PReD-Bench/PRed-Bench huggingface dataset:
LncRNA SNHG15 Contributes to Immuno-Escape of Gastric Cancer Through Targeting miR141/PD-L1
Authors: Min Gu
Jixiang Chen
Kai Yin
Jianguo Qu
Abdul Malik
Shengchun Dang
Lei Cui
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: PD-L1; gastric cancer; immuno-escape; lncRNA SNHG15; miR-141.
Affiliations: Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, People's Republic of China., Department of General Surgery, Pucheng Hospital, Weinan, Shaanxi Province 715500, People's Republic of China., Department of Oncology, Zhenjiang Hospital of Traditional Chinese and Western Medicine, Zhenjiang, Jiangsu 212001, People's Republic of China.

Abstract:  Introduction: Long non-coding RNAs (lncRNAs) have been demonstrated to participate in many biological processes and severs as important regulators during the progression of gastric cancer. Methods: Here, we introduced human lncRNA SNHG15 which was highly expressed in gastric cancer and cells. Interestingly, the expression of SNHG15 was correlated with programmed cell death ligand 1 (PD-L1), which promotes the resistance of gastric cancer cells to immune responses. Meanwhile, SNHG15 downregulation suppressed the expression of PD-L1 and resistance of immune responses. Results: Further, our results suggested that SNHG15 acted as a competing endogenous RNA (CeRNA) to sponge miR-141, which was downregulated in gastric cancers and negatively correlated to PD-L1. Conclusion: Our results suggested that SNHG15 improved the expression of PD-L1 by inhibiting miR-141, which in turn promoted the resistance of stomach cancer cells to the immune responses. 

Retracted: No

PubPeer comments:
 Typo in  mean caloric value for mesopelagic prey (2837 kcal gu22121 wet weight) - the authors probably mean calories per gram, not kilocalories. https: www.nal.usda.gov fnic how-many-calories-are-one-gram-fat-carbohydrate-or-protein says  Carbohydrates provide 4 calories per gram, protein provides 4 calories per gram, and fat provides 9 calories per gram.  , 
 Could it be the common issue with the definition of the calorie: physicists vs.nutritionists ...? (Cf Wikipedia [Calorie] ) Scientists, beware of calories, billions, tons, etc... , 
 #2 I stand corrected. Thank you, Plenodomus Influorescens! It is indeed kcal if we use the standard SI units. USDA is using the nonstandard cal unit that equals the SI kcal. ,
Confocal laser endomicroscopy in celiac disease: description of findings in two cases
Authors: E Buscarini
F De Grazia
G Brambilla
F Menozzi
A Zambelli
L La Mantia
G Bassotti
G Lupinacci
V Villanacci
Journal: Endoscopy (2007)
Discipline: CLINICAL MEDICINE
Keywords: Duodenal confocal laser endomicroscopy; histology; villous atrophy; celiac disease; mucosa
Affiliations: Gastroenterology and Endoscopy Unit, Maggiore Hospital, Crema, Italy. 

Abstract:  Duodenal confocal laser endomicroscopy (CLE) was carried out in six patients to compare the findings with histology. The visibility and quality of the endomicroscopy images were quantified using the following score: 0 = none; 1 = poor; 2 = fair; 3 = good. Four patients had a normal duodenal mucosa, whereas two patients in whom CLE indicated villous atrophy showed histologic features typical of celiac disease. Histology and CLE images were similar in both normal and celiac disease patients; patients with celiac disease had an average score of 3 for epithelial architecture, 3 for goblet cells, 3 for vessels, 1 for inflammatory infiltrate, and 2 for crypt visibility. 

Retracted: No

PubPeer comments:
 ![file] , 
 More duplications of the same image. Can the authors explain? ![file] , 
 The same image is used to illustrate a patient from Italy (left) and Iran (right). ![file] , 
 ![file] ,
Zinc oxide nanoparticles mediated cytotoxicity, mitochondrial membrane potential and level of antioxidants in presence of melatonin
Authors: S Sruthi
N Millot
P V Mohanan
Journal: International Journal of Biological Macromolecules (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Antioxidant molecules; Glial cells; Melatonin; ROS; ZnO NPs.

Abstract:  Zinc oxide nanoparticles (ZnO NPs) are widely used in a variety of products and are currently being investigated for biomedical applications. However, they have the potential to interact with macromolecules like proteins, lipids and DNA within the cells which makes the safe biomedical application difficult. The toxicity of the ZnO NP is mainly attributed reactive oxygen species (ROS) generation. Different strategies like iron doping, polymer coating and external supply of antioxidants have been evaluated to minimize the toxic potential of ZnO NPs. Melatonin is a hormone secreted by the pineal gland with great antioxidant properties. The melatonin is known to protect cells from ROS inducing external agents like lipopolysaccharides. In the present study, the protective effect of melatonin on ZnO NPs mediated toxicity was evaluated using C6 glial cells. The Cytotoxicity, mitochondrial membrane potential and free radical formation were measured to study the effect of melatonin. Antioxidant assays were done on mice brain slices, incubated with melatonin and ZnO NPs. The results of the study reveal that, instead of imparting a protective effect, the melatonin pre-treatment enhanced the toxicity of ZnO NPs. Melatonin increased antioxidant enzymes in brain slices. 

