PReD-Bench/PRed-Bench huggingface dataset:
Albumin-bioinspired iridium oxide nanoplatform with high photothermal conversion efficiency for synergistic chemo-photothermal of osteosarcoma
Authors: Dejian Li
Zhiwei Dong
Tao Zhang
Ziwen Zhao
Bo Jiang
Junsheng Gao
Yi Wang
Wenguang Gu
Hui Liu
Journal: Drug Delivery (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Iridium oxide; biomineralization; bovine serum albumin; photothermal; synergistic therapy.
Affiliations: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, China;, Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China;, Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

Abstract:  Protein-based nanocarriers with inherent biocompatibility have been widely served as building blocks to construct versatile therapeutic nanoplatforms. Herein, bovine serum albumin-iridium oxide nanoparticles (denoted BSA-IrO2 NPs) are successfully synthesized via one-step biomineralization approach. The BSA-IrO2 NPs exhibits uniform size (40 nm), superb biocompatibility and high drug loading capacity for doxorubicin (27.4 wt%). Under near-infrared (NIR) laser irradiation, the as-prepared BSA-IrO2 NPs exhibited high photothermal conversion ability (54.3%) and good photostability. The in vitro drug release experiments displayed pH and NIR laser -triggered DOX release profiles, which could enhance the therapeutic anticancer effect. By utilizing this DOX loaded nanoplatform, effective synergistic chemo-photothermal therapy against human osteosarcoma can be realized, which has been systematically verified both in vitro and in vivo. Notably, in vivo pharmacokinetics studies showed that BSA-IrO2@DOX had prolonged blood circulation time due to the BSA component can improve the stealthiness of the nanoparticles during the blood circulation. Meanwhile, in vitro and in vivo toxicity studies demonstrated that the BSA-IrO2 NPs can act as biocompatible agents for drug delivery and cancer therapy. Therefore, this work presents a biomineralized iridium-based NPs with remarkable features and be used as a very potential therapeutic nanoplatform for cancer treatment. 

Retracted: No

PubPeer comments:
 Too heavy to be Kunming mice. ![file] , 
 #1 Surely Kunming mice have normal immune systems, so a Saos-2 xenograft would be quickly destroyed. ,
LncRNA PART‐1 targets TGFBR2/Smad3 to regulate cell viability and apoptosis of chondrocytes via acting as miR‐590‐3p sponge in osteoarthritis
Authors: Kan Peng
Shouye Hu
Yuanzhen Cai
Zheng Li
Chao Lu
Journal: Journal of Cellular and Molecular Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PART-1; TGFBR2; apoptosis; chondrocytes; miR-590-3p
Affiliations: Department of Joint Surgery, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, China., Department of Emergency, the First Affiliated Hospital of Xi'an Medical University, Xi'an, China.

Abstract:  Osteoarthritis (OA) is a degenerative joint disease that commonly occurs in the elderly. This study focused on apoptosis and explored the modulating effects of long non-coding (lncRNAs) prostate androgen-regulated transcript-1 (PART-1) on chondrocytes apoptosis. In the present study, the PART-1 expression level was down-regulated in the OA cartilages. Silence of PART-1 decreased the cell viability and promoted chondrocytes apoptosis. Overexpression of PART-1 could reverse the effects induced by interleukin 1β (IL-1β) stimulation, thus slowing down the apoptosis rate. MiR-590-3p was found to be the potential target, and RNA immunoprecipitation and luciferase activity assay confirmed the binding between PART-1 and miR-590-3p. Moreover, miR-590-3p was down-regulated by PART-1 and was negatively associated with PART-1. Transforming growth factor-beta receptor type 2 (TGFBR2) was positively associated with PART-1. Down-regulation of PART-1 decreased cell viability and induced cell apoptosis, which was partially reversed by miR-590-3p silence or TGFBR2 overexpression; while overexpression of PART-1 increased the cell viability and decreased the caspase 3 activity and apoptotic rates, and the effects were partially attenuated by miR-590-3p overexpression or silence of TGFBR2 in IL-1β-stimulated chondrocytes. Knock-down of PART-1 down-regulated both Smad3 and p-Smad3 protein levels, which was reversed by miR-590-3p inhibition or TGFBR2 overexpression. Smad3 expression level was lower in the OA group than that in the normal group and was positively associated with the PART-1 expression level. Collectively, the study revealed that lncRNA PART-1 regulates the apoptosis of chondrocytes in OA by acting as a sponge for miR-590-3p, which subsequently regulates TGFBR2/Smad3 signalling. 

