PReD-Bench/PRed-Bench huggingface dataset:
Long non-coding RNA LINP1 functions as an oncogene in endometrial cancer progression by regulating the PI3K/AKT signaling pathway
Authors: X-H Zhang
Y-Q Xie
Y-X Cao
Y-J Kang
M Li
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Endometrial cancer; Long non-coding RNA; LINP1; Progression; qRT-PCR
Affiliations: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. .

Abstract:  Objective: Endometrial cancer (EC) accounts for about 6% of new cancer cases in female and about 3% of cancer-related deaths were caused by EC. The poor prognosis is mainly due to the distant spread and poor differentiation. In the current study, we want to figure out the role of long non-coding RNA (LncRNA) LINP1 in EC progression. Patients and methods: The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was involved to access the expression level of LINP1 in EC cell lines and tissues. The Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell and Matrigel assay were recruited to figure out the ability of LINP1 in cell proliferation and metastasis in EC. Subsequently, Western blotting was used to detect the expression level of PI3K/AKT in EC. Besides, we used the tumor formation assay in vivo to examine the ability of LINP1 in tumor formation in vivo. Results: LINP1 was proved to be up-regulated in EC cell lines and tissues by qRT-PCR assay. CCK-8 assay and colony formation assay were conducted and the results indicated that LINP1 over-expression can promote cell proliferation in EC in vitro. The data of transwell and Matrigel assays indicated that up-regulated LINP1 can facilitate cell migration and invasion. The results of Western blotting validated that LINP1 can activate PI3K/AKT signaling. Besides, the tumor formation assay verified that LINP1 can promote tumor formation in vivo. Conclusions: Our research validated that LINP1 served as an oncogenic role in EC progression. The PI3K/AKT signaling pathway might be the underlying mechanism of EC progression. We hope our study can provide novel treatment targets and biomarkers in EC development and progression. 

Retracted: No

PubPeer comments:
 In Figure 4, the authors appear to have accidentally uploaded the same blots twice. I suggest they contact the journal and replace the erroneous blots. ![file] ,
Localization of an actin binding domain in smooth muscle myosin light chain kinase
Authors: P J Gallagher
J T Stull
Journal: Molecular and cellular biochemistry (1997)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Phosphorylation; regulatory light chain; myosin II; myosin light chain kinase; contractile processes
Affiliations: Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202-5120, USA.

Abstract:  Phosphorylation of the regulatory light chain of myosin II by myosin light chain kinase is important for regulating many contractile processes. Smooth muscle myosin light chain kinase has been shown to be associated with both actin and myosin filaments in vitro and in vivo. In this report we define an actin binding region by using molecular deletions to generate recombinant mutant proteins that were analyzed by co-sedimentation with F-actin. An actin binding region restricted to residues 2-42 in the amino terminus of the rabbit smooth muscle myosin light chain kinase was identified. 

Retracted: No

PubPeer comments:
 Figure 2B. * Red boxes: the 2-625 and 2-293 panels look more similar to each other than expected. ![file] ,
Distinct spatial and molecular features of notch pathway assembly in regulatory T cells
Authors: Nimi Marcel
Apurva Sarin
Lakshmi R Perumalsamy
Sneha Kulkarni
Freddy Radtke
Journal: Science Signaling (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Spatial localization; Signaling networks; Notch receptor; T cell receptor; Regulatory T cells
Affiliations: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bangalore 560065, India.

Abstract:  Variations in the spatial localization of signaling components and crosstalk among signaling cascades are mechanisms through which diversity in signaling networks is generated. The receptor Notch provides an example of regulation by spatial localization: In the canonical Notch signaling pathway, Notch is cleaved to produce the Notch intracellular domain (NICD, also known as NIC), which translocates to the nucleus to regulate gene expression. We describe a T cell receptor-dependent, non-nuclear distribution and function of the processed receptor Notch, which was associated with the improved survival of regulatory T cells (T(regs)) in vitro and in vivo and was compromised by T cell-specific deletion of Notch1. Unlike a nuclear-restricted mutant of NICD, mutant NICD that underwent nuclear export or was targeted to the plasma membrane protected Notch1(-/-) T(regs) from apoptosis induced by nutrient deprivation and oxidative stress. Notch signaling integrated with phosphatidylinositol 3-kinase signaling and mammalian target of rapamycin complex 2 (mTORC2) for this cell survival function. Biochemical and imaging approaches revealed a membrane-proximal complex containing NICD and the mTORC2 component Rictor, and this complex was stabilized by specific interactions with the Notch ligand Delta-like-1 and mediated the survival of T(regs). Together, our evidence for the spatial control of Notch and the crosstalk of Notch signaling with other pathways reveals coupling between the localization of Notch and diverse intracellular signaling pathways. 

Retracted: No

PubPeer comments:
 ![file] ,
TSPAN9 and EMILIN1 synergistically inhibit the migration and invasion of gastric cancer cells by increasing TSPAN9 expression
Authors: Hui Li
Wensheng Qiu
Yixuan Wang
Jing Lv
Weiwei Qi
Yaoyue Qi
Shihai Liu
Libin Sun
Journal: BMC Cancer (2019)
Discipline: CLINICAL MEDICINE
Keywords: EMILIN1; Gastric cancer; Invasion; Migration; TSPAN9.
Affiliations: Qingdao University, Qingdao, Shandong, China., Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China., Central Laboratory, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China., Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. .

