PReD-Bench/PRed-Bench huggingface dataset:
Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress
Authors: Claudio Soto
Claudio Hetz
Karen Castillo
Andrés Stutzin
Mauricio Torres
Ricardo Armisén
Journal: PLoS ONE (2010)
Discipline: Multidisciplinary
Keywords: Prion-related disorders; neurodegenerative; ER homeostasis; calcium store; neuronal dysfunction
Affiliations: Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.

Abstract:  Prion-related disorders (PrDs) are fatal neurodegenerative disorders characterized by progressive neuronal impairment as well as the accumulation of an abnormally folded and protease resistant form of the cellular prion protein, termed PrP(RES). Altered endoplasmic reticulum (ER) homeostasis is associated with the occurrence of neurodegeneration in sporadic, infectious and familial forms of PrDs. The ER operates as a major intracellular calcium store, playing a crucial role in pathological events related to neuronal dysfunction and death. Here we investigated the possible impact of PrP misfolding on ER calcium homeostasis in infectious and familial models of PrDs. Neuro2A cells chronically infected with scrapie prions showed decreased ER-calcium content that correlated with a stronger upregulation of UPR-inducible chaperones, and a higher sensitivity to ER stress-induced cell death. Overexpression of the calcium pump SERCA stimulated calcium release and increased the neurotoxicity observed after exposure of cells to brain-derived infectious PrP(RES). Furthermore, expression of PrP mutants that cause hereditary Creutzfeldt-Jakob disease or fatal familial insomnia led to accumulation of PrP(RES) and their partial retention at the ER, associated with a drastic decrease of ER calcium content and higher susceptibility to ER stress. Finally, similar results were observed when a transmembrane form of PrP was expressed, which is proposed as a neurotoxic intermediate. Our results suggest that alterations in calcium homeostasis and increased susceptibility to ER stress are common pathological features of both infectious and familial PrD models. 

Retracted: No

PubPeer comments:
 In **Definition 4**, the authors introduced an aggregation operator for interval numbers with probability densities, which actually is a weighted sum of random variables. The authors provided an illustration in Fig. 1. However, the illustration in Fig. 1 **is not consistent** with Definition 4 because **the weighted sum of independent uniformly distributed random variables is not a uniformly distributed random variable**. Can the authors address this issue? ![file] ,
Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR
Authors: Kang Won Choe
Yu Min Kang
Baeckseung Lee
Sang Joon Park
Yu Min Seong
Moon Jung Kim
Hyun Young Shin
Wang Jun Lee
Seunghyun Jeon
Jaegyun Lim
Journal: Journal of Korean Medical Science (2020)
Discipline: CLINICAL MEDICINE
Keywords: COVID-19; Coronavirus; Pneumonia; Real-Time Reverse-Transcriptase Polymerase Chain Reaction; Tertiary Infection
Affiliations: Department of Laboratory Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea., New Horizon Cancer Institute, Myongji Hospital, Goyang, Korea., Department of Family Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea., Department of Internal Medicine, Myongji Hospital, Goyang, Korea., Office of Chief Executive Officer and Chairman, Department of General Surgery, Myongji Hospital, Goyang, Korea., Department of Infectious Diseases, Myongji Hospital, Goyang, Korea., CancerROP, Seoul, Korea., Department of Pulmonary and Critical Care Medicine, Myongji Hospital, Goyang, Korea.

Abstract:  Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed. 

Retracted: No

PubPeer comments:
 the antibiotics - azithromycin tazobactam levofloxacin (no mention of that in the text) - might actually have done the cure. Temperature started going down with azithromycin only Like [here] . ![file] , 
 In fact, [Lopinavir Ritonavir failed] to show any effect in a clinical trial - so maybe it was the anti-microbials which worked. ,
Oridonin, a diterpenoid purified from Rabdosia rubescens, inhibits the proliferation of cells from lymphoid malignancies in association with blockade of the NF-kappa B signal pathways
Authors: Shigeki Takemoto
Kazuto Togitani
Hisanori Machida
Kentaro Bandobashi
Takayuki Ikezoe
Yang Yang
Tsuyako Saito
H Phillip Koeffler
Hirokuni Taguchi
Journal: Molecular Cancer Therapeutics (2005)
Discipline: CLINICAL MEDICINE
Keywords: oridonin; apoptosis; Bcl-2; Mcl-1; BCL-x(L)
Affiliations: Department of Hematology and Respiratory Medicine, KMS, Kochi Medical School, Nankoku, 783-8505 Kochi, Japan. 

