PReD-Bench/PRed-Bench huggingface dataset:
Alpha Thalassemia/Intellectual Disability X-Linked Deficiency Sensitizes Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors
Authors: Yapeng Wang
Jin&#x27;an Ma
Xianling Liu
Chunhong Hu
Tao Hou
Yangchun Xie
Shun Jiang
Haixia Zhang
Yeqian Feng
Fang Ma
Journal: Frontiers in Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: CRISPR; immune checkpoint inhibitor; lung cancer; tumor supperssor gene; Œ±- thalassemia/intellectual disability syndrome x-linked.
Affiliations: Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.

Abstract:  Background: The immune checkpoint inhibitors (ICIs) have achieved great success in the treatment of non-small cell lung cancer (NSCLC) patients. However, the response rate is low. The molecular mechanism involved in the effectiveness of ICIs remains to be elucidated. Methods: ATRX mutation incidence among human cancers was analyzed from TCGA database. Atrx-deficient Lewis lung cancer cell line (LLC-sgAtrx) was established via AAV-CRISPR. Subcutaneous and metastasis models were established by subcutaneous and intravenous injection of LLC-sgAtrx and LLC-sgNTC cells into female C57BL/6 mice. The mice were treated with anti-PD1, anti-CLTA4 or Rat IgG2a. Tumor volume was determined by Vernier calipers and the IVIS imaging system. The proportions of CD3+ T cells, CD45+ immune cells, and the expression of pMHC I and PDL1 were determined by flow cytometry. The T cell cytotoxicity was determined by co-culture experiment. Results: TCGA data showed that Atrx is a tumor suppressor mutated at high frequency among various human cancers. The tumor volume of mice bearing LLC-sgAtrx was significantly shrinked and the median survival of mice was significantly longer after anti-PD1 and anti-CTLA4 treatment. Flowcytometry results showed that Atrx deficiency increase the penetration of CD3+ T cell into the tumor microenvironment and enhanced antigen presentation after IFNŒ≥ stimulation. Additionally, the tumor cells with Atrx deficiency were more easily to be damaged by T cells under IFNŒ≥ stimulation. Conclusion: The present study demonstrated that Atrx deficiency sensitize lung cancer cells to ICIs by multiple mechanisms. And ATRX may serve as a promising biomarker for ICIs which helps patient stratification and decision making. 

Retracted: No

PubPeer comments:
 Two images in Figure 4C may show the same animal (yellow box). Could the authors please check? *** Inverse  *** Original  , 
 Thank you for your comment. We will check the original data, and respond as soon as possible ,
NMIIA promotes tumor growth and metastasis by activating the Wnt/Œ≤-catenin signaling pathway and EMT in pancreatic cancer
Authors: Yanyan Li
Yuan Yao
Yuanhua Liu
Meichao Zhang
Pingting Zhou
Bo Li
Dong Li
Journal: Oncogene (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Non-muscle myosin IIA; pancreatic cancer; Œ≤-catenin; EMT; proliferation

Abstract:  Non-muscle myosin IIA (NMIIA) protein plays an important role in cell cytokinesis and cell migration. The role and underlying regulatory mechanisms of NMIIA in pancreatic cancer (PC) remain elusive. We found that NMIIA is highly expressed in PC tissues and contributes to PC poor progression by using open microarray datasets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and PC tissue arrays. NMIIA regulates Œ≤-catenin mediated EMT to promote the proliferation, migration, invasion, and sphere formation of PC cells in vitro and in vivo. NMIIA controls the Œ≤-catenin transcriptional activity by interacting with Œ≤-catenin. Moreover, MEK/ERK signaling is critical in MLC2 (Ser19) phosphorylation, which can mediate NMIIA activity and regulate Wnt/Œ≤-catenin signaling. These findings highlight the significance of NMIIA in tumor regression and implicate NMIIA as a promising candidate for PC treatment. 

Retracted: No

PubPeer comments:
 There appears to be similarity between 2 images used to represent different conditions. Highlighted here:  , 
 There is some overlap in two of the areas in Fig 4C:  ,
STAT1 and STAT3 phosphorylation by porins are independent of JAKs but are dependent on MAPK pathway and plays a role in U937 cells production of interleukin-6
Authors: Emilia Galdiero
Marina D&#x27;Isanto
Marilena Galdiero
Katia Raieta
Mariateresa Vitiello
Journal: Cytokine (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: transcription factors; signal transducers; activators; STATs; cytokine
Affiliations: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Faculty of Medicine, Second University of Naples, Naples, Italy.

Abstract:  A group of transcription factors, termed signal transducers and activators of transcription (STATs), appears to orchestrate the downstream events propagated by cytokine/growth factor interactions with their cognate receptors. Similarly, cytoplasmic Janus kinases (JAKs) seem to play a critical role in diverse signal transduction pathways that govern cellular survival, proliferation, differentiation and apoptosis. In this work, we analysed the effects of the Salmonella enterica serovar Typhimurium porins on signaling by the JAK/STAT pathway and IL-6 release in U937 cells. Porins and LPS of membrane from Gram-negative bacteria are factors implicated in septic shock. In our assays porins induce interleukin-6 (IL-6) release (110+/-2.6pg/ml) 24h after stimulation and STAT1/STAT3 tyrosine (Tyr701/Tyr705) and serine (Ser727) phosphorylation after 15min. By using several selective inhibitors we demonstrate that porins modulate the activation of STAT1/STAT3 through mitogen activated protein kinases (MAPKs) and not JAKs. Furthermore, we demonstrated that STAT1 and STAT3 are not involved in the modulation of IL-6 release in U937 cells stimulated with porins. Inhibition of tyrosine/serine phosphorylation mediated by MAPKs of STAT1 and STAT3 decrease the IL-6 secretion following porin stimulation. Therefore, suggesting a key role of this pathway in phosphorylation of Ser 727 in STAT1 and STAT3. These results are confirmed by porin or LPS-induced nuclear translocation of STAT1 and STAT3 in U937 cells. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: The STAT1 panels in Figures 4A and 4B look remarkably similar * Blue boxes: The STAT3 panels in Figures 4A and 4B look remarkably similar Reported to the journal in October 2015, but never addressed.  ,
Methyltransferase-like protein 7A (METTL7A) promotes cell survival and osteogenic differentiation under metabolic stress
Authors: Ju-Young Kim
Gun-Il Im
Eugene Lee
Tae-Kyung Kim
Seo-Young Park
Journal: Cell Death Discovery (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: bone healing; regenerative medicine; stem cells; glucose regulation; METTL7A

