PReD-Bench/PRed-Bench huggingface dataset:
Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity
Authors: Martin E Young
E Dale Abel
Brian T O&#x27;Neill
Prakash Tathireddy
Sandra Sena
Sihem Boudina
Journal: Circulation (2005)
Discipline: CLINICAL MEDICINE
Keywords: Obesity; Cardiovascular disease; Insulin resistance; Type 2 diabetes; Myocardial oxygen consumption
Affiliations: Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, Utah, USA., From the Division of Endocrinology, Metabolism and Diabetes and Program in Human Molecular Biology and Genetics (S.B., S.S., B.T.O., P.T., E.D.A.), University of Utah School of Medicine, Salt Lake City, Utah, and USDA/ARS Children’s Nutrition Research Center and Department of Pediatrics (M.E.Y.), Baylor College of Medicine, Houston, Tex.

Abstract:  Background: Obesity is a risk factor for cardiovascular disease and is strongly associated with insulin resistance and type 2 diabetes. Recent studies in obese humans and animals demonstrated increased myocardial oxygen consumption (MVO2) and reduced cardiac efficiency (CE); however, the underlying mechanisms remain unclear. The present study was performed to determine whether mitochondrial dysfunction and uncoupling are responsible for reduced cardiac performance and efficiency in ob/ob mice. Methods and results: Cardiac function, MVO2, mitochondrial respiration, and ATP synthesis were measured in 9-week-old ob/ob and control mouse hearts. Contractile function and MVO2 in glucose-perfused ob/ob hearts were similar to controls under basal conditions but were reduced under high workload. Perfusion of ob/ob hearts with glucose and palmitate increased MVO2 and reduced CE by 23% under basal conditions, and CE remained impaired at high workload. In glucose-perfused ob/ob hearts, mitochondrial state 3 respirations were reduced but ATP/O ratios were unchanged. In contrast, state 3 respiration rates were similar in ob/ob and control mitochondria from hearts perfused with palmitate and glucose, but ATP synthesis rates and ATP/O ratios were significantly reduced in ob/ob, which suggests increased mitochondrial uncoupling. Pyruvate dehydrogenase activity and protein levels of complexes I, III, and V were reduced in obese mice. Conclusions: These data indicate that reduced mitochondrial oxidative capacity may contribute to cardiac dysfunction in ob/ob mice. Moreover, fatty acid but not glucose-induced mitochondrial uncoupling reduces CE in obese mice by limiting ATP production and increasing MVO2. 

Retracted: No

PubPeer comments:
 ![file] , 
 Complex II blot reused in 2 publications. Appears identical in both. One claims data was obtained in db db mice. The other says it is from ob ob mice. .![file] , 
 https: pubpeer.com publications FF251D3F1D4F3A00EE96CB05230658 , 
 https: pubmed.ncbi.nlm.nih.gov 16246967 Erratum Correction to Circulation Manuscript in PubMed. Issue resolved ,
Inhibited corneal neovascularization in rabbits following corneal alkali burn by double-target interference for VEGF and HIF-1α
Authors: Zhi-Ming Xin
Ying-Cong Fu
Journal: Bioscience Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Alkali burn; Cornea neovascularization; Gene silencing; HIF-1α; Rabbit model
Affiliations: Department of Burns and Plastic Surgery, Shengli Oilfield Central Hospital, Dongying 257034, P.R. China ., Department of Burns and Plastic Surgery, Shengli Oilfield Central Hospital, Dongying 257034, P.R. China.

Abstract:  Expression of hypoxia-inducible factor (HIF) 1α has been observed in corneal neovascularization (CNV). Vascular endothelial growth factor (VEGF), one of the most well-known angiogenic factors in CNV, is under the regulation of HIF-1. The present study aims to investigate the synergistic effects of VEGF and HIF-1α gene silencing on alkali burn-induced CNV in rabbits. The models of rabbits in corneal alkali burn were established. SiRNA recombinant adenovirus was used to explore the synergistic effects of VEGF and HIF-1α gene silencing on alkali burn-induced CNV. CNV area and ultrastructure of cornea were observed. The expression of VEGF and HIF-1α was detected. CNV was observed in rabbits following alkali burn. In addition, overexpressed VEGF and HIF-1α was also observed in rabbits following alkali burn. Then, silencing HIF-1α or silencing VEGF decreased area of CNV, inhibited neovascularization and improved pathological changes, while double-target interference for VEGF and HIF-1α decreased area of CNV inhibited neovascularization, and improved pathological changes to a greater extent. Our study provides evidences emphasizing the distinct notion that VEGF and HIF-1α play the contributory role in alkali burn-induced CNV as a result of double-target interference for VEGF and HIF-1α inhibiting CNV in rabbits following corneal alkali burn. 

Retracted: No

PubPeer comments:
 According to the new Scholar Google tool, this article should be on public access based on the funding mandates (NIH, grant number: Swiss National Foundation). Could authors check this issue, please? ![file] ,
miR-30a-5p modulates traits of cutaneous squamous cell carcinoma (cSCC) via forkhead box protein G1 (FOXG1)
Authors: S Zhong
J Shao
J Liang
Journal: Neoplasma (2019)
Discipline: CLINICAL MEDICINE
Keywords: miRNA; squamous cell carcinoma; SCC; miR-30a-5p; cutaneous SCC
Affiliations: Department of Dermatology, Yantai Yuhuangding Hospital, Yantai, China., Department of Dermatology, Yantai Yeda Hospital, Yantai, China.

