wei Zhang
Yu Fu
Hongji Xu
Lijia Wen
Yahui Liu
Journal: Cancer Letters (2020)
Discipline: CLINICAL MEDICINE
Keywords: Autophagy; Drug resistance; Hepatocellular carcinoma; Long non-coding RNA LINC00160; MicroRNA-132
Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, 130021, PR China., Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, 130021, PR China. Electronic address: .

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. Following the publication of the above article, the authors found that “LINC00160 did not affect Atg5 and P65 protein expression in HCC cells, which was inconsistent with the result of this paper. Furthermore, we apologize to the readership of the Journal for any inconvenience caused.” Additionally, after publication, the journal was made aware of comments in relation to this article (https://pubpeer.com/publications/333AE65483683ADF50A723BE34AD62). The authors have not responded to our request to respond to these comments. 

Retracted: No

PubPeer comments:
 Figs 1I, 2G, 3E I, 4F, 5I, 6F. ![file] Should the LC3I and LC3II bands be more parallel? I compiled this montage of Western Blots, sourced from various papers, each with its own PP thread. To my mind there is (as it were) a family kinship among them all, all sampling a small corner of  morphological space . This may be my over-active imagination, but the present WBs seem to fit into the same genre. Is it possible for the authors to upload or link to higher-resolution scans of the original blots, to dispel any concerns? Many other family members could be adduced. Clockwise from upper left: - [Wang et al (2020)] - [Gao et al (2021)] - [Chen et al (2020)] - [He et al (2021)] . ![file] In addition, WBs from [Lv et al (2020)] *[retracted]* ![] , 
 Retracted [8 October 2022] . --------------------------- This article has been retracted at the request of the authors. Following the publication of the above article, the authors found that u201cLINC00160 did not affect Atg5 and P65 protein expression in HCC cells, which was inconsistent with the result of this paper. Furthermore, we apologize to the readership of the Journal for any inconvenience caused.u201d Additionally, after publication, the journal was made aware of comments in relation to this article . The authors have not responded to our request to respond to these comments. ,
The intrahepatic biliary epithelium is a target of the growth hormone/insulin-like growth factor 1 axis
Authors: Alfredo Cantafora
Antonio Franchitto
Domenico Alvaro
Shannon S Glaser
Gianfranco Alpini
Heather Francis
Eugenio Gaudio
Adolfo Francesco Attili
Paolo Onori
Barbara Barbaro
Veronica Drudi Metalli
Ida Blotta
Journal: Journal of hepatology (2005)
Discipline: CLINICAL MEDICINE
Keywords: GH/IGF1 axis; cholangiocyte proliferation; GH-receptors; IGF1; IGFBP3
Affiliations: Division of Gastroenterology, University of Rome, La Sapienza, Rome, Italy. 

Abstract:  Background/aims: We evaluated the role and mechanisms by which the GH/IGF1 axis modulates cholangiocyte proliferation. Methods: GH-receptors (GH-R), IGF1, IGFBP3 (binding protein 3), IGF1-R and receptor substrates (IRS) were evaluated in cholangiocytes of normal or bile duct-ligated (BDL) rat livers. The effects of GH and IGF1 on proliferation of normal quiescent cholangiocytes and the transduction pathways involved were investigated. Results: IGF1, GH-R, IGF1-R, IRS-1/2 were expressed in normal cholangiocytes and overexpressed in cholangiocytes proliferating after BDL which also secrete IGF1 in a higher amount than normal cells. IGFBP3, which may counter-regulate IGF1 effects, was decreased in BDL cholangiocytes. IGF1 promoted cholangiocyte proliferation in association with overexpression of p-IGF1R, IRS1, IRS-2, p-ERK1/2 and p-AKT. GH induced IGF1 expression and release in isolated cholangiocytes, and reproduced the effects of IGF1 but GH effects were abolished by IGF1-R blocking antibody, suggesting IGF1 as a mediator of GH. Finally, IGF1 and 17beta-estradiol reciprocally potentiated their proliferative effects on cholangiocytes, and by interacting at both receptor and post-receptor levels. Conclusions: Cholangiocytes respond to GH with production and release of IGF1 that modulates cell proliferation by transduction pathways involving IGF1-R, IRS1/2 and both ERK and PI3-kinase pathways. The biliary epithelium is a target of GH/IGF1 liver axis. 

Retracted: No

PubPeer comments:
 Unexpected similarities of beta actin bands across two papers: J Hepatol 2005 and Am J Pathol 2006 (by the same authors). ![file] , 
 Figure 5. Similar WBs in Fig.5 B indicate pIGF1 and IRS-1 [red squares]. ![file] , 
 ![file] ,
Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis in tongue squamous cell carcinoma
Authors: Y Wang
S Fan
Z Lin
D Zhang
L Sun
W Chen
Z Huang
Z Yang
J Li
Journal: British Journal of Cancer (2014)
Discipline: CLINICAL MEDICINE
Keywords: Epithelial-mesenchymal transition (EMT); Epidermal growth factor (EGF); Ezrin; NF-κB; Tongue squamous cell carcinomas (TSCCs)
Affiliations: Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China., 1] Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China [2] Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China., 1] Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China [2] Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China [3] Oral and Cranio-maxillofacial Surgery Center, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China., 1] Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China [2] Oral and Cranio-maxillofacial Surgery Center, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.

Abstract:  Background: Epithelial-mesenchymal transition (EMT) is a crucial programme in cancer metastasis. Epidermal growth factor (EGF) is a key inducer of EMT, and Ezrin has an important role in this process. However, how Ezrin is activated and whether it mediates EGF-induced EMT in tongue squamous cell carcinomas (TSCCs) through activating NF-κB remains obscure. Methods: We used two TSCC cell lines as a cell model to study invasion and EMT in vitro, and used nude mice xenografts model to evaluate metastasis of TSCC cells. Finally, we evaluated the level of pEzrin Tyr353, nuclear p65 and EMT markers in TSCC clinical samples. Results: Ezrin Tyr353 was phosphorylated through Akt (but not ERK1/2, ROCK1) pathway, and lead to the activation of NF-κB in EGF-treated TSCC cells. Akt and NF-κB inhibitors blocked EGF-induced EMT, and suppressed invasion and migration of TSCC cells. In vivo, silencing Ezrin significantly suppressed EGF-enhanced metastasis of TSCC xenografts. Finally, high levels of expression of pEzrin Tyr353, nuclear p65, vimentin and low level of expression of E-cadherin were correlated with cancer metastasis and poor patient prognosis. Conclusion: Our data suggest that Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis inTSCC, and Ezrin may serve as a therapeutic target to reverse EMT in tongue cancers and prevent TSCC progression. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have image duplications for different things ![file] ,