PReD-Bench/PRed-Bench huggingface dataset:
Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death
Authors: Liang-Liang Yu
He-Sheng Luo
Fen Liu
Yao-Wei Ai
Jin Liu
Jun Cao
Hong-Gang Yu
Song Liu
Jie-Ping Yu
Yuan-Ling Qi
Shi-Quan Liu
Quanjun Deng
Jing Chen
Jun-Hua Li
Xi-Ming Xu
Xiao-Dong Zhou
Journal: International journal of cancer (2008)
Discipline: CLINICAL MEDICINE
Keywords: chemotherapy resistance; phosphoinositide 3-kinase (PI3K)/Akt pathway; Akt expression; PTEN expression; etoposide
Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan Univeristy, Wuhan, China. 

Abstract:  The major obstacle to successful treatment of gastric cancer is chemotherapy resistance. Our study was designed to investigate the role of phosphoinositide 3-kinase (PI3K)/Akt pathway in the development of chemoresistance in gastric cancer. In the present study, elevated Akt expression and Akt phosphorylation (Ser 473), as well as decreased PTEN expression were observed in 28 cases of gastric cancer tissues. Etoposide and doxorubicin stimulated Akt and PI3K activities in 2 gastric cancer cell lines (BGC-823 and SGC-7901), and the activities were concentration and time-dependent. Up-regulation of PTEN expression in BGC-823 cells by PEAK8-PTEN transient transfection obviously decreased the basal and anticancer drugs induced Akt activities, then sensitized BGC-823 cells to etoposide and doxorubicin. Pretreatment of BGC-823 and SGC-7901 cells with wortmannin, a PI3K inhibitor, attenuated cells's resistance to etoposide and doxorubicin. In addition, pretreatment of wortmannin blocked etoposide and doxorubicin induced IkappaB-alpha degradation, NFkappaB activation, phosphorylation of Akt, MDM-2 and forkhead transcription factors. Wortmannin pretreatment also promoted the accumulation of p27/Kip, but inhibited the Mcl-1 expression. Furthermore, wortmannin promoted etoposide and doxorubicin induced caspase-3, caspase-9 activation and poly ADP-ribose polymerase cleavage. Taken together, the observations indicate the PI3K/Akt pathway plays an important role in the chemoresistance of gastric cancer cells. A new strategy for combined chemotherapy of gastric cancer should be designed to more specifically block PI3K/Akt pathway and then decrease the amount of resistant cells. 

Retracted: No

PubPeer comments:
 Figure 8C. * Red boxes: The bottom right quadrants of the  Wortmannin panels of both SGC7901 and BGC823 look unexpectedly similar to each other, while other parts of the panels look different. ![file] , 
 #1 Dear Dr. Bik, Thank for your reminding. This article is not our research. My name is Shi-Qing Liu, not Shi-Quan Liu. Please contact the first or corresponding author of the paper. Thank you! Yours sincerely Shiqing Liu , 
 Dear Dr. Liu, I apologize for including the incorrect email to you. The first author has also been notified yesterday, so I hope that their email address is still working. Kind regard regards, Elisabeth Bik ,
The immune response to Prevotella bacteria in chronic inflammatory disease
Authors: Jeppe Madura Larsen
Journal: Immunology (2017)
Discipline: IMMUNOLOGY
Keywords: Prevotella; T cells; cytokines; inflammation; inflammatory disease
Affiliations: Department of Technology; Faculty of Health and Technology; Metropolitan University College; Copenhagen Denmark, National Food Institute; Technical University of Denmark; Lyngby Denmark

Abstract:  The microbiota plays a central role in human health and disease by shaping immune development, immune responses and metabolism, and by protecting from invading pathogens. Technical advances that allow comprehensive characterization of microbial communities by genetic sequencing have sparked the hunt for disease-modulating bacteria. Emerging studies in humans have linked the increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders and low-grade systemic inflammation. Intriguingly, Prevotella abundance is reduced within the lung microbiota of patients with asthma and chronic obstructive pulmonary disease. Increased Prevotella abundance is associated with augmented T helper type 17 (Th17) -mediated mucosal inflammation, which is in line with the marked capacity of Prevotella in driving Th17 immune responses in vitro. Studies indicate that Prevotella predominantly activate Toll-like receptor 2, leading to production of Th17-polarizing cytokines by antigen-presenting cells, including interleukin-23 (IL-23) and IL-1. Furthermore, Prevotella stimulate epithelial cells to produce IL-8, IL-6 and CCL20, which can promote mucosal Th17 immune responses and neutrophil recruitment. Prevotella-mediated mucosal inflammation leads to systemic dissemination of inflammatory mediators, bacteria and bacterial products, which in turn may affect systemic disease outcomes. Studies in mice support a causal role of Prevotella as colonization experiments promote clinical and inflammatory features of human disease. When compared with strict commensal bacteria, Prevotella exhibit increased inflammatory properties, as demonstrated by augmented release of inflammatory mediators from immune cells and various stromal cells. These findings indicate that some Prevotella strains may be clinically important pathobionts that can participate in human disease by promoting chronic inflammation. 