Abstract:  miRNA has shown its potential in the regulation of squamous cell carcinoma (SCC). However, the mechanism of such an effect was not quite clear. Therefore, we aimed to investigate whether miR-30a-5p participated in the regulation of cutaneous SCC (cSCC) and the possible mechanism involved. 5-Ethynyl-2'-deoxyuridine (EdU) and cell cycle were measured using flow cytometry. The formation of cell colony was tested by colony formation assay. The capacities of migration and invasion were tested by wound healing assay and Transwell invasion assay, respectively. The target of miR-30a-5p was predicted by bioinformatics and identified by luciferase assay. Western blot was used for the determination of proteins and qPCR was for mRNA levels. miR-30a-5p expression was lowered in SCL-1 and A431 cells, and its upregulation suppressed EdU positive cells, colony numbers, migration, invasion and Bcl-2 expression, and elevated Bcl-2-associated X protein (Bax) and cleaved Caspase-3 expressions, arresting cell cycle in G1 phase. Moreover, forkhead box protein G1 (FOXG1) was proved to be the target of miR-30a-5p, and FOXG1 overexpression partially offsets the decreased colony numbers, migration and invasion rates due to miR-30a-5p overexpression in SCL-1 and A431 cells. miR-30a-5p showed a regulatory role on the expression of FOXG1 and further modulated the progressing of cSCC cells, which could be a novel pathway intervening the development of cSCC. 

Retracted: No

PubPeer comments:
 Figures 2F and 4D: * Yellow boxes: Two panels appear to show an overlap. ![file] ,
microRNA-34a inhibits epithelial mesenchymal transition in human cholangiocarcinoma by targeting Smad4 through transforming growth factor-beta/Smad pathway
Authors: Lianmeng Yang
Pengfei Qiao
Wen Bi
Dequan Wu
Lei Yao
Guodong Li
Journal: BMC Cancer (2015)
Discipline: CLINICAL MEDICINE
Keywords: Extrahepatic Cholangiocarcinoma; miR-34a; Smad4; invasion; migration
Affiliations: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Peoples Republic of China. ., Department of General Surgery, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, Peoples Republic of China. ., Bio-Bank of Department of General Surgery, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, Peoples Republic of China. .

Abstract:  Background: Extrahepatic Cholangiocarcinoma (EHCC) is one of the uncommon malignancies in the digestive system which is characterized by a poor prognosis. Aberrations of miRNAs have been shown involved in the progression of this disease. In this study, we evaluated the expression and effects of miR-34a on EHCC. Methods: miR-34a expression levels were detected in EHCC tissues, adjacent non-tumor tissues, normal bile duct (NBD) specimens of patients and cholangiocarcinoma (CC) cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Relationships between miR-34a with clinical characteristics of EHCC patients were further analyzed. Computational search, functional luciferase assay and western blot were further used to demonstrate the downstream target of miR-34a in CC cells. Immunohistochemistry was carried on to identify the downstream target gene of miR-34a in EHCC patients. Cell morphology, invasion and migration assays were further applied to confirm the anti-carcinogenic effects of miR-34a through the downstream target. Results: miR-34a expression was significantly decreased in human EHCC tissues and CC cell lines when compared with the adjacent non-tumor tissues and normal bile duct tissues. miR-34a was found correlated with the migration and invasion in EHCC patients. Smad4 was over-expressed in most of the EHCC patients and was further demonstrated as one of the downstream targets of miR-34a, which was involved in the progression of EHCC. Moreover, activation of miR-34a suppressed invasion and migration through TGF-beta/Smad4 signaling pathway by epithelial-mesenchymal transition (EMT) in vitro. Conclusions: Taken together, our results suggest that miR-34a inhibits invasion and migration by targeting Smad4 to suppress EMT through TGF- beta/Smad signaling pathway in human EHCC. 

Retracted: No

PubPeer comments:
 Figure 5. Some panels representing different treatments appear to overlap with each other. ![file] ,
Thyroid hormone receptor alpha1 directly controls transcription of the beta-catenin gene in intestinal epithelial cells
Authors: Jacques Samarut
Elsa Kress
Michelina Plateroti
Jun Ichirou Mori
Journal: Molecular and Cellular Biology (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Thyroid hormones; T3; T4; intestine development; TRs
Affiliations: IFR 128, Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR 5161, INRA UMR 1237, Ecole Normale Supérieure de Lyon, 46 Allee d'Italie, Lyon 69364, France. , IFR 128, Laboratoire de Biologie Moléculaire de la Cellule, Biosciences,CNRS UMR 5161, INRA UMR 1237, Ecole Normale Supérieure de Lyon, Lyon, France, Université Claude Bernard Lyon 1, Lyon, France

