PReD-Bench/PRed-Bench huggingface dataset:
Activation of protein tyrosine kinases by Coxiella burnetii: role in actin cytoskeleton reorganization and bacterial phagocytosis
Authors: M Remacle-Bonnet
S Meconi
J L Mege
D Raoult
C Capo
G Pommier
Journal: Infection and Immunity (2001)
Discipline: IMMUNOLOGY
Keywords: Coxiella burnetii; Q fever; intracellular microorganism; monocytes/macrophages; protein tyrosine kinases (PTKs)
Affiliations: CNRS UMR 6020, Universit√© de la M√©diterran√©e, 13385 Marseille Cedex 05, France., CNRS UMR 60201 and, CNRS UMR 6032,2 UniversiteÃÅ de la MeÃÅditerraneÃÅe, 13385 Marseille Cedex 05, France

Abstract:  Coxiella burnetii, the agent of Q fever, is an obligate intracellular microorganism that grows in monocytes/macrophages. The internalization of virulent organisms by monocytes is lower than that of avirulent variants and is associated with actin cytoskeleton reorganization. We studied the activation of protein tyrosine kinases (PTKs) by C. burnetii in THP-1 monocytes. Virulent organisms induced early PTK activation and the tyrosine phosphorylation of several endogenous substrates, including Hck and Lyn, two Src-related kinases. PTK activation reflects C. burnetii virulence since avirulent variants were unable to stimulate PTK. We also investigated the role of PTK activation in C. burnetii-stimulated F-actin reorganization. Tyrosine-phosphorylated proteins were colocalized with F-actin inside cell protrusions induced by C. burnetii, and PTK activity was increased in Triton X-100-insoluble fractions. In addition, lavendustin A, a PTK inhibitor, and PP1, a Src kinase inhibitor, prevented C. burnetii-induced cell protrusions and F-actin reorganization. We finally assessed the role of PTK activation in bacterial phagocytosis. Pretreatment of THP-1 cells with lavendustin A and PP1 upregulated the uptake of virulent C. burnetii but had no effect on the phagocytosis of avirulent organisms. Thus, it is likely that PTK activation by C. burnetii negatively regulates bacterial uptake by interfering with cytoskeleton organization. 

Retracted: No

PubPeer comments:
 It seems that this article is plagiarised by another articleuff08Rao B, Shi H. Malignant bowel obstruction: a struggle of technology, emotion and hope. Electron J Metab Nutr Cancer. 2017; 4:136-143.uff09 The second paper is just copying and translating the first paper into a second language without adding any innovation. 1. Tuca A, Guell E, Martinez-Losada E, Codorniu N. Malignant bowel obstruction in advanced cancer patients: epidemiology, management, and factors influencing spontaneous resolution. Cancer Manag Res. 2012; 4:159-169. DOI: 10.2147 CMAR.S29297 Full text link: https: www.dovepress.com getfile.php?fileID=12955 2. Rao B, Shi H. Malignant bowel obstruction: a struggle of technology, emotion and hope. Electron J Metab Nutr Cancer. 2017; 4:136-143. (In Chinese) DOI: 10.16689 j.cnki.cn11-9349 r.2017.02.002 Full text link: http: www.ejmnc.org CN article downloadArticleFile.do?attachType=PDF id=177 The problems are highlighted with yellow, and are marked with red box and arrow.      ,
Pre-gestational stress reduces the ratio of 5-HIAA to 5-HT and the expression of 5-HT1A receptor and serotonin transporter in the brain of foetal rat
Authors: Hui Li
Yuejun Huang
Hongwu Xu
Xuechuan Shi
Yunbin Chen
Hanhua Yang
Journal: BMC Neuroscience (2012)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: stress; pregestational stress; HPA axis activity; serotonergic system; maternal rats
Affiliations: Department of Pediatrics, Second Affiliated Hospital of Medical College of Shantou University, North Dongxia Rd, Shantou 515041, Guangdong, China.

Abstract:  Background: Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA) axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses. Results: We used the behavioural tests to assess the model of chronic unpredictable stress (CUS) in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT) were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA) levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT) were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group. Conclusions: Our data demonstrate that pre-gestational stress alters HPA axis activity in maternal rats and their foetuses, which is associated with functional changes in 5-HT activity (5-HT, 5-HIAA and ratio of 5-HIAA to 5-HT), as well as the levels of the 5-HT1A receptor and SERT in the hippocampus and hypothalamus of foetuses. 

Retracted: No

PubPeer comments:
 There is duplications in the western blots in Figure 2.  Could the authors look into this and perhaps obtain the original, uncropped, blots? ,
Altered gut microbiome and autism like behavior are associated with parental high salt diet in male mice
Authors: Karina Alvi√±a
Noah Reyes
Kobe Young
Kajal Parikh
Varsha Misra
Kazi Farhana Afroz
Journal: Scientific Reports (2021)
Discipline: Multidisciplinary
Keywords: Neurodevelopmental disorders; Autism spectrum disorder (ASD); maternal gut microbiome; diet; gut dysbiosis
Affiliations: Department of Biological Sciences, Texas Tech University, Lubbock, TX, 79409, USA., Honors College, Texas Tech University, Lubbock, TX, 79409, USA., Department of Biological Sciences, Texas Tech University, Lubbock, TX, 79409, USA. ., Department of Neuroscience, University of Florida, 1395 Center Drive, Room D5-33D, Gainesville, FL, 32610-0244, USA. .