Abstract:  This study found that oridonin, a natural diterpenoid purified from Rabdosia rubescens, inhibited growth of multiple myeloma (MM; U266, RPMI8226), acute lymphoblastic T-cell leukemia (Jurkat), and adult T-cell leukemia (MT-1) cells with an effective dose that inhibited 50% of target cells (ED50) ranging from 0.75 to 2.7 microg/mL. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining showed that oridonin caused apoptosis of MT-1 cells in a time-dependent manner. We explored effects of oridonin on antiapoptotic Bcl-2 family members and found that it down-regulated levels of Mcl-1 and BCL-x(L), but not Bcl-2 protein, in both MT-1 and RPMI8226 cells. Further studies found that oridonin inhibited nuclear factor-kappa B (NF-kappa B) DNA-binding activity in these cells as measured by luciferase reporter gene, ELISA-based, and electrophoretic mobility shift assays. Oridonin also blocked tumor necrosis factor-alpha- and lipopolysaccharide-stimulated NF-kappa B activity in Jurkat cells as well as RAW264.7 murine macrophages. Of note, oridonin decreased survival of freshly isolated adult T-cell leukemia (three samples), acute lymphoblastic leukemia (one sample), chronic lymphocytic leukemia (one sample), non-Hodgkin's lymphoma (three samples), and MM (four samples) cells from patients in association with inhibition of NF-kappa B DNA-binding activity. On the other hand, oridonin did not affect survival of normal lymphoid cells from healthy volunteers. Taken together, oridonin might be useful as adjunctive therapy for individuals with lymphoid malignancies, including the lethal disease adult T-cell leukemia. 

Retracted: No

PubPeer comments:
 Figure 7C. Much more similar than expected. https: imgur.com RcNw5Tc ,
Human Bocavirus Infection of Permanent Cells Differentiated to Air-Liquid Interface Cultures Activates Transcription of Pathways Involved in Tumorigenesis
Authors: Oliver Schildgen
Soumaya Khalfaoui
Wolfgang H Arnold
Monika Pieper
Verena Schildgen
Journal: Cancers (2018)
Discipline: CLINICAL MEDICINE
Keywords: human bocavirus; transcriptome analyses; tumorigenesis.
Affiliations: Kliniken der Stadt Köln gGmbH, Institut für Pathologie, Kliniken der Privaten Universität Witten/Herdecke mit Sitz in Köln, Ostmerheimer Str. 200, D-51109 Köln/Cologne, Germany. ., Universität Witten/Herdecke, Lehrstuhl für Biologische und Materialkundliche Grundlagen der Zahnmedizin, D-58448 Witten, Germany. .

Abstract:  The parvoviral human bocavirus (HBoV) is a respiratory pathogen, able to persist in infected cells. The viral DNA has been identified in colorectal and lung tumors and thus it was postulated that the virus could be associated with tumorigenesis. This assumption was supported by the fact that in HBoV-infected patients and in an in vitro cell culture system, pro-cancerogenic and -fibrotic cytokines were expressed. In this work, it is shown by a whole transcriptome analysis that, also at the mRNA level, several pathways leading to neoplasia and tumorigenesis are significantly upregulated. In total, a set of 54 transcripts are specifically regulated by HBoV, of which the majority affects canonical pathways that may lead to tumor development if they become deregulated. Moreover, pathways leading to necrosis, apoptosis and cell death are downregulated, supporting the hypothesis that HBoV might contribute to the development of some kinds of cancer. 

Retracted: No

PubPeer comments:
 The images in Figure 3a appear to be repeated in Figure 3b. *** ![file] , 
 Thanks for bringing this to our Attention, you are Right. We have submitted an Erratum to the Journal. , 
 #2 Thank you for the prompt reply. , 
 #3 Dear Colleagues, please note that the mistake was corrected and the correction is now available online: file: C: Users schildgeno Downloads cancers-13-01774.pdf Once again, many thanks for bringing this to our attention. Best regards Oliver Schildgen ,
Prostaglandin E2 stimulates human lung carcinoma cell growth through induction of integrin-linked kinase: the involvement of EP4 and Sp1
Authors: Jesse Roman
Jeffrey D Ritzenthaler
ShouWei Han
Ying Zheng
XiaoJuan Sun
Journal: Cancer research (2009)
Discipline: CLINICAL MEDICINE
Keywords: Cyclooxygenase-2; prostaglandin E(2); tumor cell growth; non-small cell lung carcinoma; integrin-linked kinase
Affiliations: Department of Medicine, Division of Pulmonary, Emory University School of Medicine, Atlanta, USA.

Abstract:  Cyclooxygenase-2-derived prostaglandin E(2) (PGE(2)) stimulates tumor cell growth and progression. However, the mechanisms by which PGE(2) increases tumor growth remain incompletely understood. In studies performed in non-small cell lung carcinoma (NSCLC) cells, we found that PGE(2) stimulates the expression of integrin-linked kinase (ILK). ILK small interfering RNA (siRNA) inhibited the mitogenic effects of PGE(2). In view of its perceived importance, we turned our attention to the mechanisms involved in PGE(2)-induced ILK expression and found that this effect was blocked by an antagonist of the PGE(2) receptor subtype EP4 and by EP4 siRNA. Furthermore, we showed that PGE(2) induction of ILK was associated with phosphorylation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt, which were abrogated by ILK siRNA. Transient transfection, gel mobility shift assays, and chromatin immunoprecipitation experiments showed that PGE(2) induced ILK promoter activity and increased Sp1, although it had no effect on nuclear factor-kappaB and AP-2 DNA-binding activity. Blockade of Sp1 abrogated the effect of PGE(2) on expression of ILK and promoter activity and on cell growth. In summary, our observations show that PGE(2) increases NSCLC cell growth through increased ILK expression, which is dependent on EP4 signaling and on induction of Sp1 protein and Sp1 DNA-binding activity in the ILK promoter. These studies suggest a novel molecular mechanism by which PGE(2) stimulates NSCLC cell growth and unveils a new molecular target for the development of therapies against NSCLC. 

