PReD-Bench/PRed-Bench huggingface dataset:
The root bark of Paeonia moutan is a potential anticancer agent in human oral squamous cell carcinoma cells
Authors: Chunnan Li
Kazunaga Yazawa
Satoru Shintani
Seiji Kondo
Yoshiki Mukudai
Takaaki Kamatani
Yuji Kurihara
Daisuke Sato
Journal: Anticancer research (2012)
Discipline: CLINICAL MEDICINE
Keywords: complementary medicine; alternative medicine; anticancer drugs; Chinese medicinal herbs; Paeonia moutan
Affiliations: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.

Abstract:  Currently there is growing use of complementary and alternative anticancer medicines worldwide, and considerable interest in finding anticancer drugs among Chinese medicinal herbs. The aim of this study was to determine the antitumor activity of the root bark of Paeonia moutan (RBPM) in human squamous cell carcinoma (OSCC) cells. Cell lines derived from human oral squamous cell carcinoma (HSC2, 3, 4, SAS) were tested with different concentrations of RBPM (1-100 μg/ml) using a series of in vitro assay systems. RBPM at a concentration of 100 μg/ml inhibited monolayer and anchorage-independent growth, and interrupted coordinated migration. RBPM activated the phosphorylation of extracellular signal-regulated kinase (ERK) and serine/threonine kinase AKT in 30 min; then, at a later stage (after 6 hours) exhibited potent cytostatic, pro-apoptotic effects through the down-regulation of the expression of cyclin-dependent kinase 4 and its partner cyclin D1, and poly(ADP-ribose) polymerase cleavage. We found direct evidence that RBPM induces apoptotic cell death via DNA fragmentation. Taken together, the antitumor activity of RBPM was demonstrated through antiproliferative and apoptotic effects. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have a repeated image. *** ![file] ,
A physically-modified saline suppresses neuronal apoptosis, attenuates tau phosphorylation and protects memory in an animal model of Alzheimer's disease
Authors: Richard Watson
Supurna Ghosh
Arundhati Jana
Khushbu K Modi
Kalipada Pahan
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Alzheimer's disease; neuritic plaques; neurofibrillary tangles; apoptosis; tau phosphorylation
Affiliations: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, United States of America., Revalesio Corporation, Tacoma, Washington, United States of America.

Abstract:  Alzheimer's disease (AD), the leading cause of dementia in the aging population, is characterized by the presence of neuritic plaques, neurofibrillary tangles and extensive neuronal apoptosis. Neuritic plaques are mainly composed of aggregates of amyloid-β (Aβ) protein while neurofibrillary tangles are composed of the hyperphosphorylated tau protein. Despite intense investigations, no effective therapy is currently available to halt the progression of this disease. Here, we have undertaken a novel approach to attenuate apoptosis and tau phosphorylation in cultured neuronal cells and in a transgenic animal model of AD. RNS60 is a 0.9% saline solution containing oxygenated nanobubbles that is generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. In our experiments, fibrillar Aβ1-42, but not the reverse peptide Aβ42-1, induced apoptosis and cell death in human SHSY5Y neuronal cells. RNS60, but not NS (normal saline), RNS10.3 (TCP-modified saline without excess oxygen) or PNS60 (saline containing excess oxygen without TCP modification), attenuated Aβ(1-42)-induced cell death. RNS60 inhibited neuronal cell death via activation of the type 1A phosphatidylinositol-3 (PI-3) kinase-Akt-BAD pathway. Furthermore, RNS60 also decreased Aβ(1-42)-induced tau phosphorylation via (PI-3 kinase-Akt)-mediated inhibition of GSK-3β. Similarly, RNS60 treatment suppressed neuronal apoptosis, attenuated Tau phosphorylation, inhibited glial activation, and reduced the burden of Aβ in the hippocampus and protected memory and learning in 5XFAD transgenic mouse model of AD. Therefore, RNS60 may be a promising pharmaceutical candidate in halting or delaying the progression of AD. 

Retracted: No

PubPeer comments:
 June 2017 correction:  In Fig 9B, the images in row Tg-FADX are incorrectly duplicates of the images in row Tg+NS, due to an error during preparation of the figure. Here is the original Figure 9B, with the duplication marked. Reported in October 2015. I thank the authors for correcting this error. ![file] ,
CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms
Authors: Ailin Lepletier
William C Dougall
Kyohei Nakamura
Mark J Smyth
Amelia Roman Aguilera
Matthias Braun
Tobias Bald
Jing Liu
Kazuyoshi Takeda
Steven W Lane
Indrajit Das
Michele Wl Teng
Venkateswar Addala
Deborah Barkauskas
Xian-Yang Li
Sebastien Jacquelin
Kimberley Stannard
Journal: Journal of Clinical Investigation (2018)
Discipline: CLINICAL MEDICINE
Keywords: Cancer immunotherapy; Immunology.
Affiliations: Immunology in Cancer and Infection Laboratory and., Medical Genomics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Division of Cell Biology, Biomedical Research Center and Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo, Japan., Gordon and Jessie Gilmour Leukaemia Research Laboratory, Immunology Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia., School of Medicine, The University of Queensland, Herston, Queensland, Australia., Cancer Immunoregulation and Immunotherapy and., Immuno-oncology Discovery, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.

