PReD-Bench/PRed-Bench huggingface dataset:
Aged Tendon Stem/Progenitor Cells Are Less Competent to Form 3D Tendon Organoids Due to Cell Autonomous and Matrix Production Deficits
Authors: Christian G Pfeifer
Denitsa Docheva
Volker Alt
Zexing Yan
Heyong Yin
Christoph Brochhausen
Journal: Frontiers in Bioengineering and Biotechnology (2020)
Discipline: Multidisciplinary
Keywords: 3D cell sheet model; tendon age-related degeneration; tendon regeneration; tendon stem/progenitor cells; tenogenesis.
Affiliations: Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Centre, Regensburg, Germany., Institute of Pathology, University of Regensburg, Regensburg, Germany., Department of Medical Biology, Medical University of Plovdiv, Plovdiv, Bulgaria.

Abstract:  Tendons are dense connective tissues, which are critical for the integrity and function of our musculoskeletal system. During tendon aging and degeneration, tendon stem/progenitor cells (TSPCs) experience profound phenotypic changes with declined cellular functions that can be linked to the known increase in complications during tendon healing process in elderly patients. Tissue engineering is a promising approach for achieving a complete recovery of injured tendons. However, use of autologous cells from aged individuals would require restoring the cellular fitness prior to implantation. In this study, we applied an established cell sheet model for in vitro tenogenesis and compared the sheet formation of TSPC derived from young/healthy (Y-TSPCs) versus aged/degenerative (A-TSPCs) human Achilles tendon biopsies with the purpose to unravel differences in their potential to form self-assembled three-dimensional (3D) tendon organoids. Using our three-step protocol, 4 donors of Y-TSPCs and 9 donors of A-TSPCs were subjected to cell sheet formation and maturation in a period of 5 weeks. The sheets were then cross evaluated by weight and diameter measurements; quantification of cell density, proliferation, senescence and apoptosis; histomorphometry; gene expression of 48 target genes; and collagen type I protein production. The results revealed very obvious and significant phenotype in A-TSPC sheets characterized by being fragile and thin with poor tissue morphology, and significantly lower cell density and proliferation, but significantly higher levels of the senescence-related gene markers and apoptotic cells. Quantitative gene expression analyses at the mRNA and protein levels, also demonstrated abnormal molecular circuits in the A-TSPC sheets. Taken together, we report for the first time that A-TSPCs exhibit profound deficits in forming 3D tendon tissue organoids, thus making the cell sheet model suitable to investigate the molecular mechanisms involved in tendon aging and degeneration, as well as examining novel pharmacologic strategies for rejuvenation of aged cells. 

Retracted: No

PubPeer comments:
 This doesn t seem to be a critical issue, but a number of the figures include insets that seem as if they are intended to show a different magnification, but don t. One example from Figure 2C shows below. Red boxes are the same size and seem to cover the same portion of the sample. *** ![file] ,
Intrapore energy barriers govern ion transport and selectivity of desalination membranes
Authors: Jae-Hong Kim
Menachem Elimelech
Razi Epsztein
John D Fortner
Zhangxin Wang
Cheng Zhan
Wenlu Li
Tuan Anh Pham
Xuechen Zhou
Journal: Science Advances (2020)
Discipline: Multidisciplinary
Keywords: desalination membranes; ion transport; selectivity; subnanometer pores; energy barrier
Affiliations: Department of Chemical and Environmental Engineering, Yale University, New Haven, CT 06511, USA., Faculty of Civil and Environmental Engineering, Technion—Israel Institute of Technology, Technion City, Haifa 32000, Israel., Lawrence Livermore National Laboratory, Livermore, CA 94551, USA.

Abstract:  State-of-the-art desalination membranes exhibit high water-salt selectivity, but their ability to discriminate between ions is limited. Elucidating the fundamental mechanisms underlying ion transport and selectivity in subnanometer pores is therefore imperative for the development of ion-selective membranes. Here, we compare the overall energy barrier for salt transport and energy barriers for individual ion transport, showing that cations and anions traverse the membrane pore in an independent manner. Supported by density functional theory simulations, we demonstrate that electrostatic interactions between permeating counterion and fixed charges on the membrane substantially hinder intrapore diffusion. Furthermore, using quartz crystal microbalance, we break down the contributions of partitioning at the pore mouth and intrapore diffusion to the overall energy barrier for salt transport. Overall, our results indicate that intrapore diffusion governs salt transport through subnanometer pores due to ion-pore wall interactions, providing the scientific base for the design of membranes with high ion-ion selectivity. 

Retracted: No

PubPeer comments:
 The authors declared  The goal of this study was to elucidate the molecular-level mechanisms underlying salt transport through the **subnanometer pores** of desalination membranes . But no pore size data for the membrane used was provided in this work. Do the authors think the commercial polyamide RO membrane only has subnanometer pores? For real, the pore size distribution of RO membranes is wide, spanning from sub-nanometer scale to several nanometer scale. The experimental energy barrier values reported in this work is more like the averaged values of RO membrane with multiple subnanometer and nanometer pores, not the  subnanometer pore the author claimed. ,
Satellite phage TLCφ enables toxigenic conversion by CTX phage through dif site alteration
Authors: M Kamruzzaman
Faizule Hassan
Shah M Faruque
John J Mekalanos
Journal: Nature (2010)
Discipline: Multidisciplinary
Keywords: Bacterial chromosomes; genetic elements; plasmids; transposons; prophages
Affiliations: Molecular Genetics Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka-1212, Bangladesh.