Retracted: No

PubPeer comments:
 Figure 1. Much more similar than you would expect. https: imgur.com 91dWlnQ , 
 https: retractionwatch.com 2015 08 11 eighth-retraction-published-for-former-physiology-researcher ,
Tenascin‑C promotes epithelial‑to‑mesenchymal transition and the mTOR signaling pathway in nasopharyngeal carcinoma
Authors: Fen Li
Zezhang Tao
Xiang Cheng
Journal: Oncology Letters (2021)
Discipline: CLINICAL MEDICINE
Keywords: epithelial-to-mesenchymal transition; gene set enrichment analysis; nasopharyngeal carcinoma; tenascin-c; weighted gene co-expression network analysis.
Affiliations: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Abstract:  Tenascin-C (TNC) is a large extracellular matrix glycoprotein that promotes cell adhesion and tissue remodeling, and is involved in the transduction of cellular signaling pathways. The present study aimed to investigate the role of TNC and determine its effect in nasopharyngeal carcinoma (NPC). TNC gene transcription and expression were analyzed using the NPC dataset and immunohistochemistry analysis of NPC tissues. Weighted gene co-expression network and gene enrichment analyses were performed to determine the potential molecular mechanisms underlying the effects of TNC in NPC. TNC expression was suppressed in NPC cells, and the effects were determined both in vitro and in vivo. The results demonstrated that TNC gene transcription and expression were high in NPC tissues compared with normal tissues. Notably, TNC knockdown inhibited NPC cell proliferation, migration and invasion. In addition, TNC knockdown inhibited tumor growth in mice. In vitro, TNC knockdown inhibited epithelial-to-mesenchymal transition (EMT) and decreased activity of the PI3K/AKT/mTOR signaling pathway in NPC cells. Taken together, these results suggest that TNC promotes cell proliferation, EMT and activity of the PI3K/AKT/mTOR signaling pathway in NPC cells, and thus functions as an oncogene. 

Retracted: No

PubPeer comments:
 Some bands in figure 4A and 6A appear to be similar ![file] ,
NFATC4 promotes quiescence and chemotherapy resistance in ovarian cancer
Authors: Shoumei Bai
Euisik Yoon
Alexander J Cole
Ronald J Buckanovich
Daniel Chan
Santiago Panesso-Gómez
Mangala Iyengar
Greg M Delgoffe
Patrick O&#x27;Hayer
Katherine M Aird
Journal: JCI Insight (2020)
Discipline: CLINICAL MEDICINE
Keywords: Cancer; Therapeutics.
Affiliations: Department of Internal Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA., Tumor Microenvironment Center, UPMC Hillman Cancer Center; and Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Department of Cellular & Molecular Physiology, Penn State College of Medicine, Hershey, Pennsylvania, USA., Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan, USA., Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Abstract:  Development of chemotherapy resistance is a major problem in ovarian cancer. One understudied mechanism of chemoresistance is the induction of quiescence, a reversible nonproliferative state. Unfortunately, little is known about regulators of quiescence. Here, we identify the master transcription factor nuclear factor of activated T cells cytoplasmic 4 (NFATC4) as a regulator of quiescence in ovarian cancer. NFATC4 is enriched in ovarian cancer stem-like cells and correlates with decreased proliferation and poor prognosis. Treatment of cancer cells with cisplatin resulted in NFATC4 nuclear translocation and activation of the NFATC4 pathway, while inhibition of the pathway increased chemotherapy response. Induction of NFATC4 activity resulted in a marked decrease in proliferation, G0 cell cycle arrest, and chemotherapy resistance, both in vitro and in vivo. Finally, NFATC4 drove a quiescent phenotype in part via downregulation of MYC. Together, these data identify NFATC4 as a driver of quiescence and a potential new target to combat chemoresistance in ovarian cancer. 

Retracted: No

PubPeer comments:
 Presumably this will not affect the results, but the caption for Figure 10(E) refers to u201ccontinuous doxycycline (n = 8),u201d however only 7 tumors are shown in the accompanying image. *** ![file] ,
Fas/FasL induces myocardial cell apoptosis in myocardial ischemia-reperfusion rat model
Authors: Z-M Yang
X-M Liu
X-K Liu
Journal: European Review for Medical and Pharmacological Sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Myocardium ischemia reperfusion; Fas/FasL signaling pathway; cell apoptosis; rat model; coronary artery ligation
Affiliations: Department of Cardiology, Tangshan Gongren Hospital, Tangshan, Hebei, China. .