Retracted: No

PubPeer comments:
 This might be whats happening in [Wuhan] ,
Follistatin gene delivery enhances muscle growth and strength in nonhuman primates
Authors: Chalonda R Handy
Christopher M Walker
Amanda M Haidet
Danielle Tucker
Walter R Therlfall
Steven E Weisbrode
Chrystal L Montgomery
K Reed Clark
Zarife Sahenk
Janaiah Kota
Louise R Rodino-Klapac
Paul M L Janssen
Christopher J Shilling
Amy Eagle
Jerry R Mendell
Brian K Kaspar
Journal: Science translational medicine (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: myostatin; follistatin; muscle growth; antagonist; therapeutic agents
Affiliations: Center for Gene Therapy, Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.

Abstract:  Antagonists of myostatin, a blood-borne negative regulator of muscle growth produced in muscle cells, have shown considerable promise for enhancing muscle mass and strength in rodent studies and could serve as potential therapeutic agents for human muscle diseases. One of the most potent of these agents, follistatin, is both safe and effective in mice, but similar tests have not been performed in nonhuman primates. To assess this important criterion for clinical translation, we tested an alternatively spliced form of human follistatin that affects skeletal muscle but that has only minimal effects on nonmuscle cells. When injected into the quadriceps of cynomolgus macaque monkeys, a follistatin isoform expressed from an adeno-associated virus serotype 1 vector, AAV1-FS344, induced pronounced and durable increases in muscle size and strength. Long-term expression of the transgene did not produce any abnormal changes in the morphology or function of key organs, indicating the safety of gene delivery by intramuscular injection of an AAV1 vector. Our results, together with the findings in mice, suggest that therapy with AAV1-FS344 may improve muscle mass and function in patients with certain degenerative muscle disorders. 

Retracted: No

PubPeer comments:
 The same set of images seem to be choosed to represent MCK-FS and CMV-FS in Fig. 3A. Could the authors check please? ![file] , 
 We have done experimental treatment with both promoters. MCK is muscle specific and CMV is more likely to express outside of muscle , 
 The authors might agree that their reply does not answer why the same set of images were used to represent two different biological conditions ,
GR silencing impedes the progression of castration-resistant prostate cancer through the JAG1/NOTCH2 pathway via up-regulation of microRNA-143-3p
Authors: Linshen Zhang
Hongjun Jiang
Yufan Zhang
Yi Sun
Chenrong Wang
Xixi Xia
Journal: Cancer Biomarkers (2020)
Discipline: CLINICAL MEDICINE
Keywords: Glucocorticoid receptor; JAG1; NOTCH2; castration-resistant prostate cancer; invasion
Affiliations: Department of Clinical Laboratory Medicine, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, China, 2016 Innovation Class, Kunming Medical University, Kunming, Yunnan, China

Abstract:  Background: Despite notable progression from a therapeutic point of view, castration resistant prostate cancer (CRPC) remains a clinical significant stumbling block. The current study aimed to elucidate the functional role of the gene glucocorticoid receptor (GR) in CRPC, and identify the contributions of the GR gene in CRPC in connection with microRNA-143-3p (miR-143-3p)/Jagged1 (JAG1)/NOTCH2. Methods: The expression of GR and miR-143-3p in CRPC tissues and cells as well as JAG1/NOTCH2 expression in CRPC tissues was initially determined by quantitative polymerase chain reaction and Western blot analyses. The relationship among GR, JAG1, NOTCH2 and miR-143-3p was subsequently verified using the dual-luciferase reporter gene assay. ChIP assay confirmed the binding of GR to miR-143-3p promoter. Gain- and loss-function approaches were applied to ascertain the role of GR and miR-143-3p in progression of CRPC. Additionally, xenograft tumor models in nude mice were established to further confirm our results. Results: GR was found to be highly expressed while miR-143-3p was lowly expressed in the CRPC tissues and cells. Silencing GR reduced migration, invasion, proliferation and increased apoptosis of CRPC cells. GR was enriched in the miR-143-3p promoter region and could down-regulate miR-143-3p expression. The overexpression of miR-143-3p led to a reduction in the migration, invasion, proliferation and increased apoptosis of CRPC cells. JAG1 and NOTCH2 were the target genes of miR-143-3p, and GR up-regulated the JAG1/NOTCH2 expression by down-regulating miR-143-3p. Silencing JAG1/NOTCH2 inhibited epithelial-mesenchymal transition and CRPC progression in vitro. Furthermore, the in vitro findings were reproduced in the in vivo experiments. Conclusion: The key findings of the current study demonstrated that silencing GR suppressed the progression of CRPC through the JAG1/NOTCH2 pathway via up-regulation of miR-143-3p. 

Retracted: No

PubPeer comments:
  Supplementary Fig. 1. The down-regulation of GR inhibits cell cycle progression and promotes CRPC cell apoptosis. A, Cell cycle distribution analyzed by PI signal staining of flow cytometry . ![file] These plots appear to be hand-drawn, by someone who was unclear on the concept. They do not make sense as flow cytometry. ,
Lithium stimulates human bone marrow derived mesenchymal stem cell proliferation through GSK-3β-dependent β-catenin/Wnt pathway activation
Authors: Yang Wang
Zhenzhong Zhu
Bin Hu
Junjie Guan
Dongxu Jin
Junhui Yin
Changqing Zhang
Xin Niu
Journal: FEBS Journal (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Wnt signal transduction pathway; glycogen synthase kinase 3β; lithium; mesenchymal stem cells; proliferation.
Affiliations: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China., Institute of Microsurgery on Extremities; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; China, Department of Orthopedic Surgery; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; China