Abstract:  Thyroid hormones, T3 and T4, are known regulators of intestine development. The best characterized example is the remodeling of the gastrointestinal tract during amphibian metamorphosis. Thyroid hormones act via nuclear receptors, the TRs, which are T3-dependent transcription factors. We previously showed that intestinal epithelial cell proliferation is controlled by thyroid hormones and the TRalpha gene. To analyze the mechanisms responsible, we studied the expression of genes belonging to and/or activated by the Wnt/beta-catenin pathway, a major actor in the control of physiological and pathological epithelial proliferation in the intestine. We show that T3-TRalpha1 controls the transcription of the beta-catenin gene in an epithelial cell-autonomous way. This is parallel to positive regulation of proliferation-controlling genes such as type D cyclins and c-myc, known targets of the Wnt/beta-catenin. In addition, we show that the regulation of the beta-catenin gene is direct, as TR binds in vitro and in chromatin in vivo to a specific thyroid hormone-responsive element present in intron 1 of this gene. This is the first report concerning in vivo transcriptional control of the beta-catenin gene. As Wnt/beta-catenin plays a crucial role in intestinal tumorigenesis, our observations open a new perspective on the study of TRs as potential tumor inducers. 

Retracted: No

PubPeer comments:
 ![file] , 
 In Figure 6B, two lanes are identical. ![file] , 
 Figure 1B. Much more similar than expected. ![file] , 
 #1 I agree. Other than a slight difference in brightness, these appear identical. Difficult to understand how this different cropping could occur by chance. *** ![file] ,
Circular RNA circ_0000950 promotes neuron apoptosis, suppresses neurite outgrowth and elevates inflammatory cytokines levels via directly sponging miR-103 in Alzheimer’s disease
Authors: Shiqi Yang
Hui Yang
Xiufen Chen
Hong Shang
Huan Wang
Jing Ding
Xuling Li
Yang Qu
Journal: Cell Cycle (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Alzheimer’s disease; Circ_0000950; apoptosis.
Affiliations: Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University , Harbin , China.

Abstract:  This study aimed to investigate the effect of circ_0000950/miR-103 network on regulating neuron apoptosis, neurite outgrowth and inflammation in Alzheimer's disease (AD). Cellular AD model of rat pheochromocytoma cell line PC12 cells and cellular AD model of rat cerebral cortex neurons were constructed, and the effect of circ_0000950 on apoptosis, neurite outgrowth and inflammation in both cellular AD models was determined through upregulation and knockdown of circ_0000950 expression by transfection. Compensation experiments and luciferase assay were further performed to validate the sponging effect of circ_0000950 on miR-103 as well as the mechanisms of circ_0000950/miR-103 on regulating apoptosis, neurite outgrowth and inflammation in both cellular AD models. Circ_0000950 reduced miR-103 expression and increased prostaglandin-endoperoxide synthase 2 (PTGS2) expression in both two cellular AD models. And circ_0000950 overexpression promoted neuron apoptosis, suppressed neurite outgrowth and elevated IL-1β, IL-6 and TNF-α levels compared with overexpression control, whereas circ_0000950 knockdown inhibited neuron apoptosis, enhanced neurite outgrowth and lowered IL-1β, IL-6 and TNF-α levels compared with shRNA control in both two cellular AD models. Compensation experiments along with luciferase reporter assay validated that circ_0000950 promoted cell apoptosis, suppressed neurite outgrowth and elevated inflammatory cytokines levels via directly sponging miR-103. In conclusion, circ_0000950 promotes neuron apoptosis, suppresses neurite outgrowth and elevates inflammatory cytokines levels through directly sponging miR-103 in AD. 

Retracted: No

PubPeer comments:
 Fig 12a; Fig 7a. ![file] These are different experiments, involving neurons and PC12 cells respectively. ,
Induction of autophagy by spermidine promotes longevity
Authors: Gino Heeren
Lucia Antonacci
Julia Ring
Luiza Deszcz
Heike Fussi
Didac Carmona-Gutierrez
Birthe Fahrenkrog
Alexandra Schauer
Michael Breitenbach
Kai-Uwe Fröhlich
Christoph Ruckenstuhl
Daniela Weiskopf
Nektarios Tavernarakis
Sabrina Schroeder
Guido Kroemer
Sabrina Büttner
Christoph Magnes
Tobias Eisenberg
Nadege Minois
Elisabeth Schraml
Alfredo Criollo
Peter Laun
Eva Herker
Frank Madeo
Beatrix Grubeck-Loebenstein
Regina Hartl
Heide Knauer
Frank Sinner
Evgenia Megalou
Journal: Nature Cell Biology (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ageing; Spermidine; Lifespan extension; Polyamines; Oxidative stress
Affiliations: Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.

Abstract:  Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity. 