Abstract:  Bacterial chromosomes often carry integrated genetic elements (for example plasmids, transposons, prophages and islands) whose precise function and contribution to the evolutionary fitness of the host bacterium are unknown. The CTXφ prophage, which encodes cholera toxin in Vibrio cholerae, is known to be adjacent to a chromosomally integrated element of unknown function termed the toxin-linked cryptic (TLC). Here we report the characterization of a TLC-related element that corresponds to the genome of a satellite filamentous phage (TLC-Knφ1), which uses the morphogenesis genes of another filamentous phage (fs2φ) to form infectious TLC-Knφ1 phage particles. The TLC-Knφ1 phage genome carries a sequence similar to the dif recombination sequence, which functions in chromosome dimer resolution using XerC and XerD recombinases. The dif sequence is also exploited by lysogenic filamentous phages (for example CTXφ) for chromosomal integration of their genomes. Bacterial cells defective in the dimer resolution often show an aberrant filamentous cell morphology. We found that acquisition and chromosomal integration of the TLC-Knφ1 genome restored a perfect dif site and normal morphology to V. cholerae wild-type and mutant strains with dif(-) filamentation phenotypes. Furthermore, lysogeny of a dif(-) non-toxigenic V. cholerae with TLC-Knφ1 promoted its subsequent toxigenic conversion through integration of CTXφ into the restored dif site. These results reveal a remarkable level of cooperative interactions between multiple filamentous phages in the emergence of the bacterial pathogen that causes cholera. 

Retracted: No

PubPeer comments:
 Can the authors provide more details about how they produced the Co-IP Figure 5? It looks like they performed the IP using a FLAG antibody, but I can not see any mention of a FLAG tagged protein in the paper, so it is not clear what the antibody would be binding. , 
 Also, there is a panel duplication between Figure 2 and Figure 6 ![file] , 
 I found some additional problems in the supplementary tables. The different categories in cohort I high column should always total 140 samples. Most of these do, however the TNM stage totals 143 samples. Similarly the cohort II low samples should total 101 samples, but the tumor differentiation and the TNM stage both have 100 samples. ![file] Also one of the Cohort II entries just says time . ![file] I also went back over the methods and noticed that while there is a description of TOPFLASH assays in the text, there is no mention of the TOPFLASH and FOPFLASH constructs that would be required to do that assay in the methods section. ,
Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-κB and PI3K/Akt3 signaling pathways
Authors: Bin Zhu
Lei Wang
Xuyu Yang
Qiuyuan Wen
Caiping Ren
Jie Liu
Huan Chen
Weidong Liu
Wei Jia
Liang Zeng
Chang Zhang
Xiaomeng Xia
Yuxiang Chen
Xiangling Feng
Lihua Zhang
Wei Huang
Journal: Scientific Reports (2015)
Discipline: Multidisciplinary
Keywords: Lipid raft proteins; Flotillin-2; Nasopharyngeal carcinoma; Metastasis; Malignancy
Affiliations: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, 410078, Changsha, Hunan, P. R. China., Department of Pathology, Hunan Cancer Hospital, Changsha, Hunan, P. R. China., Department of Gynaecology and Obstetrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China., Hepatobiliary &Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.

Abstract:  Lipid raft proteins have been confirmed to be important in cell signal transduction. Some reports have shown that the aberrant expression of lipid raft proteins is associated with malignant phenotypes in some cancers. However, the role of the lipid raft protein flotillin-2 (Flot-2) in nasopharyngeal carcinoma (NPC) remains to be comprehensively characterized. Here, overexpression of Flot-2 in NPC tissues and cell lines was detected by immunostaining, and Flot-2 expression was found to be positively associated with NPC metastasis. Furthermore, inhibiting Flot-2 expression impaired the malignancy of the highly metastatic NPC cell line 5-8F by constraining its growth and proliferation, mobility and migration, and decreasing the capacity of 5-8F cells to metastasize in nude mice. In contrast, forced overexpression of Flot-2 increased the malignancy of 6-10B, a non-metastatic NPC cell line that weakly expresses Flot-2. Moreover, in 5-8F-shFlot-2 cells, which have inhibited Flot-2 expression, the NF-κB and PI3K/Akt3 pathways were inactivated. Subsequently, MMPs expression were decreased, and Foxo1 activity was increased. In addition, enhanced NF-κB and PI3K/Akt3 activities were observed in Flot-2 overexpressing 6-10B cells. Thus, Flot-2 exerts a pro-neoplastic role in NPC and is involved in tumor progression and metastasis. Moreover, Flot-2 exerts its role through NF-κB and PI3K/Akt3 signaling. 

Retracted: No

PubPeer comments:
 Figure 8A appears to have a reused band, flipped horizontally. Original and inverse shown below to aid comparison. *** ![file] *** ![file] , 
 Published April 20, 2020 ![file] , 
 A band appears to have been used for two different conditions in Figure 2A, with a slight change in exposure. Do the authors still have access to the original data? *** ![file] ,
LncRNA SNHG16 reverses the effects of miR-15a/16 on LPS-induced inflammatory pathway
Authors: Yaowu Du
Xiaomin Zhang
Wenying Wang
Chunyan Lou
Jie Gao
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Neonatal sepsis; SNHG16; TLR4; miR-15a/16.
Affiliations: Department of Pediatrics, Huaihe Hospital of Henan University, No. 8, Baobei Road, Gulou District, Kaifeng, 475000, China., Pingdingshan University, Weilai Road, Xincheng District, Pingdingshan, 467000, China., Laboratory for Nanomedicine, School of Basic Medical Science, Henan University, Kaifeng, 475004, China. Electronic address: .

