PReD-Bench/PRed-Bench huggingface dataset:
Chronic Microdose Lithium Treatment Prevented Memory Loss and Neurohistopathological Changes in a Transgenic Mouse Model of Alzheimer's Disease
Authors: Ariadiny Lima Caetano
Suzzanna Ingryd Gonçalves Souza
Natalia Mendes Schöwe
Janaina Balthazar
Karla Cristina Monteiro-Silva
Ticiana Baraldi-Tornisielo
Tania Araujo Viel
Marielza Andrade Nunes
Marilia Silva Albuquerque
Hudson Sousa Buck
Journal: PLoS ONE (2015)
Discipline: Multidisciplinary
Keywords: lithium; microdose; Alzheimer's disease; prevention; treatment
Affiliations: Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, R. Dr. Cesario Motta Junior, 61, 11° andar, São Paulo, SP 01221-020, Brazil., Research Group on Neuropharmacology of Aging-ReGNA, Sao Paulo, Brazil., Graduation Course on Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, Avenida Professor Lineu Prestes, 1524, 05508-900 São Paulo, Brazil., School of Arts, Sciences and Humanities, Universidade de São Paulo, Av. Arlindo Bettio, 1000, São Paulo, SP 03828-080, Brazil.

Abstract:  The use of lithium is well established in bipolar disorders and the benefits are being demonstrated in neurodegenerative disorders. Recently, our group showed that treatment with microdose lithium stabilized the cognitive deficits observed in Alzheimer's disease (AD) patients. In order to verify the lithium microdose potential in preventing the disease development, the aim of this work was to verify the effects of chronic treatment with microdose lithium given before and after the appearance of symptoms in a mouse model of a disease similar to AD. Transgenic mice (Cg-Tg(PDGFB-APPSwInd)20Lms/2J) and their non-transgenic litter mate genetic controls were treated with lithium carbonate (0.25mg/Kg/day in drinking water) for 16 or 8 months starting at two and ten months of age, respectively [corrected]. Similar groups were treated with water. At the end of treatments, both lithium treated transgenic groups and non-transgenic mice showed no memory disruption, different from what was observed in the water treated transgenic group. Transgenic mice treated with lithium since two months of age showed decreased number of senile plaques, no neuronal loss in cortex and hippocampus and increased BDNF density in cortex, when compared to non-treated transgenic mice. It is suitable to conclude that these data support the use of microdose lithium in the prevention and treatment of Alzheimer's disease, once the neurohistopathological characteristics of the disease were modified and the memory of transgenic animals was maintained. 

Retracted: No

PubPeer comments:
 2nd correction appears to be warranted. Figure 8 E G appear to have been duplicated. The caption indicates that the images should be from different mice. ![file] ![file] ,
LncRNA-XIST/microRNA-126 sponge mediates cell proliferation and glucose metabolism through the IRS1/PI3K/Akt pathway in glioma
Authors: Cong Luo
Zhilin Guo
Zhihua Cheng
Journal: Journal of cellular biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: XIST; glioma; glucose metabolism; glucose transporters 1; glucose transporters 3
Affiliations: Department of Neurosurgery, Shanghai Ninth People's HospitalShanghai Jiao Tong University, School of Medicine Shanghai China

Abstract:  Abnormal glucose metabolism may contribute to cancer progression. Glioma represents a cancer resulting from an imbalance between glucose metabolism and tumor growth. However, the molecular mechanisms responsible for dysregulated brain glucose metabolism and lactate accumulation in glioma remain to be elucidated. The present study identified a long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) as a candidate to mediate glucose metabolism in glioma. Cell viability, migration, invasion, and resistance to apoptosis were evaluated in lncRNA-XIST-depleted glioblastoma cells by short hairpin RNA. Glucose uptake, lactate production, as well as levels of glucose transporter 1 (GLUT1) and GLUT3, were measured. Luciferase assay, RNA pull-down, and RNA immunoprecipitation were performed to validate the interactions among lncRNA-XIST, microRNA-126 (miR-126), and insulin receptor substrate 1 (IRS1). An in vivo analysis was carried out in nude mice bearing glioblastoma cell xenografts. The study found that lncRNA-XIST knockdown inhibited cell viability, migration, invasion, resistance to apoptosis, and glucose metabolism of glioblastoma cells. LncRNA-XIST functioned as a competing endogenous RNA of miR-126 and then regulated IRS1/PI3K/Akt pathway in glioblastoma cells. In vivo results demonstrated lncRNA-XIST knockdown reduces the tumorigenicity of glioblastoma cells. Taken together, we demonstrated a novel cellular mechanism that was dependent of the lncRNA-XIST/miR-126/IRS1/PI3K/Akt pathway in enhanced glucose metabolism in glioma. 

Retracted: No

PubPeer comments:
 Figure 2C D. Some elements appear to be visible multiple times within or between panels. Could the authors please clarify what happened here? ![file] , 
 Figure 2E. The flow cytometry panels not only differ dramatically in terms of resolution, suggesting they might not have been performed at the same time or location, but three of the panels appear to share a quadrant worth of events (marked in blue). Could the authors please check what happened here? ![file] , 
 Figure 5BC. The left most and right most panels appear to be showing the same groups of cells, albeit in a different order. Could the authors please clarify what happened here? ![file] , 
 #2 visible change in resolution of datapoints but not of axis in the left half of FIG 2E ![file] , 
 similarities spotted by clone detection software ![file] ![file] ,
MiRNA-26b inhibits the proliferation, migration, and epithelial–mesenchymal transition of lens epithelial cells
Authors: Ning Dong
Bing Xu
Silvia R Benya
Xin Tang
Journal: Molecular and Cellular Biochemistry (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MicroRNAs; miR-26b; posterior capsule opacification; lens epithelial cells; proliferation
Affiliations: Department of Ophthalmology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.

