PReD-Bench/PRed-Bench huggingface dataset:
Semaphorin-3E Produced by Immature Dendritic Cells Regulates Activated Natural Killer Cells Migration
Authors: Abdelilah S Gounni
Abdulaziz Alamri
Abeer Alamri
Sam K P Kung
Manli Zhang
Rahmat Rahman
Journal: Frontiers in Immunology (2018)
Discipline: IMMUNOLOGY
Keywords: TLR ligands; cell trafficking; cytokines activation; dendritic cells; innate immunity
Affiliations: Department of Immunology, University of Manitoba, Winnipeg, MB, Canada., Department of Oral Biology, University of Manitoba, Winnipeg, MB, Canada.

Abstract:  Natural killer (NK) cells and dendritic cells (DCs) are two innate immune cells that are critical in regulating innate and adaptive immunity. Cellular functions and migratory responses of NK or DC can be further regulated in NK-DC crosstalk that involves multiple cytokine signals and/or direct cell-cell contacts. Semaphorin-3E (Sema-3E) is a member of a large family of Semaphorin proteins that play diverse regulatory functions in different biological systems upon its binding to the cognate receptors. However, possible role(s) of Sema-3E on the regulation of NK-cell functions has not been elucidated. Here, we first demonstrated that DC and NK cells expressed Sema-3E and its receptors, respectively. To formally address the importance of DC-derived Sema-3E in regulating NK-cell migration, we compared in vitro migratory responses of activated NK cells (aNKs) toward different conditioned media of DCs (immature, lipopolysaccharide- or Poly I:C-stimulated) derived from Sema-3E+/+ or Sema-3E-/- mice. We observed that aNKs exhibited enhanced migrations toward the conditioned medium of the immature Sema-3E-/- DC, when compared with that of the immature Sema-3E+/+ DC. Addition of exogenous recombinant Sema-3E to the conditioned medium of the Sema-3E-/- immature DC (iDC) abrogated such enhanced NK-cell migration. Our current work revealed a novel role of Sema-3E in limiting NK-cell migrations toward iDC in NK-DC crosstalk. 

Retracted: No

PubPeer comments:
 Too heavy to be mice. Line is not reported. Total number and per-group numbers of mice rats are not reported.  ,
RNAi targeting STMN alleviates the resistance to taxol and collectively contributes to down regulate the malignancy of NSCLC cells in vitro and in vivo
Authors: Ting Yu
Ying Liao
Xuechi Lin
Xian Chen
Dan Long
Journal: Cell Biology and Toxicology (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Non¬†small cell lung cancer; RNA interference; Stathmin; Taxol; Xenografted tumor.
Affiliations: Department of Medical Laboratory, Changsha Medical University, 9th Kilometre's Stop at Leifeng Rd, Wangcheng District, Changsha, Hunan, China., Department of Medical Laboratory, Changsha Medical University, 9th Kilometre's Stop at Leifeng Rd, Wangcheng District, Changsha, Hunan, China. .

Abstract:  Stathmin (STMN) plays a vital role in maintaining the malignant behavior of cancer through directly regulating microtubule dynamics equilibrium. Taxol, an effective chemotherapeutics mainly acting to promote microtubule polymerization, has been commercially applied in treating solid tumors, which results in serious drug resistance. Our study demonstrated that STMN RNA interference (RNAi) enlarged taxol-induced inhibitions in cellular proliferation, colony formation, and multidimensional spaces of cell immigration and decreased half maximal inhibitory concentration (IC50) of taxol in nonsmall cell lung cancer (NSCLC) NCI-H1299 cells; STMN RNAi and taxol jointly attenuated the expressions of extracellular regulated kinase (ERK), nuclear factor kappa B (NF-Œ∫B) and B cell lymphoma-2 (Bcl-2), but up regulated Bax expression and initiated intrinsic cell death pathway by activating caspase-3 and caspase-9, while inhibited interleukin 10 (IL-10) autocrine from cell culture supernatant and xenografted mouse serum, as well as intracellular expressions of IL-10 protein and mRNA in vitro; additionally, neutralizing IL-10 alone would incur cell apoptosis to some degree; the further study confirmed that RNAi targeting STMN promoted the sensitivity of taxol in different NSCLC cells. In vivo animal experiments proved that STMN RNAi and taxol cooperatively inhibited the tumorigenicity of NCI-H1299 cells and histological atypia and Ki-67 proliferative index of xenografted tumors and promoted cell differentiation to a higher grade with well-differentiated indicators of glandular lumen-like structure and proliferative fibroblasts. These findings suggest that silencing STMN alleviates the resistance to taxol and collectively contributes to induce the dysfunction of multiple signals and down regulate the malignancy of tumors; thus, STMN is a promising target in treating refractory tumors. 

Retracted: No

PubPeer comments:
 Fig 7B has an overlap between Blank and Non  ,
Characterization of a novel protein kinase D: Caenorhabditis elegans DKF-1 is activated by translocation-phosphorylation and regulates movement and growth in vivo
Authors: Min Ren
David H Hall
Charles S Rubin
Hui Feng
Shi-Lan Wu
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Protein kinase D; PKD isoforms; diacylglycerol; DAG; PKC effectors
Affiliations: Department of Molecular Pharmacology, Atran Laboratories, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