Retracted: No

PubPeer comments:
 Concern about the flow cytometry images of Figure 2D 2J. Even with the provided low resolution, several groups of dots appear to be visible multiple times within or across different panels. I have highlighted some of these groups by boxes of the same color. Of course, the authors could take away any concerns by showing the original, raw, FACS files. ![file] ,
scFv6.C4 DNA vaccine with fragment C of Tetanus toxin increases protective immunity against CEA-expressing tumor
Authors: Bianca Ferrarini Zanetti
Sang Won Han
José Ronnie Carvalho de Vasconcelos
Camila Pontes Ferreira
Journal: Gene Therapy (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: carcinoembryonic antigen; DNA vaccine; Tetanus Toxin; adjuvant; immune response
Affiliations: Research Center for Gene Therapy, Escola Paulista de Medicina, Universidade Federal de São Paulo Rua Mirassol, 207 CEP 04044-010, São Paulo, SP, Brazil., Department of Microbiology, Immunology, and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo Rua Botucatu, 862 CEP 04023-062, São Paulo, SP, Brazil., Research Center for Gene Therapy, Escola Paulista de Medicina, Universidade Federal de São Paulo Rua Mirassol, 207 CEP 04044-010, São Paulo, SP, Brazil. .

Abstract:  The carcinoembryonic antigen (CEA) is the main tumor-associated antigen of colorectal cancers. Previously, we developed a DNA vaccine using scFv6.C4, a CEA surrogate, against CEA-expressing tumors; 40% of the vaccinated mice were tumor-free after tumor challenge. In order to enhance vaccine efficacy, fragment C of Tetanus Toxin (FrC) was tested as adjuvant. C57BL/6J-CEA2682 mice were electroporated intramuscularly 4 times with uP-PS/scFv6.C4-FrC or uP-PS/scFv6.C4, challenged by s.c. injection of 1 × 105 MC38-CEA cells, and tumor growth was monitored over 100 days. The humoral and cellular immune responses were assessed by ELISA, immunocytochemistry, in-vitro lymphocyte proliferation, and CTL cytotoxicity assays. Immunization with uP-PS/scFv6.C4-FrC or uP-PS/scFv6.C4 induced similar anti-CEA antibody titers. However, immunocytochemistry analysis showed stronger staining with uP-PS/scFv6.C4-FrC-immunized mice sera. When challenged with MC38-CEA cells, 63% of the FrC-vaccinated mice did not develop tumors, half of the rest had a significant tumor growth delay, and the probability of being free of tumors was on average 40% higher than that of scFv6.C4-immunized mice. Addition of the adjuvant led to higher CD4+ and CD8+ proliferative responses and strong CD8+ CTL response against MC38-CEA cells. DNA immunization with scFv6.C4 and FrC increased antitumor effect via induction of high and specific humoral and cellular immune responses to CEA. 

Retracted: No

PubPeer comments:
 Figure 5A. Splice upper panel, no obvious splice lower panel. https: imgur.com SEpTCWh ,
c-Jun inhibits thapsigargin-induced ER stress through up-regulation of DSCR1/Adapt78
Authors: Jun Ren
M Fatima Leite
Jinxia Xu
Agnes S Kim
Ji Li
Peng Zhao
Xiaoyan Xiao
Xinglei Zhu
Journal: Experimental Biology and Medicine (2008)
Discipline: CLINICAL MEDICINE
Keywords: Endoplasmic reticulum; ER stress; unfolded protein response; c-Jun N-terminal kinase; transcription factors
Affiliations: School of Pharmacy, University of Wyoming, Laramie, WY 82071, USA., Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; Department of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, Dept 3375, School of Pharmacy, University of Wyoming, Laramie, Wyoming 82071; Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520; and Department of...

Abstract:  The endoplasmic reticulum (ER) is exquisitely sensitive to changes in its internal environment. Various conditions, collectively termed "ER stress", can perturb ER function, leading to the activation of a complex response known as the unfolded protein response (UPR). Although c-Jun N-terminal kinase (JNK) activation is nearly always associated with cell death by various stimuli, the functional role of JNK in ER stress-induced cell death remains unclear. JNK regulates gene expression through the phosphorylation and activation of transcription factors, such as c-Jun. Here, we investigated the role of c-Jun in the regulation of ER stress-related genes. c-Jun expression levels determined the response of mouse fibroblasts to ER stress induced by thapsigargin (TG, an inhibitor of sarco/endoplasmic reticulum Ca(2+) ATPase). c-jun(-/-) mouse fibroblast cells were more sensitive to TG-induced cell death compared to wild-type mouse fibroblasts, while reconstitution of c-Jun expression in c-jun(-/-) cells (c-Jun Re) enhanced resistance to TG-induced cell death. The expression levels of ER chaperones Grp78 and Gadd153 induced by TG were lower in c-Jun Re than in c-jun(-/-) cells. Moreover, TG treatment significantly increased calcineurin activity in c-jun(-/-) cells, but not in c-Jun Re cells. In c-Jun Re cells, TG induced the expression of Adapt78, also known as the Down syndrome critical region 1 (DSCR1), which is known to block calcineurin activity. Taken together, our findings suggest that c-Jun, a transcription factor downstream of the JNK signaling pathway, up-regulates Adapt78 expression in response to TG-induced ER stress and contributes to protection against TG-induced cell death. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,
A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a proliferation-specific manner
Authors: Karl Agger
Sergio Oddi
Elena Prosperini
Kristian Helin
M Cristina Moroni
Peter Steensgaard
Peter Cartwright
Claire Attwooll
Claude Sardet
Christian Wagener
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: E2F6; PcG; complexes; DNA; repressive
Affiliations: European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, Milan, 20141, Italy.

