PReD-Bench/PRed-Bench huggingface dataset:
Candidate tumour suppressor CCDC 19 regulates miR‚Ä?84 direct targeting of C‚ÄêMyc thereby suppressing cell growth in non‚Äêsmall cell lung cancers
Authors: Xiaoli Yu
Yajie Zhang
Qiangyun Wu
Yan Zhen
Zhen Liu
Qinping Jiang
Weiyi Fang
Chunping Mai
Xin Song
Shengni Hua
Huiling Yang
Journal: Journal of Cellular and Molecular Medicine (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CCDC19; PI3K/AKT; lung cancer; miR-184; tumour suppressor.
Affiliations: Department of Pathology School of Basic Medicine Guangzhou Medical University Guangzhou China, Cancer Research Institute Southern Medical University Guangzhou China, Third Affiliated Hospital of Guangzhou Medical College Guangzhou China

Abstract:  We previously reported and revised the nasopharyngeal epithelium specific protein CCDC19 and identified it as a potential tumour suppressor in nasopharyngeal carcinoma. The purpose of this study was to investigate the involvement of CCDC19 in the pathogenesis of human non-small cell lung cancers (NSCLC). Down-regulated CCDC19 expression was observed in NSCLC tissues and cells compared to normal tissues. However, reduced protein expression did not correlate with the status of NSCLC progression. Instead, we observed that patients with lower CCDC19 expression had a shorter overall survival than did patients with higher CCDC19 expression. Lentiviral-mediated CCDC19 overexpression significantly suppressed cell proliferation and cell cycle transition from G1 to S and G2 phases in NSCLC cells. Knocking down CCDC19 expression significantly restored the ability of cell growth in CCDC19 overexpressing NSCLC cells. Mechanistically CCDC19 functions as a potential tumour suppressor by stimulating miR-184 suppression of C-Myc thus blocking cell growth mediated by the PI3K/AKT/C-Jun pathway. Our studies are the first to demonstrate that reduced expression of CCDC19 is an unfavourable factor in NSCLC. 

Retracted: No

PubPeer comments:
 Fig. 7A and Fig. 7E contain two WB bands which appear more similar than expected, when one band was subjected to vertical flipping.  ,
p53 isoforms Delta133p53 and p53beta are endogenous regulators of replicative cellular senescence
Authors: Sharon R Pine
Borivoj Vojtesek
Izumi Horikawa
Curtis C Harris
Elise D Bowman
Kaori Fujita
Aaron J Schetter
Giang H Nguyen
Helen Ji
Jane J Sohn
Jean-Christophe Bourdon
David P Lane
Abdul M Mondal
Kensuke Kumamoto
Ewy A Mathe
Journal: Nature Cell Biology (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cellular senescence; p53 isoforms; Delta133p53; p53beta; replicative senescence
Affiliations: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4258, USA.

Abstract:  The finite proliferative potential of normal human cells leads to replicative cellular senescence, which is a critical barrier to tumour progression in vivo. We show that the human p53 isoforms Delta133p53 and p53beta function in an endogenous regulatory mechanism for p53-mediated replicative senescence. Induced p53beta and diminished Delta133p53 were associated with replicative senescence, but not oncogene-induced senescence, in normal human fibroblasts. The replicatively senescent fibroblasts also expressed increased levels of miR-34a, a p53-induced microRNA, the antisense inhibition of which delayed the onset of replicative senescence. The siRNA (short interfering RNA)-mediated knockdown of endogenous Delta133p53 induced cellular senescence, which was attributed to the regulation of p21(WAF1) and other p53 transcriptional target genes. In overexpression experiments, whereas p53beta cooperated with full-length p53 to accelerate cellular senescence, Delta133p53 repressed miR-34a expression and extended the cellular replicative lifespan, providing a functional connection of this microRNA to the p53 isoform-mediated regulation of senescence. The senescence-associated signature of p53 isoform expression (that is, elevated p53beta and reduced Delta133p53) was observed in vivo in colon adenomas with senescent phenotypes. The increased Delta133p53 and decreased p53beta isoform expression found in colon carcinoma may signal an escape from the senescence barrier during the progression from adenoma to carcinoma. 

Retracted: No

PubPeer comments:
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 Figure 1b. Much more similar after vertical and horizontal resizing. The cell lines are different so there are 2 samples.  , 
 Supplementary figure 7a. Case 3. Splicing between N and A in the delta133p53 and beta-actin lanes, but not in the p16 panel.  ,
MicroRNA-19a regulates the proliferation, migration and invasion of human gastric cancer cells by targeting CUL5
Authors: Xiaodong Guo
Yu Zhu
Dezhi Hou
Linhai Li
Yongzhi Wang
Yiming Ouyang
Kunmei Gong
Jiyan Li
Journal: Archives of Biochemistry and Biophysics (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CUL-5; Gastric cancer; Invasion; Migration; Proliferation
Affiliations: Department of General Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China., Department of Pain, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China., Department of General Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China. Electronic address: .