Abstract:  Background: Globally, the incidence and mortality rates of gastric cancer are high, and its poor prognosis is closely related to tumor recurrence and metastasis. Therefore, the molecular mechanisms associated with the migration and invasion of gastric cancer cells are important for gastric cancer treatment. Previously, TSPAN9 has been reported to inhibit gastric cancer cell migration; however, the underlying molecular mechanism remains unclear. Methods: Human gastric adenocarcinoma cell lines, SGC7901 and AGS, were cultured in vitro. TSPAN9 expression was determined by RT-PCR, western blot analysis, and immunohistochemistry in gastric cancer and tumor-adjacent tissues. Following the over-expression and knockdown of TSPAN9, wound healing and cell invasion assays were performed and EMT-related protein expression was evaluated to analyze the invasion and migration of gastric cancer cells. TSPAN9 expression and the invasion and metastasis of gastric cancer cells were observed by the functional assays following EMILIN1 over-expression. Results: Inhibiting TSPAN9 expression significantly promoted the migration and invasion of gastric cancer cells. In addition, immunofluorescence co-localization and co-immunoprecipitation analysis revealed closely related expression of EMILIN1 and TSPAN9. Moreover, EMILIN1 can synergistically boost the tumor suppressive effect of TSPAN9, which may be produced by promoting TSPAN9 expression. Conclusions: We have demonstrated that EMILIN1 induces anti-tumor effects by up-regulating TSPAN9 expression in gastric cancer. Hence, membrane proteins TSPAN9 and EMILIN1 may represent novel therapeutic targets for the treatment of gastric cancer. 

Retracted: No

PubPeer comments:
 Figure 2E, 3E and 4E are tainted with serious problems of data duplication and manipulation. ![file] , 
 #1 I agree. I came across the issue with 2E independently. *** ![file] ,
Characterization of the role of a trimeric protein phosphatase complex in recovery from cisplatin-induced versus noncrosslinking DNA damage
Authors: Cristina Vázquez-Martin
Patricia T W Cohen
John Rouse
Journal: FEBS Journal (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cisplatin; DNA-crosslinking agents; Saccharomyces cerevisiae; trimeric protein; serine/threonine phosphatase
Affiliations: Medical Research Council Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, UK.

Abstract:  Cisplatin (cis-diamminedichloroplatinum) and related chemotherapeutic DNA-crosslinking agents are widely used to treat human cancers. Saccharomyces cerevisiae with separate deletions of the genes encoding the trimeric protein serine/threonine phosphatase (Pph)3p-platinum sensitivity (Psy)4p-Psy2p complex, are more sensitive than the isogenic wild-type (WT) strain to cisplatin. We show here that cisplatin causes an enhanced intra-S-phase cell cycle delay in these three deletion mutants. The C-terminal tail of histone 2AX (H2AX) is hyperphosphorylated in the same mutants, and Pph3p is found to interact with phosphorylated H2AX (gammaH2AX). After cisplatin treatment is terminated, pph3Delta, psy4Delta and psy2Delta mutants are delayed as compared with the WT strain in the dephosphorylation of Rad53p. In contrast, only pph3Delta and psy2Delta cells are more sensitive than WT cells to methylmethanesulfonate, a noncrosslinking DNA-alkylating agent that is known to cause a Rad53p-dependent intra-S-phase cell cycle delay. Dephosphorylation of Rad53p and the recovery of chromosome replication are delayed in the same mutants, but not in psy4Delta cells. By comparison with their mammalian orthologues, the regulatory subunit Psy4p is likely to inhibit Pph3p catalytic activity. The presence of a weak but active Pph3p-Psy2p complex may allow psy4Delta cells to escape from the Rad53p-mediated cell cycle arrest. Overall, our data suggest that the trimeric Pph3p-Psy4p-Psy2p complex may dephosphorylate both gammaH2AX and Rad53p, the differences lying in the more stable interaction of the Pph3 phosphatase with gammaH2AX as opposed to a transient interaction with Rad53p. 

Retracted: No

PubPeer comments:
 2008 correction. The FEBS Journal Volume 275, Issue 22 p. 5745-5745 https: febs.onlinelibrary.wiley.com doi 10.1111 j.1742-4658.2008.06684.x The paper by C. Vu00e1zquez-Martin etu2003al. [[1]] contains an error in Fig.u20033 on pageu20034215. The corrected figure appears below: ,
<p>FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53</p>
Authors: Hui Ye
Meiling Duan
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: FOXN4; P53; breast cancer; invasion; proliferation
Affiliations: Department of Galactophore, Linyi Central Hospital of Shandong, Linyi, People's Republic of China., Department of Respiratory One, Linyi Central Hospital of Shandong, Linyi, People's Republic of China.