Abstract:  Neurodevelopmental disorders are conditions caused by the abnormal development of the central nervous system. Autism spectrum disorder (ASD) is currently the most common form of such disorders, affecting 1% of the population worldwide. Despite its prevalence, the mechanisms underlying ASD are not fully known. Recent studies have suggested that the maternal gut microbiome can have profound effects on neurodevelopment. Considering that the gut microbial composition is modulated by diet, we tested the hypothesis that ASD-like behavior could be linked to maternal diet and its associated gut dysbiosis. Therefore, we used a mouse model of parental high salt diet (HSD), and specifically evaluated social and exploratory behaviors in their control-fed offspring. Using 16S genome sequencing of fecal samples, we first show that (1) as expected, HSD changed the maternal gut microbiome, and (2) this altered gut microbiome was shared with the offspring. More importantly, behavioral analysis of the offspring showed hyperactivity, increased repetitive behaviors, and impaired sociability in adult male mice from HSD-fed parents. Taken together, our data suggests that parental HSD consumption is strongly associated with offspring ASD-like behavioral abnormalities via changes in gut microbiome. 

Retracted: No

PubPeer comments:
 The image in Figure 1c seems to have a region that has been duplicated. Although the resolution isn t ideal, there are multiple similarities within the two marked regions that seem unlikely by chance. Shown below as original and with false color. Would the authors have access to a higher resolution image? ***  ***  ,
Cardiomyocyte-specific deletion of GSK-3Œ≤ leads to cardiac dysfunction in a diet induced obesity model
Authors: Prachi Umbarkar
Jennifer Y Sui
Manisha Gupte
Firdos Ahmad
Qinkun Zhang
Hind Lal
Samvruta Tumuluru
Anand Prakash Singh
Thomas Force
Shan S Parikh
Journal: International journal of cardiology (2018)
Discipline: CLINICAL MEDICINE
Keywords: Cardiac function; GSK-3Œ≤; High fat diet; Obesity.
Affiliations: Division of Cardiovascular Medicine, Vanderbilt University Medical Center, 2220 Pierce Ave, PRB, Suite#348, Nashville, TN 37232, United States. Electronic address: ., Division of Cardiovascular Medicine, Vanderbilt University Medical Center, 2220 Pierce Ave, PRB, Suite#348, Nashville, TN 37232, United States., Division of Cardiovascular Medicine, Vanderbilt University Medical Center, 2220 Pierce Ave, PRB, Suite#348, Nashville, TN 37232, United States; College of Medicine, University of Sharjah, United Arab Emirates.

Abstract:  Background and rationale: Obesity, an independent risk factor for the development of myocardial diseases is a growing healthcare problem worldwide. It's well established that GSK-3Œ≤ is critical to cardiac pathophysiology. However, the role cardiomyocyte (CM) GSK-3Œ≤ in diet-induced cardiac dysfunction is unknown. Methods: CM-specific GSK-3Œ≤ knockout (CM-GSK-3Œ≤-KO) and littermate controls (WT) mice were fed either a control diet (CD) or high-fat diet (HFD) for 55weeks. Cardiac function was assessed by transthoracic echocardiography. Results: At baseline, body weights and cardiac function were comparable between the WT and CM-GSK-3Œ≤-KOs. However, HFD-fed CM-GSK-3Œ≤-KO mice developed severe cardiac dysfunction. Consistently, both heart weight/tibia length and lung weight/tibia length were significantly elevated in the HFD-fed CM-GSK-3Œ≤-KO mice. The impaired cardiac function and adverse ventricular remodeling in the CM-GSK-3Œ≤-KOs were independent of body weight or the lean/fat mass composition as HFD-fed CM-GSK-3Œ≤-KO and controls demonstrated comparable body weight and body masses. At the molecular level, on a CD, CM-GSK-3Œ± compensated for the loss of CM-GSK-3Œ≤, as evident by significantly reduced GSK-3Œ±s21 phosphorylation (activation) resulting in a preserved canonical Œ≤-catenin ubiquitination pathway and cardiac function. However, this protective compensatory mechanism is lost with HFD, leading to excessive accumulation of Œ≤-catenin in HFD-fed CM-GSK-3Œ≤-KO hearts, resulting in adverse ventricular remodeling and cardiac dysfunction. Conclusion: In summary, these results suggest that cardiac GSK-3Œ≤ is crucial to protect against obesity-induced adverse ventricular remodeling and cardiac dysfunction. 

Retracted: No

PubPeer comments:
 Fig 4  Same Gapdh in Fig 4A and 4E (T-GSK blot, lower panel) is used. ,
LncRNA GAS5/miR‚Ä?465 axis regulates the malignant potential of nasopharyngeal carcinoma by targeting COX2
Authors: Xiaoqing Guo
Renrui Wu
Xiaohong Liao
Qiong Zhong
Zongqi Wang
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: COX2; lncRNA GAS5; miR‚Ä?465; nasopharyngeal carcinoma.
Affiliations: Department of Oncology, People's Hospital of Ganzhou , Ganzhou City, Jiangxi Province, PR. China.