Retracted: No

PubPeer comments:
 Fig. 6 c and d look strikingly similar! ![file] ,
LncRNA SNHG3 Promotes Gastric Cancer Cells Proliferation, Migration, and Invasion by Targeting miR-326
Authors: Jin Huang
Jinjin Fu
Jun Rao
Chuchen Meng
Xiangrong Qin
Shaohua Zhuang
Journal: Journal of Oncology (2021)
Discipline: CLINICAL MEDICINE
Keywords: lncRNA SNHG3; GC; miR-326; TWIST; proliferation
Affiliations: Department of Gastroenterology, Changzhou No. 2 People’s Hospital, The Affiliated Hospital of Nanjing Medical University, No. 29 Xinglong District, Changzhou 213000, China, Department of Endocrinology, Changzhou No. 2 People’s Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, China

Abstract:  The function and possible mechanism of lncRNA Small Nucleolar RNA Host Gene 3 (SNHG3) in GC have not been fully studied. The aim of our study was to investigate the role of SNHG3 in the proliferation, migration, and invasion of GC cell lines. The expressions of SNHG3, miR-326, and TWIST in GC9811-P GC cell lines were detected by RT-qPCR. Western blotting was performed to detect the protein levels of TWIST and EMT-related genes. Luciferase reporter gene analysis and RNA immunoprecipitation (RIP) analysis confirmed the interaction between lncRNA SNHG3, miR-326, and TWIST. CCK-8 and Transwell assays were performed to detect cell proliferation, invasion, and migration abilities. The results showed that lncRNA SNHG3 and TWIST were highly expressed in GC cell lines, while miR-326 was expressed to a low degree. Moreover, lncRNA SNHG3 knockdown or miR-326 overexpression significantly inhibited cell proliferation, migration, and invasion of GC cell lines. In addition, TWIST overexpression can reverse the inhibition of lncRNA SNHG3 knockdown or miR-326 overexpression on cell proliferation, migration, and invasion. In conclusion, lncRNA SNHG3 may promote GC progression through the miR-326/TWIST axis, which may provide a new diagnostic and prognostic biomarker for GC. 

Retracted: No

PubPeer comments:
 Many examples of apparent image duplications in this article.!![file] ![file] ![file] , 
 Sorry for our mistakes. The figures have been revised. ![file] ![file] ![file] ,
A Prohormone Convertase Cleavage Site within a Predicted α-Helix Mediates Sorting of the Neuronal and Endocrine Polypeptide VGF into the Regulated Secretory Pathway
Authors: William G Janssen
Angelo L Garcia
Shan-Kuo Han
Timothy Ito
Deanna L Benson
Marc J Glucksman
Zin Z Khaing
Stephen R J Salton
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: protein secretion; secretory granules; VGF; dense core vesicles; regulated secretion

Abstract:  Distinct intracellular pathways are involved in regulated and constitutive protein secretion from neuronal and endocrine cells, yet the peptide signals and molecular mechanisms responsible for targeting and retention of soluble proteins in secretory granules are incompletely understood. By using confocal microscopy and subcellular fractionation, we examined trafficking of the neuronal and endocrine peptide precursor VGF that is stored in large dense core vesicles and undergoes regulated secretion. VGF cofractionated with secretory vesicle membranes but was not detected in detergent-resistant lipid rafts. Deletional analysis using epitope-tagged VGF suggested that the C-terminal 73-amino acid fragment of VGF, containing two predicted alpha-helical loops and four potential prohormone convertase (PC) cleavage sites, was necessary and sufficient with an N-terminal signal peptide-containing domain, for large dense core vesicle sorting and regulated secretion from PC12 and INS-1 cells. Further transfection analysis identified the sorting sequence as a compact C-terminal alpha-helix and embedded 564RRR566 PC cleavage site; mutation of the 564RRR566 PC site in VGF-(1-65): GFP:VGF-(545-617) blocked regulated secretion, whereas disruption of the alpha-helix had no effect. Mutation of the adjacent 567HFHH570 motif, a charged region that might enhance PC cleavage in acidic environments, also blocked regulated release. Finally, inhibition of PC cleavage in PC12 cells using the membrane-permeable synthetic peptide chloromethyl ketone (decanoyl-RVKR-CMK) blocked regulated secretion of VGF. Our studies define a critical RRR-containing C-terminal domain that targets VGF into the regulated pathway in neuronal PC12 and endocrine INS-1 cells, providing additional support for the proposed role that PCs and their cleavage sites play in regulated peptide secretion. 

Retracted: No

PubPeer comments:
 Fig.7 There are visible white splice lines, but the author did not declared in figure legend. Could authors explain? ![file] ,
miR-15a induces cell apoptosis by targeting BCL2L2 and BCL2 in HPV-positive hypopharyngeal squamous cell carcinoma
Authors: Weihua Lou
Long Feng
Yan Zhang
Yunyun Ma
Guoqiang Zhao
Yuwen Du
Xiaonan Chen
Ping Li
Shujun Wu
Wuhao Lu
Yuanyuan Wang
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: miR-15a; HPV-positive HSCC; apoptosis; BCL2L2; BCL2
Affiliations: Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China., Department of Pathogenic Organism Biology, Henan University of Chinese Medicine, Zhengzhou, Henan 450008, P.R. China., Department of Immunology and Microbiology, Henan Medical College, Zhengzhou, Henan 451191, P.R. China., Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China., College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.