Retracted: No

PubPeer comments:
 Readers should become aware of a recent paper published in JBC showing that autophagy induction by exogenous polyamines (including spermidine) is an artifact of BSA oxidase activity in culture serum. https: www.jbc.org content early 2020 05 19 jbc.RA120.013867.abstract From the article:  Consequently, considerable caution must be used when interpreting much of the published mechanistic data produced in in vitro cell culture systems as any observed autophagy included in such systems is likely the result of the toxic metabolites formed by BSAO following polyamines addition to the serum-containing medium and not a function of the polyamines themselves , 
 #1 The authors appear to be aware of this potential cofounding factor. and have included an amine oxidase inhibitor in their media. Qujote from methods:  Therefore, 5, 7.5 or 10u2009u00b5M of either spermine or spermidine were added at the time of micromass seeding in the presence of 1u2009mM aminoguanidine to control any toxicity of the polyamines due to their oxidation by the amino oxidase present in the bovine serum. ,
Long noncoding RNA APTR contributes to osteosarcoma progression through repression of miR‐132‐3p and upregulation of yes‐associated protein 1
Authors: Xiaoya Sun
Wei Cao
Yuebai Li
Yisheng Wang
Hongya Guan
Jiu Liu
Guowei Shang
Yuanbo Cui
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Alu-mediated p21 transcriptional regulator (APTR); Yes-associated protein 1 (YAP1); long noncoding RNAs (lncRNA); miR-132-3p; osteosarcoma (OS)
Affiliations: Translational Medical Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China., Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

Abstract:  A growing amount of evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in osteosarcoma (OS). However, little knowledge is available about the functional roles and molecular mechanisms of lncRNA Alu-mediated p21 transcriptional regulator (APTR) in OS. Herein, APTR expression was demonstrated to be significantly upregulated in OS tumor tissues and four OS cell lines (including MG63, 143B, Saos-2, and HOS) compared with the adjacent tissues and human osteoblast cell line hFOB1.19, respectively. We confirmed miR-132-3p to be a target for APTR, and its expression was demonstrated to be inhibited by APTR. In functional terms, knockdown of APTR and overexpression of miR-132-3p both, remarkably repressed human OS cell proliferation, invasion and migration, and induced apoptosis. Also, Yes-associated protein 1 (YAP1) was determined as an inhibitory target of miR-132-3p. Moreover, our findings demonstrated that the repression of YAP1 protein expression and the suppression of Ki-67, MMP9, and Bcl2 expression induced by APTR knockdown required increased miR-132-3p. Thus, APTR contributed to OS progression through repression of miR-132-3p and upregulation of YAP1 expression. Therefore, we have uncovered a novel regulatory mechanism by which the APTR/miR-132-3p/YAP1 axis can regulate OS progression. 

Retracted: No

PubPeer comments:
 There appear to be some images overlapping between figure 2 and figure 4. ![file] ![file] ,
Haemolysin Sph2 of Leptospira interrogans induces cell apoptosis via intracellular reactive oxygen species elevation and mitochondrial membrane injury
Authors: Shibiao Ding
Rongbo Che
Weiqun Yang
Jie Yan
Qinchao Zhang
Xu&#x27;ai Lin
Journal: Cellular Microbiology (2019)
Discipline: MICROBIOLOGY
Keywords: Sph2; apoptosis; leptospirosis; mitochondria; sphingomyelinase haemolysin.
Affiliations: Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou, China., Department of Clinical Laboratory, Hospital of integrated traditional Chinese and Western, Hangzhou, China., Basic Medical Microbiology Division, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, China.

Abstract:  Leptospira interrogans causes widespread leptospirosis in humans and animals, with major symptoms of jaundice and haemorrhage. Sph2, a member of the sphingomyelinase haemolysins, is an important virulence factor for leptospire. In this study, the function and mechanism of Sph2 in the pathogenesis of leptospirosis were investigated to further understand the pathogenesis of leptospire. Real-time PCR analysis of expression levels during cell invasion showed that sph2 gene expression was transiently induced in human umbilical vein endothelial cells (HUVECs), human embryo liver cells (L02), and human epithelial lung cells (L132), with expression levels reaching a peak after 45 min of infection. Further functional analysis of recombinant Sph2 (rSph2) by LDH assays and confocal microscopy showed that rSph2 can be internalised by cells both by causing cell membrane damage and by a damage-independent clathrin-mediated endocytosis pathway. Subsequently, rSph2 is able to translocate to mitochondria, which led to an increase in the levels of reactive oxygen species (ROS) and a decrease of the mitochondrial membrane potential (ΔΨm ). Further flowcytometry analyses after rSph2 exposure showed that 28.7%, 31%, and 27.3% of the HUVEC, L02, and L132 cells, respectively, became apoptotic. Because apoptosis could be decreased with the ROS inhibitor N-acetyl cysteine, these experiments suggested that rSph2 triggers apoptosis through mitochondrial membrane damage and ROS elevation. The ability of leptospiral haemolysin rSph2 to cause apoptosis likely contributes to the pathogenesis of leptospirosis. 

Retracted: No

PubPeer comments:
 **DUPLICATION (Back and Forth)** in another paper back in **2018** published in **Springer!** See the link below for more: [Link] [Link] ![file] ![file] ![file] ![file] ,
Small nucleolar RNA host gene 1 promotes development and progression of colorectal cancer through negative regulation of miR‐137
Authors: Xiefu Zhang
Wen Xu
Yuhan Yin
Yanru Qin
Changqing Guo
Ge Yang
Yang Fu
Yiyu Qin
Sanfei Peng
Yang Yu
Journal: Molecular Carcinogenesis (2019)
Discipline: CLINICAL MEDICINE
Keywords: colorectal cancer; miR-137; rapamycin-insensitive companion of mTOR; small nucleolar RNA host gene 1.
Affiliations: Department of GastroenterologyThe First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China, Department of OphthalmologyThe First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China, Department of OncologyThe First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China, State Key Laboratory of Bioreactor Engineering &amp; Shanghai Key Laboratory of New Drug Design, School of PharmacyEast China University of Science and Technology, Shanghai Shanghai China, Research Centre of Biomedical TechnologyJiangsu Vocational College of Medicine Yancheng Jiangsu China