Abstract:  While bone has an inherent capacity to heal itself, it is very difficult to reconstitute large bone defects. Regenerative medicine, including stem cell implantation, has been studied as a novel solution to treat these conditions. However, when the local vascularity is impaired, even the transplanted cells undergo rapid necrosis before differentiating into osteoblasts and regenerating bone. Thus, to increase the effectiveness of stem cell transplantation, it is quintessential to improve the viability of the implanted stem cells. In this study, given that the regulation of glucose may hold the key to stem cell survival and osteogenic differentiation, we investigated the molecules that can replace the effect of glucose under ischemic microenvironment of stem cell transplantation in large bone defects. By analyzing differentially expressed genes under glucose-supplemented and glucose-free conditions, we explored markers such as methyltransferase-like protein 7A (METTL7A) that are potentially related to cell survival and osteogenic differentiation. Overexpression of METTL7A gene enhanced the osteogenic differentiation and viability of human bone marrow stem cells (hBMSCs) in glucose-free conditions. When the in vivo effectiveness of METTL7A-transfected cells in bone regeneration was explored in a rat model of critical-size segmental long-bone defect, METTL7A-transfected hBMSCs showed significantly better regenerative potential than the control vector-transfected hBMSCs. DNA methylation profiles showed a large difference in methylation status of genes related to osteogenesis and cell survival between hBMSCs cultured in glucose-supplemented condition and those cultured in glucose-free condition. Interestingly, METTL7A overexpression altered the methylation status of related genes to favor osteogenic differentiation and cell survival. In conclusion, it is suggested that a novel factor METTL7A enhances osteogenic differentiation and viability of hBMSCs by regulating the methylation status of genes related to osteogenesis or survival. 

Retracted: No

PubPeer comments:
 A micrograph panel has been duplicated and presented as something else (Figure 3B vs 4B).  , 
 It seems that a handling mistake was made during the revision process. Fig 3B panel is like below (original submission). We will ask the publisher to publish an erratum. ,
Circ-PRMT5 stimulates migration in esophageal cancer by binding miR-203
Authors: J-X Yang
L-W Zhang
H Yang
B Wang
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: circ-PRMT5; miR-203; esophageal cancer; migratory ability; metastasis
Affiliations: Department of Gastroenterology, People's Hospital of Shouguang, Shouguang, China. .

Abstract:  Objective: The study aimed to uncover the role of circ-PRMT5 in triggering the migratory ability of esophageal cancer by regulating microRNA-203 (miR-203) level. Patients and methods: Circ-PRMT5 levels in 56 matched esophageal cancer tissues and paracancerous ones were detected. The relationship between circ-PRMT5 level and clinical data of esophageal cancer patients was analyzed. Migratory abilities in TE-1 and OE33 cells influenced by circ-PRMT5 were evaluated by transwell and wound healing assay. Regulatory effect of circ-PRMT5 on miR-203 level, and the involvement of miR-203 in the development of esophageal cancer were determined through Dual-Luciferase reporter assay and rescue experiments. Results: Circ-PRMT5 was upregulated in esophageal cancer tissues and cell lines. The expression level of circ-PRMT5 was positively correlated to the rates of lymphatic metastasis and distant metastasis of esophageal cancer. Knockdown of circ-PRMT5 attenuated migratory abilities in TE-1 and OE33 cells. MiR-203 was verified to be the target gene binding circ-PRMT5, with a negative correlation between each other. Notably, miR-203 was responsible for the regulatory effect of circ-PRMT5 on migratory ability in esophageal cancer. Conclusions: Circ-PRMT5 is positively correlated to the rates of lymphatic metastasis and distant metastasis of esophageal cancer. It promotes migratory ability in esophageal cancer by targeting miR-203. 

Retracted: No

PubPeer comments:
 Table 1. Column headings promise to convert the numbers within each patient sub-group into percentages, but the table does not deliver.  In itself this would be a minor error, but Table 1s of this form are a characteristic feature of the output of a papermill. , 
 Fig 1A, and Figs 3B,C.  The distributions of Circ-PRMT5 and miR-203 plotted on the axes of 3C do not seem to match the distributions shown in 1A and 3B respectively. ,
miR-494-3p Regulates Cellular Proliferation, Invasion, Migration, and Apoptosis by PTEN/AKT Signaling in Human Glioblastoma Cells
Authors: Yong-Xin Wei
Tian-Quan Yang
Zi-Wei Du
Zhao-Hui Zhao
Xue-Shun Xie
Hang-Zhou Wang
Xue-Tao Li
You-Xin Zhou
Yu-Lun Huang
Gui-Lin Chen
Bin Li
Zhi-Wu Wu
Journal: Cellular and Molecular Neurobiology (2015)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Malignant gliomas; miR-494-3p; molecular mechanisms; gliomagenesis; cancer stem-like cells
Affiliations: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.