Abstract:  MicroRNAs (miRNAs) are a class of small endogenous gene regulators that play important roles in various developmental and pathological processes. However, little is known about the precise identity and functions of miR-26b in posterior capsule opacification (PCO). In this study, we report that the expression of miR-26b is decreased in human PCO-attached lens epithelial cells (LECs) and SRA01/04 cells in the presence of TGF-β2. Overexpression of miR-26b inhibited the proliferation of LECs based on MTT assays and BrdU incorporation assays. In addition, the overexpression of miR-26b inhibited the migration ability of LECs, as shown by wound-healing and transwell migration assays. The overexpression of miR-26b increased the level of the lens epithelial marker E-cadherin and reduced the levels of mesenchymal-related proteins, such as fibronectin, a-SMA, and type I collagen, in SRA01/04 cells in the presence of TGF-β2. Furthermore, the upregulation of E-cadherin and downregulation of mesenchymal-related proteins were induced in human PCO-attached LECs transfected with miR-26b mimics. We further demonstrated that Smad4 and COX-2 are targets of miR-26b in LECs using luciferase reporter assays. These data reveal that miR-26b can inhibit the proliferation, migration, and EMT of lens epithelial cells, and restoration of miRNA-26b may be a potential, novel therapeutic target for the prevention and treatment of posterior capsule opacification. 

Retracted: No

PubPeer comments:
 Figure 3A. * Unexpected similarities between and within images. I have marked some (but not all) with rounded boxes of the same color. ![file] Figure 4A. * Unexpected similarities between Smad4 and Fibronectin panels, as marked with square boxes. ![file] Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. ,
Tat-functionalized liposomes for the treatment of meningitis: an in vitro study
Authors: Caterina Bartomeu Garcia
Di Shi
Thomas J Webster
Journal: International journal of nanomedicine (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MIC; bacteria colony-forming units; cell-penetrating peptides; cytotoxicity; fluorescence microscopy
Affiliations: Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain., Department of Chemical Engineering, Northeastern University, Boston, MA, USA.

Abstract:  Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47-57, which is a peptide derived from the Tat protein of HIV). The purpose of this in vitro study was to demonstrate for the first time the ability of the presently prepared fusogenic liposomes, which were spherical particles with a diameter of 100 nm loaded with antibiotics and functionalized with-cell penetrating peptides (Tat47-57), to fight the main bacteria that cause meningitis. For this, vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic liposomes to fight Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Antibacterial activity of Tat-functionalized and nonfunctionalized liposomes loaded with antibiotics was tested by determining bacteria colony-forming units and growth-curve assays coupled with live/dead assays using fluorescence microscopy. Results showed a remarkable decrease in antibiotic minimum inhibitory concentration when all of the bacteria were treated with these novel liposomes, especially for the functionalized liposomes loaded with methicillin. With antibiotic concentrations of 1.7-3 µg/mL for Tat-functionalized liposomes loaded with methicillin, the bacteria population was totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells, major cellular components of the blood-brain barrier, were also performed for all of the liposomes, including free antibiotic and the Tat peptide. Results showed much promise for the further study of the presently formulated liposomes to treat meningitis. 

Retracted: No

PubPeer comments:
 Figure 7 appears to have a repeated image. *** ![file] , 
 We are looking into this. , 
 The error in figure 7 was introduced during the revision stages of the manuscript. We are proceeding with the corrigendum. Please find attached the correct figure 7. ![file] , 
 #3 Thank you for addressing this. , 
 Bartomeu Garcia C, Shi D, Webster TJ. Int J Nanomedicine. 2017;12:3009u20133021 The authors have advised Figure 7 on page 3018 is incorrect. Due to an error at the time of figure assembly, the Free antibiotic (MRSA) and Tat liposomes (S. pneumoniae) images were duplicated. The correct Figure 7 is shown below. ![file] ,
Determinants of the interaction of the spinal muscular atrophy disease protein SMN with the dimethylarginine-modified box H/ACA small nucleolar ribonucleoprotein GAR1
Authors: Xing Zhang
Xiaodong Cheng
Kevin W Jones
Michael P Terns
Rebecca M Terns
Sarah E Whitehead
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: SMN1; survival of motor neurons; spinal muscular atrophy; small nuclear ribonucleoprotein; snRNP
Affiliations: Department of Biochemistry and Molecular Biology, University of Georgia, Athens 30602, USA.

Abstract:  Deletion or mutation of the SMN1 (survival of motor neurons) gene causes the common, fatal neuromuscular disease spinal muscular atrophy. The SMN protein is important in small nuclear ribonucleoprotein (snRNP) assembly and interacts with snRNP proteins via arginine/glycine-rich domains. Recently, SMN was also found to interact with core protein components of the two major families of small nucleolar RNPs, fibrillarin and GAR1, suggesting that SMN may also function in the assembly of small nucleolar RNPs. Here we present results that indicate that the interaction of SMN with GAR1 is mediated by the Tudor domain of SMN. Single point mutations within the Tudor domain, including a spinal muscular atrophy patient mutation, impair the interaction of SMN with GAR1. Furthermore, we find that either of the two arginine/glycine-rich domains of GAR1 can provide for interaction with SMN, but removal of both results in loss of the interaction. Finally, we have found that unlike the interaction of SMN with the Sm snRNP proteins, interaction with GAR1 and fibrillarin is not enhanced by arginine dimethylation. Our results argue against post-translational arginine dimethylation as a general requirement for SMN recognition of proteins bearing arginine/glycine-rich domains. 