Abstract:  Gastric cancer is one of the prevalent types of cancers and despite improvements in its treatment, the overall survival is still far from descent. The dearth of efficient biomarkers, chemotherapeutic agents and therapeutic targets form a major hurdle in the treatment of the gastric cancer. Accumulating evidences suggest that MicroRNAs (miRs) may prove important therapeutic targets/agents for the management of cancers including gastric cancer. Herein, we examined the expression of miR-19a by qRT-PCR in gastric cancer and attempted to explore its potential role. It was found that the expression of miR-19a is significantly (p &lt; 0.05) enhanced in the gastric cancer tissues as well as the gastric cancer cell lines. Inhibition of miR-19a in gastric cancer cells suppressed the proliferation migration and invasion of the gastric cancer cells. Bioinformatic analysis revealed CUL5 to be the potential target of miR-19a. Contrary, to the expression of miR-19a, the expression of CUL5 was significantly (p &lt; 0.05) downregulated in all the gastric cancer tissues and cell lines. However, inhibition of miR-19a in SNU-16 gastric cancer cells could cause upsurge of CUL5 expression. Overexpression of CUL-5 was found to exhibit similar effects on the proliferation, migration and invasion of the SNU-16 gastric cancer cells as that of miR-19a suppression. Additionally, overexpression of CUL5 could at least partially abolish the effects of miR-19a suppression on the proliferation, migration and invasion of SNU-16 gastric cancer cells. Finally, overexpression of miR-19a caused inhibition of the xenografted tumors in vivo indicating the potential of miR-19a as therapeutic target for gastric cancer. 

Retracted: No

PubPeer comments:
 Figure 10 has a clearly visible splice (red) and other possible issues (blue). No splice appears in b-actin band. *** Inverted and contrast enhanced  *** Original  ,
RalA functions as an indispensable signal mediator for the nutrient-sensing system
Authors: Tomohiko Maehama
Hiroshi Nishina
Yasunori Kanaho
Masahiko Tanaka
Kentaro Hanada
Makoto Murakami
Journal: Journal of Biological Chemistry (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cells; nutrients; extracellular environment; intracellular signaling systems; RalA
Affiliations: Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan. 

Abstract:  Cells sense nutrients present in the extracellular environment and modulate the activities of intracellular signaling systems in response to nutrient availability. This study demonstrates that RalA and its activator RalGDS participate in nutrient sensing and are indispensable for activation of mammalian target of rapamycin complex 1 (mTORC1) induced by extracellular nutrients. Knockdown of RalA or RalGDS abolished amino acid- and glucose-induced mTORC1 activation, as judged by phosphorylation of S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1. The amount of GTP-bound RalA increased in response to increased amino acid availability. In addition, RalA knockdown suppressed Rheb-induced S6 kinase phosphorylation, and the constitutively active form of RalA induced mTORC1 activation in the absence of Rheb. These results collectively suggest that RalGDS and RalA act downstream of Rheb and that RalA activation is a crucial step in nutrient-induced mTORC1 activation. 

Retracted: No

PubPeer comments:
 There are several undeclared splicing sites in Fig. 2B. It looks like the bands were assembled together.  ,
Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro
Authors: Ludong Tan
Ze Zhang
Zhe Jin
Qingmin Chen
Yahui Liu
Journal: BioMed Research International (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CRABP2; retinoic acid; hepatocellular carcinoma; tumor development; molecular mechanisms
Affiliations: Department of General Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China, Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, Jilin 130000, China

Abstract:  Cellular retinoic acid-binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA-knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK-8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis-related protein expression and decreased ERK/VEGF pathway-related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC. 

Retracted: No

PubPeer comments:
 Figure 1B: the Western blots here look very similar to those in Figure 1B of another paper by the same group. They might be representing the same patient samples, but the top panel is representing a different protein. * Left: Qingmin Chen et al., BioMed Research International (2020), DOI: 10.1155 2020 3098327 * Right: Qingmin Chen et al., Human Cell (2020), DOI: 10.1007 s13577-020-00353-7  , 
 Dear Bik: Thank you for pointing out the misuse of pictures in our manuscript. We are very sorry about our mistake and we confess that we wrongly used this WB band in our another manuscript (Human cell) intentionally. The band in this manuscript is correct. The corrected figure in another journal is presented below. We deeply grateful for your pointing out our mistakes. We will contact the magazine for correction as soon as possible.  ,
Computational biophysical, biochemical, and evolutionary signature of human R-spondin family proteins, the member of canonical Wnt/Œ≤-catenin signaling pathway
Authors: C George Priya Doss
Ju-Suk Nam
Sang-Soo Lee
Garima Sharma
Dong-Keun Song
Chiranjib Chakraborty
Ashish Ranjan Sharma
Jeong Kyo Yoon
Journal: BioMed Research International (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Wnt/Œ≤-catenin signaling pathway; Rspo; molecular properties; biochemical; biophysical
Affiliations: Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 200704, Republic of Korea ; Institute for Skeletal Aging & Orthopedic Surgery, Hallym University Hospital, College of Medicine, Chuncheon-si, Gangwon-do 200-704, Republic of Korea., Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 200704, Republic of Korea ; Department of Bioinformatics, School of Computer Sciences, Galgotias University, Greater Noida 203201, India., Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 200704, Republic of Korea., Center for Molecular Medicine, Maine Medial Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA., Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu 632014, India.