Abstract:  Objective: Myocardium ischemia reperfusion is easy to induce myocardial injury. Fas/FasL is an important signaling pathway mediating cell apoptosis. This study aims to analyze the cell apoptosis and Fas/FasL expression in myocardial cell ischemia reperfusion rat model. Materials and methods: Coronary artery ligation method was used to establish myocardial ischemia reperfusion model. Rats were grouped according to different ischemia and reperfusion time: Group A, myocardial ischemia for 30 min and reperfusion for 24 h; Group B, myocardial ischemia for 30 min and reperfusion for 48 h; Group C, myocardial ischemia for 1 h and reperfusion for 24 h. Myocardial injury indicators were tested. Myocardial cell apoptosis was detected by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Fas and FasL mRNA and protein expressions were evaluated by Real-time PCR (RT-PCR) and Western blot. Results: Creatine kinase (CK), lactic dehydrogenase (LDH), and malondialdehyde (MDA) significantly elevated, while superoxide dismutase (SOD) obviously declined in the experimental group compared with control and blank group (p&lt;0.05). CK, LDH, and MDA gradually upregulated, whereas SOD was reduced in experimental groups following the time extension of ischemia and reperfusion (p&lt;0.05). Apoptosis cell number was markedly higher in the experimental group compared with control and blank group (p&lt;0.05). Apoptosis cell number gradually increased in the experimental groups following ischemia and reperfusion time extension (p&lt;0.05). Fas/FasL mRNA and protein markedly upregulated in the experimental group compared with control and blank group (p&lt;0.05). Fas/FasL mRNA and protein expressions enhanced in experimental groups following the time extension of ischemia and reperfusion (p&lt;0.05). Conclusions: Fas/FasL induces myocardial cell apoptosis in the process of myocardium ischemia reperfusion in rat model. 

Retracted: No

PubPeer comments:
  Figure 1. Myocardial cell apoptosis. ![file] 10 U mL panel appears to be an enlarged and slightly retouched version of the 100 U mL panel. , 
 Of additional concern are similarities between this Figure 1 (see comment #1) and Figure 2 in A Abudoureyimu and A Muhemaitibake, 2017, ERMPS, Pubmed ID: 28239804 . Areas that look similar are highlighted with boxes of the same color. It is not clear what Figure 1 here is showing (the experimental conditions did not differ in the concentration of something, but rather had different ischemia and reperfusion times). Figure 2 in the other paper shows BGC-823 cells treated with Arsenic trioxide. Could the authors please clarify which experiments we are looking at here? ![file] ,
Distinct P2Y receptor subtypes regulate calcium signaling in human retinal pigment epithelial cells
Authors: Victoria E Tovell
Julie Sanderson
Journal: Investigative ophthalmology & visual science (2008)
Discipline: CLINICAL MEDICINE
Keywords: Nucleotide signaling; retinal pigment epithelial (RPE) cells; P2Y receptor subtypes; intracellular Ca(2+) levels; real-time fluorescence imaging
Affiliations: School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, United Kingdom.

Abstract:  Purpose: Nucleotide signaling plays a role in retinal pigment epithelial (RPE) function, and receptors for nucleotides are potential therapeutic targets for various ocular diseases. The purpose of this study was to investigate the expression of P2Y receptor subtypes in native and cultured human RPE cells. Methods: Intracellular Ca(2+) levels were monitored using real-time fluorescence imaging in cultured human RPE cells loaded with Fura-2. Expression of P2Y receptors in native and cultured RPE cells was determined by quantitative RT-PCR and Western blot analysis. Results: Adenosine triphosphate (ATP), uridine triphosphate (UTP), adenosine diphosphate (ADP), 2-methylthio ATP (2MeSATP), and uridine diphosphate (UDP) produced concentration-related increases in [Ca(2+)](i) in cultured RPE cells. However, differences between the magnitude and shape of agonist responses were observed. ATP and UTP showed similar response characteristics, including a distinct Ca(2+) influx component. ATP and UTP were equipotent (EC(50), 6 muM) and maximum responses were equivalent, suggesting activation of a P2Y(2) receptor. Maximal responses to ADP and 2MeSATP were equivalent with EC(50)s of 1 muM and 0.3 muM. The P2Y(1) antagonist MRS 2179 (10 muM) inhibited these responses, confirming functional expression of P2Y(1) receptors. The presence of a response to UDP suggested P2Y(6) expression. There was no influx component to P2Y(1)- and P2Y(6)-mediated responses. mRNA for P2Y(1), P2Y(2,) P2Y(4), and P2Y(6) receptor subtypes was found in cultured RPE cells, and for P2Y(1), P2Y(2,) P2Y(4,) P2Y(6), and P2Y(12) it was found in native RPE cells. Expression of P2Y(1), P2Y(2), and P2Y(6) protein was found in native and cultured RPE cells. Conclusions: These data define the expression profile of P2Y receptors in human RPE and show that different P2Y subtypes control distinct calcium responses in these cells. 

Retracted: No

PubPeer comments:
 Undeclared splicing throughout the Figure. Contrast and brightness adjusted. The P lane is an important control that is supposed to indicate antibody-specificity (the antibody was incubated with the antigenic peptide prior to use in the western blot experiment). Can the authors comment on how these blots were assembled? ![file] ,
14-3-3β exerts glioma-promoting effects and is associated with malignant progression and poor prognosis in patients with glioma
Authors: Fuqiang Ruan
Shuai Wen
Long Chen
Liang Liu
Zhixiong Liu
Hao Wang
Jihui Zhang
Hengshan Luo
Yi Hu
Journal: Experimental and Therapeutic Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: 14-3-3β; glioma; oncogene; prognosis.
Affiliations: Department of Neurosurgery, People's Hospital of Ningxiang County, Ningxiang, Hunan 410600, P.R. China., Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.