Abstract:  Small nucleolar RNA host gene 1 (SNHG1) is critical in the progression of cancers. However, the mechanism by which SNHG1 regulates the progression of colorectal cancer (CRC) remains unclear. Expressions of SNHG1 and miR-137 in CRC tissues and cell lines were evaluated by quantitative real-time polymerase chain reaction. A luciferase reporter gene assay was conducted to investigate miR-137 target. Additionally, RNA pull-down assay was performed to explore the physical association between miR-137, SNHG1, and RNA induced silencing complex (RISC). Cell cycling and invasion were examined by flow cytometry (FCM) and transwell assays. The in vivo carcinogenic activity of SNHG1 was examined using murine xenograft models. Expression of RICTOR, serine/threonine kinase 1 (AKT), serum and glucocorticoid-inducible kinase 1 (SGK1), p70S6K1, and LC3II/LC3I ratio was examined by Western blot analysis. SNHG1 upregulation was observed in CRC tissues and cell lines, which was associated with the lymph node metastasis, advanced TNM stage and poorer prognosis. SNHG1 increased RICTOR level in CRC via sponging miR-137. In addition, SNHG1 silencing inhibited CRC cell proliferation and migration in vitro and in vivo. SNHG1 regulated RICTOR expression by sponging miR-137 and promoted tumorgenesis in CRC. 

Retracted: No

PubPeer comments:
 Figure 5C and E. Five of the six panels appear to show overlaps with each other. Boxes of the same color highlight areas that look similar to each other. ![file] , 
 The Dapi for the merged images is switched. ![file] ,
GABARAP promotes bone marrow mesenchymal stem cells-based the osteoarthritis cartilage regeneration through the inhibition of PI3K/AKT/mTOR signaling pathway
Authors: Kai Zou
Jun Yao
Jia Li
Xiaohan Zhang
Zhengyi Yang
Huiping Lu
Zhengyuan Wu
Shiting Ma
Yimei Huang
Yan Wei
Jinmin Zhao
Journal: Journal of cellular physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: His6-GABARAP; PI3K/AKT/mTOR; autophagy; bone marrow mesenchymal stem cells; osteoarthritis.
Affiliations: Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China., Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China., Department of Bone and Joint Surgery, The First Affliated Hospital of Guangxi Medical University, Nanning, China.

Abstract:  Osteoarthritis (OA) is a degenerative disease of the cartilage prevalent in the middle-aged and elderly demographic. Direct transplantation of bone marrow mesenchymal stem cells (BMSCs) or stem cell-derived chondrocytes into the damaged cartilage is a promising therapeutic strategy for OA, but is limited by the poor survival and in situ stability of the chondrocytes. Autophagy is a unique catabolic pathway conserved across eukaryotes that maintains cellular homeostasis, recycles damaged proteins and organelles, and promotes survival. The aim of this study was to determine the role of the proautophagic γ-aminobutyric acid receptor-associated protein (GABARAP) on the therapeutic effects of BMSCs-derived chondrocytes in a rat model of OA, and elucidate the underlying mechanisms. Anterior cruciate ligament transection (ACLT) was performed in Sprague-Dawley rats to simulate OA, and the animals were injected weekly with recombinant human His6-GABARAP protein, BMSCs-derived differentiated chondrocytes (DCs) or their combination directly into the knee cartilage. The regenerative effects of GABARAP and/or DCs were determined in term of International Cartilage Repair Society scores and cartilage thickness. The combination treatment of DCs and GABARAP significantly increased the levels of the ECM proteins Col II and SOX9, indicating formation of hyaline-like cartilage, and decreased chondrocyte apoptosis and inflammation. DCs + GABARAP treatment also upregulated the mediators of the autophagy pathway and suppressed the PI3K/AKT/mTOR pathway, indicating a mechanistic basis of its therapeutic action. 

Retracted: Yes

PubPeer comments:
 Some irrelevant references are cited in the paper. For example, ref[6] addresses not Apriori algorithm and does not match the in-text citation. ![file] ![file] ![file] ![file] ,
LncRNA MSTO2P promotes proliferation and autophagy of lung cancer cells by up-regulating EZH2 expression
Authors: Y-F Chen
L-J Wang
G-Z Sun
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; MSTO2P; lung cancer; EZH2; cell proliferation
Affiliations: Department of Pulmonary Disease, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China. .