Abstract:  Mesenchymal stem cells (MSCs) are multipotent cells that have been widely used in cell based transplantation therapy. The use of MSCs requires in vitro expansion in order to fulfill their regenerative capacity. Therefore the proliferative ability of MSCs is one of the key factors which determine MSC therapeutic efficacy. In the present study, we showed for the first time that lithium, a well-known antidepressant, reversibly promoted the proliferation of human bone marrow derived MSCs in vitro. MSCs treated with 5 mm lithium proliferated more rapidly than untreated cells without undergoing apoptosis. Lithium increased the proportion of cells in S phase as well as cyclin D1 expression. Mechanistic studies revealed that these effects were dependent upon the activation of the glycogen synthase kinase 3β (GSK-3β) mediated canonical Wnt pathway. Lithium induced Ser9 phosphorylation, which results in the inhibition of GSK-3β activity, β-catenin accumulation and Wnt pathway activation. Utilizing a specific GSK-3β inhibitor SB216763 or siRNA-mediated inhibition of GSK-3β produced effects similar to those induced by lithium. In contrast, either quercetin, an inhibitor of the β-catenin/TCF pathway, or siRNA-mediated knockdown of β-catenin abolished the proliferative effect of lithium, suggesting that lithium stimulates MSC proliferation via the GSK-3β-dependent β-catenin/Wnt pathway. Collectively, these studies elucidate a novel role of lithium, which may not only provide a simple and effective way to strengthen MSC transplantation therapy efficacy but also shed light on lithium's clinical application for the treatment of certain disorders resulting from β-catenin/Wnt pathway suppression. 

Retracted: No

PubPeer comments:
 Figure 3B and figure 9C appear to include the same plot. *** ![file] ,
A 3D model of ovarian cancer cell lines on peptide nanofiber scaffold to explore the cell&ndash;scaffold interaction and chemotherapeutic resistance of anticancer drugs
Authors: Xiaojun Zhao
Zehong Yang
Journal: International Journal of Nanomedicine (2011)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 3D culture; anticancer drug; cell viability; nanofiber scaffold; ovarian cancer.
Affiliations: Nanomedicine Laboratory, West China Hospital and Institute for Nanobiomedical Technology and Membrane Biology, Sichuan University, Chengdu, People's Republic of China.

Abstract:  RADA16-I peptide hydrogel, a type of nanofiber scaffold derived from self-assembling peptide RADA16-I, has been extensively applied to regenerative medicine and tissue repair in order to develop novel nanomedicine systems. In this study, using RADA16-I peptide hydrogel, a three-dimensional (3D) cell culture model was fabricated for in vitro culture of three ovarian cancer cell lines. Firstly, the peptide nanofiber scaffold was evaluated by transmission electron microscopy and atom force microscopy. Using phase contrast microscopy, the appearance of the representative ovarian cancer cells encapsulated in RADA16-I peptide hydrogel on days 1, 3, and 7 in 24-well Petri dishes was illustrated. The cancer cell-nanofiber scaffold construct was cultured for 5 days, and the ovarian cancer cells had actively proliferative potential. The precultured ovarian cancer cells exhibited nearly similar adhesion properties and invasion potentials in vitro between RADA16-I peptide nanofiber and type I collagen, which suggested that RADA16-I peptide hydrogel had some similar characteristics to type I collagen. The precultured ovarian cancer cells had two-fold to five-fold higher anticancer drug resistance than the conventional two-dimensional Petri dish culture. So the 3D cell model on peptide nanofiber scaffold is an optimal type of cell pattern for anticancer drug screening and tumor biology. 

Retracted: No

PubPeer comments:
 image duplication ![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-106a induces the proliferation and apoptosis of glioma cells through regulating JNK/MAPK pathway
Authors: X.-H. Chen
X.-M. Ling
S. Shi
Journal: European review for medical and pharmacological sciences (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-106a; proliferation; apoptosis; glioma cells; JNK/MAPK pathway

Abstract:  The article "microRNA-106a induces the proliferation and apoptosis of glioma cells through regulating JNK/MAPK pathway" by X.-H. Chen, X.-M. Ling, S. Shi, published in Eur Rev Med Pharmacol Sci 2015; 19 (18): 3412-3417 has been withdrawn. 

Retracted: No

PubPeer comments:
 A micrograph has been duplicated and presented as something else in Figure 2E. ![file] ,
Successful immortalization of endometrial glandular cells with normal structural and functional characteristics
Authors: Yoshiko Maida
Masaki Inoue
Noriyuki Yatabe
Taro Kanaya
Satoru Kyo
Mitsuhiro Nakamura
Masaaki Tanaka
Tohru Kiyono
Journal: American Journal Of Pathology (2003)
Discipline: CLINICAL MEDICINE
Keywords: endometrium; epithelial cells; immortalization; human papillomavirus; telomerase activation
Affiliations: Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Kanazawa, Japan.