Abstract:  Background: Fork head domain-containing gene family (Fox) transcription factors, consisting of over 20 members, are involved in the progression of certain types of tumor. However, whether FOXN4 is involved in carcinogenesis and tumor progression is still unclear. Purpose: In this study, we investigated the clinicopathological significance and the underlying mechanism of FOXN4 in breast cancer. Methods and results: We examined the lower expression of FOXN4 in breast cancer tissues and cancer cell lines. The expression of FOXN4 is negatively correlated with tumor size and lymph node metastasis. Using CCK-8 assay, colony formation assay, wound healing assay, and Transwell assay, we revealed that FOXN4 notably decreased breast cancer cell proliferation, epithelial-mesenchymal transition and invasion in vitro. In addition, quantitative chromatin immunoprecipitation and luciferase assays determined that FOXN4 was able to directly bind with the promoter of P53. RT-qPCR and Western blotting analysis showed that FOXN4 could directly activate P53 expression. Functionally, P53 knockdown rescued the tumor inhibition effects of FOXN4 in breast cancer cells. Conclusion: The present study provides new insights into the role of FOXN4 in breast cancer progression and suggests FOXN4 might represent a potential therapeutic target in breast cancer by modulating P53. 

Retracted: Yes

PubPeer comments:
 Retracted [16 November 2020] . ------------------------------------------------------ The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. The journal was notified of similarities between the published paper and another article published in the journal Gene: u25cf Identification of FOXN4 as a tumor suppressor of breast carcinogenesis via the activation of TP53 and deactivation of Notch signaling . In particular, it was noted both articles presented similar data in Table 1 and shared nearly identical reference lists. The article was submitted and accepted by OncoTargets and Therapy prior to publication in Gene, however it was noted the article was submitted to Gene prior to publication in OncoTargets and Therapy. The authors were unable to provide a satisfactory explanation for the similarities and were also unable to provide satisfactory raw data for the study. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,
Low density lipoprotein receptor (LDLR)-targeted lipid nanoparticles for the delivery of sorafenib and Dihydroartemisinin in liver cancers
Authors: Xinxin Duan
Zhengfeng Wang
Yinghao Lv
Yongfu Zhao
Journal: Life Sciences (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Dihydroartemisinin; Lipid nanoparticles; Liver cancer; Low density lipoprotein (LDL); Orafenib.
Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address: ., Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Abstract:  Aims: Liver cancer is one of the leading causes of cancer mortality worldwide. Inspired by the biological structure and function of low-density lipoprotein (LDL), in this study, an ApopB-100 based targeted lipid nanoparticles was synthesized to improve the therapeutic efficacy in liver cancer treatment. Main methods: The biological composition of ApopB is similar to LDL which can effectively increase the targeting efficiency of nanoparticles in LDL receptor (LDLR)-overexpressed liver tumors. Keyfindings: We have demonstrated that the co-administration of sorafenib (SRF) and Dihydroartemisinin (DHA) could exhibit synergistic anticancer effect in HepG2 liver cancer cells. DHA produced excessive cellular reactive oxygen species (ROS) and induced greater apoptosis of cancer cells. LDL-based SRF/DHA-loaded lipid nanoparticles (LD-SDN) showed remarkable decrease in the cell viability compared to that of either of single drug treated cancer cells. Combination of SRF+DHA resulted in predominant SubG1 proportion of cells. LD-SDN exhibited the highest SubG1 (%) of cells compared to that of any of the individual drugs. Most importantly, robust antitumor response and delayed tumor growth was observed for LD-SDN treated xenograft tumor model. Ki67 proliferation index of LD-SDN (22.1 ± 5.6%) is significantly lesser compared to that of either control (86.2 ± 6.9%) or SRF (75.4 ± 4.89%) or DHA (69.4 ± 6.9%). Significances: These data provide strong evidence that LDL-mimetic lipid nanoformulations could be utilized as a biocompatible and tumor targeted platform for the delivery of multiple anticancer drugs in cancer treatment. 

Retracted: No

PubPeer comments:
 Figure 2:  Physicochemical characterization of LD-SDN. ... (b) particle morphology of LD-SDN using transmission electron microscopy (TEM) . Here I have increased the contrast. You are probably wondering,  Why did you do that? ![file] The answer is that you would not otherwise believe my claim to see repeating areas of background. ,
Myricetin Increases Hepatic Peroxisome Proliferator-Activated Receptor α Protein Expression and Decreases Plasma Lipids and Adiposity in Rats
Authors: Chia Ju Chang
I-Min Liu
Shorong-Shii Liou
Thing-Fong Tzeng
Yuan-Shiun Chang
Journal: Evidence-based Complementary and Alternative Medicine (2012)
Discipline: CLINICAL MEDICINE
Keywords: myricetin; antiobesity; antihyperlipidaemic effects; triglyceride; 3T3-L1 adipocytes
Affiliations: School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan., Department of Internal Medicine, Pao Chien Hospital, Pingtung City, Pingtung County, Taiwan, Department of Pharmacy & Graduate Institute of Pharmaceutical Technology, Tajen University, Yanpu Township, Pingtung County, Taiwan, School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan

Abstract:  The aim of this study was to investigate the antiobesity and antihyperlipidaemic effects of myricetin. Myricetin exhibited a significant concentration-dependent decrease in the intracellular accumulation of triglyceride in 3T3-L1 adipocytes. The high-fat diet (HFD)-fed rats were dosed orally with myricetin or fenofibrate, once daily for eight weeks. Myricetin (300 mg kg(-1) per day) displayed similar characteristics to fenofibrate (100 mg kg(-1) per day) in reducing lowered body weight (BW) gain, visceral fat-pad weights and plasma lipid levels of HFD-fed rats. Myricetin also reduced the hepatic triglyceride and cholesterol contents, as well as lowered hepatic lipid droplets accumulation and epididymal adipocyte size in HFD-fed rats. Myricetin and fenofibrate reversed the HFD-induced down-regulation of the hepatic peroxisome proliferator activated receptor (PPAR)α. HFD-induced decreases of the hepatic protein level of acyl-CoA oxidase and cytochrome P450 isoform 4A1 were up-regulated by myricetin and fenofibrate. The elevated expressions of hepatic sterol regulatory element binding proteins (SREBPs) of HFD-fed rats were lowered by myricetin and fenofibrate. These results suggest that myricetin suppressed BW gain and body fat accumulation by increasing the fatty acid oxidation, which was likely mediated via up-regulation of PPARα and down-regulation of SREBP expressions in the liver of HFD-fed rats. 