Abstract:  Glioma is a type of tumor that affects the central nervous system. It has been demonstrated that 14-3-3β, a protein that is mainly concentrated in the brain, serves an important role in tumor regulation. However, the mechanism of action of 14-3-3β that underlies the pathogenesis of glioma remains to be elucidated. In the present study, 14-3-3β was silenced by RNA interference in the human glioma cell line U373-MG. Following knockdown of 14-3-3β, the proliferation, colony formation, cell cycle progression, migration and invasion of U373-MG cells were significantly decreased (P&lt;0.01), whereas cell apoptosis was increased (P&lt;0.01). Furthermore, in a tumor xenograft experiment, silencing 14-3-3β significantly inhibited the in vivo tumor growth of U373-MG cells (P&lt;0.01). The results demonstrated that 14-3-3β levels were significantly higher in human glioma tissues compared with normal brain tissues (P&lt;0.01) and high 14-3-3β expression was significantly associated with advanced pathological grade (P&lt;0.03) and low Karnofsky performance scale (P&lt;0.003). Patients with glioma who had high 14-3-3β levels had a significantly shorter survival time compared with those with low expression of 14-3-3β (P=0.031), suggesting that 14-3-3β may be an effective predictor of the prognosis of patients with glioma. The results of the present study indicate that 14-3-3β serves an oncogenic role in glioma, suggesting that 14-3-3β may have potential as a promising therapeutic target for glioma. 

Retracted: No

PubPeer comments:
 *[left]* Fig 3B.  Transwell assays were performed to assess cell migration. *[right]* Fig 2C from [Zhou et al (2017)] .  Transwell assay . ![file] Overlap marked. Other manifestations of the same Transwell images are linked in that thread. In a spreadsheet collecting the possible activities of a papermill, those papers have  purple in the Transwell column. https: docs.google.com spreadsheets d 1I7uuhZ7NgMtzXFaJVfBPzP92JjCHO8tJDOjL8Y_9q1U edit?usp=sharing , 
 Fig 2.  Flow cytometry was used to assess the (A) cell cycle and (B) cell apoptosis . ![file] Colored boxes mark similar panels in Figs 2C, 2F, 4E, 4F from [Su et al (2017)] : ![file] Fig 6A B from [Li et al (2014)] : ![file] -------------------------------------------------------------------------------------- ![file] For comparison, Fig 3 from [Lei et al (2015)] , and Fig 2D from [Jiang et al (2017)] . ![] ,
MicroRNA-198 inhibits proliferation and induces apoptosis of lung cancer cells via targeting FGFR1
Authors: Limin Fan
Jun Yang
Yu Xin
Heng Zhao
Journal: Journal of Cellular Biochemistry (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: APOPTOSIS; FGFR1; LUNG CARCINOGENESIS; VIABILITY; miR-198.
Affiliations: Thoracic Department, Shanghai Chest Hospital Affiliated to Shanghai JiaoTong University, Shanghai, 200030, China., Thoracic Department; Shanghai Chest Hospital Affiliated to Shanghai JiaoTong University; Shanghai 200030 China, Pulmonary Department; Shanghai Chest Hospital affiliated to Shanghai JiaoTong University; Shanghai 200030 China

Abstract:  Lung cancer is the most common cause of death from cancer worldwide and recent studies have revealed that microRNAs play critical roles to regulate lung carcinogenesis. Here we present evidence to show the role of miR-198 in lung cancer development. Our results showed that ectopic expression of miR-198 inhibits the viability and induces the apoptosis of human non-small cell lung cancer cells A549 and NCI-H460, while miR-198 inhibition resulted in opposite changes. In nude mice miR-198 inhibits A549 growth of tumor graft. We further demonstrated that miR-198 directly targets fibroblast growth factor receptor 1 (FGFR1) in lung cancer cells. Restoring FGFR1 expression blocked the inhibitory function of miR-198, while FGFR1 inhibition achieved the similar phenotypes of miR-198 overexpression. Hence, our data delineates the molecular pathway by which miR-198 inhibits lung cancer cellular proliferation and induces apoptosis, and may have important implication for the treatment of lung carcinogenesis. 

Retracted: No

PubPeer comments:
 Fig 2A.  Effect of miRu2010198 on lung cancer cells apoptosis. Apoptotic A549 ... cells in mock, scramble control (Ctrl), 50 nM of miRNA mimics or antiu2010miR198 were analyzed using double staining with Annexinu2010Vu2010FITC and PI. Two plots have a large area in common. ![file] , 
 The corresponding email address (hongjiang021@126.com) has no obvious connection to the name of the corresponding author, and differs from the various email addresses used by the corresponding author for other papers in 2014-2015. ,
Carbon monoxide inhibits human airway smooth muscle cell proliferation via mitogen-activated protein kinase pathway
Authors: Fang Liu
Augustine M K Choi
Ruiping Song
Raja S Mahidhara
Wen Ning
Leo E Otterbein
Journal: American Journal of Respiratory Cell and Molecular Biology (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: carbon monoxide; asthma; airway smooth muscle cell; proliferation; G0/G1 phase
Affiliations: Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.