Abstract:  Nasopharyngeal carcinoma is a malignant tumor that not only negatively affects the physical and mental health but also the quality of life of the patients. Growth arrest-specific transcript 5 (GAS5) is a common long-chain non-coding RNA (lncRNA) that has been reported to participate in the development of various cancers. However, the biological functions of lncRNA GAS5 in the occurrence and development of nasopharyngeal carcinoma are elusive. The expression of lncRNA GAS5 in nasopharyngeal carcinoma and normal samples were analyzed. Bioinformatic tool was utilized to predict the potential function of lncRNA in nasopharyngeal carcinoma. Transplanted mice were used for in vivo experiments. We observed that the expression of lncRNA GAS5 was upregulated in nasopharyngeal carcinoma tissues and cells. Down-regulation of lncRNA GAS5 inhibited the proliferation and promoted apoptosis of nasopharyngeal carcinoma cells. The expression of miR-4465 was down regulated in nasopharyngeal carcinoma tissues and cells. LncRNA GAS5 could directly bind to miR-4465 and regulated the expression of miR-4465. It was further confirmed that miR-4465 could directly bind with COX2 and inhibit the expression of COX2. Down-regulation of lncRNA GAS5 suppressed tumor growth, promoted the expression levels of miR-18a-5p and suppressed the expression of COX2 in vivo. LncRNA GAS5 regulated nasopharyngeal carcinoma malignancy through targeting miR-4465 and modulating COX2. The GAS5/miR-4465/COX2 axis in nasopharyngeal carcinoma pathogenesis was confirmed, which would provide a new therapeutic target for nasopharyngeal carcinoma. 

Retracted: No

PubPeer comments:
 Figure 3 includes 2 images which appear to overlap. ***  ,
Vinculin promotes gastric cancer proliferation and migration and predicts poor prognosis in patients with gastric cancer
Authors: Mingming Zhang
Xiangjun Jiang
Pei Liu
Yuanlong He
Famei Xu
Xiangjun Xie
Journal: Journal of cellular biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: gastric cancer; migration; poor prognosis; proliferation; vinculin.
Affiliations: Department of Gastroenterology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong, China., Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China., Department of Pathology, Zibo Central Hospital, Zibo, Shandong, China.

Abstract:  Vinculin is a highly conserved protein involved in cell proliferation, migration, and adhesion. However, the effects of vinculin on gastric cancer (GC) remain unclear. Therefore, we aimed to explore the functional role of vinculin in GC, as well as its underlying mechanism. Expression of vinculin in patients with GC was analyzed by real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. Overall survival was evaluated by the Kaplan-Meier method with the log-rank test. The relationship between vinculin and clinicopathological characteristics of patients with GC was further identified. In addition, we assessed the expression of vinculin in GC cell lines. Besides, vinculin was suppressed or overexpressed by transfection with small interfering (si-vinculin) or pcDNA-vinculin and then cell viability, cell apoptosis, and/or migration was respectively examined by the 3-(4, 5-dimethylthiazole-2-yl)-2, 5-biphenyl tetrazolium bromide assay, flow cytometer, and scratch assay, respectively. Moreover, the cell cycle- and apoptosis-related proteins were detected by Western blot analysis. The expression of vinculin was significantly increased in the GC tissues and cells compared with the nontumor tissues or cells. Vinculin protein positive staining was mainly located in the cell membrane and cytoplasm. Moreover, vinculin was significantly associated with Tumor Node Metastasis (TNM) and poor differentiation. Patients with high vinculin levels had significantly worse overall survival than those with low levels. Suppression of vinculin significantly decreased cell viability and migration and promoted cell apoptosis. However, overexpression of vinculin statistically increased cell viability but had no effects on cell apoptosis. Vinculin promotes GC proliferation and migration and predicts poor prognosis in patients with GC. 

Retracted: Yes

PubPeer comments:
null, 
 These two lanes were spliced. I do not think we were asked in 2004 to report splicing. , 
 In Fig 4F and Fig 6A, same alpha-Tat, different alpha-CDK9  ,
Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins
Authors: Alok Bhushan
Sirisha Jandhyam
Vikas V Dukhande
Solomon W Leung
James C K Lai
Mugdha Gokhale
Christopher K Daniels
Gayathri Ananthakrishnan
Journal: International Journal of Nanomedicine (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: cell signaling; cytotoxicity; extracellular signaling regulated kinase; mitochondrial enzyme; neural cells
Affiliations: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy and Biomedical Research Institute, Kasiska College of Health Professions.

Abstract:  Recent evidence suggests silicon dioxide micro- and nanoparticles induce cytotoxic effects on lung cells. Thus, there is an increasing concern regarding their potential health hazard. Nevertheless, the putative toxicity of nanoparticles in mammalian cells has not yet been systematically investigated. We previously noted that several metallic oxide nanoparticles exert differential cytotoxic effects on human neural and nonneural cells. Therefore, we hypothesized that silicon dioxide nanoparticles induce cytotoxicity in U87 cells by lowering their survival by decreasing cell survival signaling and disturbing mitochondrial function. To investigate this hypothesis, we determined the activities of the key mitochondrial enzymes, citrate synthase and malate dehydrogenase, in astrocytoma U87 cells treated with silicon dioxide nanoparticles. In addition, we studied the expression of the mitochondrial DNA-encoded proteins, cytochrome C oxidase II and nicotinamide adenine dinucleotide (NADPH) dehydrogenase subunit 6, and cell signaling pathway protein extracellular signal-regulated kinase (ERK) and phosphorylated ERK in treated U87 cells. The activated form of ERK controls cell growth, differentiation, and proliferation. In parallel, we determined survival of U87 cells after treating them with various concentrations of silicon dioxide nanoparticles. Our results indicated that treatment with silicon dioxide nanoparticles induced decreases in U87 cell survival in a dose-related manner. The activities of citrate synthase and malate dehydrogenase in treated U87 cells were increased, possibly due to an energetic compensation in surviving cells. However, the expression of mitochondrial DNA-encoded cytochrome C oxidase subunit II and NADH dehydrogenase subunit 6 and the cell signaling protein ERK and phosphorylated ERK were altered in the treated U87 cells, suggesting that silicon dioxide nanoparticles induced disruption of mitochondrial DNA-encoded protein expression, leading to decreased mitochondrial energy production and decreased cell survival/proliferation signaling. Thus, our results strongly suggest that the cytotoxicity of silicon dioxide nanoparticles in human neural cells implicates altered mitochondrial function and cell survival/proliferation signaling. 