Retracted: No

PubPeer comments:
 image duplications ![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. ,
Circulating insulin-like growth factor I mediates effects of exercise on the brain
Authors: S Busiguina
I Torres-Aleman
E Carro
A Nuñez
Journal: Journal of Neuroscience (2000)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Physical exercise; brain activity; rats; running; blood insulin-like growth factor I (IGF-I)
Affiliations: Laboratory of Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Cientificas, 28002 Madrid, Spain.

Abstract:  Physical exercise increases brain activity through mechanisms not yet known. We now report that in rats, running induces uptake of blood insulin-like growth factor I (IGF-I) by specific groups of neurons throughout the brain. Neurons accumulating IGF-I show increased spontaneous firing and a protracted increase in sensitivity to afferent stimulation. Furthermore, systemic injection of IGF-I mimicked the effects of exercise in the brain. Thus, brain uptake of IGF-I after either intracarotid injection or after exercise elicited the same pattern of neuronal accumulation of IGF-I, an identical widespread increase in neuronal c-Fos, and a similar stimulation of hippocampal brain-derived neurotrophic factor. When uptake of IGF-I by brain cells was blocked, the exercise-induced increase on c-Fos expression was also blocked. We conclude that serum IGF-I mediates activational effects of exercise in the brain. Thus, stimulation of the uptake of blood-borne IGF-I by nerve cells may lead to novel neuroprotective strategies. 

Retracted: No

PubPeer comments:
 This article seems to present some image duplication that might be a concern. Could the authors check please and provide an explanation for this? ![file] , 
 #1 Thank for your comment and the opportunity to clear up the confusion . In the Figure 2 we demonstrate that blood-born IGF-I is taken up by brain cells: The image shown in Fig. 2Ba correspond to inferior olive, and Fig. 2Cc correspond to Purkinje cells, stained neurons after intracarotid injection with DIG-IGF-I. In the Figure 3C demonstrated that after icv injection of unlabeled IGF-I , the entry of labeled IGF-I from the blood was blocked (b,d), compared to those images (a,c) already shown in Figure 2. In the Figure 3D the situation is very similar. We demonstrated similar staining pattern after icv injection with DIG-IGF-I (upper panel) and intracarotid injection with DIG-IGF-I (bottom panel). , 
 #2 Thank you for your reply. However, it isnu2019t clear from your reply whether you are confirming or disagreeing with the image duplication concern raised in #1. To my eye, the images marked with the respective colors appear to be identical, not merely similar. If necessary I will prepare an image overlay to demonstrate. , 
 #2 This explanation does not clear up the confusion concerning the presence of two sets of identical images with asymmetrical scaling in these figures. To summarize (H,V = horizontal vertical scaling relative to top image in each column): ![file] Can the authors please clarify, and can they also comment on the utility of the scale bars shown given the asymmetrical resizing? ,
Changes of serum adrenocorticotropic hormone and cortisol levels during sleep seizures
Authors: Shou-Wen Zhang
Yu-Xi Liu
Journal: Neuroscience Bulletin (2008)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: serum concentrations; adrenocorticotropic hormone (ACTH); cortisol; epileptic seizures; EEG changes
Affiliations: Research Institute of Epilepsy of Shanxi Medical University, Taiyuan 030001, China.

Abstract:  Objective: Measuring the serum concentrations of adrenocorticotropic hormone (ACTH) and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes. Methods: Pre-surgical evaluation was performed by video-EEG monitoring using 24 channel recording. Thirty six epilepsy patients could be attributed to two groups: 28 patients had spontaneous seizures, and the other 8 patients whose seizures were induced by bemegride. Another 11 persons with confirmed psychogenic non-epileptic seizures (PNES) served as control group. Blood samples were obtained at five points: wake (08:00 a.m.), sleep (00:00 a.m.), and shortly before, during and after an epileptic seizure. The serum ACTH and cortisol were measured and analyzed by chemiluminescent immunoassay. Results: The levels of ACTH and cortisol in serum underwent significant changes: declining below the average sleep-level shortly before seizures, increasing during seizures, and far above the average wake-level after seizures (P &lt; 0.001). Such changes did not occur in the control group (P &gt; 0.05). The ACTH and cortisol levels had no significant difference between spontaneous group and bemegride-induced group (P &gt; 0.05). Conclusion: The serum concentrations of ACTH and cortisol during sleep seizures are linked with pre-ictal and ictal EEG changes in epilepsy patients. 