Abstract:  In human, Wnt/Œ≤-catenin signaling pathway plays a significant role in cell growth, cell development, and disease pathogenesis. Four human (Rspo)s are known to activate canonical Wnt/Œ≤-catenin signaling pathway. Presently, (Rspo)s serve as therapeutic target for several human diseases. Henceforth, basic understanding about the molecular properties of (Rspo)s is essential. We approached this issue by interpreting the biochemical and biophysical properties along with molecular evolution of (Rspo)s thorough computational algorithm methods. Our analysis shows that signal peptide length is roughly similar in (Rspo)s family along with similarity in aa distribution pattern. In Rspo3, four N-glycosylation sites were noted. All members are hydrophilic in nature and showed alike GRAVY values, approximately. Conversely, Rspo3 contains the maximum positively charged residues while Rspo4 includes the lowest. Four highly aligned blocks were recorded through Gblocks. Phylogenetic analysis shows Rspo4 is being rooted with Rspo2 and similarly Rspo3 and Rspo1 have the common point of origin. Through phylogenomics study, we developed a phylogenetic tree of sixty proteins (n = 60) with the orthologs and paralogs seed sequences. Protein-protein network was also illustrated. Results demonstrated in our study may help the future researchers to unfold significant physiological and therapeutic properties of (Rspo)s in various disease models. 

Retracted: No

PubPeer comments:
 Is Figure 1b an attempt to correlate the number of amino acids with the name of the protein?  ,
Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks
Authors: Dag Jenssen
Kevin Walters
Cecilia Lundin
Thomas Helleday
Alastair S H Goldman
Matthew North
Klaus Erixon
Journal: Nucleic Acids Research (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Homologous recombination; methyl methanesulfonate; DNA double-strand breaks; Saccharomyces cerevisiae; pulsed-field gel electrophoresis
Affiliations: Department of Genetics, Microbiology and Toxicology, Stockholm University Svante Arrhenius v√§g 16, S-106 91 Stockholm, Sweden.

Abstract:  Homologous recombination (HR) deficient cells are sensitive to methyl methanesulfonate (MMS). HR is usually involved in the repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae implying that MMS somehow induces DSBs in vivo. Indeed there is evidence, based on pulsed-field gel electrophoresis (PFGE), that MMS causes DNA fragmentation. However, the mechanism through which MMS induces DSBs has not been demonstrated. Here, we show that DNA fragmentation following MMS treatment, and detected by PFGE is not the consequence of production of cellular DSBs. Instead, DSBs seen following MMS treatment are produced during sample preparation where heat-labile methylated DNA is converted into DSBs. Furthermore, we show that the repair of MMS-induced heat-labile damage requires the base excision repair protein XRCC1, and is independent of HR in both S.cerevisiae and mammalian cells. We speculate that the reason for recombination-deficient cells being sensitive to MMS is due to the role of HR in repair of MMS-induced stalled replication forks, rather than for repair of cellular DSBs or heat-labile damage. 

Retracted: No

PubPeer comments:
 I am questioning the micrographs in figure 6. In some of the micrographs the merged picture does not seem to correspond to the individual staining (please see the red squares). A figure with adjusted brightness contrast is provided to illustrate the differences in some of the cases. In figure 9, one of the curves in A and B are identical (please see red arrow), but they represent different treatment (vehicle and vehicle + IgG). I am also wondering if the authors are aware of the reported birth defects with valproate, which they are suggesting in a combined treatment strategy. The dosage (50 mg kg) you are using is quite high and probably not physiological relevant. There is no information regarding how the mice were doing, eg. weight curve etc. A general problem with your microscopy data is oversaturation. E.g. please see suppl. figure 3, which is clearly oversaturated. How can you possible make conclusions based on these data?   , 
 Note: This article has been corrected. Please see the link below: https: www.oncotarget.com article 27162 ,
Renalase attenuates hypertension, renal injury and cardiac remodelling in rats with subtotal nephrectomy
Authors: Zhenzhen Jiang
Naijun Miao
Zeyuan Lu
Jianyong Yin
Niansong Wang
Limin Lu
Feng Wang
Journal: Journal of Cellular and Molecular Medicine (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cardiac remodelling; cardiorenal syndromes; renal dysfunction; renalase; subtotal nephrectomy.
Affiliations: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China., Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.