Abstract:  The transcriptional repressor E2F6 has been identified as a component of two distinct polycomb group protein (PcG)-containing complexes, suggesting a mechanism for the recruitment of repressive complexes to target sequences in DNA. Whereas one complex is involved in the repression of classic E2F target genes in G0, a role for E2F6 within the cell cycle has yet to be defined. We searched for novel E2F6-binding proteins using a yeast two-hybrid screen and identified the PcG protein, EPC1. We showed that, both in vitro and in vivo, E2F6, DP1, and EPC1 form a stable core complex with repressive activity. Furthermore, we identified the proliferation-specific PcG, EZH2, as an EPC1-interacting protein. Using affinity purification, we showed that E2F6, DP1, EPC1, EZH2, and Sin3B co-elute, suggesting the identification of a novel E2F6 complex that exists in vivo in both normal and transformed human cell lines. EZH2 is required for cellular proliferation and consistent with this, EZH2 elutes with the E2F6-EPC1 complex only in proliferating cells. Thus we have identified a novel E2F6-PcG complex (E2F6-EPC1) that interacts with EZH2 and may regulate genes required for cell cycle progression. 

Retracted: No

PubPeer comments:
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 Figure 5B. ![file] , 
 ![file] , 
 ![file] ,
Melatonin Suppresses the Expression of 45S Preribosomal RNA and Upstream Binding Factor and Enhances the Antitumor Activity of Puromycin in MDA-MB-231 Breast Cancer Cells
Authors: Eun Jung Sohn
Yong Koo Park
Bonglee Kim
Hyo-Jeong Lee
Miyong Yun
Deok-Beom Jung
Duckgue Lee
Ji-Hyun Kim
Eun Ah Shin
Sung-Hoon Kim
Ji Hoon Jung
Journal: Evidence-based Complementary and Alternative Medicine (2013)
Discipline: CLINICAL MEDICINE
Keywords: ribosome biogenesis; melatonin; puromycin; apoptosis; MDA-MB-231
Affiliations: College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea., College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea, College of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea

Abstract:  Since the dysregulation of ribosome biogenesis is closely associated with tumor progression, in the current study, the critical role of ribosome biogenesis related signaling was investigated in melatonin and/or puromycin induced apoptosis in MDA-MB-231 breast cancer cells. Despite its weak cytotoxicity, melatonin from 3 mM attenuated the expression of 45S pre-ribosomal RNA (pre-rRNA), UBF as a nucleolar transcription factor, and fibrillarin at mRNA level and consistently downregulated nucleolar proteins such as UBF and fibrillarin at protein level in MDA-MB-231 cells. Furthermore, immunofluorescence assay revealed that UBF was also degraded by melatonin in MDA-MB-231 cells. In contrast, melatonin attenuated the expression of survival genes such as Bcl-xL, Mcl-1, cyclinD1, and cyclin E, suppressed the phosphorylation of AKT, mTOR, and STAT3, and cleaved PARP and activated caspase 3 only at a high concentration of 12 mM. However, combined treatment of melatonin (3 mM) and puromycin (1 μM) synergistically inhibited viability, attenuated the expression of 45S pre-rRNA and UBF, and consistently downregulated UBF, XPO1 and IPO7, procaspase 3, and Bcl-xL in MDA-MB 231 cells. Overall, these findings suggest that melatonin can be a cancer preventive agent by combination with puromycin via the inhibition of 45S pre-rRNA and UBF in MDA-MB 231 breast cancer cells. 

Retracted: No

PubPeer comments:
 bands look similar ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
MicroRNA-21 Mediates Isoflurane-induced Cardioprotection against Ischemia–Reperfusion Injury via Akt/Nitric Oxide Synthase/Mitochondrial Permeability Transition Pore Pathway
Authors: Yasheng Yan
Jessica M Olson
Shigang Qiao
Judy R Kersten
David C Warltier
Zhi-Dong Ge
Matthias L Riess
Mingyu Liang
Yanan Liu
Mark Paterson
Zeljko J Bosnjak
Ivan Zaja
Journal: Anesthesiology (2015)
Discipline: CLINICAL MEDICINE
Keywords: microRNA-21; isoflurane-induced cardioprotection; knockout mice; Akt; eNOS
Affiliations: Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (M.L.R.), TVHS VA Medical Center and Vanderbilt University, Nashville, Tennessee.