Retracted: No

PubPeer comments:
 The immunoblot bands of actin were similar in different panels in Figure 2C. ![file] ,
Dietary compound isoliquiritigenin inhibits breast cancer neoangiogenesis via VEGF/VEGFR-2 signaling pathway
Authors: Hui Huang
Neng Wang
Linzhong Yu
Zhiyu Wang
Kamchuen Tsui
Jianping Chen
Suilin Mo
Dongmei Wang
Shouwei Han
Jiangang Shen
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Angiogenesis; Isoliquiritigenin; Anti-angiogenic activity; VEGF; HUVECs
Affiliations: School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.

Abstract:  Angiogenesis is crucial for cancer initiation, development and metastasis. Identifying natural botanicals targeting angiogenesis has been paid much attention for drug discovery in recent years, with the advantage of increased safety. Isoliquiritigenin (ISL) is a dietary chalcone-type flavonoid with various anti-cancer activities. However, little is known about the anti-angiogenic activity of isoliquiritigenin and its underlying mechanisms. Herein, we found that ISL significantly inhibited the VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs) at non-toxic concentration. A series of angiogenesis processes including tube formation, invasion and migration abilities of HUVECs were also interrupted by ISL in vitro. Furthermore, ISL suppressed sprout formation from VEGF-treated aortic rings in an ex-vivo model. Molecular mechanisms study demonstrated that ISL could significantly inhibit VEGF expression in breast cancer cells via promoting HIF-1α (Hypoxia inducible factor-1α) proteasome degradation and directly interacted with VEGFR-2 to block its kinase activity. In vivo studies further showed that ISL administration could inhibit breast cancer growth and neoangiogenesis accompanying with suppressed VEGF/VEGFR-2 signaling, elevated apoptosis ratio and little toxicity effects. Molecular docking simulation indicated that ISL could stably form hydrogen bonds and aromatic interactions within the ATP-binding region of VEGFR-2. Taken together, our study shed light on the potential application of ISL as a novel natural inhibitor for cancer angiogenesis via the VEGF/VEGFR-2 pathway. Future studies of ISL for chemoprevention or chemosensitization against breast cancer are thus warranted. 

Retracted: No

PubPeer comments:
 Figure 6D appears to have two images which overlap. *** ![file] *** Image and caption ![file] ,
The effects of microRNA-98 inhibits cell proliferation and invasion by targeting STAT3 in nasopharyngeal carcinoma
Authors: Hongliang Yu
Feijiang Wang
Juying Liu
Wei Chen
Jing Wen
Zhenzhang Chen
Xia He
Lirong Wu
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Invasion; MicroRNA-98; Migration; Proliferation; STAT3.
Affiliations: Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China., Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China. Electronic address: .

Abstract:  MicroRNA-98 (miR-98) is downregulated in many tumors, and is closely related to tumor progression. In addition, it shows anticarcinogenic functions in various tumor. However, few study show that the biological function and regulatory mechanisms of miR-98 in nasopharyngeal carcinoma (NPC) progression. The identification and its target genes which regulate by dysregulated miRNAs may strengthen our understanding of the molecular mechanisms of NPC. In this study, we observe that miR-98 is not only significantly reduced in NPC tissues, but also decreased markedly in NPC cell lines. Moreover, silencing miR-98 expression studies not only show miR-98 induced cell proliferation, migration and invasion in vitro, but also it promoted xenograft tumor growth in vivo in NPC. Furthermore, western blot assay was used to detected the level of STAT3 protein and we demonstrate that miR-98 regulate cells poliferation, migration and invasion through directly modulating functional target STAT3 by directly binding its 3'-UTR. These findings illustrate miR-98 as a anticarcinogenic functions through targeting STAT3, the miR-98/STAT3 pathway gives new clues for understanding NPC carcinogenesis and provides novel therapeutic targetsfor NPC. 

Retracted: No

PubPeer comments:
  Fig. 5. The effect of miR-98 on NPC cell apoptosis. (A, B) HONE-1 cells were transfected with the miR-98 inhibitor and control, respectively. Cell apoptosis was determined by flow cytometry analysis ![file] Very little difference between Lv-NC and Control results, except for slightly different quadrant percentages. ,
TAZ accelerates osteogenesis differentiation of mesenchymal stem cells via targeting PI3K/Akt
Authors: H-L Dai
F-Z Tan
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: TAZ; osteogenic differentiation; mesenchymal stem cells; osteoporosis; PI3K
Affiliations: Department of Orthopedics, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China. .