Abstract:  Aberrant expression of miR-15a was recently reported in several types of cancers; however, its role in HPV-positive hypopharyngeal squamous cell carcinoma (HSCC) remains obscure. In the present study, we investigated the mechanism by which miR-15a induces HPV-positive HSCC apoptosis. Synthetic miR-15a mimics were transfected into FaDu cells (HPV-negative), and the miR-15a inhibitor was transfected into HPV-positive HSCC cells. miR-15a expression was analyzed by RT-PCR, and BCL2L2 and BCL2 were analyzed by western blotting. The Hochest 33342/propidium iodide (PI) and caspase-3/-9 assays, and Annexin V staining were used to assess the effect of miR-15a on apoptosis. After transfection, overexpression of miR-15a in the FaDu cells was associated with significantly decreased BCL2L2 and BCL2 expression and a significant increase in the apoptosis rate. The opposite results were observed in HPV-positive HSCC, where downregulation of miR-15a suppressed apoptosis. These findings indicate that miR-15a acts as a tumor suppressor in HPV-positive HSCC. 

Retracted: No

PubPeer comments:
  Figure 7. Cell death at 48 h after the transfection with miR-15a mimics inhibitor (20 nM). Fragmented nuclei stained with Hoechst 33342 PI indicate apoptotic cell death (magnification, x400). The number of apoptotic cells in the (A) miR-15a mimic-transfected FaDu cells was significantly increased compared with that in the (B) miR-15a inhibitor HPV-positive HSCC. Two panels are very similar apart from a 180-deg rotation, although some cells have been modified. ![file] , 
 [Perhaps a systemic problem] . Journals and readers may wish to proceed with caution. ,
LXR-dependent gene expression is important for macrophage survival and the innate immune response
Authors: Liming Pei
John Hogenesch
Enrique Saez
Antonio Castrillo
Puiying A Mak
Genhong Cheng
Ryan M O&#x27;connell
Jeffery F Miller
Michelle N Bradley
Kevin W Bruhn
Sean B Joseph
Peter Tontonoz
Journal: Cell (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Liver X receptors; LXRs; lipid metabolism; macrophage cholesterol metabolism; antimicrobial responses
Affiliations: Howard Hughes Medical Institute and Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.

Abstract:  The liver X receptors (LXRs) are nuclear receptors with established roles in the regulation of lipid metabolism. We now show that LXR signaling not only regulates macrophage cholesterol metabolism but also impacts antimicrobial responses. Mice lacking LXRs are highly susceptible to infection with the intracellular bacteria Listeria monocytogenes (LM). Bone marrow transplant studies point to altered macrophage function as the major determinant of susceptibility. LXR-null macrophages undergo accelerated apoptosis when challenged with LM and exhibit defective bacterial clearance in vivo. These defects result, at least in part, from loss of regulation of the antiapoptotic factor SPalpha, a direct target for regulation by LXRalpha. Expression of LXRalpha or SPalpha in macrophages inhibits apoptosis in the setting of LM infection. Our results demonstrate that LXR-dependent gene expression plays an unexpected role in innate immunity and suggest that common nuclear receptor pathways mediate macrophage responses to modified lipoproteins and intracellular pathogens. 

Retracted: No

PubPeer comments:
 Figure 7C. Differential splicing. ![file] , 
 #1 Continuation figure 7C. Signal inside 2 yellow boxes is much more similar than expected. ![file] ,
Hedamycin, a DNA alkylator, induces (gamma)H2AX and chromosome aberrations: involvement of phosphatidylinositol 3-kinase-related kinases and DNA replication fork movement
Authors: Terry A Beerman
Sei Ichi Matsui
Lan Chun Tu
Journal: Molecular Cancer Therapeutics (2005)
Discipline: CLINICAL MEDICINE
Keywords: Genotoxic treatments; DNA replication; DNA strand breaks; H2AX phosphorylation; ATR
Affiliations: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

Abstract:  Genotoxic treatments, such as UV light, camptothecin, and adozelesin, stall DNA replication and subsequently generate DNA strand breaks. Typically, DNA breaks are reflected by an increase in ataxia and Rad-related kinase (ATR)-regulated phosphorylation of H2AX (gammaH2AX) and require replication fork movement. This study examined the potential of the monofunctional DNA alkylating agent hedamycin, a powerful inhibitor of DNA replication, to induce DNA strand breaks, phosphorylated H2AX (gammaH2AX) foci, and chromosome aberrations. Hedamycin treatment of HCT116 carcinoma cells resulted in a rapid induction of DNA strand breaks accompanied by increasing H2AX phosphorylation and focalization. Unlike many other treatments that also stall replication, such as UV, camptothecin, and adozelesin, gammaH2AX formation was not suppressed in ATR-compromised cells but actually increased. Similarly, hedamycin induction of gammaH2AX is not dependent on ataxia telangiectasia mutated or DNA-protein kinase, and pretreatment of cells with the phosphatidylinositol 3-kinase-related kinase inhibitor caffeine did not substantially reduce induction of H2AX phosphorylation by hedamycin. Furthermore, the DNA replication inhibitor aphidicolin only modestly depressed hedamycin-induced gammaH2AX formation, indicating that hedamycin-induced DNA double-strand breaks are not dependent on fork progression. In contrast, camptothecin- and adozelesin-induced gammaH2AX was strongly suppressed by aphidicolin. Moreover, after 24 hours following a short-term hedamycin treatment, cells displayed high levels of breaks in interphase nuclear DNA and misjoined chromosomes in metaphase cells. Finally, focalization of a tightly bound form of Ku80 was observed in interphase cells, consistent with the subsequent appearance of chromosomal aberrations via abnormal nonhomologous end joining. Overall, this study has revealed a disparate type of DNA damage response to stalled replication induced by a bulky DNA adduct inducer, hedamycin, that seems not to be highly dependent on ATR or DNA replication. 