Abstract:  Malignant gliomas are the most common primary brain tumors, and the molecular mechanisms involving their progression and recurrence are still largely unclear. Substantial data indicate that the oncogene miR-494-3p is significantly elevated in gliomas, but the molecular functions of miR-494-3p in gliomagenesis are largely unknown. The present study aimed to explore the role of miR-494-3p and its molecular mechanism in human brain gliomas, malignant glioma cell lines, and cancer stem-like cells. The expression level of miR-494-3p in 48 human glioma issues and 8 normal brain tissues was determined using stem-loop real-time polymerase chain reaction (PCR). To study the function of miR-494-3p inhibitor in glioma cells, the miR-494-3p inhibitor lentivirus was used to transfect glioma cells. Transwell invasion system was used to estimate the effects of miR-494-3p inhibitor on the invasiveness of glioma cells. A mouse model was used to test the effect of miR-494-3p inhibitor on glioma proliferation and invasion in vivo. Results showed that the expression of miR-494-3p in human brain glioma tissues was higher than in normal brain tissues. Downregulated expression of miR-494-3p can inhibit the invasion and proliferation and promote apoptosis in glioma cells. Quantitative reverse transcription PCR and Western blotting analysis revealed that the expression of PTEN was increased after downexpression of miR-494-3p in glioma cells (U87 and U251). miR-494-3p inhibitor could prevent migration, invasion, proliferation, and promote apotosis in gliomas through PTEN/AKT pathway. Therefore, the study results have shown that miR-494-3p may act as a therapeutic target in gliomas. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have an image duplication:  And so does figure 6:  Can the authors explain? ,
The role of PTEN up-regulation in suppressing glomerular mesangial cells proliferation and nephritis pathogenesis
Authors: C-X Han
H-Y Gao
Journal: European Review for Medical and Pharmacological Sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Mesangial proliferative glomerulonephritis; PTEN-PI3K/AKT pathway; Anti-thymocyte serum nephritis; GMC counting; IL-6
Affiliations: The Kidney Internal Medicine of Xianyang First People's Hospital, Xianyang, Shaanxi, China. .

Abstract:  Objective: Over-proliferation of mesangial cells is the major pathological change of mesangial proliferative glomerulonephritis (MPGN). PTEN-PI3K/AKT pathway plays a role in regulating proliferation of mesangial cells. Anti-thymocyte serum nephritis (ATSN) is a widely used animal model for studying MPGN. This study established ATSN model, on which the role of PTEN-PI3K/AKT signal pathway in MPGN pathogenesis was investigated. Materials and methods: ASTN rat model was established in parallel with control group. Protein expressions of PTEN, p-AKT, PCNA, Cyclin D1 and Bcl-2 were quantified, along with glomerular mesangial cell (GMC) counting. Rat mesangial cell (RMC) was treated with 0 or 10 ng/mL IL-6, followed by flow cytometry analysis for apoptosis, cycle and PCNA expression. Expressions of PTEN, p-AKT, PCNA, Cyclin D1 and Bcl-2 were measured. RMC was treated with pSicoR-PTEN and/or LY294002, followed by the treatment of 10 ng/mL IL-6 for 48 h. Cell apoptosis, cycle, PCNA expression and protein expression were measured. Results: Lower PTEN expression was found in renal cortex of ATSN rats, along with increasing levels of p-AKT, PCNA, Cyclin D1, Bcl-2, and higher GMCs, compared to that in control rats. IL-6 treatment increased protein expression in RMC, facilitated cell proliferation and cycle progression and suppressed apoptosis. Over-expression of PTEN and/or LY294002 remarkably decreased protein expression in RMC, inhibited the effect of IL-6 on proliferation, and induced cell apoptosis and cycle arrest. Conclusions: The down-regulation of PTEN played a role in enhancing PI3K/AKT pathway activity, facilitating GMC proliferation and MPGN pathogenesis. 

Retracted: No

PubPeer comments:
 This paper has features suggestive of [what has elsewhere been labeled as  Papermill #2 ] , characterised by stylised geometrical WBs that are reduced to black blobs on a featureless grey background, reminiscent of a Miro painting:  The other characteristic is a small repertoire of recurring flow cytometry plots,  slightly modified by artisanal stippling on each of their occurrences.  Other examples are listed in a Google document. https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit?usp=sharing ,
The new role of riluzole in the treatment of pancreatic cancer through the apoptosis and autophagy pathways
Authors: Rulin Sun
Xujun He
Houquan Tao
Xiaoting Jiang
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: apoptosis; autophagy; chemotherapy; pancreatic cancer; riluzole.
Affiliations: Clinical Laboratory¬†CenterZhejiang Provincial People's HospitalZhejiang P. R. China, People's Hospital of Hangzhou Medical CollegeHangzhou P. R. China, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang ProvinceZhejiang Provincial People's HospitalZhejiang P. R. China, Key Laboratory of Gastroenterology of Zhejiang ProvinceZhejiang Provincial People's HospitalZhejiang P. R. China

Abstract:  Pancreatic cancer is always diagnosed at an advanced stage. Hence, chemotherapy becomes the best choice for patients. Therefore, new anticancer drugs for pancreatic cancer are needed. Riluzole (RIL) is mainly used to treat amyotrophic lateral sclerosis clinically, but many previous studies have shown that RIL could inhibit tumors. However, no report has explored the association between RIL and pancreatic cancer. To validate this association, we performed this study. Our data showed that RIL could induce cytotoxicity, block the cell cycle, and inhibit clone formation, apoptosis, and migration in pancreatic cancer cells. Moreover, we demonstrated that RIL could suppress autophagy. However, more experiments will be needed to validate the reliability of our conclusions. In summary, our data suggest that RIL might provide clues for the development of a treatment for human pancreatic cancer in the future. 