Abstract:  Nowadays, neonatal sepsis has gradually become a global problem for its high incidence and increasing mortality. Previous studies have reported that miR-15a and miR-16 are two important modulators in neonatal sepsis. However, the upstream molecular mechanism of miR-15a/16 cluster is still mysterious. This study aims to explore a lncRNA can bind with miR-15a/16 in neonatal sepsis. Microarray analysis helped us found top ten lncRNAs which were downregulated in neonatal sepsis serum. Among these ten lncRNAs, SNHG16 was uncovered to significantly downregulated both miR-15a and miR-16. According to the result of subcellular fractionation assay, SNHG16 was mainly located in the cytoplasm of RAW264.7 cell, indicating the potential ceRNA role of SNHG16. Mechanism investigations revealed that SNHG16 could act as a ceRNA to upregulate TLR4 which is the target mRNA of miR-15a/16 cluster. At last, rescue assays demonstrated that SNHG16 reversed the effects of miR-15a/16 on LPS-induced inflammatory pathway. In summary, SNHG16 can act as a ceRNA to modulate miR-15a/16 cluster, thereby affecting LSP-induced inflammatory pathway which was downregulated by miR-15a/16 cluster. 

Retracted: No

PubPeer comments:
 Fig 5C.  ... protein level of TLR4 were detected in indicated RAW264.7 cells which were treated with or without LPS.  ![file] ,
Alpinumisoflavone protects against glucocorticoid-induced osteoporosis through suppressing the apoptosis of osteoblastic and osteocytic cells
Authors: Jiangtao Liu
Dongying Tao
Yun Wang
Qingjiang Pang
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Alpinumisoflavone; Apoptosis; Nrf2; Osteoblast; Osteocyte
Affiliations: Department of Orthopedics, Ningbo No. 2 Hospital, Ningbo, 315104, China., Department of Human Morphology, Ningbo College of Health Science, No. 51 Xuefu Road, Ningbo, Zhejiang, 315104, China. Electronic address: .

Abstract:  The long-term use of glucocorticoids is found to cause osteoporosis. This study is designed to evaluate the protective effect of alpinumisoflavone (AIF), a naturally occurring flavonoid compound, on dexamethasone(Dex)-induced osteoporosis. We use a rat model to investigate the apoptosis of osteoblastic and osteocytic cells. The results indicate that AIF effectively protects against dexamethasone-induced osteoporosis. Moreover, AIF effectively reversed dexamethasone-induced apoptosis in osteoblastic and osteocytic cells through inhibiting ROS overproduction and regulating the Nrf2 pathway. In conclusion, the AIF activated Nrf2 signaling pathway was observed to suppress Dex-induced ROS production in osteoblastic and osteocytic cells, which may explain its anti-osteoporotic effects against dexamethasone-induced osteoporosis. 

Retracted: No

PubPeer comments:
 Figure 4 appears they have a repeated image, when one is intended to be at a different scale. Should not affect the conclusions. *** ![file] , 
 Figure three appears they have two images which overlap, although they seem to be differently colored (green boxes). Red boxes in original. *** ![file] ,
Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells
Authors: Shengjie Dai
Xince Huang
Bicheng Chen
Jiadong Su
Tingting Ye
Chaohao Huang
Dinglai Yu
Mengtao Zhou
Journal: OncoTargets and Therapy (2016)
Discipline: CLINICAL MEDICINE
Keywords: AMPK; VEGF; apoptosis; invasiveness; isoorientin
Affiliations: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University., Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University; Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People's Republic of China.

Abstract:  Isoorientin (or homoorientin) is a flavone, which is a chemical flavonoid-like compound, and a 6-C-glucoside of luteolin. Isoorientin has been demonstrated to have anti-cancer activities against various tumors, but its effects on pancreatic cancer (PC) have not been studied in detail. In this study, we aim to investigate whether isoorientin has potential anti-PC effects and its underlying mechanism. In PC, isoorientin strongly inhibited the survival of the cells, induced cell apoptosis, and decreased its malignancy by reversing the expression of epithelial-mesenchymal transition and matrix metalloproteinase and decreased vascular endothelial growth factor expression. Meanwhile, we investigated the activity of the AMP-activated protein kinase (AMPK) signaling pathway after isoorientin treatment, which was forcefully activated by isoorientin, as expected. In addition, in the PC cells that were transfected with lentivirus to interfere with the expression of the gene PRKAA1, there were no differences in the apoptosis rate and the expression of malignancy biomarkers in the tumors of the isoorientin-treated and untreated groups. Thus, we demonstrated that isoorientin has potential antitumor effects via the AMPK signaling pathway, and isoorientin merits further investigation. 

Retracted: No

PubPeer comments:
 https: doi.org 10.2147 OTT.S140829 The authors have advised that a number of errors were made in some of the figures within their paper. ,
Dysregulation of miR-375/AEG-1 Axis by Human Papillomavirus 16/18-E6/E7 Promotes Cellular Proliferation, Migration, and Invasion in Cervical Cancer
Authors: Maheshkumar Kannan
Sridharan Jayamohan
Hun Soon Jung
Rajesh Kannan Moorthy
Nirmal Rajasekaran
Antony Joseph Velanganni Arockiam
Young Kee Shin
Journal: Frontiers in Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: astrocyte elevated gene-1; cell proliferation; cervical cancer; human papillomavirus; miR-375.
Affiliations: Molecular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India., Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea., Laboratory of Molecular Pathology and Cancer Genomics, College of Pharmacy, Seoul National University, Seoul, South Korea., Enhancedbio Inc., Seongdong-gu, South Korea.