Retracted: No

PubPeer comments:
 Figure 4A. https: imgur.com l2sCBAR ,
WITHDRAWN: MiR-760 inhibits the progression of non-small cell lung cancer through blocking ROS1/Ras/Raf/MEK/ERK pathway
Authors: Bin He
Wei Wang
Journal: Bioscience reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MiR-760; Non-small cell lung cancer; ROS1; Ras/Raf/MEK/ERK.
Affiliations: Huzhou Central Hospital, Huzhou, China.

Abstract:  The purpose of this study was to investigate the role of miR-760 in non-small cell lung cancer (NSCLC), as well as relevant molecular mechanisms. Expression patterns of miR-760 in NSCLC tissues and cells were detected using quantitative real-time polymerase chain reaction (qRT-PCR) method. Cell transfection was performed using Lipofectamine® 2000. MTT and transwell assays were used to detect cell proliferation and migration in vitro, respectively. Potential target of miR-760 in NSCLC was predicted via bioinformatics analysis, and confirmed by luciferase reporter assay. Protein analysis was performed through western blot. The levels of miR-760 were down-regulated in NSCLC tissues and cells, compared with non-cancerous specimens (p&lt;0.05 for all). Enforced expression of miR-760 inhibited cell proliferation, migration and invasion. Furthermore, the over-expression of miR-760 could suppress the activity of ROS1/Ras/Raf/MEK/ERK pathway. ROS1 might be a target gene of miR-760 in NSCLC. ROS1 could reverse anti-tumor effect of miR-760 in the progression of NSCLC. MiR-760 may act as a tumor suppressor against NSCLC. MiR-760 could block ROS1/Ras/Raf/MEK/ERK pathway through inhibiting ROS1 expression, thus repressing the progression of NSCLC. 

Retracted: No

PubPeer comments:
 WITHDRAWN ARTICLE WITHDRAWN: MiR-760 inhibits the progression of non-small cell lung cancer through blocking ROS1 Ras Raf MEK ERK pathway Wei Wang, Bin He Bioscience Reports (2020), BSR20182483; DOI: 10.1042 BSR20182483 The Accepted Manuscript version of this article (published on 29 April 2020) was withdrawn on 8 June 2020 due to concerns over authorship and data validity. ,
Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19
Authors: Lin Yao
Zhifang Cai
Chunhua Yang
Lei Chen
Jiawei Li
Yafang Li
Yiyan Song
Journal: Journal of medical virology (2020)
Discipline: MICROBIOLOGY
Keywords: COVID-19; RT-PCR.
Affiliations: Department of Intensive Care Unit, The Sixth Affiliated HospitalSun Yat‐sen University Guangzhou China, Department of Operation and ManagementThe Sixth Affiliated Hospital, Sun Yat‐sen University Guangzhou China, Natural Language Processing GroupiFLYTEK Research South China Guangzhou China, Department of Clinical MedicineZhongshan School of Medicine Guangzhou China, Department of RespiratoryHankou Hospital of Wuhan Wuhan China

Abstract:  In this study, we collected a total of 610 hospitalized patients from Wuhan between February 2, 2020, and February 17, 2020. We reported a potentially high false negative rate of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 in the 610 hospitalized patients clinically diagnosed with COVID-19 during the 2019 outbreak. We also found that the RT-PCR results from several tests at different points were variable from the same patients during the course of diagnosis and treatment of these patients. Our results indicate that in addition to the emphasis on RT-PCR testing, clinical indicators such as computed tomography images should also be used not only for diagnosis and treatment but also for isolation, recovery/discharge, and transferring for hospitalized patients clinically diagnosed with COVID-19 during the current epidemic. These results suggested the urgent needs for the standard of procedures of sampling from different anatomic sites, sample transportation, optimization of RT-PCR, serology diagnosis/screening for SARS-CoV-2 infection, and distinct diagnosis from other respiratory diseases such as fluenza infections as well. 

Retracted: No

PubPeer comments:
 Even though this paper is about RT-PCR, there is no detailed description of the protocol used for RT-PCR. Could the authors kindly provide these details? ,
Silencing FOXA1 gene regulates liver cancer cell apoptosis and cell proliferation
Authors: Q Zhang
Z-Z Feng
N Li
H-Y Gan
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Liver cancer; Foxa1; apoptosis; cancer stem cells; CD133
Affiliations: Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui, China. .