Abstract:  Critical immune-suppressive pathways beyond programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) require greater attention. Nectins and nectin-like molecules might be promising targets for immunotherapy, since they play critical roles in cell proliferation and migration and exert immunomodulatory functions in pathophysiological conditions. Here, we show CD155 expression in both malignant cells and tumor-infiltrating myeloid cells in humans and mice. Cd155-/- mice displayed reduced tumor growth and metastasis via DNAM-1 upregulation and enhanced effector function of CD8+ T and NK cells, respectively. CD155-deleted tumor cells also displayed slower tumor growth and reduced metastases, demonstrating the importance of a tumor-intrinsic role of CD155. CD155 absence on host and tumor cells exerted an even greater inhibition of tumor growth and metastasis. Blockade of PD-1 or both PD-1 and CTLA4 was more effective in settings in which CD155 was limiting, suggesting the clinical potential of cotargeting PD-L1 and CD155 function. 

Retracted: Yes

PubPeer comments:
 Retracted [15 March 2022] . ----------------- QIMR Berghofer Medical Research Institute recently notified the JCI of concerns regarding Figures 4I and 7A and indicated that an independent panel investigation concluded that these figures contain data fabricated by Mark Smyth. In accordance with the institutional recommendation, the JCI is retracting this article. Amelia Roman Aguilera, Matthias Braun, Ailin Lepletier, and Kyohei Nakamura have agreed with the Journalu2019s decision to retract the paper. The remaining authors abstained from commenting or could not be reached. ------------------------------- For background, see https: retractionwatch.com 2021 11 22 highly-cited-cancer-immunologist-seriously-breached-research-conduct-code-australia-institute ,
Halloysites modified polyethylene glycol diacrylate/thiolated chitosan double network hydrogel combined with BMP-2 for rat skull regeneration
Authors: Qi-Bin Sun
Qin-Jun Meng
Hua-Zheng Qu
Wen-Qiang Li
Chang-Peng Xu
Journal: Artificial Cells Nanomedicine and Biotechnology (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: BMP-2; Polyethylene glycol diacrylate; bone regeneration; halloysites; thiolated chitosan.
Affiliations: Department of Spine and Joint Surgery, The Third People’s Hospital of Jinan, Jinan, Shandong, People’s Republic of China, Department of Orthopaedics, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, P.R. China, Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, China

Abstract:  Hydrogel serve as bone tissue engineering have lately received great attention for their good biocompatibility and structures similar to natural extracellular matrices. However, a single component polymer hydrogel is generally detrimental to cell adhesion due to the weaker mechanical properties, which limits their application considerably. In an effort to overcome this disadvantage, we adopt an unconventional dual network hydrogels consisting of the polyethylene glycol diacrylate (PEGDA) covalent network, a thiolated chitosan (TCS) ion crosslinking network and thiolated halloysites (T-HNTs) as reinforcing filler. In addition, bone morphogenetic protein-2 (BMP-2) was loaded into the prepared dual network (DN) hydrogel to improve the bone regeneration function of the DN hydrogel. The resulting PEGDA/TCS/T-HNTs hydrogels showed favourable mechanical property, higher crosslinking density, the lower swelling degree, excellent biocompatibility and cell adhesion ability. The histomorphometric and immunohistochemical analyses revealed the excellent bone regeneration ability for composite hydrogel after implant into rat skull defect. Thus, our results indicated that composite scaffold can be applied as a new bone regeneration biomaterial to be applied as a local drug delivery system with good bone induction performance. 

Retracted: No

PubPeer comments:
 In Figure 4b,c, a micrograph has been duplicated, modified and presented as something else. ![file] ,
Dihydromyricetin activates AMP-activated protein kinase and P38(MAPK) exerting antitumor potential in osteosarcoma
Authors: Xian-biao Xie
Qiang Jia
Jingnan Shen
Jun-qiang Yin
Tiebang Kang
Yongqian Wang
Changye Zou
Guohui Song
Man-si Wu
Jin Wang
Yuanzhong Wu
Jinchang Lu
Qinglian Tang
Zhiqiang Zhao
Journal: Cancer Prevention Research (2014)
Discipline: CLINICAL MEDICINE
Keywords: osteosarcoma; dihydromyricetin; antitumor activity; chemotherapy resistance; AMPKα
Affiliations: Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University;, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou; and., The Institute of Biology, Guizhou Academy of Sciences, Guiyang, China  ., Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University;  .