Abstract:  Objective: To investigate the promoting effects of TAZ on the osteogenic differentiation of mesenchymal stem cells in a rat model of osteoporosis through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal. Materials and methods: A total of 12 Sprague-Dawley (SD) rats were randomly divided into normal group (n=6) and model group (n=6). The rats in normal group were not given any treatment, while those in model group were used to establish a model of osteoporosis, and the bone mineral density (BMD) of the femur and lumbar in each group was detected. Then, the bone marrow mesenchymal stem cells were observed, of which those in normal group were divided into normal group and inhibitor group. The bone marrow mesenchymal stem cells in model group were enrolled as model group. Alkaline phosphatase (ALP) staining was adopted to observe the osteogenesis, cell counting kit-8 (CCK-8) was applied to determine the cell proliferation, and immunohistochemistry was performed to measure the expression of TAZ. Western blotting was utilized to detect the relative expressions of phosphorylated Akt (p-Akt) and bone morphogenetic protein 2 (BMP-2) proteins, and quantitative Polymerase Chain Reaction (qPCR) was used to measure the messenger ribonucleic acid (mRNA) expression of TAZ. Results: The average optical density of ALP-positive cells was decreased remarkably in model group and inhibitor group compared with that in normal group (p&lt;0.05), while the cell proliferation rate was increased notably in model group and inhibitor group. In comparison with normal group, model group and inhibitor group had evidently declined positive expression and mRNA expression of TAZ (p&lt;0.05). The relative expressions of p-Akt and BMP-2 proteins in model group and inhibitor group were significantly lower than those in normal group (p&lt;0.05). Conclusions: TAZ promotes the osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis by repressing the PI3K/Akt signal. 

Retracted: No

PubPeer comments:
 Let $X= {x_1, x_2}$ be the reference set and $$A={{2, 4}, { 1, 8} }$$ $$B={{2, 3}, { 1, 6} }$$ According to Definition 3.3 and Definition 3.4 $$Var(A)= 0qquad Var(B)= 0 $$ $$C(A, B)= 0$$ The correlation coefficient $rho_1(A, B)$ in Definition 3.5 cannot even be calculated. The results based on such notions are not sound. ![file] ![file] , 
 Dear Rhipidura Albiventris, For the similar questions, we have replied to you, please check following links: [https: pubpeer.com publications 173E65DEF0CB80237C6CE9AB027B7D]; [https: pubpeer.com publications D92BA21B2C74A902196F996C398F36]. Thank you for your interest. ,
KDM6B promotes ovarian cancer cell migration and invasion by induced transforming growth factor‐β1 expression
Authors: Feng Geng
Qin Wang
Qingmin Yao
Deying Wei
Shumei Liang
Ming Liu
Yun-Shan Wang
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EMT; KDM6B; TGF-β1; ovarian cancer.
Affiliations: Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China., Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China., Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, China., Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China.

Abstract:  KDM6B, also known as JMJD3, is a member of the family of histone lysine demethylase (KDMs), which is closely related to many types of cancers. However, its role and the underlying mechanisms in ovarian cancer remain unknown. Here we show that KDM6B is elevated in epithelial ovarian cancer and its expression level is closely related with metastasis and invasion. In addition, survival analysis showed that high expression of KDM6B was associated with low overall survival in ovarian cancer patients. Overexpression of KDM6B in epithelial ovarian cancer cells promoted proliferation, epithelial-mesenchymal transition (EMT), migration and invasion in vitro, and enhanced metastatic capacities in vivo. On the contrary, silencing KDM6B in invasive and metastatic ovarian cancer cells inhibited these processes. Mechanistically, we found that KDM6B exerts its function by modulating the transforming growth factor-β1 (TGF-β1) expression, and TGF-β1 signal pathway inhibitor LY2157299 significantly inhibited KDM6B-induced proliferation, migration, metastasis, and EMT in ovarian cancer cells. Our findings, for the first time, reveal the pivotal role of KDM6B in the invasion and metastatic behavior of epithelial ovarian cancer. Thus, targeting KDM6B may be a useful strategy to interfere with these behaviors of epithelial ovarian cancer. 

Retracted: No

PubPeer comments:
 Fig 7D. Results of DMSO and LY2157299 treatment are more similar than I would have expected. ![file] , 
 Retracted [5 May 2022] . -------------------------- The above article, published online on 11 September 2018 in Wiley Online Library (doi:10.1002 jcb.27405), has been retracted by agreement between the authors, the journal s Editor-in-Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed after the authors asked for a correction. An investigation revealed duplication and inappropriate manipulation in figure 7D. As a result, the experiments in this article are considered unreliable and to not sufficiently support the conclusions. ,
<p>Novel Nanocomplexes Targeting STAT3 Demonstrate Promising Anti-Ovarian Cancer Effects in vivo</p>
Authors: Yanhui Ma
Xiaolei Zhang
Yingxin Pang
Tao Lu
Peishu Liu
Hongluan Mao
Rui Li
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: SLN; STAT3; decoy ODN; in vivo; ovarian cancer.
Affiliations: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, People's Republic of China.