Abstract:  The human endometrium is a dynamic tissue, the proliferative activity of which dramatically changes throughout the menstrual cycle, with exquisite regulation by sex-steroid hormones. Primary endometrial epithelial cells fall into senescence within 2 weeks when cultured on plastic dishes, and more complete understanding of endometrial biology has been delayed because of, in part, a lack of an in vitro culture model for endometrial epithelial cells. Our goal was to establish immortalized human endometrial glandular cells that retain the normal functions and characteristics of the primary cells. Because the Rb/p16 and p53 pathways are known to be critical elements of epithelial senescence in early passages, we used human papillomavirus E6/E7 to target these pathways. The combination of human papillomavirus-16 E6/E7 expression and telomerase activation by the introduction of human telomerase reverse transcriptase (hTERT) led to successful immortalization of the endometrial glandular cells. E6/E7 expression alone was sufficient to extend their life span more than 20 population doublings, but the telomerase activation was further required to enable the cells to pass through the subsequent replicative senescence at 40 population doublings. Isolated immortalized cells contained no chromosomal abnormalities or only nonclonal aberrations, retained responsiveness to sex-steroid hormones, exhibited glandular structure on three-dimensional culture, and lacked transformed phenotypes on soft agar or in nude mice. These findings support the notion that both Rb inactivation/p53 inactivation and telomerase activation are necessary to immortalize endometrial epithelial cells, but additional factors are required for endometrial carcinogenesis. Our established cell lines show great promise for investigation of hormone functions, endometrial biology, and endometrial carcinogenesis. 

Retracted: No

PubPeer comments:
 ![file] , 
 Posting anonymously unannotated images with boxed in figures is not really a service to the community. , 
 #2 Figure 8D. Mice much more similar than expected. ![file] ,
MicroRNA‑219 exerts a tumor suppressive role in glioma via targeting Sal‑like protein 4
Authors: Yaxiong Nie
Botao Jiang
Fang Ji
Min Li
Journal: Experimental and therapeutic medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: Sal-like protein 4; glioma; microRNA-219; tumor suppressor.
Affiliations: Department of Neurology, First Hospital of Changsha, Changsha, Hunan 430100, P.R. China., Department of Nephrology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China., Teaching and Research Office of Medical Imaging, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China., Department of Neurology, First Affiliated Hospital of Nanhua University, Hengyang, Hunan 421001, P.R. China.

Abstract:  MicroRNAs (miRs) serve important roles in the development and progression of various human cancer types, including glioma. Recently, miR-219 has been suggested to function as a tumor suppressor in glioma; however, the underlying mechanism remains largely unknown. The aim of this study was to investigate the regulatory mechanism of miR-219 in the malignant phenotypes of glioma cells. Quantitative polymerase chain reaction (qPCR) and western blotting were conducted to examine the mRNA and protein expression. An MTT assay, wound healing assay and Transwell assay were used to study cell proliferation, migration and invasion. The qPCR data indicated that the expression of miR-219 was significantly decreased in glioma tissues compared with normal brain tissues. In addition, a low expression of miR-219 was identified to be associated with an advanced pathological grade. In vitro experiments demonstrated that miR-219 was also downregulated in several common glioma cell lines, including A172, U87, U251 and U373, when compared with that in normal astrocytes. Ectopic expression of miR-219 caused a significant decrease in U87 cell proliferation, migration and invasion. Luciferase reporter assay data indicated that Sal-like protein 4 (SALL4) was a direct target gene of miR-219, while the protein expression of SALL4 was negatively regulated by miR-219 in U87 cells. Furthermore, SALL4 was significantly upregulated in glioma tissues and cell lines, and upregulation of SALL4 was associated with a higher pathological grade. Furthermore, overexpression of SALL4 significantly attenuated the suppressive effects of miR-219 on U87 cell proliferation, migration and invasion, suggesting that miR-219 serves a suppressive role in glioma growth and metastasis via targeting SALL4. Therefore, the present study highlighted the clinical significance of the miR-219/SALL4 axis in glioma. 

Retracted: No

PubPeer comments:
 Fig 6D. Wound healing assay. ![file] For comparison, Fig 7A from [Zhong et al (2018)] . ![] Fig 4D from [Jiang et al (2018)] . ![] , 
 Fig 2C. At right, Fig 3B from [Liu et al (2017)] , rotated through 180 deg for ease of comparison. ![file] ,
Inhibition of phosphatidylinositol-4-phosphate 5-kinase Ialpha impairs localized actin remodeling and suppresses phagocytosis
Authors: Richard F Collins
Richard Anderson
Renee Dierckman
Jenny Jongstra-Bilen
Alan D Schreiber
William S Trimble
Sergio Grinstein
Joost Loijens
Mahmoud Pouladi
Marc G Coppolino
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Actin polymerization; PIP(2); Phosphatidylinositol-4-phosphate 5-kinase (PIPK); Phagocytosis; Phagosomes
Affiliations: Cell Biology Program, Hospital for Sick Children, and Department of Biochemistry University of Toronto, Ontario M5G 1X8, Canada.