Abstract:  Objective: Liver cancer emerged as a major health problem, and it accounts for leading cancer-related death worldwide. Due to recurrence and metastatic behavior, it is challenging to be controlled and managed. Understanding the regulative role of different proteins, which regulates liver cancer in various pathological stages, is essential to be investigated. In this study, we analyzed the correlation between Foxa1 suppression along with apoptosis and cancer stem cell proliferation. Materials and methods: CD133+ cells were used to induce the initial and advanced stage of liver cancer. Histology was used to study and confirm the tissue complications associated with initial, advanced and Foxa1 silenced liver cancer tissues. Immunohistochemistry and Western blotting were used to quantify Foxa1, CD133 expression. TUNEL assay was performed to study apoptosis. Results: Initially using CD133+ cells, we successfully developed a mouse model with the initial and advanced stage of liver cancer upon 4 and 8 weeks incubation. Histologically, as the tumor progress, it shows more proliferative cells with disorganized tissue structure. Foxa1 silencing aids in recovering from initial liver cancer, but it has only limited effects with advanced liver cancer. The apoptosis process is enhanced in initial liver cancer, and Foxa1 silenced tissue when compared with the advanced stage of liver cancer. Foxa1 silencing also suppresses the cancer stem cell proliferation. Conclusions: Overall, our results reveal the critical role of Foxa1 in regulating apoptosis and liver cancer stem cells. 

Retracted: No

PubPeer comments:
 Figure 1.  Observation of different pathological stage of liver cancer using histological sectioning. **A, Histological image of control liver with undisturbed layers of tissue.** B, Initial liver cancer tissue section is showing disorganized tissue layers with the enlarged nucleus. C, Advanced stage of a liver cancer tissue section with metastatic cells. **D, Histological image of control liver with Foxa1 silenced tissue with undisturbed layers**. E, Initial liver cancer tissue section with Foxa1 silenced showing a reorganization of tissue layers. F, Advanced stage of liver cancer with Foxa1 silenced tissue section without metastatic cells. Overlap marked. ![file] ,
Nucleotide excision repair and template-independent addition by HIV-1 reverse transcriptase in the presence of nucleocapsid protein
Authors: Arkadiusz Bibillo
Robert J Gorelick
Gilles Divita
Carole Bampi
Stuart F J Le Grice
Jean-Luc Darlix
Michaela Wendeler
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HIV replication; reverse transcriptase; nucleocapsid protein; genetic variability; nucleotide addition
Affiliations: LaboRetro, Unité de Virologie Humaine, INSERM U412, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Institut Fédératif de Recherche 128, 69364 Lyon Cedex 07, France.

Abstract:  During HIV replication, reverse transcriptase (RT), assisted by the nucleocapsid protein (NC), converts the genomic RNA into proviral DNA. This process appears to be the major source of genetic variability, as RT can misincorporate nucleotides during minus and plus strand DNA synthesis. To investigate nucleotide addition or substitution by RT, we set up in vitro models containing HIV-1 RNA, cDNA, NC, and various RTs. We used the wild type RT and azidothymidine- and didanosine-resistant RTs, because they represent the major forms of resistant RTs selected in patients undergoing therapies. Results show that all RTs can add nucleotides in a non-template fashion at the cDNA 3'-end, a reaction stimulated by NC. Nucleotide substitutions were examined using in vitro systems where 3'-mutated cDNAs were extended by RT on an HIV-1 RNA template. With NC, RT extension of the mutated cDNAs was efficient, and surprisingly, mutations were frequently corrected. These results suggest for the first time that RT has excision-repair activity that is triggered by NC. Chaperoning of RT by NC might be explained by the fact that NC stabilizes an RT-DNA binary complex. In conclusion, RT-NC interactions appear to play critical roles in HIV-1 variability. 

Retracted: No

PubPeer comments:
 Figure 3 and 4B were assembled with spliced images. Red arrowheads indicate the splicing marks. The first 4 bands of P T#1 panel in Figure 3 look very similar [Red Box] with splicing marks in-between [blue arrowheads]. Please check. ![file] , 
 Figure 3. Much more similar than expected. https: imgur.com lb6IOoF ,
Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain. Inhibition of nuclear translocation and transacting function
Authors: Weiping Wang
Jefferson Y Chan
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: antioxidant response elements; Nrf1; Nrf2; Keap1; endoplasmic reticulum
Affiliations: Department of Laboratory Medicine and Pathology, University of California, Irvine, California 92697, USA.

Abstract:  Expression of antioxidant and phase 2 xenobiotic metabolizing enzyme genes is regulated through cis-acting sequences known as antioxidant response elements. Transcriptional activation through the antioxidant response elements involves members of the CNC (Cap 'n' Collar) family of basic leucine zipper proteins including Nrf1 and Nrf2. Nrf2 activity is regulated by Keap1-mediated compartmentalization in the cell. Given the structural similarities between Nrf1 and Nrf2, we sought to investigate whether Nrf1 activity is regulated similarly to Nrf2. Nrf1 also resides normally in the cytoplasm of cells. Cytoplasmic localization however, is independent of Keap1. Colocalization analysis using green fluorescent protein-tagged Nrf1 and subcellular fractionation of endogenous Nrf1 and fusion proteins indicate that Nrf1 is primarily a membrane-bound protein localized in the endoplasmic reticulum. Membrane targeting is mediated by the N terminus of the Nrf1 protein that contains a predicted transmembrane domain, and deletion of this domain resulted in a predominantly nuclear localization of Nrf1 that significantly increased the activation of reporter gene expression. Treatment with tunicamycin, an endoplasmic reticulum stress inducer, caused an accumulation of a smaller form of Nrf1 that correlated with detection of Nrf1 in the nucleus by biochemical fractionation and immunofluorescent analysis. These results suggest that Nrf1 is normally targeted to the endoplasmic reticulum membrane and that endoplasmic reticulum stress may play a role in modulating Nrf1 function as a transcriptional activator. 