Abstract:  Cervical Cancer (CC) is a highly aggressive tumor and is one of the leading causes of cancer-related deaths in women. miR-375 was shown to be significantly down-regulated in cervical cancer cells. However, the precise biological functions of miR-375 and the molecular mechanisms underlying its action in CC are largely unknown. miR-375 targets were predicted by bioinformatics target prediction tools and validated using luciferase reporter assay. Herein, we investigated the functional significance of miR-375 and its target gene in CC to identify potential new therapeutic targets. We found that miR-375 expression was significantly downregulated in CC, and astrocyte elevated gene-1 (AEG-1) was identified as a target of miR-375. Our results also showed that ectopic expression of miR-375 suppressed CC cell proliferation, migration, invasion and angiogenesis, and increased the 5-fluorouracil-induced apoptosis and cell cycle arrest in vitro. In contrast, inhibition of miR-375 expression significantly enhanced these functions. Furthermore, HPV - 16 E6/E7 and HPV - 18 E6/E7 significantly down-regulates miR-375 expression in CC. HPV 16/18-E6/E7/miR-375/AEG-1 axis plays an important role in the regulation of cell proliferation, migration, and invasion in CC. Therefore, targeting miR-375/AEG-1 mediated axis could serve as a potential therapeutic target for CC. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have some duplicated images ![file] ,
Post-prandial decrease of circulating human ghrelin levels
Authors: R L Riepl
M Bidlingmaier
R Wawarta
R Landgraf
C Folwaczny
S Friedrich
M Tschöp
Journal: Journal of Endocrinological Investigation (2001)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ghrelin; GH secretagogue-receptor; rodents; regulation; biological function
Affiliations: Medizinische Klinik Innenstadt, Ludwig-Maximilians Universität, Munich, Germany.

Abstract:  Ghrelin, an endogenous ligand of the GH secretagogue-receptor, has recently been shown to stimulate GH secretion and to have orexigenic and adipogenic effects in rodents, but little is known about its regulation and biological function in humans. Gastric motor function is under control of the central nervous system; however, the afferent and efferent loops of this feedback control mechanism remain to be elucidated. In the study presented here we investigated the effect of nutrient intake on circulating human ghrelin levels, and a possible association between ghrelin levels and gastric emptying. Ten healthy volunteers received a standard meal after an overnight fast. Food intake significantly decreased plasma ghrelin levels from 248.5 +/- 15.0 to 179.5 +/- 17.9 fmol/ml (120 min after meal, p=0.047). Gastric emptying half-time (non-invasive 13C-octanoic acid breath test) was correlated with fasting plasma ghrelin levels (r=0.74, p=0.0013). Ghrelin appears to be one possible candidate to provide feedback signaling between nutrient intake, gastric motor function and the central nervous system. 

Retracted: No

PubPeer comments:
 According to the methods, this little experiment in 10 individuals went from 8 to 12 AM (240min) so how could the authors measure gastric empty times of 300min in Fig 1C? Fig 1C shows mean preprandial plasma! ghrelin levels (axis description is serum!) of 236 fmol ml with a SEM of 4.9. Nevertheless Fig 1B gives a value of 248.5u00b115.0 fmol per liter! Even if we correct the apparent scaling error, both mean and SEM are wrong when using the data from Fig 1C. ![file] As  all data are presented as meanu00b1SE the SEM of gastric emptying half-time of 75min in the result section looks unreasonable. There are even more discrepancies as there is a double publication in [Exp Clin Endocrinol Diabetes 2003; 111: 233] . ![file] Could the authors please clarify? ,
Alpha-fetoprotein contributes to THP-1 cell invasion and chemotaxis via protein kinase and Gi-protein-dependent pathways
Authors: Mikhail Menshikov
Igor Dudich
Ekaterina Zubkova
Elena Dudich
Yelena Parfyonova
Lidiya Semenkova
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Alpha-fetoprotein; THP-1 cell line; invasion; MMP9 expression; chemotaxis

Abstract:  Alpha-fetoprotein (AFP) for long was known as immunomodulator and tumor marker having multifaceted actions on the activity of normal and transformed cells. In present study, we have investigated the involvement of AFP in regulation of THP-1 cell line invasion and underlying mechanisms. Treatment with human recombinant AFP causes up-regulation of MMP9 expression, chemotaxis and calcium mobilization, and increases invasion through Matrigel, with no significant impact on THP-1 cell growth or viability. Using small molecule inhibitors, we have shown that the rhAFP-induced MMP9 expression depends on the activation of ERK1,2, JNK and Akt kinases, with the involvement of NFκB and likely, AP-1 transcription factors. In contrast, inhibition of p38 kinase, but not of JNK, had dramatic suppressive effect on the rhAFP-triggered chemotaxis. In addition, rhAFP-induced MMP9 expression and calcium response were completely blocked by pertussis toxin, indicating that Gi-protein-coupled receptor(s) has a mediatory role in these processes. CCR5 chemokine receptor is the only known Gi-protein binding to AFP. The action of CCR5 inhibitor Maraviroc results in partial suppression of MMP9 up-regulation and calcium response suggesting that CCR5 might be involved in these effects. 