Abstract:  Actin polymerization drives the extension of pseudopods required for phagocytosis. Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is thought to play a central role in this process, because it interacts with several actin-regulatory proteins and undergoes acute and localized changes at sites of phagocytosis. We therefore studied whether phosphatidylinositol-4-phosphate 5-kinase (PIPK), the enzyme responsible for the generation of PIP(2) from phosphatidylinositol 4-phosphate, is involved in the control of phagocytosis. PIPKIalpha was found to accumulate transiently on forming phagosomes. To test the functional involvement of PIPKIalpha in particle engulfment, we generated a double mutant (D309N/R427Q) that lacks kinase activity. When ectopically expressed in cultured cells, this mutant is targeted to the plasma membrane and accumulates at the phagosomal cup during particle engulfment. Expression of PIP5KIalpha D309N/R427Q impaired phagocytosis in RAW264.7 macrophages and in engineered phagocytes generated by transfection of Fc receptors in Chinese hamster ovary cells. Inhibition of phagocytosis could not be attributed to defects in particle binding or receptor clustering, which was monitored using green fluorescent protein-tagged Fcgamma receptors. Instead, expression of the inactive kinase diminished the accumulation of PIP(2) and of F-actin in the phagosomal cup. These data suggest that PIPKIalpha activity is involved in the actin remodeling that is a prerequisite for efficient phagocytosis. PIPKIalpha appears to contribute to the transient changes in PIP(2) levels that are associated with, and likely required for, the recruitment and regulation of actin-modulating proteins. 

Retracted: No

PubPeer comments:
 In FIG.3A, the land of Iu03b1(99-549) was unexpectedly inserted in a full membrane of Immunoblot. ![file] ,
Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion
Authors: Y Kin
F Ali-Osman
S L Jasti
S Mohanam
S K Chintala
J S Rao
G N Fuller
S S Lakka
R Sawaya
C Nirmala
A P Kyritsis
Y Adachi
S Kondraganti
Journal: Cancer Research (2000)
Discipline: CLINICAL MEDICINE
Keywords: matrix metalloproteinases; MMP-9; glioblastoma; tumor progression; antisense transcript
Affiliations: Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

Abstract:  Increased expression of matrix metalloproteinases (MMPs) has been associated with human glioblastoma tumor progression. In this study, we sought to down-regulate MMP-9 expression by stably transfecting a high-grade glioblastoma cell line with a plasmid vector capable of expressing an antisense transcript complementary to a 528-bp segment at the 5' end of human MMP-9 cDNA. Stable transfectants were obtained through selection with G418. Of the clones transfected with vector, sense, and antisense constructs, Northern blotting, Western blotting, and gelatin zymography showed that MMP-9 expression was significantly reduced only in the antisense-transfected cells. A Matrigel invasion assay revealed marked reductions in invasiveness for the antisense clones relative to the parental, vector, and sense clones. Cocultures of tumor spheroids and fetal rat brain aggregates showed that the antisense-transfected stable clones showed no invasion of the rat brain aggregates; in contrast, 90% of the parental, vector, and sense clones invaded the rat brain aggregates. Intracerebral injection of antisense stable transfectants in nude mice produced no tumors or very small tumors, but intracerebral injection of parental or vector clones did produce tumors. These results suggest that MMP-9 expression is essential for the invasiveness of glioblastoma cells. 

Retracted: No

PubPeer comments:
 Flagging this paper not so much for its own sake, but because six of the nine panels in Fig 3A later reappeared with different labels in Fig 6A of [Adachi et al. (2002)] . ![] Noted by Lotus Azoricus. , 
 Oh, let s flag this paper for its own sake too. Two images in Figure 2A appear to overlap, after 180-degree rotation. As many readers will be aware, this [author group] seems to have a number of problematic papers. *** ![file] ,
In vitro neurotoxicity by ropivacaine is reduced by silencing Cav3.3 T-type calcium subunits in neonatal rat sensory neurons
Authors: Han-Bing Wang
Heng Li
Weiming Ou
Xianjie Wen
Hongzhen Liu
Hua Liang
Shijie Li
Journal: Artificial Cells Nanomedicine and Biotechnology (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cav3.3; DRG; Local anaesthetics; neurotoxicity; ropivacaine hydrochloride.
Affiliations: Department of Anaesthesiology, The First People’s Hospital of Foshan and Foshan Hospital of Sun Yat-sen University, Foshan, Guangdong Province, China;, Department of Anaesthesiology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qinyuan, Guangdong Province, China

Abstract:  Neurotoxicity of local anaesthetics has been alerted by more and more peoples. Cav3.1 and Cav3.2 T-type calcium channels were closely related with local anaesthetics toxicity. However, the role of Cav3.3, another subtype of the T-type calcium channel, on the neurotoxicity induced by local anaesthetics remains unclear. CaMKIIγ is a kind of multifunctional kinase and associated with a variety of physiological and pathological process. T-type calcium channel is closely related with CaMKIIγ. Up-regulation CaMKIIγ can increase T-type currents at the dorsal root ganglia (DRG). On the contrary, down-regulation results in the T-type currents decrease. Is the relation between Cav3.3 T-type channel calcium and CaMKIIγ involved with the ropivacaine hydrochloride neurotoxicity? In this study, we generated pAd-Cav3.3 and pAd-shRNA adenovirus vector to up-regulate and down-regulate Cav3.3 mRNA expression of the DRG. The cells treated or untreated with ropivacaine hydrochloride (3 mM) for 4 h were used to evaluate the neurotoxicity. Cell viability, cell death rate and apoptosis rate, Cav3.3 and CaMKIIγ expression were detected with MTT method, Hoechst-PI, flow cytometry, qRT-PCR and western blotting. Results showed that the cell viability of the DRG treated with ropivacaine hydrochloride markedly decreased, death rate and apoptosis rate, Cav3.3 and CaMKIIγ mRNA and protein expression significantly increased. Cav3.3 overexpression aggravated DRG injury induced by ropivacaine hydrochloride and inhibition of Cav3.3 expression improved the cell damages. Cav3.3 can regulate CaMKIIγ mRNA and protein expression. In conclusion, Cav3.3 regulated CaMKIIγ in DRG, which was involved with the cell injury induced by ropivacaine hydrochloride. 