Abstract:  Background: Cationic solid lipid nanoparticles (SLN) have attracted intensive interest as an effective gene delivery system for its high biocompatibility, stability and low cytotoxicity. In our previous study, we successfully prepared SLN-STAT3 decoy ODN complexes and made a primary study on its antitumor behavior in ovarian cancer cells in vitro. However, there is little information available so far about the effect of SLN-STAT3 decoy ODN complexes on ovarian cancer in vivo, either little information about the pharmacological toxicology in vivo. Material and methods: We applied nanotechnology to improve the gene delivery system and synthesize SLN-STAT3 decoy ODN complexes. Xenograft mouse models were established to assess the antitumor effects of SLN-STAT3 decoy ODN on the tumor growth of ovarian cancer in vivo. To analyze the mechanisms of SLN-STAT3 decoy ODN, we investigated apoptosis, autophagy, epithelial-mesenchymal transition (EMT) in tumor tissues of nude mice and investigated the effects and toxicology of SLN-STAT3 decoy ODN complexes on the vital organs of nude mice. Results: The results showed that SLN-STAT3 decoy ODN complexes markedly inhibited tumor growth in vivo. SLN-STAT3 decoy ODN complexes could induce cell apoptosis through downregulating Bcl-2, survivin and pro caspase 3, but upregulating Bax and cleaved caspase 3. These complexes could also regulate autophagy through upregulating LC3A-II, LC3B-II and beclin-1, but downregulating p-Akt and p-mTOR. Moreover, these complexes could inhibit cancer cell invasion through reversing EMT. Besides, SLN-STAT3 decoy ODN complexes showed no obvious toxicity on vital organs and hematological parameters of nude mice. Conclusion: The molecular mechanisms that SLN-STAT3 decoy ODN complexes inhibit tumor growth involved activating the apoptotic cascade, regulating autophagy, and reversing EMT program; and these complexes showed no obvious toxicity on nude mice. Our study indicated that the nanocomplexes SLN-STAT3 decoy ODN might be a promising therapeutic approach for ovarian cancer treatment. 

Retracted: No

PubPeer comments:
 Figure 5A: * Blue boxes: Two panels appear to show an overlap. ![file] ,
Oxidative stress induces B lymphocyte DNA damage and apoptosis by upregulating p66shc
Authors: K Ma
J-X Guo
H Sun
J-Y Lang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: B lymphoma; oxidative stress; p66shc; DNA damage; cell apoptosis
Affiliations: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. .

Abstract:  Objective: B lymphoma is a type of malignant tumor originating from the lymphatic hematopoietic system. The pathogenesis and treatment methods are not clear. The change of oxidative stress is closely related to the cell DNA damage and cell apoptosis, which may be served as a target for cancer treatment. This study aims to illustrate the role of oxidative stress in the regulation of B lymphocytoma. Patients and methods: The tumor tissue was collected from patients with B lymphocytoma. The p66shc level was detected by Western blot. Hydrogen peroxide (H2O2) was assessed by the kit. The oxidative stress model of B lymphoma cell was established by H2O2 treatment. ROS inhibitor or RNAi was used to regulate ROS level. ROS level was determined by flow cytometry. 8-OHdG level (DNA damage product) was tested by the kit. Cell apoptosis was evaluated by annexin V-PI. Results: P66shc expression was significantly reduced, while H2O2 production was significantly decreased in the tumor tissue of B lymphoma compared with adjacent normal control. H2O2 stimulation markedly elevated ROS level and p66shc expression (p &lt; 0.05), accompanied by the aggravation of DNA damage and increase of apoptosis. ROS inhibitor or p66shc RNAi treatment significantly attenuated DNA damage and declined cell apoptosis (p &lt; 0.05). Conclusions: ROS production promoted p66shc expression, induced DNA damage, and facilitated cell apoptosis. Upregulation of p66shc by oxidative stress could be treated as a new therapeutic target for B lymphoma. 

Retracted: No

PubPeer comments:
 Concern about the flow cytometry panels in Figures 3, 4, 5, and 6. The same constellations of dots appear to be visible multiple times within and between panels. Boxes of the same color highlight areas that look similar to each other. ![file] ,
A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins
Authors: Hong Chen
Simona Polo
Mario Faretta
Giovanna Bossi
Sara Sigismund
Pietro De Camilli
Maria Rosaria Capua
Pier Paolo Di Fiore
Monica Guidi
Journal: Nature (2002)
Discipline: Multidisciplinary
Keywords: Ubiquitination; post-translation modification; polyubiquitination; monoubiquitination; membrane trafficking
Affiliations: Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.

Abstract:  Ubiquitination is a post-translation modification in which ubiquitin chains or single ubiquitin molecules are appended to target proteins, giving rise to poly- or monoubiquitination, respectively. Polyubiquitination targets proteins for destruction by the proteasome. The role of monoubiquitination is less understood, although a function in membrane trafficking is emerging, at least in yeast. Here we report that a short amino-acid stretch at the carboxy-termini of the monoubiquitinated endocytic proteins Eps15 and eps15R is indispensable for their monoubiquitination. A similar sequence, also required for this modification, is found in other cytosolic endocytic proteins, such as epsins and Hrs. These sequences comprise a protein motif, UIM (ref. 6), which has been proposed to bind to ubiquitin. We confirm this for the UIMs of eps15, eps15R, epsins and Hrs. Thus, the same motif in several endocytic proteins is responsible for ubiquitin recognition and monoubiquitination. Our results predict the existence of a UIM:ubiquitin-based intracellular network. Eps15/eps15R, epsins and Hrs may function as adaptors between ubiquitinated membrane cargo and either the clathrin coat or other endocytic scaffolds. In addition, through their own ubiquitination, they may further contribute to the amplification of this network in the endocytic pathway. 