Retracted: No

PubPeer comments:
 Figure 1A. The top left and top right panel appear to show a small area of overlap. ![file] ,
MALAT2-activated long noncoding RNA indicates a biomarker of poor prognosis in gastric cancer
Authors: Y Wang
L Li
F Chen
E-J Pang
Y Tian
Journal: Cancer Gene Therapy (2015)
Discipline: CLINICAL MEDICINE
Keywords: long noncoding RNA; MALAT2; gastric cancer; prognosis; stage II/III
Affiliations: Division of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Abstract:  The purpose of this study is to investigate the role of the long noncoding RNA metastasis associated lung adenocarcinoma transcript 2 (MALAT2) in the prognosis of stage II/III gastric cancer (GC) patients. The expression of MALAT2 was evaluated in cancer tissues from 146 stage II/III GC patients undergoing radical resection and 60 paired normal samples using quantitative real-time reverse transcriptase PCR. Differences in the expression of MALAT2 between 23 GC and paired normal colonic mucosa samples were analysed with the Wilcoxon test. Relationships between the expression level of MALAT2, patient clinico-pathological parameters and disease-free survival and overall survival were analysed using the uni-variate Kaplan-Meier method and the multivariate COX regression model. The quantitative polymerase chain reaction results showed that MALAT2 was frequently over-expressed in cancer tissues and this over-expression was found to significantly correlate with lymph node metastasis and tumor stage. The ectopic expression of MALAT2 contributed to the migration of human GC SGC-7901 cells, whereas knockdown of MALAT2 inhibited the migration of the SGC-7901 cells in vitro. Further investigation into the underlying mechanisms responsible for the migratory effects revealed that MALAT2 induced the epithelial-mesenchymal transition (EMT) through an MEK/extracellular signal-regulated kinase-dependent mechanism as treatment with the MEK inhibitor, U0126, decreased migration and reversed the EMT in the MALAT2 over-expressed SGC-7901 cells. The expression of MALAT2 is upregulated in GC tissues, and a higher expression level of MALAT2 might serve as a negative prognostic marker in stage II/III GC patients which implies the potential application of MALAT2 in the therapeutic treatment of GC.Cancer Gene Therapy advance online publication, 27 February 2015; doi:10.1038/cgt.2015.6. 

Retracted: Yes

PubPeer comments:
 Figure 3d. Much more similar than expected. ![file] , 
 #1 After retrieving the corresponding bands and zooming them, it is clear that although there is a resemblance between the bands, they are clearly not identical. Please note the top of the higher band and lower band that the shape is quite different. Carmen Garrido ,
HMGB1 Facilitated Macrophage Reprogramming towards a Proinflammatory M1-like Phenotype in Experimental Autoimmune Myocarditis Development
Authors: Hongxiang Lu
Ping Ni
Zhaoliang Su
Yanfang Liu
Huiling Shen
Ying Yu
Huaxi Xu
Xiaolian Su
Yueqin Liu
Pan Zhang
Dan Wang
Wenlin Xu
Jia Wang
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Macrophages; reprogramming; M1; M2; phenotype
Affiliations: Department of Immunology, Jiangsu University, Zhenjiang, China, 212013., The Central Laboratory, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China, 212001.

Abstract:  Macrophages can be reprogramming, such as the classical activated macrophage, M1 or alternative activated macrophages, M2 phenotype following the milieu danger signals, especially inflammatory factors. Macrophage reprogramming is now considered as a key determinant of disease development and/or regression. Experimental autoimmune myocarditis (EAM) is characterized by monocytes/macrophage infiltration, Th17 cells activation and inflammatory factors producing such as high mobility group box 1 (HMGB1). Whether infiltrated macrophages could be reprogramming in EAM? HMGB1 was associated with macrophage reprogramming? Our results clearly demonstrated that infiltrated macrophage was reprogrammed towards a proinflammatory M1-like phenotype and cardiac protection by monocytes/macrophages depletion or HMGB1 blockade in EAM; in vitro, HMGB1 facilitated macrophage reprogramming towards M1-like phenotype dependent on TLR4-PI3Kγ-Erk1/2 pathway; furthermore, the reprogramming M1-like macrophage promoted Th17 expansion. Therefore, we speculated that HMGB1 contributed EAM development via facilitating macrophage reprogramming towards M1-like phenotype except for directly modulating Th17 cells expansion. 