Retracted: No

PubPeer comments:
 Fig. 1K and 1N u2013 GFAP stain has a very similar pattern between vehicle and Flx+ABO conditions. Could authors check it please?  , 
 A correction was published for this paper https: www.nature.com articles s41380-020-00873-6 A similar problem in a different publication from the authors can be found here: https: pubpeer.com publications E300EA23242BD6D38F82B1E0906D41 The problem is the same, duplicated images, but with clear different imaging processing between them. Clearly GFAP channel intensity was reduced in the left image (control) and intensified in the right image (ABO injected). , 
 More similar than expected with previous dot blot published at 10.1523 JNEUROSCI.0482-13.2013 . Could authors check this issue please?  ,
Free fatty acids inhibit TM-EPCR expression through JNK pathway: an implication for the development of the prothrombotic state in metabolic syndrome
Authors: Yuanhua Yang
Zhenguo Zhai
Chen Wang
Tuguang Kuang
Wanmu Xie
Journal: Journal of thrombosis and thrombolysis (2012)
Discipline: CLINICAL MEDICINE
Keywords: Metabolic syndrome; hypercoagulable; prothrombotic tendency; plasma free fatty acids; endothelial thrombomodulin
Affiliations: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.

Abstract:  Metabolic syndrome is associated with significant hypercoagulable prothrombotic tendency; however, the mechanism for the prothrombotic state is not completely understood. We hypothesize that higher circulating plasma free fatty acids (FFAs) in metabolic syndrome inhibit the endothelial thrombomodulin (TM)-endothelial protein C receptor (EPCR) pathway, thereby promoting thrombus formation. Human umbilical vein endothelial cells were cultured in media supplemented with various doses of palmitic acid (PA), in the presence or absence of JNK inhibitor, and the expression of TM and EPCR was measured by western blot. The thrombotic state of high fat fed C57BL/6J mice was examined by tail bleeding time and deep venous thrombosis (DVT) model. As a result, PA inhibited the expression of TM and EPCR in endothelial cells, and this effect was blunted by inhibiting JNK signaling. High fat diet fed mice had higher level of circulating FFAs and exhibited prothrombotic state, evidenced by increased tail bleeding time and enlarged thrombotic size in DVT model, compared to the control diet fed mice. Hence, FFAs inhibit TM-EPCR-Protein C system in endothelial cells through activating JNK signaling, which may be a mechanism for the prothrombotic state in metabolic syndrome. 

Retracted: No

PubPeer comments:
 Figure 2A and 2B showed identical actin control across two western blot experiments, could the authors please explain?  , 
 #1 I am the first author in this paper, Wanmu Xie. Thank you for your question. The results shown in Figures 2A and 2B were from the same PVDF membrane of the same cell treatment. After b-actin was detected, the membrane was stripped and reprobed for two other antibodies, anti-EPCR and anti-TM. I apologize for not clarifying this in the figure legend and the confusion it may cause. Thank you for your comment. Please let me know if you have any further questions. ,
Typical physics Ph.D. admissions criteria limit access to underrepresented groups but fail to predict doctoral completion
Authors: Rachel T Silvestrini
Theodore Hodapp
Benjamin M Zwickl
Julie R Posselt
Casey W Miller
Journal: Science Advances (2019)
Discipline: Multidisciplinary
Keywords: admissions criteria; physics Ph.D.; undergraduate GPA; GRE Quantitative; GRE Physics
Affiliations: School of Chemistry and Materials Science, Rochester Institute of Technology, 85 Lomb Memorial Drive, Rochester, NY 14623, USA., School of Physics and Astronomy, Rochester Institute of Technology, 85 Lomb Memorial Drive, Rochester, NY 14623, USA., Rossier School of Education, University of Southern California, 3470 Trousdale Parkway, Los Angeles, CA 90089, USA., Industrial and Systems Engineering Department, Rochester Institute of Technology, 85 Lomb Memorial Drive, Rochester, NY 14623, USA., American Physical Society, One Physics Ellipse, College Park, MD 20740, USA.

Abstract:  This study aims to understand the effectiveness of typical admissions criteria in identifying students who will complete the Physics Ph.D. Multivariate statistical analysis of roughly one in eight physics Ph.D. students from 2000 to 2010 indicates that the traditional admissions metrics of undergraduate grade point average (GPA) and the Graduate Record Examination (GRE) Quantitative, Verbal, and Physics Subject Tests do not predict completion as effectively admissions committees presume. Significant associations with completion were found for undergraduate GPA in all models and for GRE Quantitative in two of four studied models; GRE Physics and GRE Verbal were not significant in any model. It is notable that completion changed by less than 10% for U.S. physics major test takers scoring in the 10th versus 90th percentile on the Quantitative test. Aside from these limitations in predicting Ph.D. completion overall, overreliance on GRE scores in admissions processes also selects against underrepresented groups. 