Abstract:  Background: The role of microRNA-21 in isoflurane-induced cardioprotection is unknown. The authors addressed this issue by using microRNA-21 knockout mice and explored the underlying mechanisms. Methods: C57BL/6 and microRNA-21 knockout mice were echocardiographically examined. Mouse hearts underwent 30 min of ischemia followed by 2 h of reperfusion in vivo or ex vivo in the presence or absence of 1.0 minimum alveolar concentration of isoflurane administered before ischemia. Cardiac Akt, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) proteins were determined by Western blot analysis. Opening of the mitochondrial permeability transition pore (mPTP) in cardiomyocytes was induced by photoexcitation-generated oxidative stress and detected by rapid dissipation of tetramethylrhodamine ethyl ester fluorescence using a confocal microscope. Results: Genetic disruption of miR-21 gene did not alter phenotype of the left ventricle, baseline cardiac function, area at risk, and the ratios of phosphorylated-Akt/Akt, phosphorylated-eNOS/eNOS, and phosphorylated-nNOS/nNOS. Isoflurane decreased infarct size from 54 ± 10% in control to 36 ± 10% (P &lt; 0.05, n = 8 mice per group), improved cardiac function after reperfusion, and increased the ratios of phosphorylated-Akt/AKT, phosphorylated-eNOS/eNOS, and phosphorylated-nNOS/nNOS in C57BL/6 mice subjected to ischemia-reperfusion injury. These beneficial effects of isoflurane were lost in microRNA-21 knockout mice. There were no significant differences in time of the mPTP opening induced by photoexcitation-generated oxidative stress in cardiomyocytes isolated between C57BL/6 and microRNA-21 knockout mice. Isoflurane significantly delayed mPTP opening in cardiomyocytes from C57BL/6 but not from microRNA-21 knockout mice. Conclusions: Isoflurane protects mouse hearts from ischemia-reperfusion injury by a microRNA-21-dependent mechanism. The Akt/NOS/mPTP pathway is involved in the microRNA-21-mediated protective effect of isoflurane. 

Retracted: No

PubPeer comments:
 Figure 7A * Red boxes: The Akt panel looks very similar to the GAPDH panel, albeit stretched differently. Note the presence of an air bubble in the second lane. ![file] ,
N-methyl-N-nitrosourea-induced neuronal cell death in a large animal model of retinal degeneration in vitro
Authors: Fredrik Ghosh
Linnéa Taylor
Karin Arnér
Journal: Experimental Eye Research (2016)
Discipline: CLINICAL MEDICINE
Keywords: Gliosis; N-methyl-N-nitrosourea; Neuronal degeneration; Porcine retina; Retinal explant culture
Affiliations: Department of Ophthalmology, Lund University, SE 22184, Lund, Sweden. Electronic address: ., Department of Ophthalmology, Lund University, SE 22184, Lund, Sweden.

Abstract:  N-methyl-N-nitrosourea (MNU) has been reported to induce photoreceptor-specific degeneration with minimal inner retinal impact in small animals in vivo. Pending its use within a retinal transplantation paradigm, we here explore the effects of MNU on outer and inner retinal neurons and glia in an in vitro large animal model of retinal degeneration. The previously described degenerative culture explant model of adult porcine retina was used and compared with explants receiving 10 or 100 μg/ml MNU (MNU10 and MNU100) supplementation. All explants were kept for 5 days in vitro, and examined for morphology as well as for glial and neuronal immunohistochemical markers. Rhodopsin-labeled photoreceptors were present in all explants. The number of cone photoreceptors (transducin), rod bipolar cells (PKC) and horizontal cells (calbindin) was significantly lower in MNU treated explants (p &lt; 0.001). Gliosis was attenuated in MNU10 treated explants, with expression of vimentin, glial fibrillary protein (GFAP), glutamine synthetase (GS), and bFGF comparable to in vivo controls. In corresponding MNU100 counterparts, the expression of Müller cell proteins was almost extinguished. We here show that MNU causes degeneration of outer and inner retinal neurons and glia in the adult porcine retina in vitro. MNU10 explants display attenuation of gliosis, despite decreased neuronal survival compared with untreated controls. Our results have impact on the use of MNU as a large animal photoreceptor degeneration model, on tissue engineering related to retinal transplantation, and on our understanding of gliosis related neuronal degenerative cell death. 

Retracted: No

PubPeer comments:
 A processed version of Figure 1A appears to have been recycled as Figure 1A in a later publication: https: pubpeer.com publications AC56D21E344CE1BDB80FB199ADAFBB ![file] , 
 We thank the reader for the comment, which for some reason has been published duplicate times . The publisher has been notified and we are in the process of correcting this inadvertent mistake. Best regards, Dr Taylor ,
Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Mansooreh Samimi
Zatollah Asemi
Hamid Reza Gilasi
Ali Soltani
Samaneh Mahmoodi
Zahra Vahedpoor
Fereshteh Bahmani
Mehran Sharifi Esfahani
Journal: Annals of Nutrition and Metabolism (2018)
Discipline: CLINICAL MEDICINE
Keywords: Cervical intraepithelial neoplasia grade 2 or 3; Metabolic profiles; Recurrence; Supplementation; Vitamin D.
Affiliations: Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran., Department of Epidemiology and Biostatistics, Faculty of Health, Kashan University of Medical Sciences, Kashan, Iran., Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Abstract:  Objective: This study was conducted to evaluate the effects of vitamin D supplementation on the recurrence and metabolic status of patients with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). Methods: This randomized, double-blind, placebo-controlled trial was carried out among 58 women diagnosed with CIN2/3. Participants were randomly assigned into 2 groups to receive either 50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Results: The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly decreased fasting plasma glucose (-7.8 ± 9.2 vs. -1.1 ± 8.6 mg/dL, p = 0.006) and insulin levels (-3.2 ± 4.8 vs. -0.9 ± 3.4 µIU/mL, p = 0.03), and significantly increased quantitative insulin sensitivity check index (0.01 ± 0.02 vs. 0.002 ± 0.01, p = 0.02) compared with the placebo. Additionally, there was a significant decrease in high-sensitivity C-reactive protein (-815.3 ± 1,786.2 vs. 717.5 ± 1,827.3 ng/mL, p = 0.002) and a significant increase in total antioxidant capacity (113.4 ± 137.4 vs. -53.7 ± 186.7 mmol/L, p &lt; 0.001) following the supplementation of vitamin D compared with the placebo. Conclusions: Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A168 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 18 publications have an expression of concern, and 6 have been retracted. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
Selective integrin subunit reduction disrupts fibronectin extracellular matrix deposition and fibrillin 1 gene expression
Authors: Brooke M Krovic
Rajeev K Boregowda
Timothy M Ritty
Journal: Molecular and Cellular Biochemistry (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Integrins; extracellular matrix (ECM) proteins; fibronectin; fibrils; fibrillin 1
Affiliations: Division of Musculoskeletal Sciences, Department of Orthopaedics, Penn State College of Medicine, Hershey, PA 17033, USA. 