Retracted: No

PubPeer comments:
 Figure 2b. More similar than you would expect. ![file] , 
 Figure 2b. A bit more. ![file] , 
 The published erratum does not mention figure 2b. , 
 #2 Figure 2b, yet a bit more (I added two pink boxes). And I notified more authors. Could these authors please comment? ![file] ,
Automatic diagnosis of the 12-lead ECG using a deep neural network
Authors: Jéssica A Canazart
Antônio H Ribeiro
Thomas B Schön
Peter W Macfarlane
Paulo R Gomes
Manoel Horta Ribeiro
Gabriela M M Paixão
Wagner Meira Jr
Antonio Luiz P Ribeiro
Carl R Andersson
Milton P S Ferreira
Derick M Oliveira
Journal: Nature Communications (2020)
Discipline: Multidisciplinary
Keywords: automatic electrocardiogram analysis; Deep Neural Networks; clinical practice; Telehealth Network of Minas Gerais; CODE study
Affiliations: Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. ., Uppsala University, Uppsala, Sweden. ., Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Telehealth Center from Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Uppsala University, Uppsala, Sweden., University of Glasgow, Glasgow, Scotland., Telehealth Center from Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. .

Abstract:  The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. Deep Neural Networks (DNNs) are models composed of stacked transformations that learn tasks by examples. This technology has recently achieved striking success in a variety of task and there are great expectations on how it might improve clinical practice. Here we present a DNN model trained in a dataset with more than 2 million labeled exams analyzed by the Telehealth Network of Minas Gerais and collected under the scope of the CODE (Clinical Outcomes in Digital Electrocardiology) study. The DNN outperform cardiology resident medical doctors in recognizing 6 types of abnormalities in 12-lead ECG recordings, with F1 scores above 80% and specificity over 99%. These results indicate ECG analysis based on DNNs, previously studied in a single-lead setup, generalizes well to 12-lead exams, taking the technology closer to the standard clinical practice. 

Retracted: No

PubPeer comments:
 Figure 1. Bands have straight, sharp edges. https: imgur.com ncFz12D , 
 Figure 2B. Much more similar than expected. https: imgur.com JAj78jP , 
 Figure 5B. Much more similar than expected. https: imgur.com wZhTgqv , 
 Figure 4A. Vertical and horizontal sharp changes in signal. Figure 4B. Lysate panel. No background. https: imgur.com JtL8G3Z , 
 #2 Figure 2B continued. Much more similar than expected. https: imgur.com CUEOSqx , 
 Figure 2B. Sharp, straight horizontal edges to bands. https: imgur.com 7YtlFam , 
 Figure 1. Much more similar than expected after vertical compression. https: imgur.com vF8v4NF , 
 Figure 1D this paper. Much more similar than expected after vertical re-sizing. https: imgur.com BVywkLb , 
 #8 Figure 1. Continuation and refinement. Much more similar than expected. https: imgur.com Cs6Zk42 , 
 Fresh analysis 3 papers. Much more similar than expected. https: imgur.com upgNKVf , 
 #10 Continuation analysis 3 papers. Green rectangles in Mol Cell Biol. 2005 Jun:25(11):4742-51 are new. https: imgur.com UQnU6DI ,
Hypothalamic neural projections are permanently disrupted in diet-induced obese rats
Authors: Richard B Simerly
Judith N Gorski
Stephen Chen
Christa M Patterson
Barry E Levin
Sebastien G Bouret
Journal: Cell Metabolism (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: arcuate nucleus; hypothalamus; energy balance; leptin; diet-induced obesity
Affiliations: Neuroscience Program, The Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.  <>

Abstract:  The arcuate nucleus of the hypothalamus (ARH) is a key component of hypothalamic pathways regulating energy balance, and leptin is required for normal development of ARH projections. Diet-induced obesity (DIO) has a polygenic mode of inheritance, and DIO individuals develop the metabolic syndrome when a moderate amount of fat is added to the diet. Here we demonstrate that rats selectively bred to develop DIO, which are known to be leptin resistant before they become obese, have defective ARH projections that persist into adulthood. Furthermore, the ability of leptin to activate intracellular signaling in ARH neurons in vivo and to promote ARH neurite outgrowth in vitro is significantly reduced in DIO neonates. Thus, animals that are genetically predisposed toward obesity display an abnormal organization of hypothalamic pathways involved in energy homeostasis that may be the result of diminished responsiveness of ARH neurons to the trophic actions of leptin during postnatal development. 

Retracted: No

PubPeer comments:
 In Figure 4B and C, the  equalize function in Photoshop reveals anomalies consistent with the erasing of pixels in the background: ![file] , 
 In Fig. 4A, several duplicated areas are visible in the DIO image: ![file] , 
 you missed a few smaller areas seemingly overlapping: ![file] ,
Antisense oligonucleotides as a potential treatment for brain deficits observed in myotonic dystrophy type 1
Authors: C Frank Bennett
Siham Ait Benichou
Thiéry De Serres-Bérard
Genevieve Gourdon
Jack Puymirat
Karen K Ling
Dominic Jauvin
Frank Rigo
Marion Pierre
Mohamed Chahine
Journal: Gene Therapy (2022)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Myotonic dystrophy; DM1; brain deficits; antisense oligonucleotide; ASO
Affiliations: LOEX, CHU de Québec-Université Laval Research Center, Quebec City, QC, Canada., CERVO Research Center, Institut universitaire en santé mentale de Québec, Quebec City, QC, Canada., Ionis Pharmaceuticals Inc., Carlsbad, CA, USA., Sorbonne Université, Inserm, Association Institut de Myologie, Centre de recherche en Myologie, Paris, France., CERVO Research Center, Institut universitaire en santé mentale de Québec, Quebec City, QC, Canada. .