Abstract:  Numerous patients with osteosarcoma either are not sensitive to chemotherapy or develop drug resistance to current chemotherapy regimens. Therefore, it is necessary to develop several potentially useful therapeutic agents. Dihydromyricetin is the major flavonoid component derived from Ampelopsis grossedentata, which has a long history of use in food and medicine. The present study examined the antitumor activity both in vitro and in vivo without noticeable side effects and the underlying mechanism of action of dihydromyricetin in osteosarcoma cells. We found that dihydromyricetin induced increased p21 expression and G2-M cell-cycle arrest, caused DNA damage, activated ATM-CHK2-H2AX signaling pathways, and induced apoptosis in osteosarcoma cells as well as decreasing the sphere formation capability by downregulating Sox2 expression. Mechanistic analysis showed that the antitumor potential of dihydromyricetin may be due to the activation of AMPKα and p38(MAPK), as the activating AMPKα led to the inactivation of GSK3β in osteosarcoma cells. Moreover, GSK3β deletion or GSK3β inhibition by LiCl treatment resulted in increased p21 expression and reduced Sox2 expression in osteosarcoma cells. Taken together, our results strongly indicate that the antitumor potential of dihydromyricetin is correlated with P38(MAPK) and the AMPKα-GSK3β-Sox2 signaling pathway. Finally, immunohistochemical analysis indicated that some patients had a lower p-AMPK expression after chemotherapy, which supports that the combination of dihydromyricetin and chemotherapy drug will be beneficial for patients with osteosarcoma. In conclusion, our results are the first to suggest that dihydromyricetin may be a therapeutic candidate for the treatment of osteosarcoma. 

Retracted: No

PubPeer comments:
 Figure 2A. More similar than expected. ![file] ,
Inositol pyrophosphates mediate the DNA-PK/ATM-p53 cell death pathway by regulating CK2 phosphorylation of Tti1/Tel2
Authors: Richa Tyagi
M Scott Vandiver
Dorothea Fiedler
Jing Xu
Chenglai Fu
Feng Rao
Solomon H Snyder
Michael A Koldobskiy
James C Barrow
Robert Tokhunts
Jiyoung Cha
Risheng Xu
Roxanne Barrow
Mingxuan Wu
Journal: Molecular Cell (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p53; phosphorylation; PIKKs; TTT; CK2
Affiliations: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Department of Chemistry, Princeton University, Princeton, NJ 08544, USA., Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: .

Abstract:  The apoptotic actions of p53 require its phosphorylation by a family of phosphoinositide-3-kinase-related-kinases (PIKKs), which include DNA-PKcs and ATM. These kinases are stabilized by the TTT (Tel2, Tti1, Tti2) cochaperone family, whose actions are mediated by CK2 phosphorylation. The inositol pyrophosphates, such as 5-diphosphoinositol pentakisphosphate (IP7), are generated by a family of inositol hexakisphosphate kinases (IP6Ks), of which IP6K2 has been implicated in p53-associated cell death. In the present study we report an apoptotic signaling cascade linking CK2, TTT, the PIKKs, and p53. We demonstrate that IP7, formed by IP6K2, binds CK2 to enhance its phosphorylation of the TTT complex, thereby stabilizing DNA-PKcs and ATM. This process stimulates p53 phosphorylation at serine 15 to activate the cell death program in human cancer cells and in murine B cells. 

Retracted: No

PubPeer comments:
 In this article, three cases of data duplication were found. In all cases, micrographs have been duplicated, and presented as something else. Figures affected: Figure 2A,D, 3D and supplemental Figure 1. ![file] , 
 There may be more image overlap in Figure 2D. ![file] ,
MiR-483 suppresses cell proliferation and promotes cell apoptosis by targeting SOX3 in breast cancer
Authors: K Cui
H Zhang
G-Z Wang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-483; breast cancer; cell proliferation; cell apoptosis; SOX3
Affiliations: Department of Pharmacy, Liaocheng Infectious Disease Hospital, Liaocheng, China. .

Abstract:  Objective: To explore the mechanism underlying the effect of microRNA-483 (miR-483) in the progression of breast cancer (BC). Patients and methods: MiR-483 expression was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in both BC cells and tissue samples. The associations between miR-483 expression level and patients' overall survival rate were explored. Furthermore, cell proliferation assay and cell apoptosis assay were conducted, respectively. In addition, Western blot analysis and Luciferase assay were performed to explore the underlying mechanism. Results: The expression level of miR-483 was significantly decreased in tumor samples compared to that in adjacent tissues, which was also associated with patients' overall survival time. Moreover, cell growth was promoted, and cell apoptosis was inhibited after miR-483 was knocked down in vitro. Furthermore, SOX3 acted as a direct target of miR-483, and the expression of SOX3 was negatively correlated with the expression of miR-483 in tumor tissues. Conclusions: These results suggested that miR-483 could suppress BC cell proliferation and promote BC cell apoptosis via targeting SOX3, which might be a potential therapeutic target in BC. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. ,
MiR-93 blocks STAT3 to alleviate hepatic injury after ischemia-reperfusion
Authors: S-Q Zhen
L Xiong
K-H Yu
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: STAT3; miR-93; liver injury; ischemia-reperfusion; apoptosis
Affiliations: Department of Infectious Disease, Clinical Medical College, Hubei University of Science and Technology, Xianning, Hubei, China. .