Retracted: No

PubPeer comments:
 In Figure 2A, a micrograph has been duplicated and presented as something else. ![file] , 
 Thanksuff0cwe have checked the data and we found that it was our negligence. When we collated the data, we misplaced the corresponding graphs. We will correct the above mistakes. Thank you for your question. ,
Endothelin-1 promotes epithelial-to-mesenchymal transition in human ovarian cancer cells
Authors: Shoukat Dedhar
Maria Rita Nicotra
Francesca Spinella
Anna Bagnato
Pier Giorgio Natali
Laura Rosanò
Valeriana Di Castro
Antonio Garcia de Herreros
Journal: Cancer Research (2005)
Discipline: CLINICAL MEDICINE
Keywords: ovarian cancer; ET-1/ET(A)R axis; epithelial-to-mesenchymal transition (EMT); ILK; GSK-3beta
Affiliations: Laboratory of Molecular Pathology and Ultrastructure, Regina Elena Cancer Institute, Rome, Italy.

Abstract:  Despite considerable efforts to improve early detection and advances in chemotherapy, metastatic relapses remain a major challenge in the management of ovarian cancer. The endothelin A receptor (ET(A)R)/endothelin-1 (ET-1) axis has been shown to have a significant role in ovarian carcinoma by promoting tumorigenesis. Here we show that the ET-1/ET(A)R autocrine pathway drives epithelial-to-mesenchymal transition (EMT) in ovarian tumor cells by inducing a fibroblastoid and invasive phenotype, down-regulation of E-cadherin, increased levels of beta-catenin, Snail, and other mesenchymal markers, and suppression of E-cadherin promoter activity. Activation of ET(A)R by ET-1 triggers an integrin-linked kinase (ILK)-mediated signaling pathway leading to glycogen synthase kinase-3beta (GSK-3beta) inhibition, Snail and beta-catenin stabilization, and regulation of transcriptional programs that control EMT. Transfection of dominant negative ILK or exposure to an ILK inhibitor suppresses the ET-1-induced phosphorylation of GSK-3beta as well as Snail and beta-catenin protein stability, activity, and invasiveness, indicating that ET-1/ET(A)R-induced EMT-promoting effects depend on ILK. ET(A)R blockade by specific antagonists or reduction by ET(A)R RNA interference reverses EMT and cell invasion by inhibiting autocrine signaling pathways. In ovarian carcinoma xenografts, ABT-627, a specific ET(A)R antagonist, suppresses EMT determinants and tumor growth. In human ovarian cancers, ET(A)R expression is associated with E-cadherin down-regulation, N-cadherin expression, and tumor grade. Collectively, these findings provide evidence of a critical role for the ET-1/ET(A)R axis during distinct steps of ovarian carcinoma progression and identify novel targets of therapeutic intervention. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
null, 
 Figure 3 continued. ![file] ,
Oncogenic kinase NPM/ALK induces expression of HIF1α mRNA
Authors: W Wong
X Liu
P Zhang
K Kantekure
M Marzec
Y Yang
T Pasha
M Cheng
A Woetmann
M A Wasik
N Odum
Journal: Oncogene (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: oncogenic anaplastic lymphoma kinase (ALK); T-cell lymphoma (TCL); nucleophosmin (NPM)/ALK fusion protein; hypoxia-induced factor 1α (HIF1α); BaF3 cells
Affiliations: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Abstract:  The mechanisms of malignant cell transformation mediated by the oncogenic anaplastic lymphoma kinase (ALK) tyrosine kinase remain only partially understood. In this study, we report that T-cell lymphoma (TCL) cells carrying the nucleophosmin (NPM)/ALK fusion protein (ALK+ TCL) strongly express hypoxia-induced factor 1α (HIF1α) mRNA, even under normoxic conditions, and markedly upregulate HIF1α protein expression under hypoxia. HIF1α expression is strictly dependent on the expression and enzymatic activity of NPM/ALK, as shown in BaF3 cells transfected with wild-type NPM/ALK and kinase-inactive NPM/ALK K210R mutant and by the inhibition of the NPM/ALK function in ALK+ TCL cells by a small-molecule ALK inhibitor. NPM/ALK induces HIF1α expression by upregulating its gene transcription through its key signal transmitter signal transducer and activator of transcription 3 (STAT3), which binds to the HIF1α gene promoter as shown by the chromatin immunoprecipitation assay and is required for HIF1α gene expression as demonstrated by its small interfering RNA-mediated depletion. In turn, depletion of HIF1α increases mammalian target of rapamycin complex 1 activation, cell growth and proliferation and decreases vascular endothelial growth factor synthesis. These results identify a novel cell-transforming property of NPM/ALK, namely its ability to induce the expression of HIF1α, a protein with an important role in carcinogenesis. These results also provide another rationale to therapeutically target NPM/ALK and STAT3 in ALK+ TCL. 