Retracted: No

PubPeer comments:
 Figure 4 and 5 appear to use the same image. ***  ,
In vitro inhibition of proliferation, migration and epithelial-mesenchymal transition of human lens epithelial cells by fasudil
Authors: Shan-Shan Du
Wen-Wen Du
Jing-Zhi Shao
Ying Qi
Fu-Zhen Li
Feng-Yan Zhang
Journal: International Journal of Ophthalmology (2018)
Discipline: CLINICAL MEDICINE
Keywords: Rho/Rock; TGF-Œ≤2; epithelial-mesenchymal transition; fasudil; human lens epithelial cells.
Affiliations: Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.

Abstract:  Aim: To study the potential role of fasudil as a treatment for posterior capsular opacification (PCO) of the human crystalline lens. Methods: Human lens epithelial cells (HLECs; line SRA01/04) was exposed to transforming growth factor-Œ≤2 (TGF-Œ≤2) to induce the process of epithelial-mesenchymal transition (EMT). Fasudil was applied to the cell samples. Its effect on overall HLECs proliferation and migration was studied, as was its influence on EMT induction by TGF-Œ≤2 using cell migration assay, MTT colorimetric assay and Western blot assay. Results: Fasudil inhibited the proliferation of SRA01/04. Its effect was time- and concentration-dependent. The migration of SRA01/04 cells was significantly reduced 24-72h after fasudil treatment, and the half maximal inhibitory concentration (IC50) was 22.37 ¬µmol/mL at 72h. Reversal of the elongated, fibroblast-like shape changes induced by TGF-Œ≤2 in SRA01/04 cells was observed. Fasudil up-regulated the expression of Connexin43 protein and down-regulated the expression of Œ±-SMA protein compared with the cells treated with TGF-Œ≤2. Furthermore, when exposed to fasudil, the phosphorylation of Rho-associated protein kinase (Rock) and myosin light chain (MLC) could not be activated in the cell preparations. Conclusion: Fasudil suppresses the proliferation and migration of SRA01/04 cells, and inhibits the process of EMT induced by TGF-Œ≤2. These results suggest that fasudil may serve as a therapeutic agent for PCO. 

Retracted: No

PubPeer comments:
  Figure 1 Cells treated with fasudil showed reversal of the cellular morphology induced by TGF-u03b22 A: Cellular morphology of untreated control samples displayed polygonal or cobblestone-like morphology; B: Cells treated with 10 ng mL TGF-u03b22 showed a spindle-shaped cellular morphology; C: HLECs treated with 10 ng mL TGF-u03b22 and subsequently treated with 10 u03bcmol mL fasudil displayed polygonal or cobblestone-like. Why the repeated areas in the upper right of each panel?  ,
LncRNA HANR aggravates the progression of non-small cell lung cancer via mediating miRNA-140-5p
Authors: Y-X Wu
A-B Wu
Y-H Liang
H-Y Zheng
Z-X Yang
S-J Li
Y Gao
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; HANR; miRNA-140-5p; NSCLC; progression
Affiliations: Department of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. .

Abstract:  Objective: The aim of this study was to elucidate the function of long non-coding ribonucleic acids (lncRNAs) HANR in aggravating non-small cell lung cancer (NSCLC) progression via targeting microRNA-140-5p (miRNA-140-5p). Patients and methods: The relative expression level of HANR in NSCLC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between HANR expression and the prognosis of NSCLC was analyzed. The regulatory effects of HANR on cellular behaviors of NSCLC cells were evaluated by Cell Counting Kit-8 (CCK-8), transwell and wound healing assay. Meanwhile, the relative expression of miRNA-140-5p in NSCLC tissues and cell lines was determined by qRT-PCR. In addition, rescue experiments were carried out to evaluate the potential influence of HANR/miRNA-140-5p on the progression of NSCLC. Results: HANR expression was significantly up-regulated in NSCLC tissues and cell lines. HANR expression was positively correlated with lymphatic metastasis and distant metastasis of NSCLC patients, whereas it was negatively correlated with the overall survival of NSCLC patients. Knockdown of HANR markedly suppressed the proliferative, migratory and invasive abilities of NSCLC cells. In NSCLC tissues, the miRNA-140-5p level was negatively associated with HANR level. Furthermore, inhibited cellular behaviors of NSCLC cells transfected with sh-HANR were partially reversed after miRNA-140-5p knockdown. Conclusions: LncRNA HANR accelerates the proliferative, migratory and invasive abilities of NSCLC via negatively mediating miRNA-140-5p. Furthermore, HANR is closely correlated with lymphatic metastasis, distant metastasis and poor prognosis of NSCLC. 