Abstract:  Integrins are transmembrane receptors that can specifically bind extracellular matrix (ECM) proteins. Assembly of the ECM protein fibronectin into fibrils has been shown to be a cell-mediated process that requires integrins. Like fibronectin, fibrillin 1 is an ECM glycoprotein that can assemble into fibrils, but the role of integrins in fibril formation is not understood. To investigate the role of integrins in fibrillin 1 ECM deposition, cells that normally produce and assemble fibrillin 1 fibers in vitro were stably transfected with plasmid constructs encoding short interfering RNAs that target specific integrin subunits. Cells that were deficient in α2- and β3-integrin subunits produced and deposited fibronectin normally, but cells that were deficient for α5 and αV were unable to elaborate a fibronectin matrix, although they continued to produce and secrete the protein. Surprisingly, the cells that were unable to elaborate a fibronectin matrix also lost fibrillin 1 gene expression. 

Retracted: No

PubPeer comments:
 Figure 5. * Blue boxes: The  Control CM and  ARPE NCP lanes in the FBN1 panel look remarkably similar. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. ![file] ,
Silencing of long non-coding RNA PCAT6 restrains gastric cancer cell proliferation and epithelial-mesenchymal transition by targeting microRNA-15a
Authors: Dongfang Dong
Yue Lun
Haiyuan Sun
Qunying Wang
Gang Yuan
Bo Sun
Jingzi Quan
Journal: General physiology and biophysics (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Gastric cancer; long non-coding RNA; PCAT6; cell proliferation; epithelial-mesenchymal transition
Affiliations: Department of Gastroenterology, No.971 Hospital of People's Liberation Army Navy, Qingdao, China.

Abstract:  Gastric cancer (GC) is a high mortality disease. We studied the function and mechanism of long non-coding RNA prostate cancer-associated transcript 6 (lncRNA PCAT6) on cell proliferation and epithelial-mesenchymal transition (EMT) in GC cells. CCK-8, flow cytometry and colony formation assay were respectively used to detect the cell viability, apoptosis and colony formation. PCAT6 and miR-15a expression were changed by cell transfection. Moreover, the level of Cyclin D1, p53, Bax, Cleaved caspase-3 and relate-proteins of EMT and cell pathways were investigated by Western blot. Besides, the level of miR-15a and PCAT6 was tested by RT-qPCR. Besides, the target relation between miR-15a and PCAT6 were tested by luciferase assay. PCAT6 was highly expressed in GC cells and tissues. Silencing of PCAT6 restrained the relate-proteins of cell proliferation and EMT. Furthermore, PCAT6 reversely regulated miR-15a and miR-15a inhibitor reversed the efficacy of sh-PCAT6 in cell proliferation and EMT. PCAT6 restrained the relate-proteins of RB/E2F and Wnt/β-catenin pathways and miR-15a reverse this progress. Finally, PCAT6 was a target of miR-15a. Silencing of lncRNA PCAT6 restrained proliferation and EMT of GC cells by targeting miR-15a via RB/E2F and Wnt/β-catenin pathways. 

Retracted: No

PubPeer comments:
 Western blots in this paper are of a peculiar stylised nature, resembling tadpoles more than conventional WBs. Here, Fig 3. ![file] Fig 6: ![file] Backgrounds of the bands (viewed with enhanced contrast) are more repetitious than one might expect. ![file] ,
IL17 producing γδT cells induce angiogenesis and are associated with poor survival in gallbladder cancer patients
Authors: Shubhada Vivek Chiplunkar
Shailesh Vinayak Shrikhande
Sagar Umesh Shah
Rushikesh Sudam Patil
Mahesh Goel
Rajesh Prabhakar Dikshit
Journal: International Journal of Cancer (2016)
Discipline: CLINICAL MEDICINE
Keywords: Th17; Treg; Tγδ17; vascular endothelial growth factor.
Affiliations: Department of Surgical Oncology.