Abstract:  Chronic kidney disease is associated with higher risk of cardiovascular complication and this interaction can lead to accelerated dysfunction in both organs. Renalase, a kidney-derived cytokine, not only protects against various renal diseases but also exerts cardio-protective effects. Here, we investigated the role of renalase in the progression of cardiorenal syndrome (CRS) after subtotal nephrectomy. Sprague-Dawley rats were randomly subjected to sham operation or subtotal (5/6) nephrectomy (STNx). Two weeks after surgery, sham rats were intravenously injected with Hanks' balanced salt solution (sham), and STNx rats were randomly intravenously injected with adenovirus-Œ≤-gal (STNx+Ad-Œ≤-gal) or adenovirus-renalase (STNx+Ad-renalase) respectively. After 4 weeks of therapy, Ad-renalase administration significantly restored plasma, kidney and heart renalase expression levels in STNx rats. We noticed that STNx rats receiving Ad-renalase exhibited reduced proteinuria, glomerular hypertrophy and interstitial fibrosis after renal ablation compared with STNx rats receiving Ad-Œ≤-gal; these changes were associated with significant decreased expression of genes for fibrosis markers, proinflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components. At the same time, systemic delivery of renalase attenuated hypertension, cardiomyocytes hypertrophy and cardiac interstitial fibrosis; prevented cardiac remodelling through inhibition of pro-fibrotic genes expression and phosphorylation of extracellular signal-regulated kinase (ERK)-1/2. In summary, these results indicate that renalase protects against renal injury and cardiac remodelling after subtotal nephrectomy via inhibiting inflammation, oxidative stress and phosphorylation of ERK-1/2. Renalase shows potential as a therapeutic target for the prevention and treatment of CRS in patients with chronic kidney disease. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have two images which overlap. Seems to be a recurring issue for this group. ***  ,
Platinum-Catalyzed Aromatization of Enediynes via a C‚àíH Bond Insertion of Tethered Alkanes
Authors: Chun-Wei Huang
Ying-Fen Ran
Bhanu Pratap Taduri
Rai-Shung Liu
Journal: Organic Letters (2006)
Discipline: CHEMISTRY
Keywords: PtCl2; catalyst; aromatization; enediynes; C-H bond insertion
Affiliations: Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, ROC

Abstract:  PtCl2 (5 mol%) is an effective catalyst for aromatization of enediynes via a C-H bond insertion of tethered alkanes. The reaction mechanism of this cyclization is proposed to involve platinum-pi-alkyne intermediates. This cyclization works not only for terminal alkynes but also for internal alkynes. 

Retracted: No

PubPeer comments:
 [Expression of concern] published on the 15th of July 2021: As of July 15, 2021, the authors and the Editor-in-Chief issue an Expression of Concern for this Letter (DOI: [10.1021 ol052962m] ) because NMR spectra of compounds **1**, **7a**, **19**, **25**, **27**, **28**, **30**, **31**, and **42** have irregularities that may be the result of editing to remove impurities and grease. The original data are no longer available for review. The authors maintain that the overall conclusions of the work are qualitatively correct, but the Editor-in-Chief advises that for the compounds in question purity levels are not fully known, and yields must be considered as approximate. ,
FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs
Authors: Takaharu Nakayoshi
Ken-Ichiro Sasaki
Shinji Yokoyama
Tsutomu Imaizumi
Masahiro Sasaki
Hidetoshi Chibana
Yoshihiro Fukumoto
Hiroshi Koiwaya
Naoki Itaya
Takafumi Ueno
Masanori Ohtsuka
Hidemi Kajimoto
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: therapeutic angiogenesis; early pro-angiogenic cells (EPCs); oxidative stress; apoptosis; Forkhead transcription factor 4 (FOXO4)
Affiliations: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan., Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan; The Cardiovascular Research Institute, Kurume University, Fukuoka, Japan., The Cardiovascular Research Institute, Kurume University, Fukuoka, Japan., International University of Health and Welfare, Fukuoka, Japan.

Abstract:  The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected into the rat ischemic limb was greater than that of apoptotic EPCs injected into the rat non-ischemic limb, FOXO4KD-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs. Taken together, the use of FOXO4KD-EPCs with resistance to oxidative stress-induced apoptosis may be a new strategy to augment the effects of therapeutic angiogenesis by intramuscular injection of EPCs. 

Retracted: No

PubPeer comments:
 April 2015 correction which reads:  Following the publication of the article, the following errors were identified in two of the figures: * The FOXO4 panel Fig 2A was duplicated as the right panel in Fig 2C. * The right panel of Fig 7A incorrectly displays the flip vertical image of the left panel in Fig 7C. The authors apologize for these errors. Here is the duplication in the original Figure 2, marked with red boxes.  Here is the duplication in the original Figure 7, marked with green boxes as reported to the journal in March 2014.  I thank the authors for correcting these errors. ,
FBXO17 promotes malignant progression of hepatocellular carcinoma by activating wnt/Œ≤-catenin pathway
Authors: Y-K He
R-H Shu
Y-P Cui
F-H Liu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: FBXO17; hepatocellular carcinoma; prognosis; expression; wnt/Œ≤-catenin pathway
Affiliations: Department of Infectious Disease, Shandong Liaocheng People's Hospital, Liaocheng, China. .