Retracted: No

PubPeer comments:
 Fig 1C.  Kaplan-Meier curve was conducted based on HANR level in NSCLC patients.  Another manifestation of  Hoya s Law for J.BUOn ERMPS :  When 40 or 50 cases of any given cancer are dichotomised into half-groups of high- or low-expression of any given noncoding RNA, survival rate for one half-group or both *always* drops to 0% at 75 months. Some other examples, from left to right: - Fig 1 from [Zang et al (2020)] - Fig 1 from [Li et al (2020)] - Fig 1, and Fig 4D, from [Cui et al (2019)] - Fig 1D from [Gao et al (2019)] .  *[left]* Figure 1C from [Wu et al (2020)] . *[right]* Figs 1D, 3E from [Wu et al (2019)] .  1D from [Luo, Yan Liu] :  ,
PTEN- and p53-mediated apoptosis and cell cycle arrest by FTY720 in gastric cancer cells and nude mice
Authors: Xianzhi Meng
Xi Chen
Jiabei Wang
Lianxin Liu
Dalong Yin
Yingjian Liang
Xuan Song
Tongsen Zheng
Shangha Pan
Hongchi Jiang
Journal: Journal of Cellular Biochemistry (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FTY720; immunosuppressant; anti-cancer properties; gastric cancer; cell proliferation
Affiliations: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China. 

Abstract:  FTY720, a new immunosuppressant, derived from ISP-1, has been studied for its putative anti-cancer properties in the recent years. In this study, we have reported that FTY720 greatly inhibited gastric cancer cell proliferation for the first time, and found this effect was associated with G1 phase cell cycle arrest and apoptosis. Results from our Western blotting and Real-time PCR showed that FTY720 induced obvious PTEN expression in a p53-independent way, consistent with a substantial decrease in p-Akt and MDM2. FTY720 dramatically increased the expression of Cip1/p21, p27, and BH3-only proteins through the accumulation of p53 by PTEN-mediated inhibition of the PI3K/Akt/MDM2 signaling. Suppression of PTEN expression with siRNA significantly reduced the p53 and p21 levels and activated Akt, resulting in decreased apoptosis and increased cell survival. Furthermore, we have observed an additive effect of FTY720 in killing gastric cancer cells when in combination with Cisplatin, partly through PTEN-mediated Akt/MDM2 inhibition. In vivo study has also shown that tumor growth was significantly suppressed after FTY720 treatment. In conclusion, our results suggest that FTY720 induces a significant increase of PTEN, which inhibits p-Akt and MDM2, and then increases the level of p53, thereby inducing G1 phase arrest and apoptosis. We have characterized a novel immunosuppressant, for the first time, which shows potential anti-tumor effects on gastric cancer by PTEN activation through p53-independent mechanism, especially in combination with Cisplatin. This PTEN target-based therapy is worth further investigation and warrants clinical evaluation. 

Retracted: No

PubPeer comments:
 Images of Migration (Control group) and Invasion (Control group) appear to be the same.  ,
A shift in microvillus membrane fucosylation to sialylation by ethanol ingestion in rat intestine
Authors: Akhtar Mahmood
Ravneet K Grewal
Journal: Molecular and Cellular Biochemistry (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: glycocalyx; ethanol ingestion; membrane glycoproteins; hexose; sialic acid
Affiliations: Department of Biochemistry, Panjab University, Chandigarh, 160014, India.

Abstract:  The luminal surface of enterocytes is covered with glycocalyx which is rich in glycoproteins. Ethanol ingestion is shown to induce morphological and biochemical changes in the intestine. In this study, the effect of ethanol ingestion on membrane glycoproteins has been investigated. Chemical analysis of microvillus membranes revealed an increase in hexose and sialic acid contents, but a reduction in fucose levels in ethanol-fed rats compared with controls. The observed changes were apparent in animals fed with ethanol for 35-56 days compared with controls. Lectin-binding assay indicated an increase in Wheat germ agglutinin (affinity for GlcNAc/sialic acid) and a decrease in Aleuria aurantia (affinity for alpha-L: -fucose) reactivity of brush borders in ethanol-fed animals for 4-8 weeks. Western blot analysis using biotin-labeled Wheat germ agglutinin revealed increased binding to proteins of M(r) 66-205 kDa in ethanol-fed rats compared with controls. The binding of Aleuria aurantia to membrane proteins of M(r) 97-185 kDa was reduced in ethanol-fed animals. These findings suggest that long-term ethanol feeding modulates the sialylation and fucosylation processes of microvillus membrane proteins in rat intestine. This could affect the intestinal digestive and absorptive functions in chronic alcoholism. 

Retracted: No

PubPeer comments:
 Could the authors comment on what appear to be several repeated features?  ,
Ravens parallel great apes in flexible planning for tool-use and bartering
Authors: Can Kabadayi
Mathias Osvath
Journal: Science (2017)
Discipline: Multidisciplinary
Keywords: planning; ravens; corvids; cognitive evolution; self-control
Affiliations: Department of Cognitive Science, Lund University, Helgonav√§gen 3, 22100 Lund, Sweden., Department of Cognitive Science, Lund University, Helgonav√§gen 3, 22100 Lund, Sweden. .

Abstract:  The ability to flexibly plan for events outside of the current sensory scope is at the core of being human and is crucial to our everyday lives and society. Studies on apes have shaped a belief that this ability evolved within the hominid lineage. Corvids, however, have shown evidence of planning their food hoarding, although this has been suggested to reflect a specific caching adaptation rather than domain-general planning. Here, we show that ravens plan for events unrelated to caching-tool-use and bartering-with delays of up to 17 hours, exert self-control, and consider temporal distance to future events. Their performance parallels that seen in apes and suggests that planning evolved independently in corvids, which opens new avenues for the study of cognitive evolution. 