Abstract:  Despite conventional treatment modalities, gallbladder cancer (GBC) remains a highly lethal malignancy. Prognostic biomarkers and effective adjuvant immunotherapy for GBC are not available. In the recent past, immunotherapeutic approaches targeting tumor associated inflammation have gained importance but the mediators of inflammatory circuit remain unexplored in GBC patients. In the current prospective study, we investigated the role of IL17 producing TCRγδ(+) (Tγδ17), CD4(+) (Th17), CD8(+) (Tc17) and regulatory T cells (Tregs) in pathogenesis of GBC. Analysis by multi-color flow cytometry revealed that compared to healthy individuals (HI), Tγδ17, Th17 and Tc17 cells were increased in peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TIL) of GBC patients. Tregs were decreased in PBMCs but increased in TILs of GBC patients. The suppressive potential of Tregs from GBC patients and HI were comparable. Serum cytokines profile of GBC patients showed elevated levels of cytokines (IL6, IL23 and IL1β) required for polarization and/or stabilization of IL17 producing cells. We demonstrated that Tγδ17 cells migrate toward tumor bed using CXCL9-CXCR3 axis. IL17 secreted by Tγδ17 induced productions of vascular endothelial growth factor and other angiogenesis related factors in GBC cells. Tγδ17 cells promote vasculogenesis as studied by chick chorioallantoic membrane assay. Survival analysis showed that Tγδ17, Th17 and Treg cells in peripheral blood were associated with poor survival of GBC patients. Our findings suggest that Tγδ17 is a protumorigenic subtype of γδT cells which induces angiogenesis. Tγδ17 may be considered as a predictive biomarker in GBC thus opening avenues for targeted therapies. 

Retracted: No

PubPeer comments:
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 The conclusion made on the effect of anti IL17+ Tgd17 sup on the cells is based on questionable data. The panel in the center is an overexposed form of the lower autorad, beyond doubt. Awaiting commentsu200b from the authors. ,
The Influence of Stabilized Deconjugated Ursodeoxycholic Acid on Polymer-Hydrogel System of Transplantable NIT-1 Cells
Authors: Armin Mooranian
Rebecca Negrulj
Hani Al-Salami
Journal: Pharmaceutical Research (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: artificial cell microencapsulation; bioenergetics; biomaterials; pancreatic β-cells; ursodeoxycholic acid.
Affiliations: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia., Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia. .

Abstract:  Purpose: The encapsulation of pancreatic β-cells in biocompatible matrix has generated great interest in diabetes treatment. Our work has shown improved microcapsules when incorporating the bile acid ursodeoxycholic acid (UDCA), in terms of morphology and cell viability although cell survival remained low. Thus, the study aimed at incorporating the polyelectrolytes polyallylamine (PAA) and poly-l-ornithine (PLO), with the polymer sodium alginate (SA) and the hydrogel ultrasonic gel (USG) with UDCA and examined cell viability and functionality post microencapsulation. Methods: Microcapsules without (control) and with UDCA (test) were produced using 1% PLO, 2.5% PAA, 1.8% SA and 4.5% USG. Pancreatic β-cells were microencapsulated and the microcapsules' morphology, surface components, cellular and bile acid distribution, osmotic and mechanical stability as well as biocompatibilities, insulin production, bioenergetics and the inflammatory response were tested. Results: Incorporation of UDCA at 4% into a PLO-PAA-SA formulation system increased cell survival (p &lt; 0.01), insulin production (p &lt; 0.01), reduced the inflammatory profile (TNF-α, IFN-ϒ, IL-6 and IL-1β; p &lt; 0.01) and improved the microcapsule physical and mechanical strength (p &lt; 0.01). Conclusions: β-cell microencapsulation using 1% PLO, 2.5% PAA, 1.8% SA, 4.5% USG and the bile acid UDCA (4%) has good potential in cell transplantation and diabetes treatment. 

Retracted: No

PubPeer comments:
 The report contains duplicated images. Figure 1b and Figure 4 seem the same. The same applies to Figure 1c and Figure 2d. Figure 1b ![file] Figure 4 ![file] Figure 1c ![file] Figure 2d ![file] ,
microRNA-1298 inhibits the malignant behaviors of breast cancer cells via targeting ADAM9
Authors: Weili Chen
Xiaohong Xue
Qing Lu
Xinyue Zhang
Siyu Li
Journal: Bioscience Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ADAM9; Breast cancer; miR-1298.
Affiliations: Department of Mammary, YueYang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Hongkou District, Shanghai City, China, 200080