Abstract:  Objective: Signal transducer and activator of transcription 3 (STAT3) is correlated with ischemia-reperfusion (I-R) injury. The previous studies showed a decreased miR-93 expression after I-R injury of heart or brain organs, but without knowledge in liver tissues. This study aims to investigate effects of MiR-93 on the hepatic injury after ischemia/reperfusion. Materials and methods: Rat liver I-R model was generated. Liver function indexes including alanine transaminase (ALT) and aspartate aminotransferase (AST) were quantified, and serum tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels were quantified. Hepatic tissue apoptosis was measured by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), and expression of microRNA-93 (miR-93), STAT3, and phosphorylated STAT3 (p-STAT3) were measured. Dual luciferase reporter gene assay confirmed targeted relationship between miR-93 and STAT3. Agomir or miR-93 agomir was injected into the peritoneal cavity of I-R model, followed by ALT and AST assays. Serum levels of TNF-α, IL-1β, and IL-6 were measured, followed by TUNEL assay for comparing STAT3 and p-STAT3 expression. Results: Comparing to sham group, I-R group rat showed significantly elevated serum ALT, AST, TNF-α, IL-1β, and IL-6 contents, along with significantly elevated hepatic cell apoptosis, plus decreased miR-93 expression, whilst STAT3 and p-STAT3 expression was enhanced. Intraperitoneal injection of miR-93 agomir significantly decreased STAT3 or p-STAT3 expression, and decreased cell apoptotic rate. Serum levels of ALT, AST, TNF-α, IL-1β, and IL-6 were significantly decreased, accompanied by improved liver function. Conclusions: Hepatic I-R injury is accompanied by miR-93 down-regulation, plus STAT3 up-regulation. Overexpression of miR-93 significantly depressed STAT3 expression in liver I-R injury, alleviated hepatic injury or apoptosis, decreased inflammatory response, and improved liver function. 

Retracted: No

PubPeer comments:
 This paper has features suggestive of [what has elsewhere been labeled as  Papermill #2 ] , characterised by stylised geometrical WBs that are reduced to black blobs on a featureless grey background, reminiscent of a Miro painting: ![file] ![file] Other examples are itemised in a Google document. https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit?usp=sharing One curious feature of this papermill is the frequent disconnect between the name of the putative corresponding author and the email address provided for correspondence. ![file] ,
Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin
Authors: Hui Ouyang
Zhong-Sheng Xia
Tao Yu
Yu Lai
Hong-Sheng Yang
Jie-Yao Li
Ti-Dong Shan
Qi-Kui Chen
Wa Zhong
Journal: PLoS ONE (2015)
Discipline: Multidisciplinary
Keywords: rebamipide; intestinal mucosal damage; nonsteroidal anti-inflammatory drugs; regeneration; aspirin-induced
Affiliations: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.

Abstract:  Background: The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. Methods: BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. Results: COX expression was significantly down-regulated in aspirin induced SII (P &lt; 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P &lt; 0.05). Conclusion: Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin. 

Retracted: No

PubPeer comments:
 Figure 2A appears to have two images which overlap, indicated by red boxes. Green arrows appeared in original manuscript. *** ![file] , 
 Figure 2D appears to have undisclosed splicing in some bands but not in all. I did not see this described in the methods. Could authors explain? *** Contrast enhanced ![file] *** Caption ![file] ,
Flot2 targeted by miR-449 acts as a prognostic biomarker in glioma
Authors: Hui Cheng
Wei Lin
Ying Lin
Shaosong Huang
Shihao Zheng
Yuxing Wen
Shengyue Huang
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: FLOT2; glioma; miR-449; migration and invasion; viability.
Affiliations: Department of Neurosurgery, Fujian Provincial Hospital of Fujian Medical University, Fuzhou, China;, Department of Pathology, Fujian Provincial Hospital of Fujian Medical University, Fuzhou, China

Abstract:  Flotillin-2 (FLOT2) was reported as oncogene and involves in the pathogenic process of several cancers, yet the precise mechanism of FLOT2 in glioma is still limited. In this study, we demonstrated that FLOT2 expression levels were greatly upregulated in glioma tissues and cell lines, and the FLOT2 expression in glioma tissue was markedly associated with tumour stage and size. Overexpression of FLOT2 was correlated with poor prognosis of glioma patients. The functional assay revealed that silenced FLOT2 repressed the viability, migration, and invasion of glioma cells. And then, we detected the relationship between miR-449 and FLOT2. Luciferase reporter assay and Western blot results showed that miR-449 directly binding the 3'UTR sequence of FLOT2 and regulated FLOT2 expression in glioma cells. Finally, we detected the expression levels of miR-449 in glioma tissue and cell lines and found that miR-449 was significantly downregulated in glioma tissues and cell lines. In conclusion, we demonstrated that overexpression FLOT2 was associated with poor prognosis of glioma patients and involved in the progression of glioma, identifying a novel prognostic biomarker and therapeutic target for glioma progression. 