Retracted: No

PubPeer comments:
 Several other researchers have questioned the conclusion of this study for reasons mentioned above. This post is to gather these references in one place. Redshaw, J., Taylor, A. H., Suddendorf, T. (2017). Flexible planning in ravens?. Trends in cognitive sciences, 21(11), 821-822. Lind, J. (2018). What can associative learning do for planning? Royal Society open science, 5(11), 180778. Hampton, R. (2019). Parallel overinterpretation of behavior of apes and corvids. Learning Behavior, 47(2), 105-106. See also comment: https: www.researchgate.net profile Jonathan_Redshaw publication 325882935_Clarifying_animal_planning_capacities links 5b2ae5cea6fdcc72db507f9b Clarifying-animal-planning-capacities.pdf ,
miR-154 targeting ZEB2 in hepatocellular carcinoma functions as a potential tumor suppressor
Authors: Yujiao Zhang
Kexin Huang
Qianqian Zhang
Junqi Niu
Xiaoli Pang
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNA-154; tumor suppressor; human hepatocellular carcinoma; clinical significance; cellular function

Abstract:  MicroRNA-154 (miR-154) has been identified as a tumor suppressor in several types of human cancers; however, its clinical significance and function in human hepatocellular carcinoma (HCC) remain unclear. The aim of the present study was to analyze the clinical significance and cellular function of miR-154 in HCC patients. The data showed that miR-154 expression was consistently lower in HCC tissues and cell lines compared to that in matched tumor-adjacent tissues and a normal hepatic cell line, and its expression was negatively correlated with tumor differentiation (P&lt;0.01), TNM stage (P&lt;0.01) and lymph node metastasis (P&lt;0.01). Restoration of miR-154 expression in HepG2 cells inhibited cell proliferation, migration and invasion, and induced apoptosis and cell arrest at the G1 phase in vitro, as well as suppressed tumor growth in a nude mouse model. Using a luciferase assay, we identified that miR-154 was able to target the 3'-untranslated region (3'UTR) of ZEB2 mRNA. Then, we revealed that miR-154 was able to reduce ZEB2 expression at the levels of mRNA and protein using qRT-PCR and western blot analysis. Notably, restoration of expression of ZEB2 weakened miR-154-mediated suppression of tumor progression. In conclusion, these results indicate that miR-154 functions as a tumor suppressor in HCC by suppressing ZEB2, suggesting that miR-154 may serve as a potential target for HCC. 

Retracted: Yes

PubPeer comments:
 This paper presents three SEM images of the same material three times in Figure 7, claiming that the images represent different materials. Although the images were clearly collected at different scales, the scale bars are the same.  , 
  ,
Expression of the v-Src oncoprotein in fibroblasts disrupts normal regulation of the CDK inhibitor p27 and inhibits quiescence
Authors: J A Wyke
D Johnson
M C Frame
Journal: Oncogene (1998)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: oncogenic tyrosine kinase; cell cycle control; fibroblasts; v-Src; G1 phase
Affiliations: Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, UK.

Abstract:  To determine how an oncogenic tyrosine kinase disturbs cell cycle control we examined expression of cell cycle proteins and growth of fibroblasts reversibly transformed by a temperature sensitive mutant of v-Src (ts LA 29). ts LA 29 Rat-1 cells and normal Rat-1 cells had similar growth rates but the transformed cells traversed the G1 phase of the cell cycle more rapidly and failed to exit cycle efficiently in response to serum starvation and cell confluence. Cyclin D1 and cyclin E levels were not elevated in growing ts LA 29 Rat-1 cells and the abbreviated G1 was further accelerated by overexpression of cyclin E. A fall in cyclin E and cyclin A dependent kinase activities in Rat-1 cells in response to inhibitory growth conditions was abrogated in ts LA 29 Rat-1 cells and correlated with lack of p27 accumulation or cyclin A down regulation, the latter due to sustained cyclin A promoter activity. The expression of p27 mRNA was lower in ts LA 29 Rat-1 cells than Rat-1 cells and was elevated following v-Src inactivation concurrent with an increase in p27 promoter activity and temporary cell cycle exit. The suppression of mRNA or transcription is a novel way an oncoprotein can induce down regulation of p27 and contributes to the G1 shortening and perturbed cell cycle regulation of the v-Src transformed cells. 

Retracted: No

PubPeer comments:
 Figure 4a. Much more similar than expected. Vertical, straight changes between lanes in some panels, but not others.  , 
 Figure 5a. Vertical, straight changes in signal between different lanes in cyclin A and p27 panels.  ,
Chronic gastric ulceration causes matrix metalloproteinases-9 and -3 augmentation: alleviation by melatonin
Authors: Snehasikta Swarnakar
Krishnendu Ganguly
Journal: Biochimie (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Matrix metalloproteinases; MMP-9; MMP-3; chronic gastric ulceration; mice
Affiliations: Department of Physiology, Drug Development Diagnostics and Biotechnology Division, CSIR-Indian Institute of Chemical Biology, 4, Raja SC Mullick Road, Jadavpur, Kolkata 700032, India.