Retracted: Yes

PubPeer comments:
 Fig 2F. Two right plots, HMGB1 and HMGB1 + anti-TLR4 mAb, have many of their dots overlapped. ![file] , 
 Retracted [8 April 2022] . ------------------------- The Authors have retracted this Article. After publication, the Authors informed the journal that Fig. 4 contained incorrectly reported results, and the images in Fig. 5 had been published elsewhere. In addition, concerns were raised regarding partial overlap in the flow cytometry plots in Fig. 2F (HMGB1 and HMGB1u2009+u2009anti-TLR4 groups). The Authors are unable to provide raw data used to produce the figures, and therefore retract this Article. All Authors agree with this retraction. ,
ORF73 of Herpesvirus Saimiri Strain C488 Tethers the Viral Genome to Metaphase Chromosomes and Binds to cis -Acting DNA Sequences in the Terminal Repeats
Authors: Erle S Robertson
Subhash C Verma
Journal: Journal of Virology (2003)
Discipline: MICROBIOLOGY
Keywords: Kaposi's sarcoma; herpesvirus; latency; nuclear antigen; episome
Affiliations: Department of Microbiology. Tumor Virology Program, Abramson Comprehensive Cancer Center, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Department of Microbiology, Tumor Virology Program, Abramson Comprehensive Cancer Center, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Abstract:  Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), a human oncogenic gamma-2-herpesvirus, transforms human endothelial cells and establishes latent infection at a low efficiency in vitro. During latent infection, only a limited number of genes are expressed, and the circularized viral genome is maintained as a multicopy episome. Latency-associated nuclear antigen (LANA), exclusively expressed during latency, has been shown to have a multifunctional role in KS pathogenesis. LANA tethers the viral episome to the host chromosome, thus ensuring efficient persistence of the viral genome during successive rounds of cell division. Besides episome maintenance, LANA modulates the expression of genes of various cellular and viral pathways, including those of retinoblastoma protein and p53. Herpesvirus saimiri (HVS), another gamma-2-herpesvirus, primarily infects New World primates. Orf73, encoding the nuclear antigen of HVS, is the positional homolog of the LANA gene, and the ORF73 protein has some sequence homology to KSHV LANA. However, the function of ORF73 of HVS has not been thoroughly investigated. In this report, we show that HVS ORF73 may be important for episome persistence and colocalizes with the HVS genomic DNA on metaphase chromosomes. Furthermore, HVS terminal repeats (TRs) contain a cis-acting sequence similar to that in KSHV TRs, suggesting that the LANA binding sequence is conserved between these two viruses. This cis-acting element is sufficient to bind HVS ORF73 from strains C488 and A11, and plasmids containing the HVS C488 TR element are maintained and replicate in HVS C488 ORF73-expressing cells. 

Retracted: No

PubPeer comments:
 Figure 10A. * Red boxes: Parts of the background appear to look repetitive. ![file] ,
Cross-talk between STAT1 and PI3K/AKT signaling in HIV-1-induced blood-brain barrier dysfunction: role of CCR5 and implications for viral neuropathogenesis
Authors: Rafael Bressani
Georgette D Kanmogne
Bo Yang
Sangya Singh
Journal: Journal of neuroscience research (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: neuroinflammation; signaling pathways; blood-brain barrier dysfunction; HIV-1 infection; STAT1
Affiliations: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nerbraska, USA.

Abstract:  How neuroinflammation affects signaling pathways leading to human blood-brain barrier (BBB) dysfunction during HIV-1 infection is incompletely understood. We previously demonstrated that signal transducers and activators of transcription-1 (STAT1) signaling is involved in HIV-1 induced BBB damage and is relevant to viral neuropathogenesis. The objective of this study was to delineate the signaling pathways upstream and downstream of STAT1 involved in HIV-1-induced endothelial dysfunction. We show that HIV-1 activation of STAT1 and STAT3 in human brain microvascular endothelial cells (HBMEC) is associated with induction of promoter activity of the interferon-stimulated response element (ISRE)/interferon-γ-activated sequence (GAS). The STAT1 inhibitor fludarabine diminished HIV-1-induced ISRE/GAS promoter activity. CCR5 neutralizing antibodies and the phosphoinositide-3-kinase (PI3K) inhibitor LY-294002 diminished HIV-1-induced phosphorylation of STAT1 and STAT3, significantly diminished HIV-1-induced ISRE/GAS promoter activity, and diminished virus-induced monocyte adhesion and transendothelial migration. HIV-1 infection did not phosphorylate janus kinases but induced activation of the phosphoinositide-dependent kinase-1 (PDK1) and the serine-threonine protein kinase AKT, both downstream effectors of PI3K. CCR5 antibodies also diminished virus-induced phosphorylation ofPDK1 and AKT. These results suggest that the chemokine receptor CCR5 is partially involved in HIV-1 binding to HBMEC and show cross-talk between STAT1 and PI3K pathways in HIV-1-induced BBB dysfunction. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] , 
 Figures 1A and 1B. Same actin loading control used for both panels. *** ![file] , 
 Figs 1E 6D. Same actin loading control used for both panels, with different exposure and vertical re-sizing. *** ![file] ,
MicroRNA-29 targets FGF2 and inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via PI3K/AKT signaling pathway
Authors: D-J Zha
K Liang
C-C Hao
G-L Tian
M Shi
M Xu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miRNA; therapeutic targets; cancer; miR-29; nasopharyngeal cancer
Affiliations: Department of Radiation Oncology, Air Force Medical University, Xi'an, Shaanxi, China. .

Abstract:  Objective: Studies have indicated that miRNAs may prove essential therapeutic targets for the treatment of cancer. The study was designed to investigate the role and therapeutic potential of miR-29 in nasopharyngeal cancer. Materials and methods: The quantitative Real-time polymerase chain reaction (qRT-PCR) was used for expression analysis. WST-1 assay was used for cell viability assessment. The 4',6-diamidino-2-phenylindole (DAPI) staining and electron microscopic analysis was used for the detection of apoptosis and autophagy, respectively. Transwell assays were used for cell migration and invasion assay. Results: It was found that miR-29 is significantly downregulated in nasopharyngeal cancer cell lines. Overexpression of miR-29 causes decrease in the viability of CNE2 nasopharyngeal cancer cells via induction of apoptosis and autophagy. Bioinformatics analysis indicated FGF2 to be the target of miR-29 in CNE2 cells, which was also confirmed by luciferase reporter assay. The qRT-PCR results showed fibroblast growth factor 2 (FGF2) to be significantly upregulated in the nasopharyngeal cancer cell lines. However, miR-29 overexpression in CNE2 cells resulted in post-transcriptional suppression of FGF2 expression. Nonetheless, silencing of FGF2 also caused inhibition of CNE2 cell proliferation via induction of apoptosis and autophagy. Overexpression of FGF2 could reverse the effects of miR-29 overexpression on the proliferation of CNE2 cells. Moreover, overexpression of miR-29 causes significant decline in the phosphorylation of PI3K and AKT expression cells and inhibits their migration and invasion of the CNE2 cells. Finally, miR-29 overexpression could also suppress the subcutaneous xenografted tumor growth. Conclusions: The findings of the present study indicate the therapeutic implications of miR-29 in nasopharyngeal carcinoma. 