Abstract:  Protein kinase D (PKD) isoforms are protein kinase C (PKC) effectors in diacylglycerol (DAG)-regulated signaling pathways. Key physiological processes are placed under DAG control by the distinctive substrate specificity and intracellular distribution of PKDs. Comprehension of the roles of PKDs in homeostasis and signal transduction requires further knowledge of regulatory interplay among PKD and PKC isoforms, analysis of PKC-independent PKD activation, and characterization of functions controlled by PKDs in vivo. Caenorhabditis elegans and mammals share conserved signaling mechanisms, molecules, and pathways Thus, characterization of the C. elegans PKDs could yield insights into regulation and functions that apply to all eukaryotic PKDs. C. elegans DKF-1 (D kinase family-1) contains tandem DAG binding (C1) modules, a PH (pleckstrin homology) domain, and a Ser/Thr protein kinase segment, which are homologous with domains in classical PKDs. DKF-1 and PKDs have similar substrate specificities. Phorbol 12-myristate 13-acetate (PMA) switches on DKF-1 catalytic activity in situ by promoting phosphorylation of a single amino acid Thr(588) in the activation loop. DKF-1 phosphorylation and activation are unaffected when PKC activity is eliminated by inhibitors. Both phosphorylation and kinase activity of DKF-1 are extinguished by substituting Ala for Thr(588) or Gln for Lys(455) ("kinase dead") or incubating with protein phosphatase 2C. Thus, DKF-1 is a PMA-activated, PKC-independent D kinase. In vivo, dkf-1 gene promoter activity is evident in neurons. Both dkf-1 gene disruption (null phenotype) and RNA interference-mediated depletion of DKF-1 protein cause lower body paralysis. Targeted DKF-1 expression corrected this locomotory defect in dkf-1 null animals. Supraphysiological expression of DKF-1 limited C. elegans growth to approximately 60% of normal length. 

Retracted: No

PubPeer comments:
  There are multiple undeclared spicing sites in the immunoblots in Figure 2B and 2C. The lanes of immunoblots in red or blue boxes are duplicated. They are all negative for band signal. ,
CSB promoter downregulation via histone H3 hypoacetylation is an early determinant of replicative senescence
Authors: Cl√©ment Crochemore
Cristina Fern√°ndez-Molina
Audrey Salles
Benjamin Montagne
Miria Ricchetti
Journal: Nature Communications (2019)
Discipline: Multidisciplinary
Keywords: Cellular senescence; ageing; age-related diseases; progeroid factors; CSB
Affiliations: Institut Pasteur, Stem Cells and Development, Department of Developmental and Stem Cell Biology, 75015, Paris, France., CNRS UMR 3738, Team Stability of Nuclear and Mitochondrial DNA, 75015, Paris, France., Sorbonne Universit√©s, UPMC, University of Paris 06, IFD-ED 515, Paris, France., Institut Pasteur, UTechS Photonic BioImaging PBI (Imagopole), Centre de Recherche et de Ressources Technologiques C2RT, Paris, France., Institut Pasteur, Stem Cells and Development, Department of Developmental and Stem Cell Biology, 75015, Paris, France. ., CNRS UMR 3738, Team Stability of Nuclear and Mitochondrial DNA, 75015, Paris, France. .

Abstract:  Cellular senescence has causative links with ageing and age-related diseases, however, it remains unclear if progeroid factors cause senescence in normal cells. Here, we show that depletion of CSB, a protein mutated in progeroid Cockayne syndrome (CS), is the earliest known trigger of p21-dependent replicative senescence. CSB depletion promotes overexpression of the HTRA3 protease resulting in mitochondrial impairments, which are causally linked to CS pathological phenotypes. The CSB promoter is downregulated by histone H3 hypoacetylation during DNA damage-response. Mechanistically, CSB binds to the p21 promoter thereby downregulating its transcription and blocking replicative senescence in a p53-independent manner. This activity of CSB is independent of its role in the repair of UV-induced DNA damage. HTRA3 accumulation and senescence are partially rescued upon reduction of oxidative/nitrosative stress. These findings establish a CSB/p21 axis that acts as a barrier to replicative senescence, and link a progeroid factor with the process of regular ageing in human. 

Retracted: No

PubPeer comments:
 Since $S(h)$ in eq.(4) is an interval, the term $phi(h)$ in eq.(5) is not well defined because the square of an interval is not explicitly defined. The method for multi-attribute decision making based on such notions and operations is merely symbol manipulation and makes no sense. See also https: pubpeer.com publications B7B66CD22C7D67B350D0311E0C6ECA  ,
lncRNA HOTAIR upregulates COX-2 expression to promote invasion and migration of nasopharyngeal carcinoma by interacting with miR-101
Authors: Weiqi Hu
Yi Shi
Weimin Xu
Weijun Dai
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: COX-2; HOTAIR; Nasopharyngeal carcinoma; Tumorigenesis and progression; miR-101.
Affiliations: Department of Otorhinolaryngology, Minhang Hospital, Fudan University, Shanghai, 201199, PR China., Gongli Hospital of Pudong District, Shanghai, PR China. Electronic address: .

Abstract:  Background: Nasopharyngeal carcinoma (NPC) is the most common type of head and neck cancers which is notable for its distinctive pattern of geographical distribution. HOTAIR has been reported to regulate nasopharyngeal carcinoma tumorigenesis and progression. However, the detailed mechanism underlying HOTAIR-promoted nasopharyngeal carcinoma remains not fully understood. Methods: We used RT-qPCR approach to examine genes expression and mRNA level. MTT assay and soft agar assay were used to detect cell growth rate in culture and under suspended condition, respectively. Besides, we employed wound healing assay and transwell invasion assay to determine migration and invasion ability of nasopharyngeal carcinoma cells. We predicted direct downstream targets of miR-101 by bioinformatic analysis, which was confirmed by dual luciferase reporter assay. Results: HOTAIR was upregulated in NPC tissues and cells. miR-101 inhibitor greatly enhanced HOTAIR knockdown-regulated cell proliferation, migration and invasion of CNE1 and CNE2 cells. miR-101 was shown to directly bind 3'-UTR of COX-2 and downregulate COX-2 expression. Finally, COX-2 overexpression was demonstrated to rescue the tumor phenotypes of nasopharyngeal carcinoma cells attenuated by HOTAIR knockdown or miR-101 mimic. Conclusions: Here, we highlight the importance of HOTAIR/miR-101/COX-2 axis in progression of nasopharyngeal carcinoma cells. Our findings provide a novel mechanism for explaining HOTAIR-induced nasopharyngeal carcinoma and help developing the therapeutical strategies by targeting HOTAIR. 