Abstract:  Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable of degradation of extracellular matrix (ECM) and key player in various inflammatory diseases. We investigated the regulation of MMPs in chronic gastric ulceration in mice. We generated chronic gastric ulcers in mice by indomethacin and examined the activity and expression of MMP-9 and -3 in stomach. Melatonin (N-acetyl-5-methoxytryptamine) treatment has also been applied to mice to characterize the changes in expression and activities of MMPs in gastric tissues. We observed significant upregulation of MMP-9 and -3 expressions and activities in stomach with increasing doses and duration of indomethacin that corroborated with increased activity of activator protein (AP)-1. Substantial damage in gastric epithelial layer was found during chronic ulceration. Melatonin suppressed MMP-9 and -3 expressions and activities during prevention and healing of chronic gastric ulcers. It also suppressed protein oxidation, lipid peroxidation and antioxidant enzymes. Additionally, expression of tumor necrosis factor (TNF)-Œ±, interleukin (IL)-1Œ≤ and IL-8 was significantly high in ulcerated stomachs while melatonin treatment blocked them to control level. We found elevated phosphorylation of extracellular-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) during chronic gastric ulceration, which were significantly reversed by melatonin. Moreover, expression of NF-Œ∫B, c-fos and c-jun were inhibited by melatonin resulting down regulation of MMP-9 and -3 expressions. In summary, oxidative stress is preceded by chronic inflammation that enhances the expression of MMP-9 and -3, while melatonin arrests both of them via reduction of AP-1 activity during protection of ulcer. 

Retracted: No

PubPeer comments:
 An unexpected similarity between some lanes. Red arrow indicates a sharp boundary between lanes.  ,
LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer
Authors: Hyo Joo Byun
Sang Kil Lee
Jung Ho Yoon
Journal: Yonsei Medical Journal (2020)
Discipline: CLINICAL MEDICINE
Keywords: LUCAT1; Long non-coding RNA; epigenetic modulation; gastric cancer.
Affiliations: Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea., Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea.

Abstract:  Purpose: The mechanisms of Wnt/Œ≤-catenin pathway signaling and abnormal expression of tumor suppressor genes is not well known in gastric cancer (GC). Long non-coding RNA (lncRNA) has recently been identified as a possible link therein. In this study, we investigated the role of lung cancer associated transcript 1 (LUCAT1) in GC. Materials and methods: The expression of LUCAT1 in GC cell lines and 100 tissue samples was examined by qRT-PCR. Two different siRNAs were used for knockdown of LUCAT1 expression. Cell viability was assessed by MTT assay. To analyze metastasis, scratch wound-healing assay, a Matrigel invasion assay, and colony formation assay were performed. Apoptosis was analyzed by PI/Annexin-V staining. To check the methylation status in tumor suppressor genes, methylation-specific PCR was carried out. Western blot was performed to detect epithelial-mesenchymal transition and apoptosis markers upon silencing of LUCAT1 (siLUCAT1). Results: LUCAT1 expression in GC cell lines and tissues was significantly elevated, compared to that in normal gastric cells and adjacent non-tumor tissues (p&lt;0.001). Two different siRNAs for LUCAT1 reduced cell proliferation, invasion, and migration, compared to siCT (p&lt;0.05), and these reductions were restored by pcDNA-LUCAT1 (p&lt;0.05). siLUCAT1 elicited upregulation of the expression of CXXC4 and SFRP2. The expression of H3K27me3 was reduced by siLUCAT1, and this reduction was correlated with methylation of CXXC4 and SFRP2. Inhibition of LUCAT1 up-regulated EZH2 expression and resulted in demethylation of CXXC4 and SFRP2 through the Wnt/Œ≤-catenin signaling pathway. Conclusion: We concluded that LUCAT1 induces methylation of CXXC4 and SFRP2, thereby regulating Wnt/Œ≤-catenin signaling in GC. 

Retracted: No

PubPeer comments:
 Images in Figure 3A appear to overlap. One appears to have been edited. ***  ***  ,
Antagonism of betulinic acid on LPS-mediated inhibition of ABCA1 and cholesterol efflux through inhibiting nuclear factor-kappaB signaling pathway and miR-33 expression
Authors: Shi-Lin Tang
Qian Lu
Wu-Jun Chen
Chao-Ke Tang
Yun-Cheng Lv
Feng Yao
Yan-Yan Tang
Min Zhang
Ping-Ping He
Da-Wei Zhang
Yuchang Fu
Xin-Ping Ouyang
Guo-Jun Zhao
Kai Yin
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: ABCA1; betulinic acid; cholesterol efflux; miR-33s; NF-Œ∫B
Affiliations: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, China ; Department of Histology and Embryology, University of South China, Hengyang, Hunan, China.

Abstract:  ATP-binding cassette transporter A1 (ABCA1) is critical in exporting cholesterol from macrophages and plays a protective role in the development of atherosclerosis. The purpose of this study was to investigate the effects of betulinic acid (BA), a pentacyclic triterpenoid, on ABCA1 expression and cholesterol efflux, and to further determine the underlying mechanism. BA promoted ABCA1 expression and cholesterol efflux, decreased cellular cholesterol and cholesterol ester content in LPS-treated macrophages. Furthermore, we found that BA promoted ABCA1 expression via down-regulation of miR-33s. The inhibition of LPS-induced NF-Œ∫B activation further decreased miR-33s expression and enhanced ABCA1 expression and cholesterol efflux when compared with BA only treatment. In addition, BA suppressed IŒ∫B phosphorylation, p65 phosphorylation and nuclear translocation, and the transcription of NF-Œ∫B-dependent related gene. Moreover, BA reduced atherosclerotic lesion size, miR-33s levels and NF-Œ∫B activation, and promoted ABCA1 expression in apoE(-/-) mice. Taken together, these results reveal a novel mechanism for the BA-mediated ABCA1 expression, which may provide new insights for developing strategies for modulating vascular inflammation and atherosclerosis. 