Retracted: No

PubPeer comments:
 Figure 7A.  , 
 #1 Figure 7A. Higher resolution detail.  ,
Cordyceps militaris polysaccharide converts immunosuppressive macrophages into M1-like phenotype and activates T lymphocytes by inhibiting the PD-L1/PD-1 axis between TAMs and T lymphocytes
Authors: Zhongyi Guo
Jianhua Zhu
Rongmin Yu
Sixue Bi
Liyan Song
Chunhua Huang
Chunlei Li
Jianing Yang
Shan Chen
Weijuan Huang
Journal: International Journal of Biological Macromolecules (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cordyceps militaris polysaccharide; PD-L1/PD-1; TLR2; Tumour-associated macrophages.
Affiliations: Department of Pharmacology, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China., Biotechnological Institute of Chinese Materia Medica, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China., Department of Natural Products Chemistry, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China., Department of Natural Products Chemistry, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. Electronic address: ., Department of Pharmacology, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. Electronic address: ., Biotechnological Institute of Chinese Materia Medica, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China; Department of Natural Products Chemistry, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. Electronic address: .

Abstract:  Tumour-associated macrophages (TAMs) inhibit the killing effect of T lymphocytes on tumour cells through the immunocheckpoint programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis. TAMs-targeted therapy is a promising approach that could be used to reverse the immunosuppressive tumour microenvironment. Here, we further report CMPB90-1, a novel natural polysaccharide from Cordyceps militaris, could function as an anti-tumour modulator that resets TAMs from a tumour-promoting M2 phenotype to a tumour-killing M1 phenotype. This process involves reversing the functional inhibition of T lymphocytes by inhibiting the PD-L1/PD-1 axis between TAMs and T lymphocytes. Mechanistically, the membrane receptor of CMPB90-1 binding to M2 macrophages was identified by tandem mass spectrometry. CMPB90-1 converts immunosuppressive TAMs via binding to toll-like receptor 2 (TLR2), which causes the release of Ca2+ and the activation of p38, Akt and NF-Œ∫B, or ERK. This process then leads to the polarization of TAMs from M2 phenotype to the M1 phenotype. In vivo experiment shows that CMPB90-1 is able to polarize TAMs into the M1 phenotype and has anti-tumour effects with improved safety. Additionally, the anti-tumour effects of CMPB90-1 in vivo depend on the phenotypic conversion of TAMs. The results demonstrated that CMPB90-1 could be developed as a potential immune-oncology treatment reagent. 

Retracted: No

PubPeer comments:
 All the Western Blots in this paper have the curious stylised appearance associated with products of the  Tadpole papermill . Here, Fig 6.  ,
MiR-200c-3p inhibits cell migration and invasion of clear cell renal cell carcinoma via regulating SLC6A1
Authors: Naibijiang Maolakuerban
Ayiding Xireyazidan
Anniwaer Yasheng
Hamulati Tusong
Asimujiang Abula
Baihetiya Azhati
Journal: Cancer Biology & Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: SLC6A1; clear cell renal cell carcinoma; invasion; miR-200c-3p; migration
Affiliations: a Department of Urology , the First Affiliated Hospital of Xinjiang Medical University , 830054 Urumchi , Xinjiang , China.

Abstract:  In this study, we investigated the mechanism of miR-200c-3p and SLC6A1 in regulating cell activity of clear cell renal cell carcinoma (CCRCC). The mRNA and miRNA expressions of tissue specimens were analyzed by CapitalBio Corporation (Beijing, China). The expression of SLC6A1 in CCRCC cells was examined through qRT-PCR and western blot. The migration and invasion ability of 786-O cells was testified by transwell assay after transfected. 786-O cell proliferation ability was detected by MTT assay. Dual luciferase reporter assay verified the association between SLC6A1 and miR-200c-3p. SLC6A1 was high expressed and miR-200c-3p was low expressed in CCRCC tissues and cells. Besides, lower SLC6A1 expression indicated longer survival time and higher survival rate. MiR-200c-3p could directly target at SLC6A1 and reduce its expression. MiR-200c-3p inhibited the proliferation, migration and invasion in 786-O cells by down-regulating SLC6A1 expression. The results suggested that the miR-200c-3p served as a suppressor for CCRCC via down-regulating SLC6A1. 

Retracted: No

PubPeer comments:
 **Overlapped sections in Figure 2D Figure 4D**  **Also, the email address, chenrui4647@163.com, it seems that this address belongs to chen rui, and the last four phone number is 4647**  ,
circRAE1 promotes colorectal cancer cell migration and invasion by modulating miR-338-3p/TYRO3 axis
Authors: Pengcheng Wang
Weinan Liu
Kai Ye
Jiabin Du
Junxing Chen
Jianhua Xu
Journal: Cancer Cell International (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Colorectal cancer; TYRO3; circRAE1; circRNAs; miR-338-3p.
Affiliations: Department of Gastrointestinal Surgery, Second Affiliated Hospital of Fujian Medical University, No.950 Donghai Dajie, Fengze District, Quanzhou, 362000 Fujian China.