Abstract:  Objective: This study was to investigate the expression of FBXO17 in hepatocellular carcinoma (HCC) and its relationship with clinical HCC features and patient prognosis. Patients and methods: The expression of FBXO17 at mRNA level and protein level in tumor tissues and paracancerous tissues of 45 patients with HCC was respectively detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Besides, FBXO17 expression and its pathological characteristics of HCC, as well as the prognosis of patients, were also analyzed. Then, the expression level of FBXO17 in HCC cell lines was further verified using qRT-PCR assay. In addition, FBXO17 overexpression and knockdown models were constructed using lentivirus in HCC cell lines including Bel-7402 and HepG2. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EDU), cell clone experiment, flow cytometry, and transwell assay were used to explore the effect of FBXO17 on the biological function of HCC cells. Finally, whether FBXO17 could exert its biological characteristics through wnt/Œ≤-catenin pathway was determined. Results: Results showed that FBXO17 expression in tumor tissues of HCC patients was markedly higher than that in adjacent tissues. Meanwhile, compared with patients with low FBXO17 expression, the pathological grade was higher and the overall survival rate was lower in patients with high expressed FBXO17. In vitro experiments showed that the cell proliferation and metastasis ability in the Anti-FBXO17 group was markedly decreased, and the apoptosis was significantly enhanced compared with the NC group. In contrast, overexpression of FBXO17 markedly increased cell proliferation and metastasis ability while decreased cell apoptosis. Finally, Western blot results indicated that silencing FBXO17 might function through downregulating the expression of proteins in wnt/Œ≤-catenin pathway such as c-Myc, MMP-9, and MMP-2 while upregulating GSK-3Œ≤ level, thereby promoting the malignant progression of HCC. Conclusions: FBXO17 was significantly increased in tumor tissues of HCC patients, which was significantly associated with pathological stage and poor prognosis of these patients. In addition, FBXO17 might promote the malignant progression of HCC by inhibiting wnt/Œ≤-catenin pathway. 

Retracted: No

PubPeer comments:
 Figure 5. * Red boxes: The CNP (100 ug ml) and CNP-L (100 ug ml) panels appear to look the same. In addition, the green signal in the merged panel of CNP (200 ug ml) also looks similar.  ,
IQ discrepancy differentiates levels of fine motor skills and their relationship in children with autism spectrum disorders
Authors: Tzu-Ying Yu
Julie Chi Chow
Kuan-Lin Chen
Chien-Ho Lin
Willy Chou
Li-Chen Tung
Journal: Neuropsychiatric disease and treatment (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: autistic disorder; child; intelligence discrepancy; motor development.
Affiliations: Department of Occupational Therapy, College of Medicine, I-Shou University, Kaohsiung., Department of Physical Medicine and Rehabilitation, Chi-Mei Medical Center., Department of Recreation and Health Care Management, Cha Nan University of Pharmacy and Science., Department of Pediatrics., Department of Psychiatry, Chi Mei Medical Center, Tainan., Department of Physical Medicine and Rehabilitation, Da Chien General Hospital, Miaoli., Department of Occupational Therapy, College of Medicine, National Cheng Kung University., Department of Physical Medicine and Rehabilitation, National Cheng Kung University Hospital, Tainan, Taiwan.

Abstract:  Purpose: We investigated 1) the impact of differences in intelligence quotient discrepancy (IQD) on motor skills of preschool-aged children with autism spectrum disorders (ASD); 2) the relationships between IQD and motor skills in preschool-aged children with ASD. Methods: A total of 127 ASD preschool-aged children were divided into three groups according to the size of the IQD: IQD within 1 standard deviation (1SD; EVENIQ; n=81), discrepantly higher verbal intelligence quotient (VIQ; n=22; VIQ&gt;performance intelligence quotient [PIQ] above 1SD [‚â?5 points]), and discrepantly higher PIQ (n=24; PIQ&gt;VIQ above 1SD [‚â?5 points]). Children's IQD and motor skills were determined with the Wechsler Preschool and Primary Scale of Intelligence‚Ñ?- Fourth Edition and the motor subtests of the Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT), respectively. Results: One-way analysis of variance revealed significant group differences for the fine motor domain of the CDIIT and the visual-motor coordination subtest (F=3.37-4.38, p&lt;0.05). Children with discrepantly higher PIQ were associated with better fine motor skills than were children with even IQD and those with discrepantly higher VIQ, and vice versa. IQD (PIQ - VIQ) had significant positive correlations with the fine motor domain and fine motor subtests of the CDIIT (r=0.18-0.29, p&lt;0.05). Conclusion: The IQD can identify different levels of fine motor skills in preschool-aged children with ASD. This study suggests important implications for clinicians, therapists, and researchers: discrepantly higher PIQ could be related to better visual-motor coordination, and discrepantly higher VIQ could be related to poor visual-motor coordination. Furthermore, the results support that when therapists are working with preschool-aged children with ASD who are developing fine motor skills or undertaking fine motor tasks related to visual-motor coordination, they may need to pay attention to the children's IQD. 