Retracted: No

PubPeer comments:
 Figure 1H appears to have some images which overlap, although they seem to be representing different cell lines. Could the authors please comment? TAM ***  ,
Evaluation of fusion protein cleavage site sequences of Newcastle disease virus in genotype matched vaccines
Authors: Asuka Yoshida
Shin-Hee Kim
Anandan Paldurai
Sa Xiao
Zongyan Chen
Siba K Samal
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: Newcastle disease virus; NDV; vaccine development; reverse genetics system; virulent strain
Affiliations: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, Greenmead Drive, College Park, Maryland, United States of America.

Abstract:  Newcastle disease virus (NDV) causes a devastating poultry disease worldwide. Frequent outbreaks of NDV in chickens vaccinated with conventional live vaccines suggest a need to develop new vaccines that are genetically matched against circulating NDV strains, such as the genotype V virulent strains currently circulating in Mexico and Central America. In this study, a reverse genetics system was developed for the virulent NDV strain Mexico/01/10 strain and used to generate highly attenuated vaccine candidates by individually modifying the cleavage site sequence of fusion (F) protein. The cleavage site sequence of parental virus was individually changed to those of the avirulent NDV strain LaSota and other serotypes of avian paramyxoviruses (APMV serotype-2, -3, -4, -6, -7, -8, and -9). In general, these mutations affected cell-to-cell fusion activity in vitro and the efficiency of the F protein cleavage and made recombinant Mexico/01/10 (rMex) virus highly attenuated in chickens. When chickens were immunized with the rMex mutant viruses and challenged with the virulent parent virus, there was reduced challenge virus shedding compared to birds immunized with the heterologous vaccine strain LaSota. Among the vaccine candidates, rMex containing the cleavage site sequence of APMV-2 induced the highest neutralizing antibody titer and completely protected chickens from challenge virus shedding. These results show the role of the F protein cleavage site sequence of each APMV type in generating genotype V-matched vaccines and the efficacy of matched vaccine strains to provide better protection against NDV strains currently circulating in Mexico. 

Retracted: No

PubPeer comments:
  After this article [1] was published, it came to light that the Data Availability Statement is inaccurate: the underlying data are not included with the published article. Additionally, there are six statements in the Results that rely on data not shown which is not allowable per the journalu2019s Data Availability Policy. The authors clarified that the underlying data for this study are not available, and so the article does not comply with PLOS ONEu2019s Data Availability Policy. The PLOS ONE Editors issue this Expression of Concern to notify readers of this issue. We regret that this was not addressed prior to publication. ,
The new face of the old molecules: crustin Pm4 and transglutaminase type I serving as rnps down-regulate astakine-mediated hematopoiesis
Authors: Cheng-Yung Lin
Huai-Jen Tsai
Vinu S Siva
Che-Yiang Tsai
Chia-Ying Chu
Yen-Ling Song
Yun-Tsan Chang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Astakine; cytokine; hematopoiesis; 3'-UTR; protein expression
Affiliations: Institute of Zoology, National Taiwan University, Taipei, Taiwan, ROC.

Abstract:  Astakine is an important cytokine that is involved in crustacean hematopoiesis. Interestingly, the protein levels of astakine increased dramatically in plasma of LPS-injected shrimp while mRNA levels remained unchanged. Here, we investigated the involvement of astakine 3'-untranslated region (UTR) in its protein expression. The 3'-UTR of astakine down-regulated the expression of reporter protein but the mRNA stability of reporter gene was unaffected. We identified the functional regulatory elements of astakine 3'-UTR, where 3'-UTR242-483 acted as repressor. The electrophoresis mobility shift assay (EMSA), RNA pull-down assay and LC/MS/MS were performed to identify the protein association. We noted that crustin Pm4 and shrimp transglutaminase I (STG I) were associated to astakine 3'-UTR242-483, while two other proteins have yet to be revealed. Depletion of hemocytic crustin Pm4 and STG I significantly increased the protein level of astakine while astakine mRNA level remained unaffected. Lipopolysaccharide (LPS) stimulated the secretion of crustin Pm4 and STG I from hemocytes to plasma and increased the astakine level to stimulate the hemocytes proliferation. Altogether, we identified the shrimp crustin Pm4 and STG I as novel RNA binding proteins that play an important role in down-regulating astakine expression at post-transcriptional level and are crucial for the maintenance of hematopoiesis. 