Abstract:  Background: Growing evidence has revealed the involvement of circular RNAs (circRNAs) in numerous carcinogenesis. However, the role of circRNAs in the cancer biology of colorectal cancer (CRC) remains vague. Methods: Quantitative RT-PCR was used to detect the expression level of circRAE1 in CRC tissues and CRC cell lines. Cell proliferation, migration, and invasion were detected using CCK8 assay, Colony formation assay, wound-healing and Transwell assays. The interaction between circRAE1 and miR-338-3p and TRYO3 was confirmed using dual-luciferase reporter assays. Results: We uncovered a novel circRNA Hsa_circ_0060967 (also known as circRAE1) that was remarkably increased in CRC tissues. The high circRAE1 level was positively associated with advanced tumor stage, lymph node metastasis, and tumor size. The loss-of-function assay showed that circRAE1 accelerated cell proliferation, migration, and invasion. Besides, miR-338-3p was lowly expressed in the CRC tissues and CRC cell lines. The dual-luciferase reporter assays showed that circRAE1 could sponge miR-338-3p, which targeted TRYO3 in CRC cells. Furthermore, the overexpression of circRAE1 could rescue the impaired migration and invasion triggered by miR-338-3p mimics or si-TYRO3 in CRC cells and vice versa. Conclusion: We identified the network of circRAE1, miR-338-3p, and TYRO3 in CRC cells and determined that the increase in circRAE1 could serve as an oncogene by sponging miR-338-3p, which resulted in an upregulated TYRO3 expression. The finding suggests that circRAE1 is a potential therapeutic target and diagnostic marker for CRC treatment. 

Retracted: No

PubPeer comments:
 Fig 6e has an overlap between 2 images  ,
Sequential loss of cell cycle checkpoint control contributes to malignant transformation of murine embryonic fibroblasts induced by 20-methylcholanthrene
Authors: Debolina Pal
Pratima Mukherjee
Sugata Manna
Chinmay K Panda
Sudeshna Mukherjee
Journal: Journal of Cellular Physiology (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: tumorigenesis; carcinogenesis; in vitro model; fibroblast cells; chromosomal aberrations
Affiliations: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India.

Abstract:  Definitive information about the number and nature of discrete steps of tumorigenesis is enigmatic. To understand the multistep nature of carcinogenesis, an in vitro model of 20-Methylcholanthrene-treated primary fibroblast cells CNCI-PM-20, from 20-day old Swiss mouse embryo was used. Visible neoplastic changes with distinct morphological variations along with specific chromosomal aberrations like Robertsonian metacentrics, double and single-minute chromosomes and aneuploidy were observed from Passage-20 onwards. The cell cycle profile showed gradual increase in G(2)/M population till P-32, followed by evasion of block from P-36 onwards. Gradual increase in expression of C-myc, CyclinD1 and a decrease in expression of P21 was observed from P-20 onwards. CDC25A expression was significantly increased at P-27 and remained more or less constant in subsequent passages. Additionally, an increased P16 and P53 expression were seen at P-20 followed by their significant down-regulation at P-32. An increased level of phosphorylated retinoblastoma (ppRb) was observed from P-27, probably responsible for a compromised G(1)/S checkpoint. The inactivation of p21 and p16 might be due to their promoter hyper-methylation as suggested through de-methylation experiment by 5-aza-deoxycytidine at P-42. G(2)/M checkpoint abrogation was marked by gradual increase in expression of CyclinB1 and Cdc20, and a significant increase of Mad2 at P-20. Interestingly, increased expression of phospho-ATM, ATR and phospho-Chk1 were also seen at P-20 followed by their down-regulation at subsequent passages, indicating a perturbation of DNA damage response pathway at early passages. Our findings therefore dramatize the multiple genetic events that can cooperate to promote tumorigenesis. 

Retracted: No

PubPeer comments:
  Figure 6 C. displaying immunofluorescence microscopy image of cells for pChk1, the marked the last lane, has the same image just the field is shifted. ,
Effect of VEGF on neuronal degeneration and interaction between Alzheimer's disease biomarkers
Authors: Y-J Liu
H-C Yuan
K Liu
G Sun
Y-B Lv
L-F Guo
C-W Jiang
X-Z Feng
B Xu
L-Y Hou
C-Y Wang
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: VEGF; neuronal degeneration; Alzheimer's disease biomarkers; interaction; withdrawn
Affiliations: Department of Neurology, Qingdao Central Hospital, Qingdao, Shandong, China.

Abstract:  The article "Effect of VEGF on neuronal degeneration and interaction between Alzheimer's disease biomarkers" by H.-C. Yuan, C.-W. Jiang, L.-Y. Hou, Y.-B. Lv, X.-Z. Feng, L.-F. Guo, G. Sun, K. Liu, Y.-J. Liu, B. Xu, C.-Y. Wang, published in Eur Rev Med Pharmacol Sci 2017; 21 (16): 3649-3657 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,
Acetylation is important for MyoD function in adult mice
Authors: Anna Polesskaya
Matthieu Gerard
Patrick H√©ry
Arnaud Duquet
Annick Harel-Bellan
Sylvain Cuvellier
Slimane Ait-Si-Ali
Linda L Pritchard
Journal: EMBO reports (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Acetylation; MyoD; myogenesis; lysines; transcriptional activity
Affiliations: Laboratoire Epig√©n√©tique et cancer, CNRS FRE 2944, Institut Andr√© Lwoff, 7 rue Guy Moquet, 94801 Villejuif, France., Laboratoire ‚ÄòEpig√©n√©tique et cancer‚Ä? CNRS FRE 2944, Institut Andr√© Lwoff 7 rue Guy Moquet 94801 Villejuif France

Abstract:  Acetylation is a post-translational modification that influences the activity of numerous proteins in vitro. Among them, the myogenic transcription factor MyoD shows an increased transcriptional activity in vitro when acetylated on two lysines (K): lysines 99 and 102. Here, we have investigated the biological relevance of this acetylation in vivo. Using specific antibodies, we show that endogenous MyoD is acetylated on lysines 99 and 102 in myoblasts. Moreover, we show the functional importance of acetylation in live animals by using a mutant of MyoD in which lysines 99 and 102 were replaced by arginines (R). Knock-in embryos homozygous for the MyoD(R99,102) allele expressed slightly reduced levels of MyoD but developed normally. However, the knock-in homozygous adult mice showed a phenotype that was almost identical to that of MyoD-knockout animals, including delayed muscle regeneration in vivo and an increased number of myoblasts but with reduced differentiation potential in vitro. Together, these results show the importance of MyoD acetylation for adult myogenesis. 