Abstract:  The gaseous molecule carbon monoxide (CO) is elevated in the breath of individuals with asthma. The physiologic function of CO in asthma is poorly understood. Here we demonstrate that CO (250 ppm) markedly inhibits human airway smooth muscle cell (HASMC) proliferation, arresting cells at the G0/G1 phase. This CO-induced cell growth arrest of HASMC was associated with upregulation of p21 and downregulation of cyclin D1 expression. It is generally believed that the signaling pathway by which CO affects biologic processes is primarily mediated via the guanylyl cyclase/3',5'-Guanylate cyclic monophosphate (cGMP) pathway. To examine whether guanylyl cyclase/cGMP was involved in CO-induced growth arrest of HASMC, Rp-8-Br-cGMP, a selective inhibitor of cGMP-dependent protein kinase and ODQ, a selective inhibitor of soluble guanylate cyclase, were administered to HASMC in the presence of CO. Interestingly, CO-induced cell growth arrest was not reversed by these inhibitors. We next examined whether the extracellular signal-regulated kinase (ERK) 1/ERK2 mitogen-activated protein kinase (MAPK) signaling pathway may regulate the antiproliferative effect of CO. We first showed time-dependent activation of the various MAPKs in HASMC in response to serum, including phosphorylated ERK1/ERK2, p38, and JNK and then demonstrated that CO exerted negligible effect on activated p38 and JNK; however, ERK activation was significantly attenuated in the presence of CO. These data suggest that CO can inhibit HASMC proliferation via the ERK1/ERK2 MAPK pathway, independent of a guanylyl cyclase/cGMP independent pathway. CO may act as an important mediator of remodeling of human airways in asthma via its ability to regulate cell growth of airway smooth muscle cells. 

Retracted: No

PubPeer comments:
 Figures 5 and 6. Much more similar than expected. https: imgur.com KDD3iky , 
 Figure 6. Much more similar than expected. https: imgur.com iKyUmRC , 
 #2 Figure 4B continued. Much more similar than expected. https: imgur.com YWS9vcI , 
 #3 It is figure 6B. , 
 Figures 5 and 6. Much more similar than expected. https: imgur.com xw37sZG ,
WITHDRAWN: Countering fake news in the COVID-19 era: The public's opinion on the role of an honest and reliable website
Authors: Victor Grech
Mariella Scerri
Journal: Early Human Development (2020)
Discipline: CLINICAL MEDICINE
Keywords: Article withdrawal; Author(s); Editor; Publisher; Elsevier Policy
Affiliations: Mater Dei Hospital, Malta. Electronic address: .

Abstract:  This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal. 

Retracted: No

PubPeer comments:
 Why is this article on Covid-19 not open access? Elsevier is a signatory to this agreement: https: wellcome.org coronavirus-covid-19 open-data , 
 See https: retractionwatch.com 2021 03 31 beam-us-up-elsevier-pulls-26-covid-19-papers-by-researcher-with-a-penchant-for-star-trek ,
Distribution of the Secondary Type III Secretion System Locus Found in Enterohemorrhagic Escherichia coli O157:H7 Isolates among Shiga Toxin-Producing E. coli Strains
Authors: Sou-Ichi Makino
Chihiro Sasakawa
Koichi Takeshi
Hiroshi Asakura
Masahisa Watarai
Testuya Ikeda
Toru Tobe
Journal: Journal of Clinical Microbiology (2003)
Discipline: MICROBIOLOGY
Keywords: Genome sequence; Enterohemorrhagic Escherichia coli O157; Type III secretion system; Gene cluster; Locus
Affiliations: Department of Applied Veterinary Science, Research Center for Animal Hygiene and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido Institute of Public Health, Hokkaido, Japan. , Division of Applied Bacteriology, Graduate School of Medicine, Osaka University, Osaka, Department of Applied Veterinary Science, Hokkaido Institute of Public Health, Hokkaido, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Abstract:  The ability of the complete genome sequence of enterohemorrhagic Escherichia coli O157 led to the identification of a 17-kb chromosomal region which contained a type III secretion system gene cluster at min 64.5. This locus contains open reading frames whose amino acid sequences show high degrees of similarity with those of proteins that make up the type III secretion apparatus, which is encoded by the inv-spa-prg locus on a Salmonella SPI-1 pathogenicity island. This locus was designated ETT2 (E. coli type III secretion 2) and consisted of the epr, epa, and eiv genes. ETT2 was found in enteropathogenic E. coli strains and also in some non-O157 Shiga toxin-producing E. coli (STEC) strains, but most of them contained a truncated portion of ETT2. Most O157 isolates had a complete collection of toxin-encoding genes eae and hlyA and the ETT2 locus, while most O26 strains had toxin-encoding genes eae and hlyA genes but an incomplete ETT2 locus. Thus, an intact copy of ETT2 might mark a pathogenic distinction for particular STEC strains. Therefore, the presence of the ETT2 locus can be used for identification of truly pathogenic STEC strains and for molecular fingerprinting of the epidemic strains in humans and animals. 

Retracted: No

PubPeer comments:
 Figure 2 raises some concerns. * Blue and yellow boxes: the background of the Region D gel appears to show repeats. ![file] This issue was reported to the journal in December 2014, but no action has been taken in the past seven years. This paper was found during a systematic screen of biomedical papers for image duplications, as published in Bik et al., mBio (2016), doi: 10.1128 mBio.00809-16, https: journals.asm.org doi 10.1128 mBio.00809-16. ,
Cysteine string protein limits expression of the large conductance, calcium-activated K⁺ (BK) channel
Authors: Barry Kyle
Eva Ahrendt
Janice E A Braun
Andrew P Braun
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: BK channels; CSPα; regulation; neurotransmitter release; presynaptic terminal
Affiliations: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada., Libin Cardiovascular Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.