Retracted: No

PubPeer comments:
 Figure 2 is a copy of Figure 1! Figure 2 fails to show the Cortisol levels in different time points in the case group vs. the control group. ![file] ,
Long non-coding RNA MEG3 promotes the proliferation of glioma cells through targeting Wnt/β-catenin signal pathway
Authors: M Huang
X Gong
Journal: Cancer Gene Therapy (2017)
Discipline: CLINICAL MEDICINE
Keywords: Glioma; Long non-coding RNAs; MEG3; Carcinogenesis; Proliferation
Affiliations: Department of Neurosurgery, Hunan Provincial People's Hospital, Changsha, 410005, Hunan Province, China., The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan Province, China.

Abstract:  Glioma has been identified as one of the most aggressive primary tumors. Long non-coding RNAs (lncRNAs), with length larger than 200 bp, have drawn increasing attention to their abnormal expression and regulation function in carcinogenesis. However, the role of lncRNAs in glioma remains largely unknown. Maternally expressed gene 3 (MEG3), also known as gene-trap locus 2 (GTL2), is an imprinted gene, and is encoded by the MEG3 transcript of the DLK1/MEG3 locus on human chromosome, or Meg3 on mouse chromosome. In this study, we found that lncRNA MEG3 was significantly downregulated in malignant glioma tissues and cell lines. The employment of the loss-of and gain-of functions assays presented that MEG3 suppressed glioma cells proliferation and induced cell-cycle arrest. Furthermore, our findings showed that highly expressed MEG3 could weaken Wnt/β-catenin signaling in glioma. Collectively, our findings revealed that downregulated lncRNA MEG3 could promote glioma cell proliferation through targeting Wnt/β-catenin signaling, which mainly influenced cell cycle. 

Retracted: No

PubPeer comments:
 Figure 2C and 3C are falsified. In addition the western immunoblot is unusual. ![file] ,
APLNR stimulates the development of glioma via the NFAT5/AKT feedback loop
Authors: X-Q Sun
Z-P Zhang
S-J Yuan
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: APLNR; glioma; proliferative ability; development; NFAT5
Affiliations: Department of Brain Center, Sunshine Integration Hospital Shandong Chine, Weifang, China. .

Abstract:  Objective: To detect the role of APLNR in influencing the proliferative ability and development of glioma. Patients and methods: APLNR levels in 42 matched glioma tissues and adjacent normal brain tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between APLNR level and clinical features of glioma patients was assessed. Regulatory effects of APLNR on glioma cell functions were evaluated by cell counting kit-8 (CCK-8), colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assay, respectively. At last, the involvement of NFAT5 in APLNR-regulated glioma cell phenotypes was examined. Results: APLNR was upregulated in glioma tissues than the adjacent ones. Glioma patients expressing higher level of APLNR had more advanced stage and worse prognosis. Knockdown of APLNR inhibited proliferative ability of glioma. NFAT5 level was negatively regulated by APLNR. Notably, NFAT5 could partially abolish the regulatory effect of APLNR on glioma cell phenotypes. Conclusions: APLNR level is closely linked to tumor grading and prognosis of glioma patients. It stimulates proliferative ability in glioma cells by targeting NFAT5. 

Retracted: No

PubPeer comments:
 Fig 3C.  A negative correlation between expression levels of APLNR and NFAT5 in glioma tissues . Rescaled for better comparison with (at right) a superimposition of 20 variants of a correlation scatterplot, from different papers. Data-points are darker if they appear in more of those 20 versions. ![file] Here is 3C, in red, superimposed on that composite. It appears to be another of the variants. ![file] , 
 Fig 1C.  Overall survival in glioma patients with high or low level of APLNR . ![file] The precipitous nose-dive of one Kaplan-Meier curve towards 0% survival at 55 months after patient recruitment is slightly atypical in this ERMPS oeuvre... usually the nose-dive happens at 75 months. There are) precedents, however. Here, for instance, Fig 1D from [Gao et al (2020)] . ![] , 
 Another characteristic feature of this particular papermill is a Table 1 where the column headings promise to convert the numbers within each patient subgroup into percentages, but do not deliver. ![file] ,
Silencing of Pokemon enhances caspase-dependent apoptosis via fas- and mitochondria-mediated pathways in hepatocellular carcinoma cells
Authors: Jing-Jing Liu
Chuan-Xing Xiao
Bayasi Guleng
Bi-Yun Lin
Jian-Lin Ren
Yun-Peng Liu
Yu-Qin Zhang
Ying Shi
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Pokemon; hepatocellular carcinogenesis; apoptosis; oxaliplatin; p53
Affiliations: Department of Gastroenterology, Zhongshan Hospital affiliated to Xiamen University, Xiamen, China.

Abstract:  The role of Pokemon (POK erythroid myeloid ontogenic actor), a recently identified POK transcription factor with proto-oncogenic activity, in hepatocellular carcinogenesis has only been assessed by a few studies. Our previous study revealed that Pokemon is overexpressed in hepatocellular carcinomas (HCC) and promotes HCC cell proliferation and migration via an AKT- and ERK- dependent manner. In the present study, we used the TUNEL assay and FACS analysis to demonstrate that oxaliplatin induced apoptosis was significantly increased in cells with silenced Pokemon. Western blots showed that p53 expression and phosphorylation were significantly increased in Pokemon defective cells, thereby initiating the mitochondria-mediated and death receptor-mediated apoptotic pathways. In the mitochondria-mediated pathway, expression of pro-apoptotic Bcl-2 family members (including Bad, Bid, Bim and Puma) as well as AIF was increased and decreasing the mitochondrial membrane potential resulted in cytochrome C released from mitochondrial in HepG2 si-Pokemon cells. In addition, upon oxaliplatin treatment of Pokemon-silenced cells, the FAS receptor, FADD and their downstream targets caspase-10 and caspase-8 were activated, causing increased release of caspase-8 active fragments p18 and p10. Increased activated caspase-8-mediated cleavage and activation of downstream effector caspases such as caspase-9 and caspase-3 was observed in HepG2 si-Pokemon cells as compared to control. Therefore, Pokemon might serve as an important mediator of crosstalk between intrinsic and extrinsic apoptotic pathways in HCC cells. Moreover, our findings suggest that Pokemon could be an attractive therapeutic target gene for human cancer therapy. 