Abstract:  Myotonic dystrophy, or dystrophia myotonica type 1 (DM1), is a multi-systemic disorder and is the most common adult form of muscular dystrophy. It affects not only muscles but also many organs, including the brain. Cerebral impairments include cognitive deficits, daytime sleepiness, and loss of visuospatial and memory functions. The expression of mutated transcripts with CUG repeats results in a gain of toxic mRNA function. The antisense oligonucleotide (ASO) strategy to treat DM1 brain deficits is limited by the fact that ASOs do not cross the blood-brain barrier after systemic administration, indicating that other methods of delivery should be considered. ASO technology has emerged as a powerful tool for developing potential new therapies for a wide variety of human diseases, and its potential has been proven in a recent clinical trial. Targeting DMPK mRNA in neural cells derived from human induced pluripotent stem cells obtained from a DM1 patient with the IONIS 486178 ASO abolished CUG-expanded foci, enabled nuclear redistribution of MBNL1/2, and corrected aberrant splicing. Intracerebroventricular injection of the IONIS 486178 ASO in DMSXL mice decreased the levels of mutant DMPK mRNAs by up to 70% throughout different brain regions. It also reversed behavioral abnormalities following neonatal administration. The present study indicated that the IONIS 486178 ASO targets mutant DMPK mRNAs in the brain and strongly supports the feasibility of a therapy for DM1 patients based on the intrathecal injection of an ASO. 

Retracted: No

PubPeer comments:
 ![file] Duplication and altered coloring in Figure 5, top right and bottom left panels are almost completely overlapping. ,
PKCδ-dependent signaling mediates ethambutol-induced toxic effects on human retinal pigment cells
Authors: Rong Kung Tsai
Zih-Yao Chen
Wen Chen Wu
Wen Sheng Wu
Ming Shan He
Journal: Molecular vision (2011)
Discipline: CLINICAL MEDICINE
Keywords: ethambutol; cytoplasmic vacuolization; photoreceptor rod outer segments; retinal pigment epithelium; protein kinase C
Affiliations: Department of Ophthalmology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.

Abstract:  Purpose: Our previous report demonstrated that ethambutol (EMB) might induce cytoplasmic vacuolization and reduce the uptake of photoreceptor rod outer segments (ROS) in retinal pigment epithelium (RPE) cells, which are mediated via a protein kinase C (PKC)-dependent pathway. In the present study, we sought to identify the PKC isozyme(s) involved. Methods: EMB-induced cytoplasmic vacuolization and uptake of ROS were observed under a phase contrast microscope. Western blots were performed to observe the membrane translocation of PKC isozymes and cytoplasmic release of cathepsin D. Quantitative PCR were performed to analyze gene expression of PKCδ. Human RPE cell line RPE50 and ARPE19 cells were pretreated with specific inhibitors or transfected with shRNAs of various PKC isozymes, including PKCα, β, ε, γ, and δ, to examine whether EMB-induced toxic effects were prevented. Results: In RPE50 cells, gene expression of PKCδ on both mRNA and protein levels was induced by EMB within 30 min to 3 h. EMB-induced cytoplasmic vacuolization in both RPE50 and ARPE19 cells was prevented by pretreating the cells with a specific inhibitor of PKCδ, Rottlerin, or depletion of PKCδ by shRNA. EMB-triggered reduction of ROS uptake was also significantly suppressed by pretreatment with Rottlerin, or depletion of PKCδ by shRNA technology. In contrast, pretreatment of the cells with specific inhibitors of PKCα, β, ε, or γ, or depletion of PKCα or β didn't influence the aforementioned EMB-triggered toxic effects. In addition, in RPE50, EMB induced the release of lysosomal enzyme cathepsin D into cytosol within 30 min to 6 h, which was also prevented by Rottlerin. Conclusions: EMB-induced vacuole formation, cytoplasmic release of cathepsin D, and reduction of phagocytosis in RPE are intimately correlated and regulated by the PKCδ signal pathway. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 Figures 1 and 5 appear to have more extensive issues. *** ![file] ,
Test-retest reliability, validity, and minimum detectable change of visual analog, numerical rating, and verbal rating scales for measurement of osteoarthritic knee pain
Authors: Ahmad H Alghadir
Amir Iqbal
Zaheen Ahmed Iqbal
Shahnawaz Anwer
Journal: Journal of Pain Research (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: knee; numerical rating scale; osteoarthritis; pain; verbal rating scale
Affiliations: Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

Abstract:  Objective: Several scales are commonly used for assessing pain intensity. Among them, the numerical rating scale (NRS), visual analog scale (VAS), and verbal rating scale (VRS) are often used in clinical practice. However, no study has performed psychometric analyses of their reliability and validity in the measurement of osteoarthritic (OA) pain. Therefore, the present study examined the test-retest reliability, validity, and minimum detectable change (MDC) of the VAS, NRS, and VRS for the measurement of OA knee pain. In addition, the correlations of VAS, NRS, and VRS with demographic variables were evaluated. Methods: The study included 121 subjects (65 women, 56 men; aged 40-80 years) with OA of the knee. Test-retest reliability of the VAS, NRS, and VRS was assessed during two consecutive visits in a 24 h interval. The validity was tested using Pearson's correlation coefficients between the baseline scores of VAS, NRS, and VRS and the demographic variables (age, body mass index [BMI], sex, and OA grade). The standard error of measurement (SEM) and the MDC were calculated to assess statistically meaningful changes. Results: The intraclass correlation coefficients of the VAS, NRS, and VRS were 0.97, 0.95, and 0.93, respectively. VAS, NRS, and VRS were significantly related to demographic variables (age, BMI, sex, and OA grade). The SEM of VAS, NRS, and VRS was 0.03, 0.48, and 0.21, respectively. The MDC of VAS, NRS, and VRS was 0.08, 1.33, and 0.58, respectively. Conclusion: All the three scales had excellent test-retest reliability. However, the VAS was the most reliable, with the smallest errors in the measurement of OA knee pain. 