Retracted: Yes

PubPeer comments:
 Fig 1  C, Kaplan-Meier curves of progression-free survival in HCC patients based on circ_0000515 levels. D, Kaplan-Meier curves of overall survival in HCC patients based on circ_0000515 levels . ![file] Here, C and D (in red) are superimposed. ![file] For both subgroups, and for most of the post-surgery observation, there are more **progression-free** patients alive than there are **overall** patients alive (progression-free, plus recurrence progression). How does this work? Kaplan-Meier plots of this form - crenellated along the top so as to resemble combs or walls built of Lego, and nose-diving precipitously at 75 months - are frequent within a particular subset of ERMPS papers. ,
Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria
Authors: Damilare D Akintade
Bhabatosh Chaudhuri
Journal: Cells (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: human α-synuclein; mitochondria-dependent; mitochondria-independent; yeast apoptosis; yeast petites.
Affiliations: School of Life Sciences, Medical School, University of Nottingham, Nottingham NG7 2UH, UK., Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK.

Abstract:  Human α-synuclein expression in baker's yeast reportedly induces mitochondria-dependent apoptosis. Surprisingly, we find that, under de-repressing conditions of the inducible MET25/GAL1 promoters, yeast cells expressing chromosomally-integrated copies of the human α-synuclein gene are not killed, but spontaneously form respiration-deficient rho-minus (ρ-) petites. Although yeast cells can undergo cell death (apoptosis) from loss of mitochondrial function, they can also survive without functional mitochondria. Such cells are referred to as ρ0 or ρ- petites. This study reports that minimal expression of human α-synuclein in yeast, from MET25/GAL1 promoter, gives rise to ρ- petites. Interestingly, the full expression of α-synuclein, from the same promoters, in α-synuclein-triggered ρ- petites and also in ρ0 petites (produced by treating ρ+ cells with the mutagen ethidium bromide) initiates apoptosis. The percentages of petites increase with increasing α-synuclein gene copy-number. ρ- petites expressing α-synuclein from fully-induced MET25/GAL1 promoters exhibit increased ROS levels, loss of mitochondrial membrane potential, and nuclear DNA fragmentation, with increasing copies of α-synuclein. Our results indicate that, for the first time in yeast, α-synuclein-triggered apoptosis can occur independently of functional mitochondria. The observation that α-synuclein naturally forms petites and that they can undergo apoptosis may have important implications in understanding the pathogenesis of Parkinson's disease. 

Retracted: No

PubPeer comments:
 Figure 3B. Some areas, in particular lanes  Control and  EMJH at the left of most panels appear to look repetitive. Marked with boxes of the same color. In addition, some lanes look unexpectedly straight and thin with straight (blunt) ends, and in the Sph2 panel, the 0h J774A.1 lane appears to contain a strange  smear . Could the authors please show us the uncropped blots? Image made a bit darker to bring out details. ![file] , 
 #1 Thank you for bringing this issue to our attention. The data is 10 years old, and we need to repeat the experiment. We are also contacting the journal to report this problem and ask for advice. ,
Post-ischemic treatment with L-kynurenine sulfate exacerbates neuronal damage after transient middle cerebral artery occlusion
Authors: L Gellért
J Herédi
K Németh
L Vécsei
T Farkas
K Kocsis
A Menyhárt
Z Kis
G Oláh
J Toldi
D Varga
L Knapp
Journal: Neuroscience (2013)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: 3-HK; 3-hydroxykynurenine; CNS; EEG; I/H

Abstract:  Since brain ischemia is one of the leading causes of adult disability and death, neuroprotection of the ischemic brain is of particular importance. Acute neuroprotective strategies usually have the aim of suppressing glutamate excitotoxicity and an excessive N-methyl-d-aspartate (NMDA) receptor function. Clinically tolerated antagonists should antagonize an excessive NMDA receptor function without compromising the normal synaptic function. Kynurenic acid (KYNA) an endogenous metabolite of the tryptophan metabolism, may be an attractive neuroprotectant in this regard. The manipulation of brain KYNA levels was earlier found to effectively enhance the histopathological outcome of experimental ischemic/hypoxic states. The present investigation of the neuroprotective capacity of L-kynurenine sulfate (L-KYNs) administered systemically after reperfusion in a novel distal middle cerebral artery occlusion (dMCAO) model of focal ischemia/reperfusion revealed that in contrast with earlier results, treatment with L-KYNs worsened the histopathological outcome of dMCAO. This contradictory result indicates that post-ischemic treatment with L-KYNs may be harmful. 

Retracted: No

PubPeer comments:
 Fig.5 There are visible white splice lines, but the authors did not declared in figure legend. Could the authors explain? ![file] ,
The follicle epithelium in the Drosophila ovary is maintained by a small number of stem cells
Authors: Jocelyne Fadiga
Todd G Nystul
Journal: eLife (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: D. melanogaster; clonal analysis; epithelial stem cells; follicle cells; ovary
Affiliations: Department of Anatomy, University of California, San Francisco, San Francisco, United States., Department of OB/GYN-RS, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, United States.