Retracted: No

PubPeer comments:
null, 
 deleted; wrong thread ,
Insulin receptor substrate-2 proteasomal degradation mediated by a mammalian target of rapamycin (mTOR)-induced negative feedback down-regulates protein kinase B-mediated signaling pathway in beta-cells
Authors: John C Lawrence
Christopher J Rhodes
Isabelle Briaud
Melissa K Lingohr
Lorna M Dickson
Jill F McCuaig
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: insulin receptor substrate (IRS)-2; beta-cell survival; glucose; IGF-1; Ser/Thr phosphorylation
Affiliations: Pacific Northwest Research Institute, and Department of Pharmacology, University of Washington, Seattle, Washington 98122, USA.

Abstract:  Regulation of insulin receptor substrate (IRS)-2 expression is critical to beta-cell survival, but the mechanisms that control this are complex and undefined. Here in pancreatic beta-cells (INS-1), chronic exposure (&gt;8 h) to 15 mm glucose and/or 5 nm IGF-1, increased Ser/Thr phosphorylation of IRS-2, which correlated with decreased IRS-2 levels. This glucose/IGF-1-induced decrease in IRS-2 levels was prevented by the proteasomal inhibitor, lactacystin. In addition, the glucose/IGF-1-induced increase in Ser/Thr phosphorylation of IRS-2 and the subsequent decrease in INS-1 cell IRS-2 protein levels was thwarted by the mammalian target of rapamycin(mTOR) inhibitor, rapamycin. Moreover, adenoviral-mediated expression of constitutively active mTOR (mTORDelta) further increased glucose/IGF-1-induced Ser/Thr phosphorylation of IRS-2 and decreased IRS-2 protein levels, whereas adenoviral-mediated expression of "kinase-dead" mTOR (mTOR-KD) conversely reduced Ser/Thr phosphorylation of IRS-2 and maintained IRS-2 protein levels. In adenoviral-infected beta-cells expressing mTORDelta, the decrease in IRS-2 protein levels was also prevented by rapamycin or lactacystin, further indicating a proteasomal mediated degradation of IRS-2 mediated via mTOR-induced Ser/Thr phosphorylation of IRS-2. Finally, we found that chronic activation of mTOR leading to decreased levels of IRS-2 in INS-1 cells led to a significant decrease in PKB activation and consequently increased beta-cell apoptosis. Thus, chronic activation of mTOR by glucose (and/or IGF-1) in beta-cells leads to increased Ser/Thr phosphorylation of IRS-2 that targets it for proteasomal degradation, resulting in decreased IRS-2 expression and increased beta-cell apoptosis. This may be a contributing mechanism as to how beta-cell mass is decreased by chronic hyperglycemia in the pathogenesis of type-2 diabetes. 

Retracted: No

PubPeer comments:
 Fig. 6 u2013 more similar than expected ![file] ,
Green synthesis of magnetic FeO nanoparticles using Couroupita guianensis Aubl. fruit extract for their antibacterial and cytotoxicity activities
Authors: Pradeep K Jha
C Rajkuberan
N Senthilkumar
S Sarathbabu
S Sivaramakrishnan
V Logeshwaran
G Sathishkumar
M Jeyaraj
Journal: Artificial Cells Nanomedicine and Biotechnology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: C. guianensis; Phytosynthesis; SQUID VSM; bactericidal; liver cancer
Affiliations: a Department of Biotechnology , Bharathidasan University , Tiruchirappalli , India., b Department of Biotechnology , Mizoram University , Aizawl , India., c School of Medical Science and Technology , Indian Institute of Technology , Kharagpur , India., d National Centre for Nanosciences and Nanotechnology , University of Madras , Chennai , India.

Abstract:  In the present study, a sustainable green chemistry approach was established to fabricate magnetic Fe3O4 nanoparticles (Fe3O4NPs) using the aqueous fruit extract of edible C. guianensis (CGFE). Synthesized NPs were further confirmed with different high-throughput characterization techniques such as UV-visible spectroscopy, FT-IR, XPS, DLS and zeta potential analysis. Additionally, XRD, AFM, HRTEM and SQUID VSM demonstrate the generation of crystalline CGFe3O4NPs with mean diameter of 17 ± 10 nm. Interestingly, CGFe3O4NPs exhibit a stupendous bactericidal action against different human pathogens which depicts its antimicrobial value. A significant dose-dependent cytotoxic effect of CGFe3O4NPs was noticed against treated human hepatocellular carcinoma cells (HepG2). 