Retracted: No

PubPeer comments:
 July 2017 correction. The correction reads:  The authors would like to correct Fig 7, as errors were introduced in the preparation of this figure for publication. The GAPDH band in the Ctrl. lane of Fig 7A is the same as the GAPDH band in the Cru lane of Fig 7B. The authors apologize for the mismatch of astakine expression and its GAPDH expression and note that the mismatch will not influence the conclusion of the article since they loaded the same amount of proteins for every group and confirmed again with GAPDH expression by MataMorph(r) version 7.0 software. The GAPDH expression for every group was almost the same. Here is the duplication in Figure 7, as reported to the journal in October 2015, marked with pink boxes.  ,
Targeting MMP-9, uPAR, and cathepsin B inhibits invasion, migration and activates apoptosis in prostate cancer cells
Authors: B Gorantla
A K Nalla
S S Lakka
C S Gondi
J S Rao
Journal: Cancer Gene Therapy (2010)
Discipline: CLINICAL MEDICINE
Keywords: Prostate cancer; metastasis; siRNA; matrix metalloproteinase-9; urokinase plasminogen activator receptor
Affiliations: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, USA.

Abstract:  Prostate cancer is one of the most commonly diagnosed cancers and the second leading cause of cancer deaths in Americans. The high mortality rate is mainly attributed to the invasiveness and metastasis of advanced prostate cancer. Targeting the molecules involved in metastasis could be an effective mode of treatment for prostate cancer. In this study, the therapeutic potential of siRNA-mediated targeting of matrix metalloproteinase-9 (MMP-9), urokinase plasminogen activator receptor (uPAR), and cathepsin B (CB) in prostate cancer was carried out using single and bi-cistronic siRNA-expressing constructs. Downregulation of MMP-9, uPAR, and CB inhibited matrigel invasion, in vitro angiogenesis and wound-healing migration ability of PC3 and DU145 prostate cancer cell lines. In addition, the siRNA treatments induced apoptosis in the tumor cells as determined by TUNEL and DNA laddering assays. An attempt to elucidate the apoptotic pathway showed the involvement of FAS-mediated activation of caspases-8 and -7. Further, mice with orthotopic prostate tumors treated with siRNA-expressing vectors showed significant inhibition in tumor growth and migration. In conclusion, we report that the siRNA-mediated knockdown of MMP-9, uPAR, and CB inhibits invasiveness and migration of prostate cancer cells and leads to apoptosis both in vitro and in vivo. 

Retracted: No

PubPeer comments:
 Figure 3A. Several panels, representing cells transfected with different plasmids, appear to show areas of overlap.  , 
 Figure 4A. Two panels appear to show an overlap.  , 
 Figure 3C. Two panels appear to show an overlap.  , 
 There seem to be an additional overlap in Figure 4a and 5a, which I will leave to the journal to identify if they wish. I notified them today in case the original poster never did. As many readers will be aware, this [author group] seems to have a number of problematic papers. ,
Bifidobacterium breve as a delivery vector of IL-24 gene therapy for head and neck squamous cell carcinoma in vivo
Authors: I Vuletic
H Sun
Z Xie
Q Ren
L Wang
W Crielaard
C Guo
K Zhou
D Deng
J Zhang
Journal: Gene Therapy (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Beneficial bacteria; gene delivery; hypoxia-tumor targeting; Bifidobacterium breve; interleukin-24
Affiliations: Deparment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China., Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China., Department of Preventive Dentistry, Academic Center for Dentistry Amsterdam, Gustav Mahlerlann, Amsterdam, Netherlands., General Hospital of Chinese People's Liberation Army, Beijing, China.

Abstract:  Beneficial bacteria are becoming ever more popular gene delivery method for hypoxia-tumor targeting in vivo. In this study we investigated the therapeutic effect of new recombinant Bifidobacterium breve strain expressing interleukin (IL)-24 gene (B. breve-IL24) on head and neck tumor xenograft in mice. Briefly, B. breve transformants were obtained through electro-transformation. Bacteria-tumor-targeting ability were analyzed in vivo over different time points (1, 3 and 7 days post-bacteria injection). Furthermore, the therapeutic effect of bacteria on tumor cells in vivo were analyzed as follows: 30 Balb/c nude mice bearing subcutaneous tumor were randomly divided in three groups (Drug group, green fluorescent protein (GFP) group and Saline group). The therapy lasted for 2 weeks and included B. breve-IL24 administration via tail vein for Drug group, B. breve-GFP for GFP group and phosphate buffered saline for Saline group. The tumor growth was monitored using standard caliper technique, while the apoptosis induction in vivo was analyzed by Real-time Positron Emission Tomography/Computed Tomography (PET/CT) imaging ([18F]-ML-10 tracer). At the end of the experiment, tumor tissues were collected and analyzed by western blotting. Briefly, our results suggested that our new recombinant bacterium has the capability of targeting tumor tissue in vivo. As for the therapeutic effect, our new strain has revealed to be a promising therapeutic approach against tumor growth in vivo. Briefly, higher tumor growth inhibition and higher tumor cell apoptosis induction were observed in Drug group compared with the GFP and Saline groups. To conclude, a new recombinant strain B. breve-IL24 offers a novel, safe and clinically acceptable therapeutic approach for tumor therapy in vivo. 

Retracted: No

PubPeer comments:
 Figure 1B and 3D, same micrograph (red boxes) was used to describe different tissue sections stained with different antibodies. Could the authors please check?  ,
Protein kinase C-Œ¥ negatively regulates T cell receptor-induced NF-Œ∫B activation by inhibiting the assembly of CARMA1 signalosome
Authors: Hai-Yun Liu
Shuai Wang
Yi Li
Yu Liu
Yan Gao
Yan Wang
Ren Song
Yun-Hong Hu
Hong-Bing Shu
Journal: Journal of Biological Chemistry (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: T-cell receptor; T-cell activation; CARMA1; PKCŒ¥; NF-Œ∫B activation
Affiliations: College of Life Sciences, Wuhan University, Wuhan 430072, China. 