Retracted: No

PubPeer comments:
 ![file] There are multiple undeclared splicing sites in the immunoblots in Figure 6B and C. ,
Can brain scans reveal behaviour? Bombshell study says not yet
Authors: Ewen Callaway
Journal: Nature (2022)
Discipline: Multidisciplinary
Keywords: Brain; Neuroscience.

Abstract: Most studies linking features in brain imaging to traits such as cognitive abilities are too small to be reliable, argues a controversial analysis. Most studies linking features in brain imaging to traits such as cognitive abilities are too small to be reliable, argues a controversial analysis.

Retracted: No

PubPeer comments:
 Marek speculates that bigger datasets might cure the problem -   For brain imaging, Marek says, u201cI donu2019t know if we need hundreds of thousands or millions. But thousands is a safe bet. ... What the Marek paper suggests is that a lot of the time, if you donu2019t have these really large samples, you are most likely wrong or lucky in finding a good brainu2013behaviour correlation,u201d says Caterina Gratton... However, Calude and Longo (2016), analyzing the issue, have argued that bigger datasets simply lead to more spurious correlations. In The AI Delusion, and in his [related article] in WIRED, Gary Smith explains why data diving is expected to fail in principle and gives example after example of big data failing to deliver reliable results. That Marek s result can be characterized as a  bombshell says the field has its eyes wide shut to these facts. Not yet? Not ever. ,
CHCHD2 decreases docetaxel sensitivity in breast cancer via activating MMP2
Authors: Z-M Fan
D-G Zhang
L Ma
L-H Zheng
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: CHCHD2; MMP2; docetaxel resistance; breast cancer; prognosis
Affiliations: Department of Breast Surgery, the First Hospital of Jilin University, Changchun, China. .

Abstract:  Objective: This study aims to clarify the influences of CHCHD2 and MMP2 on docetaxel resistance in breast cancer. Patients and methods: Differential levels of CHCHD2 in breast cancer and para-tumor tissues were detected. The relationship between CHCHD2 and prognosis in breast cancer patients was analyzed. After generating Docetaxel-resistant breast cancer cell lines (MCF-7/DTX and SKBR3/DTX), the regulatory effects of CHCHD2 on proliferative and migratory potentials were assessed by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. The interaction between CHCHD2 and MMP2 was tested by Western blot and Pearson correlation test. At last, the involvement of MMP2 in CHCHD2-regulated proliferation and migration in Docetaxel-resistant breast cancer cells was analyzed. Results: CHCHD2 was upregulated in breast cancer tissues. It predicted high incidence of distant metastasis and poor prognosis in breast cancer patients. Proliferation inhibition rate was lower in MCF-7/DTX and SKBR3/DTX cells compared with their parental cells. After knockdown of CHCHD2 in MCF-7/DTX and SKBR3/DTX cells, their proliferative and migratory potentials were markedly reduced. MMP2 was upregulated in breast cancer tissues, and its level was positively regulated by CHCHD2. Overexpression of MMP2 could reverse the regulatory effects of CHCHD2 on proliferative and migratory potentials in MCF-7/DTX and SKBR3/DTX cells. Conclusions: Upregulated CHCHD2 in breast cancer is related to distant metastasis rate and poor prognosis. CHCHD2 and MMP2 are positively correlated to each other. CHCHD2 stimulates proliferative and migratory potentials in Docetaxel-resistant breast cancer cells by upregulating MMP2. 

Retracted: No

PubPeer comments:
 Figure 3.  Knockdown of CHCHD2 inhibited proliferative and migratory potentials in Docetaxel-resistant breast cancer cells. ... B, Migration in MCF7 DTX and SKBR3 DTX cells transfected with sh-NC or sh-CHCHD2 . Two cell lines have produced overlapping Migration images. ![file] , 
 Fig 1C.  Overall survival in breast cancer patients based on CHCHD2 expressions . ![file] These K-M plots with the appearance of Lego walls, declining rapidly towards 75 months, are one of the characteristic features of a papermill with productions tabulated in a Google spreadsheet. https: docs.google.com spreadsheets d 1_762PbYYTCJhek5PdBuiDuN1q48UDgMa-rT6gi_jA8c edit?usp=sharing Another regular feature is a Table 1, with column heads promising to convert the numbers within the patient subgroups into percentages, but not delivering. ![file] ,
Chromobox homolog 4 is correlated with prognosis and tumor cell growth in hepatocellular carcinoma
Authors: Gang Wang
Shengping Li
Yi Sang
Jianjun Tang
Tiebang Kang
Dan Liao
Wei Ding
Meifang Zhang
Jingying Cao
Boqing Wang
Ruhua Zhang
Yuanzhong Wu
Guoqing Zhang
Journal: Annals of Surgical Oncology (2013)
Discipline: CLINICAL MEDICINE
Keywords: CBX4; hepatocellular carcinoma; cytoplasmic expression; clinical relevance; immunohistochemistry
Affiliations: Department of Hepatopancreatobiliary Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China.