Abstract:  MicroRNAs (miRNAs) regulate the progression of human malignancy by targeting oncogenes or tumor suppressors, which are 12 promising targets for cancer treatment. Increasing evidence has suggested the aberrant expression and tumor-suppressive function of miR-1298 in cancers, however, the regulatory mechanism of miR-1298 in breast cancer (BC) remains unclear. Here, our findings showed that miR-1298 was down-regulated in BC tissues and cell lines. Lower level of miR-1298 was significantly correlated with the advanced progression of BC patients. Experimental study showed that overexpression of miR-1298 inhibited the proliferation, induced apoptosis and cell cycle arrest in BC cells. The in vivo xenograft mice model showed that highly expressed miR-1298 significantly reduced the tumor growth and metastasis. Further mechanism analysis revealed that miR-1298 bound the 3'-untranslated region (UTR) of a disintegrin and metalloproteinase 9 domain (ADAM9) and suppressed the expression of ADAM9 in BC cells. ADAM9 was overexpressed in BC tissues and inversely correlated with miR-1298. Down-regulation of ADAM9 induced apoptosis and cell cycle arrest of BC cells. Moreover, ectopic expression of ADAM9 by transiently transfecting with vector encoding the full coding sequence of ADAM9 attenuated the inhibitory effects of miR-1298 on the proliferation and cell cycle progression of BC cells. Collectively, our results illustrated that miR-1298 played a suppressive role in regulating the phenotype of BC cells through directly repressing ADAM9, suggesting the potential application of miR-1298 in the therapy of BC. 

Retracted: No

PubPeer comments:
 Could the authors help me understand why some of the plot lines in Figure 5H appear to backtrack on themselves? Some examples shown with green arrows. *** ![file] , 
 April 9, 2021 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. ,
Long noncoding RNA NEAT1 functions as an oncogene in human laryngocarcinoma by targeting miR-29a-3p
Authors: J Zhou
Z-W Li
W Wang
Y-C Xu
T Liu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; NEAT1; laryngocarcinoma; progression; development
Affiliations: Department of Otolaryngology-Head and Neck Surgery, Xiaogan Hospital Affiliated to Wuhan University of Science and Technology, Xiaogan, China. .

Abstract:  Objective: Long noncoding RNAs (lncRNAs) have been reported to participate in the progression and development of many human diseases. In this study, we are committed to uncover the potential function of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in the development of laryngocarcinoma. Patients and methods: LncRNA NEAT1 expression in laryngocarcinoma cells and 54 paired laryngocarcinoma samples was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, the regulatory effects of NEAT1 on the proliferation and metastasis of laryngocarcinoma cells were evaluated. Biological role of NEAT1/miR-29a-3p axis was finally explored in regulating the progression of laryngocarcinoma. Results: NEAT1 was upregulated in laryngocarcinoma tissues and cell lines. NEAT1 knockdown suppressed growth and invasive abilities in laryngocarcinoma cells, while overexpression of NEAT1 enhanced such abilities. Further experiments showed that miR-29a-3p was directly targeted by NEAT1, and participated in NEAT-mediated progression of laryngocarcinoma. Conclusions: NEAT1 is a novel oncogene in laryngocarcinoma and could enhance growth and invasion of laryngocarcinoma cells by targeting miR-29a-3p. 

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. ,
p14ARF induces G2 arrest and apoptosis independently of p53 leading to regression of tumours established in nude mice
Authors: Camille Leduc
Jean-Luc Coll
Elisabeth Brambilla
Sylvie Gazzeri
Béatrice Eymin
Journal: Oncogene (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ARF; tumour-suppressor protein; p53; cell growth; G(2) arrest
Affiliations: Groupe de Recherche sur le Cancer du Poumon, EA 2021, Equipe INSERM 9924, Institut Albert Bonniot, La Tronche, France.

Abstract:  Until recently, the ability of ARF (human p14(ARF), murine p19(ARF)) tumour-suppressor protein, encoded by the INK4A/ARF locus, to inhibit cell growth in response to various stimuli was related to its ability to stabilize p53 through the so-called ARF/MDM2/p53 pathway. However, recent data have demonstrated that ARF is not implicated in this unique p53-dependent pathway. By use of transient and stable expression, we show here that human p14(ARF) inhibits the growth of human tumoral cells lacking functional p53 by inducing a transient G(2) arrest and subsequently apoptosis. This p14(ARF)-induced G(2) arrest was correlated with inhibition of CDC2 activity, inactivation of CDC25C phosphatase and induction of the CDK inhibitor p21(WAFI). Apoptosis was demonstrated using Hoechst 33352 staining, proteolytic activation of caspase-3 and PARP cleavage. Similar results were obtained in experiments with cells synchronized by hydroxyurea block. Importantly, we were able to reproduce these effects 'in vivo' by showing that p14(ARF) inhibits the growth of p53 nullizygous human tumours in nude mice and induces the regression of p53 -/- established tumours. In these experiments, tumoral regression was associated with inhibition of cell proliferation as well as induction of apoptosis confirming the data obtained in cell lines. 