Retracted: Yes

PubPeer comments:
 Figure 2c and d ![file] , 
 Color-reversing the Migration panels and superimposing them on the Invasion panels, the areas of cancellation (where images are identical) are impressively large. ![file] , 
 **Retracted** February 3, 2022 u201cWe, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article: Shaosong Huang, Shihao Zheng, Shengyue Huang, Hui Cheng, Ying Lin, Yuxing Wen Wei Lin (2019) Flot2 targeted by miR-449 acts as a prognostic biomarker in glioma. Artificial Cells, Nanomedicine, and Biotechnology, 47(1), 250u2013255, DOI: 10.1080 21691401.2018.1549062 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unresponsive, and we have been unable to verify their original data. We are therefore retracting this article and the corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. u201c ,
Liposomes encapsulated iridium(III) polypyridyl complexes enhance anticancer activity in vitro and in vivo
Authors: Yi-Ying Gu
Wei-Dong Fei
Miao He
Fan Du
Lin-Lin Yang
Lan Bai
Yun-Jun Liu
Wen-Yao Zhang
Journal: Journal of Inorganic Biochemistry (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cytochrome c; Cytotoxic activity in vivo; Iridium (III) complexes; Liposomes; Microtubules.
Affiliations: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China., Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, PR China., Department of Pediatrics, Guangdong Women and Children Hospital, Guangzhou 510000, PR China. Electronic address: ., School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: .

Abstract:  Three iridium(III) complexes [Ir(ppy)2(CPIP)](PF6) (Ir-1, ppy = 2-phenylpyridine, CPIP = 2-(4-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy)2(DCPIP)](PF6) (Ir-2, DCPIP = 2-(3,4-dichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(ppy)2(TCPIP)](PF6) (Ir-3, TCPIP = 2,3,5-trichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The complexes Ir-1, Ir-2 and Ir-3 were encapsulated in liposomes to form Ir-1-Lipo, Ir-2-Lipo and Ir-3-Lipo. Morphology, size distribution, and zeta potential of liposomes were examined by transmission electron microscopy (TEM) and Zetasizer. The cytotoxic activity in vitro of Ir-1, Ir-2 and Ir-3 against cancer A549, HTC-116, HepG2, BEL-7402, Eca-109, B16, HeLa SGC-7901 and normal NIH3T3 cells was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. Ir-2 and Ir-3 show no cytotoxic activity against the selected cancer cells, and Ir-1 displays moderate cytotoxic effect on the cell growth in A549 cells. However, Ir-1, Ir-2 and Ir-3 were encapsulated in liposomes, the cytotoxic activity was greatly enhanced. In particular, Ir-1-Lipo and Ir-2-Lipo can effectively inhibit the cell growth in A549 cells with a low IC50 value of 3.1 ± 0.3 and 1.2 ± 0.4 μM. The apoptosis was assayed by flow cytometry. Ir-1, Ir-2 and Ir-3 reveal weak apoptotic effect, whereas Ir-1-Lipo, Ir-2-Lipo and Ir-3-Lipo induce an apoptotic percentage of 55.6%, 69.3% and 16.7% in A549 cells, respectively. Specially, in the assay of antitumor activity in vivo, the inhibiting percentage of tumor growth induced by Ir-2 is 27.65%, while inhibiting percentage of tumor growth caused by Ir-2-Lipo is 57.45%. Obviously, the liposomes can enhance anticancer activity in vitro and in vivo compared with the complexes. The results show that the iridium(III) complexes encapsulated liposomes induce apoptosis in A549 cells through ROS-mediated lysosome-mitochondria dysfunction pathway and target the microtubules. 

Retracted: No

PubPeer comments:
 It appears there may be a labeling error in Figure 11. Nr-3-Lipo should be Ir-2-Lipo as shown in legend and Figure 7. *** ![file] ,
Gene 33/RALT is induced by hypoxia in cardiomyocytes, where it promotes cell death by suppressing phosphatidylinositol 3-kinase and extracellular signal-regulated kinase survival signaling
Authors: Dazhong Xu
Thomas Force
Richard D Patten
John M Kyriakis
Journal: Molecular and Cellular Biology (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ischemia; cardiomyocytes; hypoxia; Gene 33; myocardial infarction
Affiliations: Molecular Cardiology Research Institute, Tufts-New England Medical Center, 750 Washington Street, Box 8486, Boston, MA 02111, USA., Molecular Cardiology Research Institute, Tufts-New England Medical Center and Department of Medicine, Tufts University School of Medicine, 750 Washington Street, Boston, Massachusetts, Center for Translational Medicine, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, Pennsylvania 19107

Abstract:  Ischemia in the heart deprives cardiomyocytes of oxygen, triggering cell death (myocardial infarction). Ischemia and its cell culture model, hypoxia, elicit a stress response program that contributes to cardiomyocyte death; however, the molecular components required to promote this process remain nebulous. Gene 33 is a 50-kDa cytosolic adapter protein that suppresses signaling from receptor Tyr kinases of the epidermal growth factor receptor/ErbB family. Here we show that adenoviral expression of Gene 33 swiftly stimulates cardiomyocyte death coincident with reduced Akt and extracellular signal-regulated kinase (ERK) signaling. Subjecting cardiomyocytes to hypoxia and then reoxygenation induces gene 33 mRNA and Gene 33 protein. RNA interference experiments indicate that endogenous Gene 33 reduces Akt and ERK signaling and is required for maximal hypoxia-induced cardiomyocyte death. Gene 33 levels are also strikingly increased in myocardial ischemic injury and infarction. Our results identify a new role for Gene 33 as a component in the molecular pathophysiology of ischemic injury. 