Abstract:  T-cell receptor (TCR)-induced T-cell activation is a critical event in adaptive immune responses. The engagement of TCR complex by antigen along with the activation of the costimulatory receptors trigger a cascade of intracellular signaling, in which caspase recruitment domain-containing membrane-associated guanylate kinase 1 (CARMA1) is a crucial scaffold protein. Upon stimulation, CARMA1 recruits downstream molecules including B-cell CLL/lymphoma 10 (Bcl10), mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1), and TRAF6 to assemble a specific TCR-induced signalosome that triggers NF-Œ∫B and JNK activation. In this report, we identified protein kinase CŒ¥ (PKCŒ¥) as a CARMA1-associated protein by a biochemical affinity purification approach. PKCŒ¥ interacted with CARMA1 in TCR stimulation-dependent manner in Jurkat T cells. Overexpression of PKCŒ¥ inhibited CARMA1-mediated NF-Œ∫B activation, whereas knockdown of PKCŒ¥ potentiated TCR-triggered NF-Œ∫B activation and IL-2 secretion in Jurkat T cells. Reconstitution experiments with PKCŒ¥ kinase-dead mutant indicated that the kinase activity of PKCŒ¥ was dispensable for its ability to inhibit TCR-triggered NF-Œ∫B activation. Furthermore, we found that PKCŒ¥ inhibited the interaction between MALT1 and TRAF6, but not the association of CARMA1 with PKCŒ∏, Bcl10, or MALT1. These observations suggest that PKCŒ¥ is a negative regulator in T cell activation through inhibiting the assembly of CARMA1 signalosome. 

Retracted: No

PubPeer comments:
 siRNA # 2 and # 4 were not provided.  , 
 #1 We didnu2019t show the target sequences for siRNA # 2 and # 4 in the paper, because they didnu2019t work. But indeed someone may need the information. Thanks for pointing out. The target sequence for human PKCu03b4-siRNA # 2 is 5u2032-ACACTATATTCCAGAAAGA-3u2032; for PKCu03b4-siRNA # 4 is 5u2032-GAGTGACCGGAAACATCAA-3u2032. ,
RETRACTED: The long noncoding RNA CASC2 inhibits tumorigenesis through modulating the expression of PTEN by targeting miR-18a-5p in esophageal carcinoma
Authors: Wenqiao Zang
Jianfeng Gao
Ziming Dong
Wei He
Guoqiang Zhao
Yuanyuan Wang
Wenjing Zhang
Journal: Experimental Cell Research (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Esophageal carcinoma; Long noncoding RNA CASC2; PTEN; miR-18a-5p.
Affiliations: School of Basic Medicine Sciences, Henan University of Chinese Medicine, Zhengzhou450046, China. Electronic address: ., Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., School of Basic Medicine Sciences, Henan University of Chinese Medicine, Zhengzhou450046, China., School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China., School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; Collaborative Innovation Center of Cancer Chemoprevention, Zhengzhou, Henan, China., School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; Collaborative Innovation Center of Cancer Chemoprevention, Zhengzhou, Henan, China. Electronic address: .

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. In the article Figure 3A top and center panel are duplicated and in Figure 5A elements are duplicated from previous publications from the same authors in Tumor Biol. (2014) 35:12583‚Ä?2592 DOI 10.1007/s13277-014-2579-4 (Figure 3) and Dig Dis Sci (2013) 58:706‚Ä?14 DOI 10.1007/s10620-012-2395-x (Figure 8). The authors recognize mishandling of these images which affects the validation of the study and would like to apologize to readers. 

Retracted: Yes

PubPeer comments:
 2020 correction. https: doi.org 10.1002 ijc.33194 It has come to our attention that incorrect images had been inadvertently included in the paper. The Fig. 2d and HCT116 control figure in Fig. 2g and Fig. 2h have now been corrected as shown below. This correction has not changed the description, interpretation, or the original conclusions of the article. The authors apologize for these errors and any consequent inconvenience to authors and readers. ,
Co-infection with respiratory pathogens among COVID-2019 cases
Authors: Xiaojuan Zhu
Kangchen Zhao
Tao Wu
Bin Wu
Fengcai Zhu
Baoli Zhu
Lunbiao Cui
Yiyue Ge
Yin Chen
Journal: Virus Research (2020)
Discipline: MICROBIOLOGY
Keywords: COVID-19; Co-infection; RT-PCR; SARS-CoV-2.
Affiliations: NHC Key laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China., NHC Key laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China; From Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: ., NHC Key laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China. Electronic address: .

Abstract:  Accumulating evidence shows that microbial co-infection increases the risk of disease severity in humans. There have been few studies about SARS-CoV-2 co-infection with other pathogens. In this retrospective study, 257 laboratory-confirmed COVID-19 patients in Jiangsu Province were enrolled from January 22 to February 2, 2020. They were re-confirmed by real-time RT-PCR and tested for 39 respiratory pathogens. In total, 24 respiratory pathogens were found among the patients, and 242 (94.2 %) patients were co-infected with one or more pathogens. Bacterial co-infections were dominant in all COVID-19 patients, Streptococcus pneumoniae was the most common, followed by Klebsiella pneumoniae and Haemophilus influenzae. The highest and lowest rates of co-infections were found in patients aged 15-44 and below 15, respectively. Most co-infections occurred within 1-4 days of onset of COVID-19 disease. In addition, the proportion of viral co-infections, fungal co-infections and bacterial-fungal co-infections were the highest severe COVID-19 cases. These results will provide a helpful reference for diagnosis and clinical treatment of COVID-19 patients. 