Abstract:  Objective: This study was designed to investigate the specific mechanism underlying the regulatory effect of long noncoding ribonucleic acids (lncRNAs) MSTO2P on lung cancer (LCa) cell proliferation and autophagy via regulating enhancer of zeste homolog (EZH2) expression. Patients and methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to analyze the levels of MSTO2P and EZH2 in 40 pairs of LCa tissues and corresponding adjacent tissues, as well as in LCa cell lines (H1299, H23, A549) and human bronchial epithelial cells (BEAS-2B). Besides, the effect of MSTO2P on cell proliferation ability was detected by cell counting kit-8 (CCK-8) and plate cloning experiments. The interaction between MTS02P and EZH2 as well as their effects on cell autophagy ability were examined by qRT-PCR and Western blot. Results: The qRT-PCR results showed that MSTO2P expression in LCa tissues was remarkably higher than that in adjacent tissues. Meanwhile, compared with human bronchial epithelial cells, the level of MSTO2P was remarkably up-regulated in LCa cells. After down-regulating MSTO2P, the cell proliferation ability was weakened, and the protein levels of autophagy-related genes including Agt5, LC-3I, and LC-3II were remarkably down-regulated. At the same time, EZH2 expression in LCa tissues was also remarkably up-regulated relative to adjacent tissues, and it was positively correlated with the expression of MSTO2P. In addition, after down-regulating MSTO2P, the EZH2 level was also remarkably reduced. Further experimental results revealed that EZH2 down-regulation could impair the cell proliferation ability and down-regulate the expressions of autophagy genes such as Agt5, LC-3I, and LC-3II. Conclusions: LncRNA MSTO2P promotes LCa cell proliferation and autophagy by up-regulating EZH2. Therefore, MSTO2P may be a potential therapeutic target for LCa. 

Retracted: No

PubPeer comments:
 Fig 3B.  There was a positive correlation between the expression level of EZH2 and the expression level of MSTO2P in lung cancer tissues . ![file] I can only suppose that someone put this together as a placeholder for a scatterplot that was still to come, and then forgot to replace it in the final version of the manuscript. ,
Flavocoxid, a Natural Antioxidant, Protects Mouse Kidney from Cadmium-Induced Toxicity
Authors: Herbert Marini
Giuseppe Santoro
Antonio Micali
Domenica Altavilla
Giovanni Pallio
Domenico Puzzolo
Natasha Irrera
Rosalba Laurà
Antonina Pisani
Antonino Germanà
Francesco Squadrito
Domenico Santoro
Vincenzo Trichilo
Letteria Minutoli
Consuelo Malta
Journal: Oxidative Medicine and Cellular Longevity (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cadmium; Flavocoxid; Antioxidant; Kidney; Mice
Affiliations: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy., Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy., Department of Veterinary Sciences, University of Messina, Messina, Italy.

Abstract:  Background: Cadmium (Cd), a diffused environmental pollutant, has adverse effects on urinary apparatus. The role of flavocoxid, a natural flavonoid with antioxidant activity, on the morphological and biochemical changes induced in vivo by Cd in mice kidney was evaluated. Methods: C57 BL/6J mice received 0.9% NaCl alone, flavocoxid (20 mg/kg/day i.p.) alone, Cd chloride (CdCl2) (2 mg/kg/day i.p.) alone, or CdCl2 plus flavocoxid (2 mg/kg/day i.p. plus 20 mg/kg/day i.p.) for 14 days. The kidneys were processed for biochemical, structural, ultrastructural, and morphometric evaluation. Results: Cd treatment alone significantly increased urea nitrogen and creatinine, iNOS, MMP-9, and pERK 1/2 expression and protein carbonyl; reduced GSH, GR, and GPx; and induced structural and ultrastructural changes in the glomeruli and in the tubular epithelium. After 14 days of treatment, flavocoxid administration reduced urea nitrogen and creatinine, iNOS, MMP-9, and pERK 1/2 expression and protein carbonyl; increased GSH, GR, and GPx; and showed an evident preservation of the glomerular and tubular structure and ultrastructure. Conclusions: A protective role of flavocoxid against Cd-induced oxidative damages in mouse kidney was demonstrated for the first time. Flavocoxid may have a promising antioxidant role against environmental Cd harmful effects on glomerular and tubular lesions. 

Retracted: No

PubPeer comments:
 Figure 3(a) appears to have at least two repeated regions (red and green boxes). Could the authors please comment? *** ![file] , 
  Conflicts of Interest. The authors declare no actual or potential competing financial interests. I am interested if the authors might address the issue of this or other patents on Flavocoxid, studied in this paper, which is available here: https: patentimages.storage.googleapis.com 2b 6e 33 461f02fdc34be6 US20130210753A1.pdf. It appears the authors could have a relationship that should be disclosed to readers and peer reviewers. ![file] , 
 From Dr. Squadrito s CV last updated in 2018, [currently available here] , he does appear to acknowledge a financial relationship between he and Primus Pharmaceuticals Inc. Could the authors explain why the conflicts of interest statement does not describe this relationship? *** ![file] ,
Med19 is involved in chemoresistance by mediating autophagy through HMGB1 in breast cancer
Authors: Zijian Guo
Danfeng Gao
Beibei Liu
Xiufen Zhang
Kai Fang
Lihua Li
Xiaowei Qi
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: adriamycin; autophagy; breast cancer; drug sensitivity; mediator complex subunit 19.
Affiliations: Oncology Institute, The Affiliated Hospital of Jiangnan University, Wuxi, China., Department of Pathology, The Affiliated Hospital of Jiangnan University, Wuxi, China., Department of Oncological Surgery, The Affiliated Hospital of Jiangnan University, Wuxi, China.