Retracted: No

PubPeer comments:
 Figure 4B and 6C. * Red boxes: unexpected similarities between the p-p65 and NF-kB p65 panels. * Blue boxes: unexpected similarities between the Histon H1p65 panels. The two figures appear to be showing very different experiments, at least that is how I interpreted them by reading the legends. Can the authors please comment?   ,
Ad-PUMA sensitizes drug-resistant choriocarcinoma cells to chemotherapeutic agents
Authors: Chen Lin
Haili Qian
Yan Chen
Xueyan Zhang
Ming Fu
Haijuan Wang
Qimin Zhan
Yang Xiang
Yan Ma
Xiao Liang
Journal: Gynecologic oncology (2007)
Discipline: CLINICAL MEDICINE
Keywords: exogenous PUMA expression; drug-resistant choriocarcinoma cells; chemotherapeutic agents; growth suppression; apoptosis
Affiliations: State Key Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100021, China.

Abstract:  Purpose/objective: To investigate whether exogenous PUMA expression suppresses the growth of drug-resistant choriocarcinoma cells and sensitizes them to chemotherapeutic agents. Methods: An adenovirus expressing PUMA (Ad-PUMA), alone or in combination with chemotherapeutic agents (5-FU, vp16, MTX), was used to treat drug-resistant choriocarcinoma cells jeg-3/vp16 and parental jeg-3. The growth inhibitory and proapoptotic effects of Ad-PUMA both in vitro and in vivo were examined. The mechanisms of PUMA-mediated growth suppression and apoptosis were investigated by an analysis of caspase 3 activation and the change of mitochondrial membrane potential. The levels of PUMA, p53 and caspase 3 were detected by Western blotting. Result: PUMA was expressed lower in jeg-3/vp16 than in jeg-3. jeg-3/vp16 responded much less sensitively to 5-FU and vp16 treatment than jeg-3, though PUMA was up-regulated in both cells. Exogenous PUMA expression resulted in potent growth suppression of jeg-3/vp16 and jeg-3 through induction of apoptosis. Ad-PUMA sensitized jeg-3 and jeg-3/vp16 to chemotherapeutic agents. When Ad-PUMA 10MOI and 5-FU, vp16 or MTX were combined respectively, IC50 of drugs decreased by 8.66-, 18.66- and 13.06-fold compared with those treated by anticancer drugs alone in jeg-3/vp16, while in jeg-3, IC50 decreased only by 1.80-, 1.78- and 2.76-fold. Ad-PUMA restored the sensitivity of choriocarcinoma cells to chemotherapeutic agents by enhancing apoptosis induced by anticancer drugs. Similar results could be observed in vivo. Xenograft tumors were inhibited by Ad-PUMA or vp16. In the drug-resistant group, the inhibitory rate increased from 14.57% to 78.93% in vp16 and vp16 combined with Ad-PUMA subgroups. While in the parental group, the inhibitory rate increased but slightly, from 66.39% to 71.56%. Conclusion: PUMA is an important player in the therapeutic responses to chemotherapeutic agents of choriocarcinoma cells. In addition to its role in inhibiting tumor growth, low dose of Ad-PUMA significantly restored the sensitivity of choriocarcinoma cells to chemotherapeutic agents in vitro and in vivo. Exogenous PUMA is potentially useful as a sensitizer in treating drug-resistant choriocarcinoma. 

Retracted: No

PubPeer comments:
 2020 correction. http: www.jbc.org content 295 3 898.short The wrong images were used for the long form of Stra6 and RARu03b3 in Fig. 4D. These errors have now been corrected and do not affect the results or conclusions of this work. ,
Trehalose-based eye drops preserve viability and functionality of cultured human corneal epithelial cells during desiccation
Authors: Krzysztof Marycz
Marta Misiuk-Hoj≈Ço
Jakub Grzesiak
Aneta Hill-Bator
Journal: BioMed Research International (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: cytoprotective ability; trehalose-based eye drops; desiccation; human corneal epithelial cells; cell viability
Affiliations: Department of Ophthalmology, Medical University Wroclaw, Borowska 213, 50-556 Wroclaw, Poland., Electron Microscopy Laboratory, University of Environmental and Life Sciences in Wroclaw, Kozuchowska 5b, 51-631 Wroclaw, Poland.

Abstract:  This paper presents the evaluation of cytoprotective ability of trehalose-based eye drops in comparison with commercially available preparations during the experimental desiccation of cultured human corneal epithelial cells. Cultured human corneal epithelial cells (hCEC) underwent incubation with 7 different, commercially available medicaments used commonly in dry eye syndrome treatment, followed by desiccation trial performed on air under the flow hood for 5, 15, 30, and 45 minutes. Cell viability was quantified by live/dead fluorescent assay, while the presence of apoptotic cells was estimated by immunofluorescent staining for active caspase 3 protein. The preservation of membrane functions was evaluated using neutral red staining, while the preservation of proper morphology and phenotype was determined by fluorescent staining for actin filaments, nuclei, and p63 protein. The trehalose-based eye drops showed the highest efficiency in prevention of cell death from desiccation; moreover, this preparation preserved the normal cellular morphology, functions of cell membrane, and proliferative activity more effectively than other tested medicaments. 

Retracted: No

PubPeer comments:
 numerous image duplications  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. ,