Retracted: No

PubPeer comments:
 If you dont look, they will not find. Only 39 is not enough - it doesnt [include the anaerobes] . The pathogens detected in Covid19 patients from [sequencing data] are unbiased (and include these) - but they are not the ones causing damage.  ,
MTSS1 hypermethylation is associated with prostate cancer progression
Authors: Zhao Wang
Liang Huang
Junjie Chen
Quan Zhu
Zhengyan Tang
Journal: Journal of cellular physiology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: 5-Aza-dC; DNA methylation; mRNA; prostate cancer; western blot analysis.
Affiliations: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China., Department of Urology, Hunan Provincial People's Hospital, Changsha, Hunan, China., Hunan Engineering Laboratory for Diagnosis and Treatment Technology of Urogenital Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract:  This study was conducted to evaluate the influence of DNA methylation of metastasis suppressor 1 (MTSS1) on prostate cancer (PCa) progression. Forty-nine paired PCa tissue samples and normal tissue samples from The Cancer Genome Atlas were analyzed. Methylome analysis, CpG island arrays and Hierarchical clustering were used to analyze methylation profiles of PCa tissues. MTSS1 methylation level was detected by methylation-specific PCR. Relative messenger RNA and the expression level of MTSS1 protein were identified by quantitative real-time PCR (qRT-PCR) and western blot analysis. The migration, invasion, proliferation, and cell cycle were detected separately by wound-healing assay, transwell chamber assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. The roles of MTSS1 in PCa progression were demonstrated in vivo by tumor formation assays in nude mice. MTSS1 expression was decreased in PCa tissues in comparison with paired adjacent normal prostate tissues. Compared to the methylation of MTSS1 in normal prostate tissues based on the MethHC website, the MTSS1 in PCa tissues was hypermethylated. The expression of MTSS1 detected by qRT-PCR and western blot analysis was found to be downregulated in PCa cells and tissues. The reduced expression of MTSS1 by small interfering RNA-MTSS1 was recovered by 5-aza-2'-deoxycytidine treatment. Besides, MTSS1 demethylation inhibited migration, invasion, and proliferation of PCa cells, and induced cell cycle to be arrested at G0/G1 phase. Furthermore, it was shown by tumor xenograft assay that MTSS1 inhibited the growth of tumor in vivo. Hypermethylated MTSS1 promoted PCa cells migration, invasion, and proliferation, and suppressed cell cycle arrest at the G0/G1 phase. 

Retracted: No

PubPeer comments:
 In Fig4b, the TSA group and the 5-Aza-dC+TSA group has the same field, can the authors explain it?  ,
Long non-coding RNA PVT1 regulates glioma proliferation, invasion, and aerobic glycolysis via miR-140-5p
Authors: H-T Chen
Q-R Ma
J Liu
Y-W Zhang
Y Shao
Y-Q He
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: LncRNA PVT1; miR-140-5p; proliferation; invasion; aerobic glycolysis
Affiliations: Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, P.R. China. .

Abstract:  Objective: To investigate the regulation of long non-coding RNA plasmacytoma variant translocation 1 (LncRNA PVT1) on proliferation, invasion, and aerobic glycolysis in glioma cells via miR-140-5p. Patients and methods: Sixty patients with glioma treated in our hospital were recruited. The expression of PVT1 in tissues and cells was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the effects on the prognosis were observed. Glioma cell lines U87 and T98MG were either stably or transiently transfected with over-expression or inhibition vectors. Cell counting kit-8 (CCK-8), transwell, glucose, and lactate detection were employed to measure cell proliferation, invasion, and aerobic glycolysis after transfection. The correlation between PVT1 and miR-140-5p was determined by Dual-Luciferase reporter assay. RNA pull-down and RNA immunoprecipitation (RIP) test were adopted to indicate the correlation between PVT1 and miR-140-5p. Results: PVT1 was highly expressed and had superior diagnostic value in gliomas, and the high expression of PVT1 resulted in poor prognosis of patients. Over-expressing PVT1 increased cell proliferation, invasion, and aerobic glycolysis, while inhibiting PVT1 yielded opposite outcome. Dual-Luciferase reporter assay confirmed that PVT1 could target miR-140-5p. Functional analysis showed that over-expression of miR-140-5p inhibited proliferation, invasion, and aerobic glycolysis in glioma cells. Rescue experiment found that the inhibitory effect of miR-140-5p could be eliminated by up-regulating PVT1 expression. Conclusions: PVT1 promotes proliferation, invasion, and aerobic glycolysis in glioma cells by regulating miR-140-5p. 

Retracted: Yes

PubPeer comments:
 Fig.2B: Some background pattern appear much more similar than expect after contrast enhancing. Additionally, the actin control appears spliced between sh1 and sh2? Could the authors please provide the original uncropped blots for review?  ,
Activation of estrogen receptor-alpha by the anion nitrite
Authors: Sivanesan Dakshanamurthy
Geoffrey B Storchan
Shailaja Divekar
Adriana Stoica
Jasmine M A Turner
David J Veselik
Mary Beth Martin
Li Huang
Kelly L Graham
Journal: Cancer Research (2008)
Discipline: CLINICAL MEDICINE
Keywords: nitrite; nitrate; estradiol; growth; gene expression
Affiliations: Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia, USA.