Retracted: No

PubPeer comments:
 Unreferenced images where 2 of them are identical as it (marked with ***X*** ) has also been used in 3 other papers commented in the link below: [Link] Authors have put images from dissimilar unreferenced sources with different scales and qualities. Only one of them at the bottom (third paper below) has an unclear legend! ![file] , 
 Please clarify if the basis for the developed models given in two papers, one in **2017** (Figures 12.b 13.b) and the other one in **2018** (Figures 2.a 2.b) shown below are the same. The other two papers in **2019** are self-referenced, but please clarify the strength of influence for the previously developed model applied in these newer works. There are also a few other items commented below. The first author (**Amin Shahsavar**) of the paper below published in **2016** is the common co-author in those papers, and wondering if the necessary and effective similarity checks were accordingly performed by the **journals editors!** Thanks. ![file] ![file] , 
 Duplications: **Appendix (A)** and **figure 2!** See the relevant texts. ![file] ,
Silencing of CerS6 increases the invasion and glycolysis of melanoma WM35, WM451 and SK28 cell lines via increased GLUT1-induced downregulation of WNT5A
Authors: Huiqing Xie
Jianda Zhou
Jia Chen
Qi Wang
Shaohua Wang
Yuanyuan Tang
Rui Liu
Ke Cao
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Ceramide synthases; CerS6; melanoma; glycolysis; proliferation
Affiliations: Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China., Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China., Department of Rehabilitation, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

Abstract:  Ceramide synthases (CerSs) have been shown to regulate numerous aspects of cancer development. CerS6 has been suggested to be involved in cancer etiology. However, little is known concerning the exact effect of CerS6 on the malignant behavior of melanoma, including glycolysis, proliferation and invasion. In the present study, we found that the expression of CerS6 was low in the melanoma cell lines, including WM35, WM451 and SK-28, and the expression level was related to the malignanct behavior of the melanoma cell lines. We constructed overexpression and silencing models of CerS6 in three melanoma cell lines and found that silencing of CerS6 promoted the ability of proliferation and invasion in the melanoma cell lines. Additionally, downregulation of CerS6 upregulated the activity of glycolysis-related enzyme, and enhanced the expression of glycolysis-related genes, including GLUT1 and MCT1. Furthermore, we identified the genes whose expression levels were changed after silencing of CerS6 by gene microarray. The expression of glycolysis-related gene SLC2A1 (also known as GLUT1) was found to be upregulated, while notably WNT5A was downregulated. The altered expression of GLUT1 and WNT5A was verified by qPCR and western blotting. Furthermore, silencing of GLUT1 in the melanoma cells resulted in the increased expression of WNT5A and the decreased ability of invasion and proliferation in the melanoma cells. Collectively, silencing of CerS6 induced the increased expression of GLUT1, which downregulated the expression of WNT5A and enhanced the invasion and proliferation of melanoma cells. Thus, CerS6 may provide a novel therapeutic target for melanoma treatment. 

Retracted: No

PubPeer comments:
 Fig 2E. I have concerns. First, there are overlaps. ![file] The first and third panels on the SK-28 row overlap, but clearly there are cells in the third panel with no counterparts in the first. ![file] Cells duplicate between non-overlapping panels. ![file] I could only mark a few of the concerns with the WM451 row before I lost the will to go on. ![file] ,
Acute kidney injury leading to CKD is associated with a persistence of metabolic dysfunction and hypertriglyceridemia
Authors: Sunjae Lee
Sujit Saha
Azadeh Harzandi
Claire C Sharpe
Bruce M Hendry
Saeed Shoaie
Gholamreza Bidkhori
Adil Mardinoglu
Journal: iScience (2021)
Discipline: Multidisciplinary
Keywords: Human Metabolism; Omics; Systems Biology.
Affiliations: Renal Sciences, Department of Inflammation Biology, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, SE5 9NU London, UK., School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea, 61005., Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, SE1 9RT London, UK.

Abstract:  Fibrosis is the pathophysiological hallmark of progressive chronic kidney disease (CKD). The kidney is a highly metabolically active organ, and it has been suggested that disruption in its metabolism leads to renal fibrosis. We developed a longitudinal mouse model of acute kidney injury leading to CKD and an in vitro model of epithelial to mesenchymal transition to study changes in metabolism, inflammation, and fibrosis. Using transcriptomics, metabolic modeling, and serum metabolomics, we observed sustained fatty acid metabolic dysfunction in the mouse model from early to late stages of CKD. Increased fatty acid biosynthesis and downregulation of catabolic pathways for triglycerides and diacylglycerides were associated with a marked increase in these lipids in the serum. We therefore suggest that the kidney may be the source of the abnormal lipid profile seen in patients with CKD, which may provide insights into the association between CKD and cardiovascular disease. 

Retracted: No

PubPeer comments:
 Fig.4 contains two images which appear to overlap. ![file] ,
Nestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4
Authors: Grégory Hans
Françoise Bruyère
Bernard Rogister
Gustave Moonen
Sabine Wislet-Gendebien
Pierre Leprince
Journal: BMC Neuroscience (2004)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: CNS injury; neurogenesis; axonal regrowth; cell transplantation; foetal brain tissue
Affiliations: Centre for Cellular and Molecular Neurobiology, University of Liège, Liège, Belgium. 

Abstract:  Background: Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies. Results: In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings) and we report here that nestin-positive (but not nestin-negative) mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1) this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2) anti-BMP4 antibodies inhibit the nestin-positive mesenchymal stem cells conditioned medium inducing effect on astrogliogenesis. Conclusions: When thinking carefully about mesenchymal stem cells as candidates for cellular therapy in neurological diseases, their effects on resident neural cell fate have to be considered. 

Retracted: No

PubPeer comments:
 Figure 4A. Much more similar than expected. ![file] ,