Retracted: No

PubPeer comments:
 In the correction, the entire figure 7b, six images in total, were simply replaced: https: www.tandfonline.com doi pdf 10.1080 21691401.2020.1785096 ,
MiR-214 inhibits human mesenchymal stem cells differentiating into osteoblasts through targeting β-catenin
Authors: H-T Zhuang
J-P Li
M-Y Xin
Y-L Zhou
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Wnt/β-catenin signaling pathway; osteoblast differentiation; miR-214; β-catenin; bone marrow mesenchymal stem cells
Affiliations: Department of Outpatient Injection Room Emergency, Weifang People's Hospital, Weifang, Shandong, China. .

Abstract:  Objective: Wnt/β-catenin signaling pathway promotes osteoblasts (OBs) differentiation through up-regulating osteoblast-specific gene runt-related transcription factor 2 (RUNX2) expression. It was showed that microRNA-214 (miR-214) was abnormally increased in bone tissue from osteoporosis patients, suggesting its role in osteogenesis. Bioinformatics analysis revealed the complementary binding site between miR-214 and 3'-UTR of β-catenin. This study investigated the effects of miR-214 in regulating β-catenin expression and bone marrow mesenchymal stem cells (BMSCs) differentiating into OB. Materials and methods: BMSCs were induced to differentiate to OB in a specific medium. MiR-214, β-catenin, and RUNX2 expressions were detected. The regulatory relationship between miR-214 and β-catenin was confirmed by dual luciferase reporter gene assay. BMSCs were divided into five groups, including agomir-control, miR-214 agomir, pGPU6-normal control group (pGPU6-NC), pGPU6-β-catenin, and miR-214 agomir + pGPU6-β-catenin groups. β-catenin and RUNX2 levels were tested after 21 days' induction. OB differentiation degree was evaluated by alizarin red staining. Results: MiR-214 was down-regulated, while β-catenin and RUNX2 were enhanced in the process of BMSCs differentiating into OBs. MiR-214 agomir and/or β-catenin shRNA pGPU6-β-catenin transfection significantly reduced β-catenin expression, declined RUNX2 level, and attenuated OB differentiation in BMSCs. Conclusions: Wnt/β-catenin signaling pathway was enhanced, while the miR-214 level was decreased in the process of BMSCs differentiating into OBs. Up-regulation of miR-214 inhibited the OB differentiation of BMSCs through targeted suppressing β-catenin expression and attenuating Wnt/β-catenin signaling pathway activity. 

Retracted: No

PubPeer comments:
 These are not realistic Western Blots. ![file] ,
Human sulfatase-1 inhibits the migration and proliferation of SMMC-7721 hepatocellular carcinoma cells by downregulating the growth factor signaling
Authors: Kai Liu
Mengchao Wu
Jiahe Yang
Weidan Ji
Hu Liu
Changqing Su
Xiaohui Fu
Longlong Bao
Yan Yan
Journal: Hepatology Research (2013)
Discipline: CLINICAL MEDICINE
Keywords: hSulf-1; AKT; ERK; hepatocellular carcinoma; angiogenesis
Affiliations: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital and Institute Department of Laparoscopic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.

Abstract:  Aim: The human sulfatase-1 (hSulf-1) gene regulates the sulfation of heparan sulfate proteoglycans (HSPG) and suppresses tumorigenesis and angiogenesis by inhibiting several growth factor signaling pathways. Because the serine-threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways are critical in cell survival, proliferation, migration and angiogenesis, the possible correlation between hSulf-1 and AKT/ERK signaling in hepatocellular carcinoma (HCC) cells needs further exploration. Methods: Adenovirus Ad5-hSulf1 carrying the hSulf-1 gene, and vectors carrying hSulf-1 shRNA, AKT shRNA and ERK shRNA were constructed and used to manipulate the expression of hSulf-1, AKT and ERK in SMMC-7721 cells. The scarification test, transwell and 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide assays were used to examine the cellular migration and proliferation, and the expression of hSulf-1 and signaling factors, including the total and phosphorylated AKT and ERK, was analyzed by western blot in SMMC-7721 cells. Results: After infection with Ad5-hSulf1, the expression of hSulf-1 was increased with viral multiplicity of infection in SMMC-7721 cells. Compared with the control adenovirus Ad5-EGFP and blank control groups, cells in the Ad5-hSulf1 group were showed that the phosphorylation of AKT and ERK was decreased. Meanwhile, the cell migration and cell viability were obviously suppressed. Conclusion: The expression of hSulf-1 mediated by adenovirus in HCC cells could downregulate the activity of AKT and ERK signaling pathways, and inhibit HCC cell migration and proliferation. The hSulf-1 gene may be considered as a candidate of antitumor factor for cancer gene therapy. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have a repeated image. More image concerns from [this group] . *** ![file] ,
DGCR5 promotes cancer stem cell-like properties of radioresistant laryngeal carcinoma cells by sponging miR-506 via Wnt pathway
Authors: Tian Tang
Guang Shan
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CSCs; DGCR5; Wnt; human laryngeal carcinoma; miR-506.
Affiliations: Department of Oncology, RenMin Hospital of Wuhan University, Wuhan, China.