Retracted: No

PubPeer comments:
 Identified by another reader. It appears that the penultimate author is deceased. I have been unable to find a current email address for the last author. *** ![file] ,
Valsartan reduces AT1-AA-induced apoptosis through suppression oxidative stress mediated ER stress in endothelial progenitor cells
Authors: H-Y Xu
Z-C Wang
J Qi
J Li
B Li
L-M Liu
B Liang
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Valsartan; AT1-AA; apoptosis; endothelial progenitor cells; oxidative stress
Affiliations: Shanxi Medical University, Taiyuan, Shanxi, China. .

Abstract:  Objective: Valsartan has been reported to have the function of treating hypertension and improving the prognosis of patients. Many studies indicated that valsartan can also increase angiotensin II, andosterone and plasma renin activity (PRA). Autoantibodies against the angiotensin II type 1 receptor (AT1-AA) have been showed to increase reactive oxygen species (ROS) and calcium (Ca2+) and result in apoptosis in vascular smooth muscle cells. In this study, we attempted to explore the effect of valsartan on AT1-AA-induced apoptosis in endothelial progenitor cells. Materials and methods: Endothelial progenitor cells (EPCs) were cultured. The cytotoxicity was determined by MTT assay. EPCs apoptosis was determined by DAPI staining and flow cytometry. Reactive oxygen species, intracellular calcium concentration and calpain activity were measured using Fluostar Omega Spectrofluorimeter. The expression of p-ERK, p-eIF-2a, CHOP, Bcl-2 and caspase-3 were detected by Western blot. Results: MTT assays showed valsartan significantly inhibited AT1-AA- induced decline of the viability of EPCs. DAPI staining and flow cytometry results indicated valsartan inhibited AT1-AA-induced decline of the viability of EPCs via inhibiting AT1-AA-induced apoptosis. Furthermore, the increasing of reactive oxygen species, intracellular calcium and calpain activity induced by AT1-AA in EPCs were also recovered after pre-treated with valsartan. Meanwhile, the upregulation of p-ERK, p-eIF-2a and CHOP, downregulation of Bcl-2, and activation of Caspase-3 caused by AT1-AA were reversed after pre-incubated with valsartan. Conclusions: Valsartan could inhibit AT1-AA-induced apoptosis through inhibiting oxidative stress mediated ER stress in EPCs. 

Retracted: No

PubPeer comments:
 Figure 2C. * Pink boxes: Four of the six panels shown here look very similar to each other. Yet, the gated percentages differ. ![file] , 
 Figure 4 and 5: * Red boxes: Four lanes in the a-tubulin panel in Figure 4A appear to look very similar to the a-tubulin panel in Figure 5A (legend borrowed from Figure 5B). Note a vertical scratch in the second band from the left. ![file] ,
MicroRNA-338-3p suppresses ovarian cancer cells growth and metastasis: implication of Wnt/catenin beta and MEK/ERK signaling pathways
Authors: Pengcheng Ji
Fang Ren
Wei Feng
Ruitao Zhang
Gailing Li
Yuan Cao
Minghui Zhang
Huirong Shi
Zheying Liu
Journal: Journal of Experimental & Clinical Cancer Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: Growth; MACC1; Met; Metastasis; Ovarian cancer
Affiliations: Department of Gynecology, First Affiliated Hospital, Zhengzhou University, NO.1 East Jianshe Road, Erqi District, Zhengzhou, Henan, 450052, People's Republic of China. ., Department of Gynecology, First Affiliated Hospital, Zhengzhou University, NO.1 East Jianshe Road, Erqi District, Zhengzhou, Henan, 450052, People's Republic of China.

Abstract:  Background: Downregulation of microRNA-338-3p (miR-338-3p) was detected in many malignant tumors, which indicated miR-338-3p might serve as a role of antioncogene in those cancers. The present study aimed to explore the roles of miR-338-3p in the growth and metastasis of ovarian cancer cells and elaborate the underlying possible molecular mechanism. Methods: Multiply biomedical databases query and KEGG pathway enrichment assay were used to infilter possible target genes and downstream pathways regulated by miR-338-3p. Overexpression miR-338-3p lentiviral vectors were transfected into ovarian cancer OVCAR-3 and OVCAR-8 cells, cell proliferation, migration and invasion were analyzed by MTT, colony formation, transwell, Matrigel assay and xenograft mouse model. One 3'-untranslated regions (UTRs) binding target gene of miR-338-3p, MACC1 (MET transcriptional regulator MACC1), and its regulated gene MET and downstream signaling pathway activities were examined by western blot. Results: Biomedical databases query indicated that miR-338-3p could target MACC1 gene and regulate Met, downstream Wnt/Catenin beta and MEK/ERK pathways. Rescue of miR-338-3p could inhibit the proliferation, migration and invasion of ovarian cancer cells, and suppress the growth and metastasis of xenograft tumor. Restoration of miR-338-3p could attenuate MACC1 and Met overexpression induced growth, epithelial to mesenchymal transition (EMT) and activities of Wnt/Catenin beta and MEK/ERK signaling in vitro and in vivo. Conclusions: The present data indicated that restoration of miR-338-3p could suppress the growth and metastasis of ovarian cancer cells, which might due to the inhibition of proliferation and EMT induced by MACC1, Met and its downstream Wnt/Catenin beta and MEK/ERK signaling pathways. 