Abstract:  The follicle stem cells (FSCs) in the Drosophila ovary are an important experimental model for the study of epithelial stem cell biology. Although decades of research support the conclusion that there are two FSCs per ovariole, a recent study used a novel clonal marking system to conclude that there are 15-16 FSCs per ovariole. We performed clonal analysis using both this novel clonal marking system and standard clonal marking systems, and identified several problems that may have contributed to the overestimate of FSC number. In addition, we developed new methods for accurately measuring clone size, and found that FSC clones produce, on average, half of the follicle cells in each ovariole. Our findings provide strong independent support for the conclusion that there are typically two active FSCs per ovariole, though they are consistent with up to four FSCs per germarium. 

Retracted: No

PubPeer comments:
 Readers and authors should become aware of a recent preprint entitled  Follicle Stem Cells (FSCs) in the Drosophila ovary; a critique of published studies defining the number, location and behavior of FSCs  that calls into question the conclusions of Fadiga Nystul, 2019 paper. https: www.biorxiv.org content 10.1101 2020.06.25.171579v1 From the Abstract:  A paper by Reilein et al., (2017) presented several key new insights into the behavior of adult Follicle Stem Cells (FSCs) in the Drosophila ovary, including overwhelming evidence that each ovariole hosts a large number of FSCs (about 14-16) maintained by population asymmetry (Reilein et al., 2017), rather than just two FSCs, dividing with largely individually asymmetric outcomes, as originally proposed (Margolis and Spradling, 1995; Nystul and Spradling, 2007). Here we provide further discussion asserting the merits of the conclusions of Reilein et al., (2017) and the deficiencies in the contrary assertions recently presented by Fadiga and Nystul (Fadiga and Nystul, 2019). The principles that we discuss here, particularly with regard to lineage tracing and population asymmetry, are common to the investigation of most types of adult stem cell and should therefore be instructive and of interest to investigators studying any type of adult stem cell. The improved understanding of FSC numbers, location and behavior afforded by Reilein et al., (2017) and Reilein et al., (2018) can only provide a firm foundation for future progress once they are widely appreciated and seen to be resistant to challenge, as described in detail here.  ,
Montelukast promotes mitochondrial biogenesis via CREB/PGC-1α in human bronchial epithelial cells
Authors: Jiang Shi
Yali Cheng
Ying Liu
Zhe Cheng
Huan Wang
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bronchial asthma; PGC-1α; mitochondrial biogenesis; montelukast.
Affiliations: Department of Respiratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

Abstract:  Bronchial epithelial mitochondrial dysfunction including impaired mitochondrial biogenesis has been linked with the initiation and development of bronchial asthma. Montelukast, a robust antagonist of cysteinyl leukotriene receptors, has been widely applied for the therapies of bronchial asthma. However, the effects of montelukast in airway epithelial mitochondrial dysfunction are less reported. In the present study, we report that montelukast treatment in human bronchial epithelial cells of Beas-2b increased the expressions of PGC-1α, NRF-1 and TFAM. As expected, montelukast promoted mitochondrial biogenesis in Beas-2b cells through increasing mitochondrial mass, mtDNA/nDNA and the expression of cytochrome B. Importantly, we found that montelukast caused a functional gain in mitochondria of Beas-2b cells. Mechanistically, we found that montelukast treatment increased intracellular cAMP levels and activation of CREB. Blockage of CREB with H89 abolished montelukast-induced expression of PGC-1α. These findings report a novel pharmacological function of montelukast in stimulating mitochondrial biogenesis in Beas-2b cells, mediating by the CREB/PGC-1α pathway. 

Retracted: No

PubPeer comments:
 A Western immunoblot panel in Figure 1B is surprisingly similar to another panel presented in FIgure 7C. In Figure 3A, the merged micrographs does not correspond with the DAPI staining (both color strength and position of the DAPI staining is different). ![file] ,
The Wnt/beta-catenin-->Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs
Authors: Roberto Gherzi
Christoph Moroni
Paola Briata
Michael G Rosenfeld
Ching-Yi Chen
Giorgio Corte
Cristina Ilengo
Journal: Molecular Cell (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Wnt/beta-catenin pathway; Pitx2; mRNA turnover rate; stabilization; c-Jun
Affiliations: Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genova, Italy.

Abstract:  The Wnt/beta-catenin pathway rapidly induces the transcription of the cell-type-restricted transcription factor Pitx2 that is required for effective cell-specific proliferation activating growth-regulating genes. Here we report that Pitx2 mRNA displays a rapid turnover rate and that activation of the Wnt/beta-catenin pathway stabilizes Pitx2 mRNA as well as other unstable mRNAs, including c-Jun, Cyclin D1, and Cyclin D2, encoded by critical transcriptional target genes of the same pathway. Our data indicate that Pitx2 mRNA stabilization is due to a reduced interaction of Pitx2 3'UTR with the destabilizing AU-rich element (ARE) binding proteins (BPs) KSRP and TTP as well as to an increased interaction with a stabilizing ARE-BP, HuR. Pitx2 itself is a mediator of Wnt/beta-catenin-induced mRNA stabilization. Our previous and present data support the hypothesis that a single pathway can coordinately regulate sequential transcriptional and posttranscriptional events leading to an integrated functional gene regulatory network. 

Retracted: No

PubPeer comments:
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 Figure 5G. Much more similar than expected. https: imgur.com HAcUmMY ,