Abstract:  Cancer stem cells (CSCs) have been recognized as the significant cause of tumor recurrence. Long noncoding RNAs (lncRNAs) are involved in various cancers, including human laryngeal cancer. So far the correlation between lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) and CSC-like properties in human laryngeal cancer remains barely known. In our current study, two human larynx squamous carcinoma cell lines (Hep-2 and Hep-2R) with different radio sensitivities were cultured. Interestingly, CSC-like phenotypes were much more enriched in Hep-2R cells. We found that DGCR5 was upregulated and microRNA-506 (miR-506) was downregulated in Hep-2R cells. In addition, silence of DGCR5 could inhibit the stemness and enhance the radiosensitivity of Hep-2R cells. Meanwhile, overexpression of miR-506 also suppressed the CSC-like traits and the radiosensitivity was increased significantly. In addition, miR-506 was predicted as target of DGCR5 and the correlation between them was validated in our study. Finally, we observed that Wnt pathway exerted a significant role in human laryngeal CSCs and DGCR5 inhibition could repress Wnt signaling activity by sponging miR-506. In vivo assays were performed and we found that DCGR5 depressed stemness of human laryngeal cancer cells through modulating miR-506 and Wnt signaling pathway. Taken these together, we reported that DGCR5 induced CSC-like properties by sponging miR-506 through activating Wnt in human laryngeal carcinoma cells. 

Retracted: No

PubPeer comments:
 Figure 2D: * Red boxes: the Sox2 and Nanog panels appear to look unexpectedly similar to each other ![file] ,
Alveolar type II cells escape stress failure caused by tonic stretch through transient focal adhesion disassembly
Authors: Xiao-Fei Chen
Xiao-Yang Liu
Chun Yang
Qing-Yuan Zhan
Chen Wang
Yan-Hong Ren
Journal: International journal of biological sciences (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: cell culture; cell morphologic remodeling; cellular stress failure; focal adhesion disassembly; tonic stretch.
Affiliations: Beijing Chao-Yang Hospital, Capital Medical University, China.

Abstract:  Mechanical ventilation-induced excessive stretch of alveoli is reported to induce cellular stress failure and subsequent lung injury, and is therefore an injurious factor to the lung. Avoiding cellular stress failure is crucial to ventilator-induced lung injury (VILI) treatment. In the present study, primary rat alveolar type II (ATII) cells were isolated to evaluate their viability and the mechanism of their survival under tonic stretch. By the annexin V/ PI staining and flow cytometry assay, we demonstrated that tonic stretch-induced cell death is an immediate injury of mechanical stress. In addition, immunofluorescence and immunoblots assay showed that the cells experienced an expansion-contraction-reexpansion process, accompanied by partial focal adhesion (FA) disassembly during contraction. Manipulation of integrin adherent affinity by altering bivalent cation levels in the culture medium and applying an integrin neutralizing antibody showed that facilitated adhesion affinity promoted cell death under tonic stretch, while lower level of adhesion protected the cells from stretch-induced stress failure. Finally, a simplified numerical model was established to reveal that adequate disassembly of FAs reduced the forces transmitting throughout the cell. Taken together, these results indicate that ATII cells escape stress failure caused by tonic stretch via active cell morphological remodeling, during which cells transiently disassemble FAs to unload mechanical forces. 

Retracted: No

PubPeer comments:
 Retracted [19 July 2021] . ---------------------------------------------- The above article, published online on 14 September 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. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid. -------------------------------- The paper contains Western Blots of a stylised  string of sausages appearance, and for that reason it had been listed in [a spreadsheet dedicated to products of the  Contractor papermill ] , but it had not been flagged on Pubpeer. ![file] ,
Activation of the mTOR signaling pathway is required for asthma onset
Authors: Zhe Song
Bin Luan
Xiufang Wang
Yanli Zhang
Junying Qiao
Ying Jing
Li Wang
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: mTOR pathway; asthma; Th17 cells; Treg cells; Th1/Th2 balance
Affiliations: Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. ., School of Medicine for Basic Research, Zhengzhou University, Zhengzhou, Henan, 450001, China., Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.

Abstract:  The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and IL-4, and decreased Treg cells and IFN-γ. In patients experiencing asthma, mTOR activation was positively correlated with the loss of Th17/Treg and Th1/Th2 balance. The role of mTOR in asthma was further confirmed using an ovalbumin-induced asthmatic mouse model. The mTOR pathway was activated in asthmatic mice, demonstrated by elevated levels of p-PI3K, p-Akt, p-mTOR, and p-p70S6k, and this activation was significantly reduced by treatment with budenoside or mTOR pathway inhibitors. Moreover, mTOR pathway inhibitor treatment reduced asthmatic markers and reversed the Th17/Treg and Th1/Th2 imbalances in asthmatic mice. Finally, different mTOR pathway inhibitor treatments have different inhibitory effects on signaling molecules in asthmatic mice. In summary, mTOR is activated during asthma onset and suppressed during asthma remission, and inhibiting the mTOR pathway in asthmatic mice alleviates asthmatic markers and restores the balances of Th17/Treg and Th1/Th2 cytokines. These data strongly suggest a critical requirement for mTOR pathway activation in asthma onset, suggesting potential targets for asthma treatments. 

Retracted: No

PubPeer comments:
 Figure 5c appears to have a repeated band, at different exposures? Could the authors post the original uncropped scans? *** ![file] *** Caption and WB methods description ![file] , 
 In Figure 1c, flow cytometric analysis appears identical. Image prepared by another reader on social media. *** ![file] ,