Retracted: No

PubPeer comments:
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Influence of nonprotective autophagy and the autophagic switch on sensitivity to cisplatin in non-small cell lung cancer cells
Authors: Jingwen Xu
Nipa H Patel
David A Gewirtz
Yingliang Wu
Santiago Lima
Tareq Saleh
Journal: Biochemical Pharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Autophagic switch; Autophagy; Cisplatin; Drug resistance; Drug sensitivity
Affiliations: Departments of Pharmacology, Toxicology and Medicine and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA., School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China., Department of Basic Medical Sciences, Faculty of Medicine, The Hashemite University, Zarqa, Jordan., Department of Biology, Virginia Commonwealth University, Richmond, VA, USA., Departments of Pharmacology, Toxicology and Medicine and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: .

Abstract:  While therapy-induced autophagy is conventionally conceived to be cytoprotective in nature, previous studies have identified multiple functions of autophagy, including a nonprotective form, as well as the existence of a switch between the different forms of autophagy. The current work provides further evidence of an autophagic switch, in this case in response to the antitumor drug, cisplatin, in non-small cell lung cancer cells that are either wild-type (p53wt) or functionally null in p53 (crp53), the latter generated using CRISPR/Cas9 technology. Pharmacological and genetic inhibition of autophagy identified nonprotective autophagy in p53wt cells and cytoprotective autophagy in crp53 cells. Furthermore, differences in cisplatin sensitivity between the two cell lines proved to be largely a function of the nature of the autophagy. Specifically, autophagy inhibition in the crp53 cells converts the temporal profile for the loss of cell viability in response to cisplatin to essentially parallel that observed in the p53wt cells. This enhanced sensitivity is due to cisplatin-induced apoptosis that occurs without necessitating the restoration of functional p53. In contrast, inhibition of autophagy has no observable impact on the temporal response profile exhibited in response to cisplatin in the p53wt cells, or the extent of cisplatin-induced apoptosis in the p53wt cells, consistent with the functional definition of nonprotective autophagy. Taken together, our current studies provide evidence that nonprotective autophagy in p53wt non-small cell lung cancer cells can be "switched" to protective autophagy in isogenic crp53 cells, and furthermore that inhibition of cytoprotective autophagy is sufficient to restore cisplatin sensitivity in the crp53 cells, largely through the increased promotion of apoptosis, despite the absence of functional p53. 

Retracted: No

PubPeer comments:
 Figure 4E. These two graphs are so similar that I guess the author misplaced one or two there.  ,
Development of in vivo drug-induced neurotoxicity models
Authors: Jos√© Vicente Lafuente
Preeti Menon
Aruna Sharma
Dafin F Muresanu
Hari S Sharma
Z Ryan Tian
Ranjana Patnaik
Journal: Expert Opinion on Drug Metabolism & Toxicology (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: blood‚Äìbrain barrier; brain edema; de-addiction; drug-induced neurotoxicity; nanodelivery of drugs
Affiliations: Uppsala University, University Hospital, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Cerebrovascular Research Laboratory , SE-75185 Uppsala , Sweden.

Abstract:  Introduction: Neurotoxicity caused by diverse psychostimulant drugs, for example, methamphetamine, 3,4-methylenedioxy-methamphetamine, cocaine or morphine is a cause of concern to human populations especially the young generation across the world. These recreational drugs affect brain function severely leading to addiction and brain pathology. Use of psychostimulants may induce breakdown of the blood-brain barrier to serum proteins resulting in adverse brain microenvironment, edema cell injury or eventually neuronal death. Thus, there is an urgent need to find out detailed mechanisms of psychostimulants-induced neurotoxicity in vivo models for suitable therapeutic strategies to induce neuroprotection and also to help de-addiction in clinical situations. Areas covered: In this review, psychostimulants drugs-induced neurotoxicity is discussed in view of recent literature and the financial burden it may pose on our society due to rehabilitation and de-addiction. Furthermore, experimental evidences of drug-induced neuroprotection are also discussed. Expert opinion: Use of in vivo models of neurotoxicity caused by psychostimulants is discussed based on author's own research and to find suitable drugs that could induce neuroprotection including nanodelivery. Furthermore, novel therapeutic agents for de-addiction and reducing neurotoxicity following psychostimulants administration are presented. 

Retracted: No

PubPeer comments:
 Some images in Figure 5 and 12 appear to overlap. If I understand correctly, these are described differently. Red and green boxes. ***  ,
miR-342-5p inhibits expression of Bmp7 to regulate proliferation, differentiation and migration of osteoblasts
Authors: Chuanan Liu
Guisheng Yu
Chuandong Yu
Xuesen Li
Kang Li
Journal: Molecular immunology (2019)
Discipline: IMMUNOLOGY
Keywords: Bmp7; Fracture healing; MEK/ERK; Osteoblasts; microRNA-342-5p.
Affiliations: Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao 266555, Shandong, China., Department of Orthopedics, Heze Municipal Hospital, Heze 274031, Shandong, China., Department of Orthopedics, Heze Municipal Hospital, Heze 274031, Shandong, China. Electronic address: .