Retracted: No

PubPeer comments:
 Could the authors please comment on the reason for choosing the intraclass correlation coefficient ($ICC_{2,1}$ after Shrout Fleiss 1979) to determine the test-retest reliability of self-rating data? It would also be greatly appreciated if the authors would share the raw data. References: Shrout, P. E. Fleiss, J. L. Intraclass correlations: uses in assessing rater reliability. *Psychol Bull.*, 1979, *86*, 420-428 ,
Effect of the Interaction of Veratrum Nigrum with Panax Ginseng on Estrogenic Activity In Vivo and In Vitro
Authors: Jie Ding
Ying Xu
Guo-Jing Dai
Xin Li
Jin-Na An
Na Lin
Xiao-Ping Ma
Yi-Min Zhang
Ya-Kun Qu
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Panax ginseng; Veratrum nigrum; estrogenic activity; interaction; in vivo
Affiliations: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District Dongzhimen Nanxiao Road 16, Beijing 100700, China., Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Pudong District cailu Road 1200, Shanghai 100101, China.

Abstract:  Panax ginseng (GS) and Veratrum nigrum (VN) are representative of incompatible pairs in "eighteen antagonistic medicaments" that have been recorded in the Chinese medicinal literature for over 2,000 years. However, evidence linking interference effects with combination use is scare. Based on the estrogen-like effect of GS described in our previous studies, we undertake a characterization of the interaction on estrogenic activity of GS and VN using in vivo models of immature and ovariectomized (OVX) mice and in vitro studies with MCF-7 cells for further mechanism. VN decreased the estrogenic efficacy of GS on promoting the development of the uterus and vagina in immature mice, and reversing the atrophy of reproductive tissues in OVX mice. VN interfered with the estrogenic efficacy of GS by decreasing the increase of the serum estradiol and the up-regulation of ERα and ERβ expressions by treatment with GS. And VN antagonized the estrogenic efficacy of GS on promoting the viability of MCF-7 cells and up-regulation of protein and gene expressions of ERs. In conclusion, this study provided evidence that GS and VN decreased effects on estrogenic activity, which might be related to regulation of estrogen secretion and ERs. 

Retracted: No

PubPeer comments:
 This paper has a corrigendum for an incorrect reference #5. In addition, Figure S3 appears to show some panels with repetitive elements. Boxes of the same color highlight areas that look more similar than expected. ![file] ,
Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein
Authors: Michelle Zhang
MacRae F Linton
Sergio Fazio
Yvonne Hui
Daping Fan
Fen Du
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PCSK9; LDL receptor; structure-function relation; mutagenesis; transfection
Affiliations: Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.

Abstract:  PCSK9 (proprotein convertase subtilisin/kexin type 9) has emerged as a novel therapeutic target for hypercholesterolemia due to its LDL receptor (LDLR)-reducing activity. Although its structure has been solved, the lack of a detailed understanding of the structure-function relation hinders efforts to develop small molecule inhibitors. In this study, we used mutagenesis and transfection approaches to investigate the roles of the prodomain (PD) and the C-terminal domain (CD) and its modules (CM1-3) in the secretion and function of PCSK9. Deletion of PD residues 31-40, 41-50, or 51-60 did not affect the self-cleavage, secretion, or LDLR-degrading activity of PCSK9, whereas deletion of residues 61-70 abolished all of these functions. Deletion of the entire CD protein did not impair PCSK9 self-cleavage or secretion but completely abolished LDLR-degrading activity. Deletion of any one or two of the CD modules did not affect self-cleavage but influenced secretion and LDLR-reducing activity. Furthermore, in cotransfection experiments, a secretion-defective PD deletion mutant (ΔPD) was efficiently secreted in the presence of CD deletion mutants. This was due to the transfer of PD from the cotransfected CD mutants to the ΔPD mutant. Finally, we found that a discrete CD protein fragment competed with full-length PCSK9 for binding to LDLR in vitro and attenuated PCSK9-mediated hypercholesterolemia in mice. These results show a previously unrecognized domain interaction as a critical determinant in PCSK9 secretion and function. This knowledge should fuel efforts to develop novel approaches to PCSK9 inhibition. 

Retracted: No

PubPeer comments:
 ![file] , 
 When we ran the first blot for cellular PCSK9, we found out that the WT PCSK9 8 23 transfection did not work, while the 9 13 WT transfection was good. Then we ran another blot putting WT 9 13 sample as the first sample in PCSK9 transfection samples, we used this new blot for b-actin and LDLR blotting. Therefore when prepared the slide, for the cell PCSK9 blot image, we  moved the 9 13 WT sample to the position to be consistent with the sample order in the b-actin and cell LDLR blots. Please see attached original blot image for reference. We were not aware that in 2011, we were required to declare the splice in figure legend.![file] ,