Abstract:  In this study, the ability of nitrite and nitrate to mimic the effects of estradiol on growth and gene expression was measured in the human breast cancer cell line MCF-7. Similar to estradiol, treatment of MCF-7 cells with either 1 mumol/L nitrite or 1 mumol/L nitrate resulted in approximately 4-fold increase in cell growth and 2.3-fold to 3-fold increase in progesterone receptor (PgR), pS2, and cathepsin D mRNAs that were blocked by the antiestrogen ICI 182,780. The anions also recruited estrogen receptor-alpha (ERalpha) to the pS2 promoter and activated exogenously expressed ERalpha when tested in transient cotransfection assays. To determine whether nitrite or nitrate was the active anion, diphenyleneiodonium was used to inhibit oxidation/reduction reactions in the cell. The ability of diphenyleneiodonium to block the effects of nitrate, but not nitrite, on the induction of PgR mRNA and the activation of exogenously expressed ERalpha suggests that nitrite is the active anion. Concentrations of nitrite, as low as 100 nmol/L, induced a significant increase in PgR mRNA, suggesting that physiologically and environmentally relevant doses of the anion activate ERalpha. Nitrite activated the chimeric receptor Gal-ER containing the DNA-binding domain of GAL-4 and the ligand-binding domain of ERalpha and blocked the binding of estradiol to the receptor, suggesting that the anion activates ERalpha through the ligand-binding domain. Mutational analysis identified the amino acids Cys381, His516, Lys520, Lys529, Asn532, and His547 as important for nitrite activation of the receptor. 

Retracted: No

PubPeer comments:
  , 
 Here is the same figure in reverse with additional contrast adjustments. I think this supports the concerns expressed in #1. ***  ,
ATPL2 (MAP3K8)disease-risk polymorphism increases TPL2 expression thereby leading to increased pattern recognition receptor-initiated caspase-1 and caspase-8 activation, signalling and cytokine secretion
Authors: Clara Abraham
Matija Hedl
Journal: Gut (2016)
Discipline: CLINICAL MEDICINE
Keywords: IBD BASIC RESEARCH; IMMUNOLOGY; MACROPHAGES.
Affiliations: Department of Internal Medicine, Yale University, New Haven, CT, USA.

Abstract:  Objective: IBD is characterised by dysregulated intestinal immune homeostasis and cytokine secretion. In the intestine, properly regulating pattern recognition receptor (PRR)-mediated signalling and cytokines is crucial given the ongoing host-microbial interactions. TPL2 (MAP3K8, COT) contributes to PRR-initiated pathways, yet the mechanisms for TPL2 signalling contributions in primary human myeloid cells are incompletely understood and its role in intestinal myeloid cells is poorly defined. Furthermore, functional consequences for the IBD-risk locus rs1042058 in TPL2 are unknown. Methods: We analysed protein, cytokine and RNA expression, and signalling in human monocyte-derived macrophages (MDMs) through western blot, ELISA, real-time PCR and flow cytometry. Results: PRR-induced cytokine secretion was increased in MDMs from rs1042058 TPL2 GG risk individuals. TPL2 activation by the Crohn's disease-associated PRR nucleotide-oligomerisation domain (NOD)2 required PKC, and IKKŒ≤, IKKŒ± and IKKŒ≥ signalling. TPL2, in turn, significantly enhanced NOD2-induced ERK, JNK and NFŒ∫B signalling. We found that another major mechanism for the TPL2 contribution to NOD2 signalling was through ERK-dependent and JNK-dependent caspase-1 and caspase-8 activation, which in turn, led to early autocrine interleukin (IL)-1Œ≤ and IL-18 secretion and amplification of long-term cytokines. Importantly, Salmonella typhimurium-induced cytokines from human intestinal myeloid-derived cells required TPL2 as well as autocrine IL-1Œ≤ and IL-18. Finally, rs1042058 GG risk carrier MDMs from healthy individuals and patients with Crohn's disease had increased TPL2 expression and NOD2-initiated TPL2 phosphorylation, ERK, JNK and NFŒ∫B activation, and early autocrine IL-1Œ≤ and IL-18 secretion. Conclusions: Taken together, the rs1042058 GG IBD-risk polymorphism in TPL2 results in a gain-of-function by increasing TPL2 expression and signalling, thereby amplifying PRR-initiated outcomes. 

Retracted: No

PubPeer comments:
   ,
Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis
Authors: Yanfei Chen
Jun Yao
Ce Zhang
Shegan Gao
Journal: Life Sciences (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Circ-LDLRAD3; Circular RNA; Pancreatic cancer; Pleiotrophin; miR-137-3p.
Affiliations: Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan Province, China; The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan Province, China., Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan Province, China; The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan Province, China. Electronic address: .

Abstract:  Emerging evidence suggests that dysregulation of circular RNAs (circRNAs) closely associated with cancer progression. In this paper, we focus on exploring the functional role of circ-LDLRAD3 in pancreatic cancer. Gene expression was determined using quantitative reverse transcriptase polymerase chain reaction and Western blot. Cell count kit-8 and 5-ethynyl-2'-deoxyuridine assay were applied to evaluate the proliferation of PANC-1 and SW1990 cells. The migration and invasion of PANC-1 and SW1990 cells were assessed using wound healing assay and transwell invasion assay. Luciferase reporter assay was performed for target validation. The results showed that circ-LDLRAD3 was overexpressed in pancreatic cancer tissues and cell lines. Increased expression of circ-LDLRAD3 was indicative of a poor prognosis in patients with pancreatic cancer. Knockdown of circ-LDLRAD3 repressed the growth of pancreatic cancer in vitro and in vivo. miR-137-3p was identified as a direct target of circ-LDLRAD3. More importantly, upregulation of circ-LDLRAD3 could mitigate the inhibitory effect of miR-137-3p on the proliferation, migration and invasion of pancreatic cancer cells. Besides, circ-LDLRAD3 could regulate the expression of pleiotrophin (PTN) through miR-137-3p. Taken together, knockdown of circ-LDLRAD3 repressed the proliferation, migration and invasion of pancreatic cancer cells through miR-137-3p/PTN axis, providing a new mechanism for pancreatic cancer progression. 