Retracted: No

PubPeer comments:
 Figure 5B. Alpha-tubulin panel does not look like it comes from the same blot as any of the other 5 panels. https: imgur.com xS98I3E , 
 Figure 5D. Much more similar than expected. https: imgur.com hLPkMWp , 
 #2 Dear PubPeer, Please find uploaded the original scans of these western blots, initially saved by me in tiff format, but re-saved today in jpg in order to upload. Best regards, Anna Polesskaya    , 
 #1 Dear Pub Peer, For some reason, this gel ran like this. Here is a full-size scan where you can see that tubulin ran in a crooked line, whereas most proteins ran in a straight line (this is a non-specific signal when the membrane was re-probed with anti-tubulin antibody, but it gives a good idea of what happened). Best regards, Anna Polesskaya  , 
 #4 Figure 5B. MyoD and alpha-Tubulin have similar molecular weights. The MyoD and alpha-Tubulin panels do not look like they come from the same blot. , 
 Figures 5B and 5D. Much more similar than expected. https: imgur.com rAaG4NJ ,
ORMDL3 Promotes Angiogenesis in Chronic Asthma Through the ERK1/2/VEGF/MMP-9 Pathway
Authors: Lina Shi
Ning Jiao
Jinghong Wan
Fei Yu
Yan Sun
Zhen Ding
Qinghua Liu
Journal: Frontiers in Pediatrics (2022)
Discipline: CLINICAL MEDICINE
Keywords: MMP-9; ORMDL sphingolipid biosynthesis regulator 3; ORMDL3; VEGF; angiogenesis
Affiliations: Department of Pediatrics, Zibo Hospital of Traditional Chinese Medicine, Zibo, China., Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Abstract:  Aim: Angiogenesis plays a vital role in airway remodeling in chronic asthma. ORMDL3 has been identified to be closely associated with the development of asthma remodeling. This study was to investigate the mechanism of ORMDL3 in angiogenesis of chronic asthma. Methods: BALB/c mice were divided into three groups, including an asthmatic group (group A), a budesonide-treated group (group B), and a normal control group (group C). Hematoxylin and eosin and Masson staining were used to evaluate the pathological changes. Angiogenesis in lung tissue was examined by CD31 staining. The changes of ORMDL3, ERK1/2, and angiogenesis-associated MMP-9 and Vascular endothelial growth factor (VEGF) expression were examined. Furthermore, ORMDL3, MMP-9, and VEGF mRNA and protein levels were examined after transfection in BEAS-2B cells with the ORMDL3-overexpressed lentiviral vector. Results: Compared with the control group, asthmatic mice indicated more severe airway angiogenesis with increased ORMDL3, ERK1/2, MMP-9, and VEGF expression. Budesonide alleviated airway angiogenesis, and CD31 expression was positive with the levels of ORMDL3, MMP-9, and VEGF (P &lt; 0.01). After successful transfection in BEAS-2B cells with the ORMDL3-overexpressing lentiviral vector, VEGF, and MMP-9 expression were activated in vitro (P &lt; 0.01). Conclusion: In conclusion, our study provides novel evidence that ORMDL3 promotes angiogenesis through upregulating VEGF and MMP-9 in chronic asthma. 

Retracted: No

PubPeer comments:
 Positive control and overexpressing ORMDL3 BEAS-2B cells could be similar but identical?  ,
Taxol-Resistant Gene 1 (Txr1) Mediates Oxaliplatin Resistance by Inducing Autophagy in Human Nasopharyngeal Carcinoma Cells
Authors: Jing-Dong Du
Hua-Ming Chi
Jie Cheng
Hua-Dong Mao
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: Oxaliplatin; Txr1; drug resistance; nasopharyngeal carcinoma; autophagy
Affiliations: Department of Otolaryngology, Renhe Hospital of China Three Gorges University, Yichang, Hubei, China (mainland).

Abstract:  BACKGROUND Oxaliplatin (L-OHP) is an important chemotherapy regimen for nasopharyngeal carcinoma (NPC), but can fail due to drug resistance. In this study, the role of Txr1 (taxol-resistant gene 1) in oxaliplatin resistance was investigated. MATERIAL AND METHODS Cell viability assay was carried out using the CellTiter-Glo Luminescent Cell Viability Assay Kit. CNE1 and CNE2 cells were cultured continuously with gradually increasing concentrations of L-OHP for 6 months to establish drug-resistant cell lines. Autophagy was detected by electron microscopy. Txr1 expression in NPC cells was detected via Western blotting and real-time quantitative PCR (qRT-PCR). RESULTS In L-OHP-resistant CNE1/L-OHP and CNE2/L-OHP cells, mRNA and protein expression of Txr1 increased compared to the parental cells, and downregulation of Txr1 re-sensitized drug-resistant cells to L-OHP. Moreover, we found that Txr1-mediated L-OHP resistance was associated with increased autophagy. Txr1-overexpression cells developed L-OHP resistance and a high level of autophagy. Inhibiting autophagy using 2 different methods - inhibition of autophagy-related gene expression and autophagy inhibitor - attenuated L-OHP resistance of NPC cells. CONCLUSIONS We conclude that the detection of Txr1 might become a good indicator to evaluate the treatment and prognosis of nasopharyngeal carcinoma. Our data suggest that further investigation of Txr1 in the setting of L-OHP resistance is warranted. 