Abstract:  Background: Fracture healing is a complex process, and patients with fracture will undergo non-union or compromised regeneration. MicroRNA (miR)-342-5p is a Notch downstream molecule, and its roles in fracture healing remain unclear. We aimed to explore the functional roles of miR-342-5p in osteoblasts as well as the underlying mechanisms. Methods: The expression of miR-342-5p in differentiation of MC3T3-E1 cells or hMSCs was examined by quantitative reverse transcription PCR (qRT-PCR). The effects of aberrantly expressed miR-342-5p on cell proliferation, apoptosis, migration, and expressions of proteins associated with proliferation and osteogenic differentiation were determined by Cell Counting Kit-8, trypan blue staining, flow cytometry, Transwell assay, Western blot and qRT-PCR assays, respectively. The downstream factor and the target genes of miR-342-5p as well as the involvements of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway were finally assessed. Results: miR-342-5p level was decreased during differentiation of MC3T3-E1 cells or hMSCs. After cell transfection, miR-342-5p overexpression significantly reduced cell viability, induced apoptosis, inhibited proliferation, migration and differentiation, and down-regulated Bmp7 expression. Subsequent experiments showed the effects of miR-342-5p inhibition on MC3T3-E1 cells were abrogated by Bmp7 knockdown. Additionally, COL4A6 and Bmp2 were predicated as target genes of miR-342-5p. Finally, phosphorylated levels of MEK and ERK were increased by miR-342-5p inhibition via up-regulating Bmp7 expression. Conclusion: miR-342-5p inhibition promoted proliferation, migration and differentiation of osteoblasts via regulating Bmp7, along with activation of the MEK/ERK pathway. 

Retracted: No

PubPeer comments:
 Figure 1C. Much more similar than you would expect. https: imgur.com neT72gU , 
 Last author appears to be on this journalu2019s editorial board: https: jvi.asm.org content board-editors ,
Cables links Robo-bound Abl kinase to N-cadherin-bound beta-catenin to mediate Slit-induced modulation of adhesion and transcription
Authors: Tim Buchan
Lawrence Zukerberg
Jinseol Rhee
Jack Lilien
Janne Balsamo
Journal: Nature Cell Biology (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Slit; Robo receptor; N-cadherin; Abl tyrosine kinase; Cables
Affiliations: Department of Biological Sciences, The University of Iowa, Iowa City, Iowa 52242-1324, USA.

Abstract:  Binding of the secreted axon guidance cue Slit to its Robo receptor results in inactivation of the neural, calcium-dependent cell-cell adhesion molecule N-cadherin, providing a rapid epigenetic mechanism for integrating guidance and adhesion information. This requires the formation of a multimolecular complex containing Robo, Abl tyrosine kinase and N-cadherin. Here we show that on binding of Slit to Robo, the adaptor protein Cables is recruited to Robo-associated Abl and forms a multimeric complex by binding directly to N-cadherin-associated beta-catenin. Complex formation results in Abl-mediated phosphorylation of beta-catenin on tyrosine 489, leading to a decrease in its affinity for N-cadherin, loss of N-cadherin function, and targeting of phospho-Y489-beta-catenin to the nucleus. Nuclear beta-catenin combines with the transcription factor Tcf/Lef and activates transcription. Thus, Slit-induced formation of the Robo-N-cadherin complex results in a rapid loss of cadherin-mediated adhesion and has more lasting effects on gene transcription. 

Retracted: No

PubPeer comments:
 Figures 2A and S3D: * Red boxes: Two panels that appear to show different experiments might overlap. Legend Figure 2A: E8 cells were plated on 24-well plates coated with NCD-2. After 2 h in culture, CdkP or control peptide were added to wells with or without Slit. Legend Figure S3D: E8 neural retina cells were plated on 24-well plates coated with anti-N-cadherin antibody NCD- 2. After approximately 2h, Roscovitine was added to some wells and the cultures kept overnight at 37 u030aC in a humidified incubator. The cells were then examined and photographed and representative fields of cultures with (Rosco) or without (Co) Roscovitine are shown.  , 
 Figure 4C: * Cyan boxes: Two panels that appear to show different experiments might overlap.  ,
Protein tyrosine phosphatase-like A regulates myoblast proliferation and differentiation through MyoG and the cell cycling signaling pathway
Authors: Xiangsheng Yang
Dacheng He
Jiang Chang
Xi Lin
Robert J Schwartz
Qi Li
Yanlin Ma
Shuang Cui
Xia Lin
Journal: Molecular and Cellular Biology (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PTPLa; myogenesis; myoblast; differentiation; MyoG
Affiliations: Texas A&M Health Science Center, Institute of Biosciences and Technology, Houston, Texas, USA., Texas A&amp;M Health Science Center, Institute of Biosciences and Technology, Houston, Texas, USA, Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Affiliated Hospital of Hainan Medical College, Hainan, China, Beijing Normal University, Beijing, China, Surgery/General Surgery Division, Baylor College of Medicine, Houston, Texas, USA, Biology and Biochemistry Department, University of Houston, Houston, Texas, USA