Abstract:  Adriamycin (ADM)-based regimens are the most effective chemotherapeutic treatments for breast cancer. However, intrinsic and acquired chemoresistance is a major therapeutic problem. Our goal was to clarify the role of mediator complex subunit 19 (Med19) in chemotherapy resistance and to elucidate the related molecular mechanisms. In this study, ADM-resistant human cells (MCF-7/ADM) and tissues exhibited increased Med19 expression and autophagy levels relative to the corresponding control groups. Additionally, MCF-7/ADM cells showed changes in two selective markers of autophagy. There was a dose-dependent increase in the light chain 3 (LC3)-II/LC3-I ratio and a decrease in sequestosome 1 (P62/SQSTMl) expression. Furthermore, lentivirus-mediated Med19 inhibition significantly attenuated the LC3-II/LC3-I ratio, autophagy-related gene 3 (Atg3) and autophagy-related gene 5 (Atg5) expression, P62 degradation, and red fluorescent protein-LC3 dot formation after treatment with ADM or rapamycin, an autophagy activator. Furthermore, the antiproliferative effects of ADM, cisplatin (DDP), and taxol (TAX) were significantly enhanced after suppressing Med19 expression. Notably, the effects of Med19 on autophagy were mediated through the high-mobility group box-1 (HMGB1) pathway. Our findings suggest that Med19 suppression increased ADM chemosensitivity by downregulating autophagy through the inhibition of HMGB1 signaling in human breast cancer cells. Thus, the regulatory mechanisms of Med19 in autophagy should be investigated to reduce tumor resistance to chemotherapy. 

Retracted: No

PubPeer comments:
 Fig 4E.  The colony formation assay shows cell proliferation after treatments with ADM, DDP, and TAX. F, MCFu20107 and MCFu20107 ADM cells, with or without Med19 suppression, were treated with Rap . ![file] -ADM, NC and KD panels overlap after a vertical flip. ![file] Another overlap. ![file] ,
Persistent nicotine treatment potentiates amplification of the dihydrofolate reductase gene in rat lung epithelial cells as a consequence of Ras activation
Authors: Chang-Yan Chen
Tetteh Abbeyquaye
Jinjin Guo
Michelle Chu
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: nicotine; lung carcinogenesis; intracellular pathways; protein kinase C; phosphoinositide 3-OH-kinase
Affiliations: Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

Abstract:  Although nicotine has been suggested to promote lung carcinogenesis, the mechanism of its action in this process remains unknown. The present investigation demonstrates that the treatment of rat lung epithelial cells with nicotine for various periods differentially mobilizes multiple intracellular pathways. Protein kinase C and phosphoinositide 3-OH-kinase are transiently activated after the treatment. Also, Ras and its downstream effector ERK1/2 are activated after long term exposure to nicotine. The activation of Ras by nicotine treatment is responsible for the subsequent perturbation of the methotrexate (MTX)-mediated G1 cell cycle restriction as well as an increase in production of reactive oxygen species. When p53 expression is suppressed by introducing E6, persistent exposure to nicotine enables dihydrofolate reductase gene amplification in the presence of methotrexate (MTX) and the formation of the MTX-resistant colonies. Altering the activity of phosphoinositide 3-OH-kinase has no effect on dihydrofolate reductase amplification. However, the suppression of protein kinase C dramatically affects the colony formation in soft agar. Thus, our data suggest that persistent exposure to nicotine perturbs the G1 checkpoint and causes DNA damage through the increase of the production of reactive oxygen species. However, a third element rendered by loss of p53 is required for the initiation of the process of gene amplification. Under p53-deficient conditions, the establishment of a full oncogenic transformation, in response to long term nicotine exposure, is achieved through the cooperation of multiple signaling pathways. 

Retracted: No

PubPeer comments:
 Figures 1a and 3b. Much more similar than you would expect even though the treatments are different. https: imgur.com Egsn4ME ,
Loss of IFN-γ Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy
Authors: Qiuming He
Jennifer A Wargo
Lewis Zhichang Shi
Scott E Woodman
Andrew Futreal
Jason Roszik
Chantale Bernatchez
Jianjun Gao
Patrick Hwu
Hao Zhao
Tenghui Chen
Pei-Ling Chen
Liangwen Xiong
James P Allison
Padmanee Sharma
Jianfeng Chen
Journal: Cell (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: IFN-γ signaling; Melanoma; anti-CTLA-4; copy-number alteration; ipilimumab
Affiliations: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Melanoma Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: .

Abstract:  Antibody blockade of the inhibitory CTLA-4 pathway has led to clinical benefit in a subset of patients with metastatic melanoma. Anti-CTLA-4 enhances T cell responses, including production of IFN-γ, which is a critical cytokine for host immune responses. However, the role of IFN-γ signaling in tumor cells in the setting of anti-CTLA-4 therapy remains unknown. Here, we demonstrate that patients identified as non-responders to anti-CTLA-4 (ipilimumab) have tumors with genomic defects in IFN-γ pathway genes. Furthermore, mice bearing melanoma tumors with knockdown of IFN-γ receptor 1 (IFNGR1) have impaired tumor rejection upon anti-CTLA-4 therapy. These data highlight that loss of the IFN-γ signaling pathway is associated with primary resistance to anti-CTLA-4 therapy. Our findings demonstrate the importance of tumor genomic data, especially IFN-γ related genes, as prognostic information for patients selected to receive treatment with immune checkpoint therapy. 