Retracted: Yes

PubPeer comments:
 Fig 2C.  Autophagy induced by L-OHP protects CNE1 and CNE2 cells from the cytotoxicity of L-OHP. .. (C) Representative fluorescence microscope images of drug-resistant cells and parental cells stably expressing GFP-LC3, with serum starvation as a positive control . Fig 3B.  Txr1 promotes autophagy and oxaliplatin resistance in CNE1 and CNE2 cells. ... (B) Representative fluorescence microscope images of Txr1-overexpression cells stably expressing GFP-LC3, with serum starvation as a positive control. A panel is repeated (with a vertical flip), representing two different conditions.  , 
 Retracted [25 March 2021] .  An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. ,
The G-patch domain of Mason-Pfizer monkey virus is a part of reverse transcriptase
Authors: Iva Pichov√°
Ivana K≈ô√≠zov√°
Romana Hadravov√°
Michaela Rumlov√°
Jitka ≈†tokrov√°
Jana G√ºnterov√°
Michal Dole≈æal
Tom√°≈° Ruml
Journal: Journal of Virology (2012)
Discipline: MICROBIOLOGY
Keywords: Mason-Pfizer monkey virus; betaretroviruses; G-patch domain; RNA binding module; ribosomal frameshift
Affiliations: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, vvi, IOCB & Gilead Research Center, Prague, Czech Republic.

Abstract:  Mason-Pfizer monkey virus (M-PMV), like some other betaretroviruses, encodes a G-patch domain (GPD). This glycine-rich domain, which has been predicted to be an RNA binding module, is invariably localized at the 3' end of the pro gene upstream of the pro-pol ribosomal frameshift sequence of genomic RNAs of betaretroviruses. Following two ribosomal frameshift events and the translation of viral mRNA, the GPD is present in both Gag-Pro and Gag-Pro-Pol polyproteins. During the maturation of the Gag-Pro polyprotein, the GPD transiently remains a C-terminal part of the protease (PR), from which it is then detached by PR itself. The destiny of the Gag-Pro-Pol-encoded GPD remains to be determined. The function of the GPD in the retroviral life cycle is unknown. To elucidate the role of the GPD in the M-PMV replication cycle, alanine-scanning mutational analysis of its most highly conserved residues was performed. A series of individual mutations as well as the deletion of the entire GPD had no effect on M-PMV assembly, polyprotein processing, and RNA incorporation. However, a reduction of the reverse transcriptase (RT) activity, resulting in a drop in M-PMV infectivity, was determined for all GPD mutants. Immunoprecipitation experiments suggested that the GPD is a part of RT and participates in its function. These data indicate that the M-PMV GPD functions as a part of reverse transcriptase rather than protease. 

Retracted: No

PubPeer comments:
 Concern about Figure 6B. * Boxes in shades of red and orange show areas between the two panels that appear to look similar. Note that the Pr78 band appears to be the only feature different between these areas.  ,
Enriched environment prevents hypobaric hypoxia induced memory impairment and neurodegeneration: role of BDNF/PI3K/GSK3Œ≤ pathway coupled with CREB activation
Authors: Vishal Jain
Dipti Prasad
Govindasamy Ilavazhagan
Iswar Baitharu
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Hypobaric hypoxia; Enriched environment; Neuroprotection; Spatial memory; Neurotrophin
Affiliations: Department of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), Delhi, India.

Abstract:  Adverse environmental conditions such as hypobaric hypoxia (HH) cause memory impairment by affecting cellular machinery leading to neurodegeneration. Providing enriched environment (EE) is found to be beneficial for curing several neurodegenerative disorders. The protective role of EE in preventing HH induced neuronal death has been reported previously but the involved mechanism is still not clearly understood. The present study is an attempt to verify the impact of EE on spatial memory during HH and also to explore the possible role of neurotrophin in EE mediated neuroprotection. Signaling mechanism involved in neuroprotection was also explored. Male Sprague Dawley rats were simulated to HH condition in an Animal Decompression Chamber at an altitude of 25000 feet in standard and enriched cages for 7 days. Spatial memory was assessed through Morris Water Maze. Role of different neurotrophins was explored by gene silencing and inhibitors for their respective receptors. Further, using different blockers signaling pathway was also explored. Finding of the present study suggested that EE prevents HH mediated memory impairment and neurodegeneration. Also brain-derived neurotrophic factor (BDNF) plays a major role in EE mediated neuroprotection and it effectively prevented neurodegeneration by activating PI3K/AKT pathway resulting in GSK3Œ≤ inactivation which further inhibits apoptosis. Moreover GSK3Œ≤ phosphorylation and hence its inactivation upregulates CREB phosphorylation which may also accounts for activation of survival machinery in cells and provides neuroprotection. From these observations it can be postulated that EE has a therapeutic potential in amelioration of HH induced memory impairment and neurodegeneration. Hence it may be used as a non invasive and non pharmacological intervention against various neurological disorders. 

Retracted: No

PubPeer comments:
 Figure 2: * Red boxes: In the Fluoro Jade row, panels I (Normoxia) and IV (Normoxia + EE) appear to share an overlap * Blue boxes: In the Crresyl Violet row, panels I (Normoxia) and IV (Normoxia + EE) appear to share an overlap  This was reported to the journal in May 2014. ,