Retracted: No

PubPeer comments:
 Figure 3 appears to include a repeated image. *** ![file] , 
 Two images in Figure 4a seem to overlap. Reported to journal in October 2021. *** ![file] ,
UCHL1 enhances the malignant development of glioma via targeting GAS2
Authors: H-Z Piao
R Sui
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: UCHL1; glioma; metastasis; expression pattern; GAS2
Affiliations: Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China. .

Abstract:  Objective: To detect the expression pattern of UCHL1 in glioma samples and its influence on the metastasis of glioma, as well as the underlying mechanism. Patients and methods: UCHL1 levels in 42 paired glioma tissues and paracancerous ones were detected. The relationship between UCHL1 level and pathological indexes in glioma patients was analyzed. After establishing UCHL1 knockdown model in U251 and T98-G cells, their migratory ability was assessed by transwell and wound healing assay. At last, Luciferase assay, Western blot and rescue experiments were conducted to explore the role of UCHL1 in aggravating the development of glioma through targeting GAS2. Results: UCHL1 was upregulated in glioma samples than paracancerous ones. High level of UCHL1 indicated high rates of lymphatic metastasis and distant metastasis, as well as low rates of overall survival and progression-free survival in glioma. Knockdown of UCHL1 markedly inhibited migratory ability in glioma cells. GAS2 was the downstream gene of UCHL1. A positive correlation was found between expression levels of UCHL1 and GAS2 in glioma tissues. Overexpression of GAS2 could reverse the inhibitory effects of silenced UCHL1 on migratory ability in glioma cells. Conclusions: UCHL1 level is linked to lymphatic metastasis, distant metastasis and prognosis in glioma patients. It stimulates migratory ability in glioma by positively regulating GAS2 level. 

Retracted: No

PubPeer comments:
 Fig 1  E, Overall survival in glioma patients based on their UCHL1 level. F, Progression-free survival in glioma patients based on their UCHL1 level . ![file] Here superimposed, with the Progression-free survival curves in red. After 45 months, there appear to be more survivors in the Low-UCHL1 half-group **without** progression then there were survivors **with or without** progression. How does that work? ![file] ,
Fragile X mental retardation protein regulates the levels of scaffold proteins and glutamate receptors in postsynaptic densities
Authors: Katrin Falley
Stefan Kindler
Hans-Jürgen Kreienkamp
Dietmar Richter
Janin Schütt
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: fragile X syndrome; FMRP; dendritic spine morphology; RNA-binding protein; postsynaptic protein synthesis
Affiliations: Institute for Human Genetics, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.

Abstract:  Functional absence of fragile X mental retardation protein (FMRP) causes the fragile X syndrome, a hereditary form of mental retardation characterized by a change in dendritic spine morphology. The RNA-binding protein FMRP has been implicated in regulating postsynaptic protein synthesis. Here we have analyzed whether the abundance of scaffold proteins and neurotransmitter receptor subunits in postsynaptic densities (PSDs) is altered in the neocortex and hippocampus of FMRP-deficient mice. Whereas the levels of several PSD components are unchanged, concentrations of Shank1 and SAPAP scaffold proteins and various glutamate receptor subunits are altered in both adult and juvenile knock-out mice. With the exception of slightly increased hippocampal SAPAP2 mRNA levels in adult animals, altered postsynaptic protein concentrations do not correlate with similar changes in total and synaptic levels of corresponding mRNAs. Thus, loss of FMRP in neurons appears to mainly affect the translation and not the abundance of particular brain transcripts. Semi-quantitative analysis of RNA levels in FMRP immunoprecipitates showed that in the mouse brain mRNAs encoding PSD components, such as Shank1, SAPAP1-3, PSD-95, and the glutamate receptor subunits NR1 and NR2B, are associated with FMRP. Luciferase reporter assays performed in primary cortical neurons from knock-out and wild-type mice indicate that FMRP silences translation of Shank1 mRNAs via their 3'-untranslated region. Activation of metabotropic glutamate receptors relieves translational suppression. As Shank1 controls dendritic spine morphology, our data suggest that dysregulation of Shank1 synthesis may significantly contribute to the abnormal spine development and function observed in brains of fragile X syndrome patients. 