Abstract:  Background: Chromobox homolog 4 (CBX4) is a member of the chromobox family of Polycomb group proteins involved in the chromatin remodeling and transcriptional regulation. However, its clinical relevance in hepatocellular carcinoma (HCC) has not yet been explored. Methods: Immunohistochemistry was used to analyze cytoplasmic expression of CBX4 in 246 HCC specimens. The expression of CBX4 in HCC cell lines and LO2 was detected by Western blot test. Cell cycle and MTT assays were used to determine the changes of cell growth capacity. The expression of downstream genes related to proliferation was detected by Western blot test. Results: The expression of CBX4 was up-regulated in multiple HCC cell lines and clinical samples. Although the CBX4 protein was detectable in both nucleus and cytoplasm in HCC tumor tissues, the high expression of CBX4 in cytoplasm was correlated with the α-fetoprotein level in serum (P = 0.036), tumor size (P = 0.029), pathologic differentiation (P = 0.033), and tumor, node, metastasis classification system stages (P = 0.032). Moreover, HCC patients who had a high level of CBX4 in cytoplasm had a shorter overall survival (P = 0.003) and recurrence-free survival (P = 0.012). Indeed, using HCC cell line, knockdown of CBX4 led to down-regulating proliferating cell nuclear antigen and cyclin E2 as well as up-regulating p16, followed by decreased cell proliferation and impaired cell cycle progression. Conclusions: The cytoplasmic CBX4 protein may be a useful prognostic biomarker and a potential therapeutic target for HCC. 

Retracted: No

PubPeer comments:
 Fig. 3d contains a set of duplicated plots, but interestingly, with different G1, S and G2 M ratios. ![file] ,
CHARMM36m: an improved force field for folded and intrinsically disordered proteins
Authors: Michael Feig
Bert L de Groot
Sarah Rauscher
Jing Huang
Alexander D MacKerell Jr
Helmut Grubmüller
Ting Ran
Grzegorz Nawrocki
Journal: Nature Methods (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CHARMM36; protein force field; refinement; CHARMM36m; molecular modeling
Affiliations: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, USA., Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany., Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA.

Abstract:  The all-atom additive CHARMM36 protein force field is widely used in molecular modeling and simulations. We present its refinement, CHARMM36m (http://mackerell.umaryland.edu/charmm_ff.shtml), with improved accuracy in generating polypeptide backbone conformational ensembles for intrinsically disordered peptides and proteins. 

Retracted: No

PubPeer comments:
 Figure 6. Any reason for no loading control? No general background. , 
 Figure 2a appears to have two images which overlap. Update: I didnu2019t recognize one of the authoru2019s names, but now see a variety of concerns [have previously been expressed] . *** ![file] ,
Combination of sphingosine-1-phosphate receptor 1 (S1PR1) agonist and antiviral drug: a potential therapy against pathogenic influenza virus
Authors: Jiangnan Zhao
Meiying Zhu
Yi Shi
Hao Jiang
Xin Su
Simen Shen
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: pandemic 2009 influenza A H1N1 virus; S1PR1; immune response; endothelial cell-specific; knockout mice
Affiliations: Department of Respiratory and Critical Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China., Department of Emergency Medicine, the Second Affiliated Hospital, Southeast University, Nanjing, 210002, China., Department of Respiratory Medicine, the First People's Hospital of Nantong, Nantong, 226000, China., Department of Respiratory and Critical Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China. .

Abstract:  The pandemic 2009 influenza A H1N1 virus is associated with significant mortality. Targeting S1PR1, which is known to modulate the immune response, provides protection against pathogenic influenza virus. The functional role and molecular mechanism of S1PR1 were analysed by generating inducible endothelial cell-specific S1PR1 knockout mice and assessing the therapeutic efficacy of the selective S1PR1 agonist CYM5442 against acute lung injury (ALI) induced by the 2009 influenza A H1N1 virus. Immune-mediated pulmonary injury is aggravated by the absence of endothelial S1PR1 and alleviated by treatment with CYM-5442, suggesting a protective function of S1PR1 signaling during H1N1 infection. S1PR1 signaling does not affect viral clearance in mice infected with influenza. Mechanistically, the MAPK and NF-kB signaling pathways are involved in the ALI mediated by S1PR1 in infected mice. Combined administration of the S1PR1 agonist CYM-5442 and the antiviral drug oseltamivir provides maximum protection from ALI. Our current study provides insight into the molecular mechanism of S1PR1 mediating the ALI induced by H1N1 infection and indicates that the combination of S1PR1 agonist with antiviral drug could potentially be used as a therapeutic remedy for future H1N1 virus pandemics. 

Retracted: No

PubPeer comments:
 July 2020 correction for an overlap in Figure 3D:  This Article contains an error in Panel D of Figure 3. The third pathological image (S1PR1 ECKOu2009+u2009Vehicle) is a duplicate of the fourth pathological image (S1PR1 ECKOu2009+u2009CYM-5442), and therefore incorrect. The correct version of Figure 3 is reproduced below. Here are the original and the updated Figures 3D compared, with the overlap marked with blue boxes. It appears that the updated panel now overlaps with a panel in Figure 2C as shown here with green boxes. Could the authors clarify if this is expected? The samples are labeled differently. ![file] ,
Activation of the phosphatidylinositol 3-kinase/Akt pathway contributes to survival of primary epithelial cells infected with the periodontal pathogen Porphyromonas gingivalis
Authors: Ozlem Yilmaz
Philippe Verbeke
Thomas Jungas
David M Ojcius
Journal: Infection and Immunity (2004)
Discipline: IMMUNOLOGY
Keywords: Porphyromonas gingivalis; periodontal pathogen; gingival epithelial cells; phosphatidylserine exposure; caspase activation
Affiliations: Department of Pathobiology, University of Washington, School of Public Health, HSC Box 357238, Seattle, WA 98195, USA. 