Abstract:  Large-conductance, calcium-activated K(+) (BK) channels are widely distributed throughout the nervous system and play an essential role in regulation of action potential duration and firing frequency, along with neurotransmitter release at the presynaptic terminal. We have previously demonstrated that select mutations in cysteine string protein (CSPα), a presynaptic J-protein and co-chaperone, increase BK channel expression. This observation raised the possibility that wild-type CSPα normally functions to limit neuronal BK channel expression. Here we show by Western blot analysis of transfected neuroblastoma cells that when BK channels are present at elevated levels, CSPα acts to reduce expression. Moreover, we demonstrate that the accessory subunits, BKβ4 and BKβ1 do not alter CSPα-mediated reduction of expressed BKα subunits. Structure-function analysis reveals that the N-terminal J-domain of CSPα is critical for the observed regulation of BK channels levels. Finally, we demonstrate that CSPα limits BK current amplitude, while the loss-of-function homologue CSPαHPD-AAA increases BK current. Our observations indicate that CSPα has a role in regulating synaptic excitability and neurotransmission by limiting expression of BK channels. 

Retracted: No

PubPeer comments:
 October 2015 correction:  * Fig 1C is incorrect as it shows the wrong actin blot. The authors have provided a corrected version of Fig 1 here. * Additionally, there is a sentence missing from the caption for Fig 3. Please see the complete, correct Fig 3 caption here. The missing sentence is highlighted in bold. Here is the original Figure 1 with the duplication marked with colored boxes, as reported to the journal in April 2014. I thank the authors for correcting this. ![file] ,
Refolding of β-stranded class I chitinases of Hippophae rhamnoides enhances the antifreeze activity during cold acclimation
Authors: Ravi Gupta
Renu Deswal
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Class I chitinases; antifreeze activity; cold stress; seabuckthorn seedlings; chitin affinity chromatography
Affiliations: Molecular Plant Physiology and Proteomics Laboratory, Department of Botany, University of Delhi, Delhi, India.

Abstract:  Class I chitinases hydrolyse the β-1,4-linkage of chitin and also acquire antifreeze activity in some of the overwintering plants during cold stress. Two chitinases, HrCHT1a of 31 kDa and HrCHT1b of 34 kDa, were purified from cold acclimated and non-acclimated seabuckthorn seedlings using chitin affinity chromatography. 2-D gels of HrCHT1a and HrCHT1b showed single spots with pIs 7.0 and 4.6 respectively. N-terminal sequence of HrCHT1b matched with the class I chitinase of rice and antifreeze proteins while HrCHT1a could not be sequenced as it was N-terminally blocked. Unlike previous reports, where antifreeze activity of chitinase was cold inducible, our results showed that antifreeze activity is constitutive property of class I chitinase as both HrCHT1a and HrCHT1b isolated even from non-acclimated seedlings, exhibited antifreeze activity. Interestingly, HrCHT1a and HrCHT1b purified from cold acclimated seedlings, exhibited 4 and 2 times higher antifreeze activities than those purified from non-acclimated seedlings, suggesting that antifreeze activity increased during cold acclimation. HrCHT1b exhibited 23-33% higher hydrolytic activity and 2-4 times lower antifreeze activity than HrCHT1a did. HrCHT1b was found to be a glycoprotein; however, its antifreeze activity was independent of glycosylation as even deglycosylated HrCHT1b exhibited antifreeze activity. Circular dichroism (CD) analysis showed that both these chitinases were rich in unusual β-stranded conformation (36-43%) and the content of β-strand increased (∼11%) during cold acclimation. Surprisingly, calcium decreased both the activities of HrCHT1b while in case of HrCHT1a, a decrease in the hydrolytic activity and enhancement in its antifreeze activity was observed. CD results showed that addition of calcium also increased the β-stranded conformation of HrCHT1a and HrCHT1b. This is the first report, which shows that antifreeze activity is constitutive property of class I chitinase and cold acclimation and calcium regulate these activities of chitinases by changing the secondary structure. 

Retracted: No

PubPeer comments:
 Figure 6E. * Red boxes: Two panels appear to overlap. Reported to the journal in October 2015, but no action taken as of today. ![file] , 
 With the aid of ImageTwin, I found two other possible overlapping panels, in Figure 4 and between Figure 4 and 6. Marked here with green and yellow boxes. Note the 180 degree rotations. ![file] ,
Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer
Authors: Joel S Brown
Robert A Gatenby
Jingsong Zhang
Jessica J Cunningham
Journal: Nature Communications (2017)
Discipline: Multidisciplinary
Keywords: Abiraterone; metastatic castrate-resistant prostate cancer; CYP17A; testosterone; treatment failure
Affiliations: Department of Genitourinary Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA., Department of Integrated Mathematical Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA., Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, 60607, USA., Department of Integrated Mathematical Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA. ., Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA. .