Retracted: No

PubPeer comments:
 ![file] The lower two panels of immunoblots in Fig 1C (in blue and red boxes) looks much more similar than expected. Apparently they are of different groups. ,
Baicalin Inhibits Human Cervical Cancer Cells by Suppressing Protein Kinase C/Signal Transducer and Activator of Transcription (PKC/STAT3) Signaling Pathway
Authors: Qianqian Wang
Haiou Xu
Xiaofeng Zhao
Journal: Medical Science Monitor (2018)
Discipline: CLINICAL MEDICINE
Keywords: cervical cancer; baicalin; PKCζ; apoptosis; migration
Affiliations: Department of Gynecology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China (mainland)

Abstract:  BACKGROUND Like other human cancers, the malignancy of cervical cancer is also characterized by abilities of proliferation, migration, and invasion. Protein kinase C-zeta (PKCζ) has been highly correlated with several human cancers. Baicalin was proven to regulate PKC. This study aimed to investigate the anti-cancer effect and involved molecular mechanisms of baicalin on human cervical cancer. MATERIAL AND METHODS Baicalin at various concentrations was used to treat 2 human cervical cancer cell lines HeLa and SiHa. The proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenylterazolium bromide (MTT) assay. The apoptosis was detected by terminal transferase UTP nick end labeling (TUNEL) assay. Wound healing assay and Transwell assay were used to evaluate the migration and invasion respectively. Western blotting was performed to assess the protein expression levels. RESULTS Baicalin administration significantly reduced the viability by facilitating the apoptosis in HeLa and SiHa cells. Baicalin treatment also significantly reduced the wound closure and cell amount invaded as measured by Transwell assay. The expression levels of PKCζ, survivin, matrix metalloproteinase (MMP)2, MMP9 as well as the phosphorylation of signal transducer and activator of transcription (STAT) 3 were reduced in baicalin administrated cervical cancer cells. CONCLUSIONS Baicalin exerted anti-cancer effects on human cervical cancer cells by targeting STAT3 regulated signaling pathways. 

Retracted: No

PubPeer comments:
 There seems to be a duplication in Figure 2. The authors should probably contact the journal to have the correct image uploaded. ![file] ,
Inflammatory myofibroblastic tumor of the thigh without bone involvement: a case report
Authors: Jun Lin
Hao Liu
Yin Zhuang
Yifei Zheng
Peng Yang
Huilin Yang
Yan Yang
Journal: World Journal of Surgical Oncology (2014)
Discipline: CLINICAL MEDICINE
Keywords: Inflammatory myofibroblastic tumors; extremities; bone involvement; Chinese male patient; right thigh
Affiliations: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China. .

Abstract:  Inflammatory myofibroblastic tumors are rare, and those located in the extremities without bone involvement are even rarer. We present the case of a 61-year-old Chinese male patient with an inflammatory myofibroblastic tumor of the right thigh. It was excised and a histopathologic examination revealed an inflammatory myofibroblastic tumor. This case is presented by virtue of its rare location. 

Retracted: No

PubPeer comments:
 There appears to be a repeated image in Figure 3. *** ![file] ,
Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine
Authors: Xiangyu Ke
Tianyi Deng
Shou-Jiang Gao
Qingsong Qin
Yueyan Liao
Journal: Cancers (2020)
Discipline: CLINICAL MEDICINE
Keywords: Epstein–Barr virus (EBV); Tenovin-6; autophagy; chloroquine; gastric cancer
Affiliations: Laboratory of Human Virology and Oncology, Shantou University Medical College, Shantou 515000, Guangdong, China., UPMC Hillman Cancer Center, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Abstract:  Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer death. Approximately 15% of GC is associated with Epstein-Barr virus (EBV). GC is largely incurable with a dismal five-year survival rate. There is an urgent need to identify new therapeutic agents for the treatment of GC. Tenovin-6 was initially identified as a p53 activator, but it was later found to inhibit autophagy flux, and the protein deacetylase activity of sirtuins. Tenovin-6 shows promising therapeutic effect in various malignancies. However, it remains unknown whether Tenovin-6 is effective for GC. In this study, we found that EBV-positive and -negative GC cell lines were sensitive to Tenovin-6 but with different response times and doses. Tenovin-6 suppressed anchorage-independent growth of GC cells. Tenovin-6 induced different levels of apoptosis and phases of cell-cycle arrest depending on the cell lines with some manifesting gap 1 (G1) and others showing synthesis (S) phase cell-cycle arrest. Mechanistically, Tenovin-6 induced autophagy or p53 activation in GC cells depending on the status of TP53 gene. However, initiation of autophagy following treatment with Tenovin-6 conferred some protective effect on numerous cells. Combined treatment with Tenovin-6 and autophagy inhibitor chloroquine increased the cytotoxic effect by inducing microtubule-associated protein 1 light chain 3B (LC3B)-II accumulation, and by enhancing apoptosis and cell-cycle arrest. These results indicated that Tenovin-6 can be used as a potential therapeutic agent for GC, but the genetic background of the cancer cells might determine the response and mechanism of action. Treatment with Tenovin-6 alone or in combination with chloroquine could be a promising therapeutic approach for GC. 

Retracted: No

PubPeer comments:
 This paper is one of a small collection of papers which appears to include a typographical error in the spelling of an manufacturer. The company name is ACEA Biosciences headquartered in San Diego. In this paper and the others, the name is spelled ACEC. This suggests that the paper was written from a common template, although the author groups are mostly different. *** ![file] ,