Retracted: No

PubPeer comments:
 Figures 1d and 2c much more similar than expected. https: imgur.com wnFIGVm ,
Poly(A) Signals Located near the 5′ End of Genes Are Silenced by a General Mechanism That Prevents Premature 3′-End Processing
Authors: Gos Micklem
Matthew Garrett
Jiannan Guo
Saverio Brogna
Journal: Molecular and Cellular Biology (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Poly(A) signals; 3' end; cleavage; polyadenylation; pre-mRNA
Affiliations: School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

Abstract:  Poly(A) signals located at the 3' end of eukaryotic genes drive cleavage and polyadenylation at the same end of pre-mRNA. Although these sequences are expected only at the 3' end of genes, we found that strong poly(A) signals are also predicted within the 5' untranslated regions (UTRs) of many Drosophila melanogaster mRNAs. Most of these 5' poly(A) signals have little influence on the processing of the endogenous transcripts, but they are very active when placed at the 3' end of reporter genes. In investigating these unexpected observations, we discovered that both these novel poly(A) signals and standard poly(A) signals become functionally silent when they are positioned close to transcription start sites in either Drosophila or human cells. This indicates that the stage when the poly(A) signal emerges from the polymerase II (Pol II) transcription complex determines whether a putative poly(A) signal is recognized as functional. The data suggest that this mechanism, which probably prevents cryptic poly(A) signals from causing premature transcription termination, depends on low Ser2 phosphorylation of the C-terminal domain of Pol II and inefficient recruitment of processing factors. 

Retracted: No

PubPeer comments:
 2017 correction. http: mcb.asm.org content 37 13 e00189-17.full , 
 The Correction reads:  *Fig. 8A: When the original paper was prepared, lanes 1 to 3 of the 18S panel of Fig. 7A were accidently reused as lanes 1 to 3 of the Fig. 8A 18S panel. The correct 18S panel should appear as shown below. We apologize to the readers. The change does not affect the interpretation of any of the experiments described in the paper.* Here are the original Figures 7A and 8A, with the duplication marked with red boxes, as reported to the journal in September 2016. ![file] I thank the authors and journal staff for addressing this duplication. This paper was part of a structured search for image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long ,
MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade
Authors: Tae Il Jeon
Hyunjung Lee
Jiyun Ahn
Chang Hwa Jung
Tae Youl Ha
Journal: EMBO Molecular Medicine (2013)
Discipline: CLINICAL MEDICINE
Keywords: SIRT1; adipogenesis; fat mass; microRNA-146b; obesity.
Affiliations: Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon, Korea.

Abstract:  Sirtuin 1 (SIRT1) plays a critical role in the maintenance of metabolic homeostasis and promotes fat mobilization in white adipose tissue. However, regulation of SIRT1 during adipogenesis, particularly through microRNAs, remains unclear. We observed that miR-146b expression was markedly increased during adipogenesis in 3T3-L1 cells. Differentiation of 3T3-L1 was induced by overexpression of miR-146b. Conversely, inhibition of miR-146b decreased adipocyte differentiation. Bioinformatics-based studies suggested that SIRT1 is a target of miR-146b. Further analysis confirmed that SIRT1 was negatively regulated by miR-146b. We also observed that miR-146b bound directly to the 3'-untranslated region of SIRT1 and inhibited adipogenesis through SIRT1 downregulation. The miR-146b/SIRT1 axis mediates adipogenesis through increased acetylation of forkhead box O1 (FOXO1). Expression of miR-146b was increased and SIRT1 mRNA subsequently decreased in the adipose tissues of diet-induced and genetically obese mice. Furthermore, in vivo knockdown of miR-146b by a locked nucleic acid miR-146b antagomir significantly reduced body weight and fat volume in accordance with upregulation of SIRT1 and subsequent acetylation of FOXO1. Therefore, the miR-146b/SIRT1 pathway could be a potential target for obesity prevention and treatment. 

Retracted: No

PubPeer comments:
 Would the authors be able to provide a higher resolution image of Figure 1C? At the resolution of the figure I am able to find shows some unexpected similarities. *** Contrast adjusted ![file] ,
Evaluation of cytotoxicity of some common ophthalmic drugs
Authors: L Gan
X Lv
Y Qiao
X-M Chen
D-M Wang
J-J Liu
M Li
Journal: European review for medical and pharmacological sciences (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Evaluation; cytotoxicity; ophthalmic drugs; withdrawn; research paper
Affiliations: Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

Abstract:  The article "Evaluation of cytotoxicity of some common ophthalmic drugs" by M. Li, X.-M. Chen, J.-J. Liu, D.-M. Wang, L. Gan, X. Lv, Y. Qiao, published in Eur Rev Med Pharmacol Sci 2015; 19 (11): 1945-1950 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,
Loss of vinculin and membrane-bound β-catenin promotes metastasis and predicts poor prognosis in colorectal cancer
Authors: Yongquan Shi
Yongzhan Nie
Xiaodi Zhao
Hanqing Guo
Ting Li
Daiming Fan
Ying Song
Yuanyuan Lu
Sijun Hu
Kaichun Wu
Journal: Molecular Cancer (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cell-cell adhesion; cancer invasion; metastasis; vinculin; colorectal cancer