Retracted: No

PubPeer comments:
 Appears to have an image duplication:  ,
S-palmitoylation of gamma-secretase subunits nicastrin and APH-1
Authors: Phuong Nguyen
Taisuke Tomita
Xavier Meckler
Ying Chen
Jae Yoon Leem
Renaldo C Drisdel
Gopal Thinakaran
Kulandaivelu S Vetrivel
Ping Gong
Philip C Wong
Haipeng Cheng
Meghan Carter
Maria Z Kounnas
William N Green
Tong Li
Takeshi Iwatsubo
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Proteolytic processing; Amyloid precursor protein; Beta-amyloid peptides; Alzheimer disease; Detergent-resistant membrane microdomains
Affiliations: Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA.

Abstract:  Proteolytic processing of amyloid precursor protein (APP) by beta- and gamma-secretases generates beta-amyloid (Abeta) peptides, which accumulate in the brains of individuals affected by Alzheimer disease. Detergent-resistant membrane microdomains (DRM) rich in cholesterol and sphingolipid, termed lipid rafts, have been implicated in Abeta production. Previously, we and others reported that the four integral subunits of the gamma-secretase associate with DRM. In this study we investigated the mechanisms underlying DRM association of gamma-secretase subunits. We report that in cultured cells and in brain the gamma-secretase subunits nicastrin and APH-1 undergo S-palmitoylation, the post-translational covalent attachment of the long chain fatty acid palmitate common in lipid raft-associated proteins. By mutagenesis we show that nicastrin is S-palmitoylated at Cys(689), and APH-1 is S-palmitoylated at Cys(182) and Cys(245). S-Palmitoylation-defective nicastrin and APH-1 form stable gamma-secretase complexes when expressed in knock-out fibroblasts lacking wild type subunits, suggesting that S-palmitoylation is not essential for gamma-secretase assembly. Nevertheless, fractionation studies show that S-palmitoylation contributes to DRM association of nicastrin and APH-1. Moreover, pulse-chase analyses reveal that S-palmitoylation is important for nascent polypeptide stability of both proteins. Co-expression of S-palmitoylation-deficient nicastrin and APH-1 in cultured cells neither affects Abeta40, Abeta42, and AICD production, nor intramembrane processing of Notch and N-cadherin. Our findings suggest that S-palmitoylation plays a role in stability and raft localization of nicastrin and APH-1, but does not directly modulate gamma-secretase processing of APP and other substrates. 

Retracted: No

PubPeer comments:
 Several tables (2 examples below) include repeating SEM figures of + - 0.58 or 0.01 or 1.16. This pattern appears unexpected. Could the authors comment? Apologies if Iu2019ve misunderstood something. ***  ,
Familial Interstitial 6q23.2 Deletion Including Eya4 Associated With Otofaciocervical Syndrome
Authors: Benedetta Toschi
Irene Sardelli
Susanna Cappelli
Angelo Valetto
Diego Peroni
Veronica Bertini
Simone Gana
Journal: Frontiers in Genetics (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: 6q23 deletion; EYA1; EYA4; array CGH; otofaciocervical syndrome.
Affiliations: Medical Genetics, IRCCS Mondino Foundation, Pavia, Italy., Section of Cytogenetics, Medicine of Laboratory Department, Santa Chiara University Hospital, Pisa, Italy., Department of Clinical and Experimental Medicine, Santa Chiara University Hospital, Pisa, Italy., Section of Pediatric, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Abstract:  We report on a 34-year-old woman and her mother who both have clinical features suggestive for otofaciocervical syndrome (OTFCS), a disorder characterized by a combination of facial dysmorphisms, ear abnormalities with hearing loss, and shoulder girdle anomalies. OTFCS presents overlapping features with branchiootorenal spectrum disorders, including branchiootorenal syndrome and branchiootic syndrome. These disorders have been described as clinically distinct entities, but molecular studies have shown that all the causative genes belong to the Pax-Six-Eya-Dach network (PSEDN). So far, the genetic diagnosis of OTFCS has been performed only in very few cases and involves two genes, EYA1 and PAX1; thus, it is likely that other genes have still to be identified. In the present patient, array CGH analysis showed a 3.7-Mb deletion in 6q23; a smaller 1.9-Mb deletion in the same region was detected in her mother. The minimal overlapping region harbors the EYA4 gene. The cases here described are interesting, since they all showed the typical clinical features of OTFCS, associated with a deletion in 6q23.2. Even if we cannot exclude the contribution of other genes to the phenotype, EYA4 is a good candidate for OTFCS according to its pattern of expression, its sequence similarity to EYA1, and its involvement in PSEDN. 

Retracted: No

PubPeer comments:
 This rare expansion of a maternal 6q23.2 deletion compares with at least three other maternally expanded deletions involving 4p, 18q, and 1q (Favarelli et al. Am J Med Genet 143A:1169, 2007; South et al. J Med Genet 45:391, 2008; Guastadisegni et al. Eur J Med Genet 55:120, 2012) that were overlooked in this report. Actually, Gana et al. say nothing about such a likely meiotic expansion. These remarkable flaws are inconsistent with both the u201crigorous peer reviewu201d and the high impact factor boasted by Frontiers in Genetics, a Gold Open Access journal. In this regard, Aguzzi (Nature 570: 139, 2019) has warned that the author-pays model or u201cbroken accessu201d publishing may not offer a stringent quality control. ,