Retracted: No

PubPeer comments:
 The size distribution of Mg particles shown in Figure 1 does not correspond to the SEM micrograph presented. Many of the particles shown in the SEM image are 50 u00b5m in diameter, and there is no indication of this in the size distribution. The TEM image look strange, with no background noise. The particle size is also unusually small compared to the particles shown in the SEM image. ![file] ,
Hsa_circ_0001361 promotes bladder cancer invasion and metastasis through miR-491-5p/MMP9 axis
Authors: Chaohui Gu
Hui Zhang
Fei Xie
Miao Wang
Xiaoping Zhang
Guosong Jiang
Dan Tao
Chao Huang
Xingyuan Xiao
Feng Liu
Journal: Oncogene (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Circular RNAs; circRNAs; bladder cancer; circHIPK3; circRNA BCRC-3
Affiliations: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China., Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266013, China., Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, 430050, China., Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China., Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. .

Abstract:  Circular RNAs (circRNAs) have been increasingly indicated to be important participants in the development and progression of various malignant tumors. Our previous studies found that hundreds of circRNAs were aberrantly expressed in bladder cancer (BC) by high-throughput sequencing and we have confirmed that the downregulated circRNAs circHIPK3, circRNA BCRC-3, and circNR3C1 played inhibitory roles in BC progression. In this study, we focused on the upregulated circRNAs and identified a novel circular RNA, hsa_circ_0001361 (circ0001361), was expressed at high levels in BC tissues and cell lines based on RNA-Seq data and qRT-PCR analysis, and it was positively corelated with pathologic grade and muscle invasion. Moreover, Kaplan-Meier survival analysis implied that BC patients with high circ0001361 expression level had a poor overall survival. Functionally, circ0001361 promoted BC cell invasion and metastasis both in vitro and in vivo, but had no effect on cell cycle and proliferation. Mechanistically, RNA sequencing analysis indicated that MMP9 was upregulated in circ0001361-overexpressed BC cells, and MMP9 was verified to mediate circ0001361-induced cell migration and invasion. Furthermore, we demonstrated that circ0001361 could directly interact with miR-491-5p to upregulate MMP9 expression. Collectively, our findings indicate that circ0001361 plays oncogenic role in BC invasion and metastasis through targeting the miR-491-5p/MMP9 axis, and it might be a potential novel target for BC therapy. 

Retracted: No

PubPeer comments:
 It seems like the data in Figures 2-6 are all faked. Lots of obvious examples of copy and pasting between rows of the plots. What was the point of publishing this Photoshop exercise? What did the journal intend to get out of it? , 
 The journal has now retracted this article, following on concerns that I posted here. That post was moderated away by admin. ,
MiR-935 Promotes Clear Cell Renal Cell Carcinoma Migration and Invasion by Targeting IREB2
Authors: Yuedong Chen
Jinchun Xing
Fei Liu
Bin Chen
Chunxiao Liu
Journal: Cancer management and research (2019)
Discipline: CLINICAL MEDICINE
Keywords: IREB2; clear cell renal cell carcinoma; invasion; miR-935; migration.
Affiliations: Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, People's Republic of China., Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People's Republic of China.

Abstract:  Purpose: Clear cell renal cell carcinoma (ccRCC) has the highest rate of metastasis and invasion in RCC and is the third most common adult urinary malignancy. miRNA may serve a critical role in human cancer development and progression, has been confirmed to play a pivotal role in RCC cell invasion and migration. Since miR‑935 had been verified to be an oncogene or tumor suppressor in various cancers, the role of miR‑935 in RCC was unclear. Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify miR-935 expression. CCK-8 assay, wound healing assay and transwell assay were used to investigate the cell proliferation, migration and invasion of miR-935. Receiver operating characteristic (ROC) curve analysis was applied to discriminate different clinical classifications. Gain or loss of function approaches were used to investigate the cell proliferation, migration and invasion of miR-935 in vitro. Bioinformatics analysis and dual-luciferase reporter assay were used to identify the target of miR-935. Results: MiR-935 had a higher expression level in RCC cells and cancer tissues. MiR-935 mimics promoted cell proliferation, migration and invasion, and miR-935 inhibitor inhibited cell inhibit malignancy of cancer cells. Bioinformatics analysis and dual-luciferase reporter assay identified iron-responsive element-binding protein 2 (IREB2) as a direct target of miR-935. qRT-PCR showed IREB2 expression was downregulated in ccRCC cancer tissues and high IREB2 expression had a longer overall survival (OS) and disease-free survival (DFS). Silencing IREB2 could reverse the function of miR-935 inhibitor on cell proliferation and metastasis in renal cancer cells. Conclusion: The study indicated that miR-935 may act as an oncomiRNA and influenced migration and invasion progress of ccRCC by targeting IREB2. Oncogene miR-935 may be a molecular marker and uncover new strategies for ccRCC. 

Retracted: Yes

PubPeer comments:
 In Figure 4, a micrograph has been duplicated and presented as something else. ![file] ,