Abstract:  Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka-Volterra equations with three competing cancer "species": androgen dependent, androgen producing, and androgen independent. Simulations with standard abiraterone dosing demonstrate strong selection for androgen-independent cells and rapid treatment failure. Adaptive therapy, using patient-specific tumor dynamics to inform on/off treatment cycles, suppresses proliferation of androgen-independent cells and lowers cumulative drug dose. In a pilot clinical trial, 10 of 11 patients maintained stable oscillations of tumor burdens; median TTP is at least 27 months with reduced cumulative drug use of 47% of standard dosing. The outcomes show significant improvement over published studies and a contemporaneous population. 

Retracted: No

PubPeer comments:
 Fig 5A: could authors explain why there was a mirror image of the background illustrated below? ![file] ,
Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module
Authors: Alberto Macone
Marta Moretti
Sara Cairoli
Laura Di Magno
Luca Battistini
Carlo Capalbo
Sonia Coni
Bianca Maria Goffredo
Lucia Di Marcotullio
Enrico De Smaele
Simona Manni
Carmine Nicoletti
Marella Maroder
Fiorella Di Pastena
Manolo Sambucci
Paola Infante
Egidio Iorio
Gianluca Canettieri
Enzo Agostinelli
Marialaura Petroni
Giuseppe Giannini
Journal: Cell reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CtBP2; Hedgehog; NADH; biguanides; cancer
Affiliations: Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, 00161 Rome, Italy., Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy., Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, 00185 Rome, Italy., Division of Metabolism and Research Unit of metabolic Biochemistry, Children's Hospital and Research Institute Bambino Gesù IRCCS, 00146 Rome, Italy., IRCCS Santa Lucia Foundation, Neuroimmunology Unit, 00143 Rome, Italy., Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy., Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy; Istituto Pasteur, Fondazione Cenci-Bolognetti, Sapienza University of Rome, 00161 Rome, Italy., Core Facilities, Istituto Superiore di Sanità, 00161 Rome, Italy., Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, 00185 Rome, Italy; International Polyamines Foundation-ONLUS, 00159 Rome, Italy., Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy; Istituto Pasteur, Fondazione Cenci-Bolognetti, Sapienza University of Rome, 00161 Rome, Italy; International Polyamines Foundation-ONLUS, 00159 Rome, Italy. Electronic address: .

Abstract:  The antidiabetic drug phenformin displays potent anticancer activity in different tumors, but its mechanism of action remains elusive. Using Shh medulloblastoma as model, we show here that at clinically relevant concentrations, phenformin elicits a significant therapeutic effect through a redox-dependent but complex I-independent mechanism. Phenformin inhibits mitochondrial glycerophosphate dehydrogenase (mGPD), a component of the glycerophosphate shuttle, and causes elevations of intracellular NADH content. Inhibition of mGPD mimics phenformin action and promotes an association between corepressor CtBP2 and Gli1, thereby inhibiting Hh transcriptional output and tumor growth. Because ablation of CtBP2 abrogates the therapeutic effect of phenformin in mice, these data illustrate a biguanide-mediated redox/corepressor interplay, which may represent a relevant target for tumor therapy. 

Retracted: No

PubPeer comments:
 ![file] ,
TNFalpha and IL-8 regulate the expression and function of CD44 variant proteins in human colon carcinoma cells
Authors: Yehuda Chowers
Amiram Ariel
Michal Barshishat
Liora Cahalon
Ofer Lider
Betty Schwartz
Journal: Clinical & Experimental Metastasis (2002)
Discipline: CLINICAL MEDICINE
Keywords: inflammatory processes; metastatic processes; pathways; adhesion; migration
Affiliations: Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Israel.

Abstract:  The mechanisms underlying the inflammatory and metastatic processes share a number of similar pathways, such as those involving adhesion, migration and extravasation. In this article, the effects of pro-inflammatory cytokines on metastatic-related activities of colon cancer cells were tested. The expression and biological activity of the proteoglycan CD44 in low (LS174T) and high metastatic (HM7) cell lines following exposure to TNFalpha and IL-8 were assessed. Treated cells expressed more CD44 splice variants (CD44v), while CD44 standard protein (CD44s) expression remained unchanged. Treatment with TNFalpha induced IL-8 secretion and IL-8 gene transcription in a time-dependent manner. Both cytokines enhanced the ability of the cells to adhere to the CD44-specific ligand hyaluronic acid, an effect that was specifically blocked by an anti-IL-8 antibody. These results suggest that the effect of TNFalpha on IL-8 is responsible for the regulation of the expression of CD44 isoforms. Additional experiments showed that neither of the cytokines tested regulate the expression of CD44 gene regulation via activation of a well-characterized specific 22-bp epidermal growth factor regulatory element present in the CD44 promoter sequence, suggesting that this is not the mechanism of activation. We conclude that immuno-modulatory mediators can modify the expression of cell-to-cell or cell-to-matrix adhesion proteins, implicated in the determination of phenotypes associated with aggressiveness and metastasis of colon cancer cells. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: Lanes  0 and  2 appear to look more similar than expected. ![file] , 
 Figure 4B. * Yellow boxes: Lanes  0 ,  4 , and  18 appear to look more similar to each other than expected. * Updated with green and blue boxes to highlight additional similarities between lanes found by a reader on Twitter. ![file] ,