Abstract:  Porphyromonas gingivalis, an important periodontal pathogen, infects primary gingival epithelial cells (GECs). Despite the large number of bacteria that replicate inside the GECs, the host cell remains viable. We demonstrate that P. gingivalis triggers rapid and reversible surface phosphatidylserine exposure through a mechanism requiring caspase activation. However, after 1 day of infection, the bacteria no longer induce phosphatidylserine externalization and instead protect infected cells against apoptosis. Infection exerts its effect at the level of mitochondria, as P. gingivalis also blocks depolarization of the mitochondrial transmembrane potential and cytochrome c release. Interestingly, protein kinase B/Akt is phosphorylated during infection, which can be blocked with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Suppression of the PI3K/Akt pathway following staurosporine treatment results in mitochondrial-membrane depolarization, cytochrome c release, DNA fragmentation, and increased apoptosis of infected GECs. Thus, P. gingivalis stimulates early surface exposure of phosphatidylserine, which could downmodulate the inflammatory response, while also promoting host cell survival through the PI3K/Akt pathway. 

Retracted: No

PubPeer comments:
 There are some unexpectedly similar features in different panels in Figuge 1B. ![file] Zoom in: ![file] In addiction the panel top left seems different from the others, like it is less sharpened. ,
Downregulation of miR-16 via URGCP pathway contributes to glioma growth
Authors: Ouyang Qing
Xu Lunshan
Chen Ying
Xu Minhui
Zhou Ji
Liang Hong
Zhang Chengqu
Cui Hao
Journal: Scientific reports (2017)
Discipline: Multidisciplinary
Keywords: URGCP; glioma; oncogenic roles; molecular mechanisms; prognosis
Affiliations: Department of Neurosurgery, Daping Hospital & Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, China., Department of Neurosurgery, the General Hospital of Rocket Army, Beijing, 100088, China., Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China., Department of Neurosurgery, Daping Hospital & Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, China. .

Abstract:  Experimental and clinical evidence points to a critical role of Upregulator of cell proliferation (URGCP/URG4) in controlling the progression of multiple tumors. However, the oncogenic role of URGCP in glioma still remains elusive. In this study we tried to investigate the oncogenic roles and molecular mechanisms of URGCP in glioma. We found that the levels of URGCP were upregulated in glioma, and that the high-levels of URGCP indicated a worse prognosis in glioma patients. URGCP and miR-16 are critical for glioma growth: silencing URGCP (shURGCP) inhibited glioma growth, while, the shURGCP-mediated proliferative inhibition could be recovered by antagonizing miR-16 (anta-miR-16) in vivo and in vitro. Mechanically, URGCP repressed miR-16 expression via activating NF-κB/c-myc pathway in glioma; Cyclins D1 and Cyclin E1 were identified as the direct targets of miR-16, thus, URGCP-mediated miR-16 downregulation accelerated cell proliferation by upregulating Cyclin D1 and Cyclin E1 expression. All these results suggested that URGCP accelerates glioma growth through the NF-κB/c-myc/miR-16/Cyclin D1/E1 pathway, and both URGCP and miR-16 function as a novel cell cycle regulators in glioma and could be considered as potential targets for glioma therapy. 

Retracted: No

PubPeer comments:
 Figure 5g appears to have two images which overlap, but which are described differently. Roughly indicated in red. *** ![file] *** Full figure ![file] ,
S-protected thiolated hyaluronic acid: In-situ crosslinking hydrogels for 3D cell culture scaffold
Authors: Stefanie Silberhumer
Mulazim Hussain Asim
Iram Shahzadi
Andreas Bernkop-Schnürch
Barbara Matuszczak
Aamir Jalil
Journal: Carbohydrate Polymers (2020)
Discipline: CHEMISTRY
Keywords: 3D scaffold; Cell proliferation; Disulfide-crosslinked hydrogels; Hyaluronic acid; Rheological properties
Affiliations: Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; Department of Pharmaceutics, Faculty of Pharmacy, University of Sargodha, 40100 Sargodha, Pakistan., Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria., Center for Chemistry and Biomedicine, Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria., Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: .

Abstract:  The purpose of this study was to synthesize S-protected thiolated hyaluronic acid (HA) and to evaluate its potential for 3D cell culture scaffold. S-protected thiolated HA was synthesized by the covalent attachment of N-acetyl-S-((3-((2,5-dioxopyrrolidin-1-yl)oxy)-3-oxopropyl)thio)cysteine hydrazide ligand to the HA. Hydrogels were characterized for texture, swelling behavior and rheological properties. Furthermore, the potential of S-protected thiolated HA hydrogels as a scaffold for tissue engineering was evaluated by cell proliferation studies with Caco-2 and NIH 3T3 cells. It showed enhanced cohesion upon addition of N-acetyl cysteine (NAC). Dynamic viscosity of S-protected thiolated HA hydrogel was increased up to 19.5-fold by addition of NAC and 10.1-fold after mixing with mucus. Furthermore, Caco-2 and NIH 3T3 cells encapsulated into hydrogels proliferated in-vitro. As this novel S-protected thiolated HA is stable towards oxidation and forms highly cohesive gels when getting into contact with endogenous thiols due to disulfide-crosslinking, it is a promising tool for 3D cell culture scaffold. 

Retracted: No

PubPeer comments:
 From the 1H NMR spectra, I don t think they had a successful synthesis of SPDP-NAC ligand, which was the starting point for further modification of hyaluronic acid. ![file] ,