Abstract:  Protein tyrosine phosphatase-like A (PTPLa) has been implicated in skeletal myogenesis and cardiogenesis. Mutations in PTPLa correlated with arrhythmogenic right ventricular dysplasia in humans and congenital centronuclear myopathy with severe hypotonia in dogs. The molecular mechanisms of PTPLa in myogenesis are unknown. In this report, we demonstrate that PTPLa is required for myoblast growth and differentiation. The cells lacking PTPLa remained immature and failed to differentiate into mature myotubes. The repressed MyoG expression was responsible for the impaired myoblast differentiation. Meanwhile, impeded cell growth, with an obvious S-phase arrest and compromised G(2)/M transition, was observed in PTPLa-deficient myoblasts. Further study demonstrated that the upregulation of cyclin D1 and cyclin E2 complexes, along with a compromised G(2)/M transition due to the decreased CDK1 (cyclin-dependent kinase 1) activity and upregulated p21, contributed to the mutant cell S-phase arrest and eventually led to the retarded cell growth. Finally, the transcriptional regulation of the PTPLa gene was explored. We identified PTPLa as a new target gene of the serum response factor (SRF). Skeletal- and cardiac-muscle-specific SRF knockouts resulted in significant decreases in PTPLa expression, suggesting a conserved transcriptional regulation of the PTPLa gene in mice. 

Retracted: No

PubPeer comments:
 This paper was part of a structured search of articles published in Molecular and Cellular Biology, which was published here: https: mcb.asm.org content 38 20 e00309-18.long Here are the findings, both of which were addressed with a Correction in 2017, found here: https: mcb.asm.org content 37 16 e00236-17.long * Figure 2C:  *The WT panel was accidently chosen from the control group.* Here is how I marked Figure 2C and reported it to the journal:  * Figure 8:  *Fig. 8D: The GAPDH panel is erroneous. The corrected panel should appear as shown below.* Here is the original Figure 8, in which I marked the duplication with cyan boxes:  ,
MiR-506 Targets UHRF1 to Inhibit Colorectal Cancer Proliferation and Invasion via the KISS1/PI3K/NF-Œ∫B Signaling Axis
Authors: Ji Gao
Shaoqin Chen
Yisu Liu
Yan Zheng
Suyong Lin
Yilin Lin
Zhihua Chen
Journal: Frontiers in Cell and Developmental Biology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CRC; UHRF1; invasion; miR-506; proliferation.
Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China., School of Nursing, Fujian Medical University, Fuzhou, China.

Abstract:  Background: The UHRF1 gene is an epigenetic modification factor that mediates tumor suppressor gene silencing in a variety of cancers. Related studies have reported that UHRF1 can inhibit the expression of the KISS1 gene. However, the regulatory mechanism underlying UHRF1 expression in colorectal cancer (CRC) is still unclear. The aim of this study was to gain a better understanding of the regulation of UHRF1 expression in CRC and to determine whether it regulates the mechanism by which KISS1 promotes CRC metastasis. Methods: In the present study, the levels of miR-506, UHRF1 and KISS1 expression in CRC tissues and in human CRC cell lines were studied using quantitative real-time PCR (qRT-PCR) and Western blotting. Cell proliferation, migration, and invasion assays are used to detect cell proliferation, migration, and invasion. A dual-luciferase reporter system was used to confirm the target gene of miR-506. Results: This study found that UHRF1 protein is highly expressed in CRC tissues and negatively correlated with KISS1 protein expression. UHRF1 overexpression activates the PI3K/NF-Œ∫B signaling pathway by inhibiting the mRNA expression levels of pathway mediators. Bioinformatics analysis and luciferase reporter gene assays confirmed that miR-506 targets UHRF1. Conclusion: This study identified the regulation of UHRF1 expression in CRC and the mechanism of CRC metastasis. UHRF1 may be a new potential target molecule for future CRC metastasis treatment. 

Retracted: No

PubPeer comments:
 Figure 8C. * Pink boxes: Two panels appear to overlap.  , 
 Figure 4A and 7A. * Yellow boxes: A panel in Figure 4A appears to overlap with a panel in Figure 7A. Shown for the DAPI photos but also true for the EdU and Merge images. * Orange boxes: Two DAPI (and Edu, not marked) panels in Figure 7A appear to look similar.  , 
 #2 Dear Elisabeth M Bikuff1a After comparing the data, we found that figure4A and all the statistics are correct. But in figure7 (miR-506+UHRF1) we made the same mistake as figure8. In figure7A (sw480), the two pictures are the same, which is caused by copy and paste errors in the editing process. Thank you very much for discovering this error. We will contact the editor for correction as soon as possible. #1 Dear Elisabeth M Bikuff1a Thank you very much for carefully reviewing our article. After checking the data, we found that in figure8 (NF-u03baB), we opened the folder by mistake when editing the picture in the AI software. Thank you very much for discovering this error. We will contact the editor for correction as soon as possible. ,