Abstract:  Background: Loss of cell-cell adhesion is important for the development of cancer invasion and metastasis. Vinculin, a key adhesion-related protein, can affect metastasis and prognosis in several tumours. Here, we determined the biological roles of vinculin in the metastasis of colorectal cancer (CRC) and evaluated its clinical significance as a potential disease biomarker. Methods: The expression level of vinculin in CRC cell lines and tissues was measured using Real-Time PCR and western blotting. Moreover, vinculin function was analysed using Transwell assays and in vivo metastasis assays in gain- and loss-of-function experiments. Furthermore, the impact of vinculin together with membrane-bound β-catenin on the prognosis of 228 CRC patients was investigated by immunohistochemistry. Additionally, the expression of epithelial-mesenchymal transition (EMT) indicators was verified by immunohistochemistry in CRC tissues obtained from these patients. Result: Vinculin expression was found to be significantly downregulated in highly metastatic CRC cell lines and metastatic tissues. Both in vitro and in vivo experiments showed that vinculin suppressed invasion, migration and metastasis in CRC cells and that this suppression could be attenuated by silencing β-catenin. Moreover, the expression of vinculin and membrane-bound β-catenin were positively correlated in CRC tissues, and lack of vinculin expression emerged as an independent prognostic factor in patients with CRC. Finally, the loss of vinculin and membrane-bound β-catenin was associated with node metastasis, organ metastasis and expression of EMT indicators. Conclusion: Our results suggest that vinculin may play specific roles in the EMT and metastasis of CRC and that loss of vinculin could be used as a prognostic factor for CRC. 

Retracted: No

PubPeer comments:
 Fig. 2D contains two sets of image overlap. ![file] , 
 #1 Thank you for the question. I will check with the original data and get back to you as soon as possible. , 
 Images in Figure 3D seem to overlap, but not all features are identical. Could the authors please comment? TAM. *** https: imgur.com a eQMQzWf , 
 #2 Thank you for your concern. We checked the original version of this manuscript and found that the representative images belonging to Fig.2D (bottom panel) was accidentally misplaced when assembling the figures in imaging software. We sincerely apologize for this mistake. We are currently contacting the journal for correction. This change does not affect the results or conclusions reported in the manuscript. Thank you for your interest in our work! Sincerely, Kaichun Wu ,
Isoflurane preconditioning confers cardioprotection by activation of ALDH2
Authors: Xiao-E Lang
Jian-Hua Jin
Qing-Shan Li
Ji-Yuan Lv
Xiong Wang
Ke-Rang Zhang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: isoflurane; ALDH2; cardioprotection; ischemia/reperfusion injury; LDH
Affiliations: Department of Cardiology, The First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, China.

Abstract:  The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R) injury. Aldehyde dehydrogenase 2 (ALDH2) is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKCε) inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKCε inhibitor. Activation of ALDH2 by mitochondrial PKCε plays an important role in the cardioprotection of isoflurane in myocardium I/R injury. 

Retracted: No

PubPeer comments:
null, 
 Because something went wrong with the second illustration during the PubPeer upgrade, here is the illustration for Figure 4Ba again. Both concerns, for Figure 3 and 4, have been reported to the journal in 2014. ![file] ,
Telomerase activity and hepatic functions of rat embryonic liver progenitor cell in nanoscaffold-coated model bioreactor
Authors: Sanja Pavlica
Karen Nieber
Mario Keller
Ali Acikgöz
Augustinus Bader
Shibashish Giri
Journal: Molecular and Cellular Biochemistry (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: telomerase activity; cell proliferation; hepatic functions; nanostructured scaffold; cell-scaffold interaction
Affiliations: Department of Cell Technologies and Applied Stem Cell Biology, Biomedical-Biotechnological Center (BBZ), Deutscher Platz 5, 04103, Leipzig, Germany .

Abstract:  Presently, there is growing interest on telomerase activity in all cells (somatic cells, stem cells, cancerous cells and others) since this activity is associated with cellular changes such as proliferation, differentiation, immortalization, cell injury and ageing. Telomerase activity is absent in most of the somatic cells but present in over 90% of cancerous cells and other immortalized cell lines. In our present study, we cultured a rat embryonal liver progenitor cell line RLC-18 in a self-assembly nanostructured scaffold-coated bioreactor (NCB), collagen-coated plates (CCP) and uncoated plates (UP), and evaluated changes of telomerase activity by non radioactive techniques (Telo TAGGG Telomerase PCR ELISA, cell proliferation based on mitochondria number by MTT assay and hepatic functions such as albumin secretion, urea metabolism, Cytochrome P450 activity like ethoxyresorufin-O-deethylase (EROD) activity. We found less telomerase activity and less cell proliferation, but more hepatic functions on the NCB than on the CCP and UP. Our data support the concept that cell-scaffold interaction may play a significant in controlling the telomerase activity as well as enhanced hepatic functions. Although our present study does not focus on the exact mechanism of telomerase regulation, our result may provide basic clues on cell differentiation whereby telomerase activity inhibits differentiation of cells as in the rat embryonic liver cell line, may be regulated by cell-scaffold interaction and where there is less proliferation, cells perform enhanced hepatic functions, thereby implying that bioartificial liver support may be possible. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have a repeated image. *** ![file] ,