PReD-Bench/PRed-Bench huggingface dataset:
An Interleukin-25-Mediated Autoregulatory Circuit in Keratinocytes Plays a Pivotal Role in Psoriatic Skin Inflammation
Authors: Yuping Lai
Chen Dong
Kewei Liu
Yelin Wu
Miao Xu
Huiping Lu
Yuling Shi
Xiaohu Wang
Young-Hee Lee
Haoran An
Jingren Zhang
Journal: Immunity (2018)
Discipline: IMMUNOLOGY
Keywords: IL-25; cytokines; keratinocytes; psoriasis.
Affiliations: Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing 100084, China., Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China., Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054, USA., Shanghai Key Laboratory of Regulatory Biology, School of Life sciences, East China Normal University, Shanghai 200241, China., Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China., Center for Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China., Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Beijing Key Lab for Immunological Research on Chronic Diseases, Beijing 100084, China. Electronic address: .

Abstract:  Psoriasis is a chronic autoinflammatory skin disease. Although interleukin-17, derived from lymphocytes, has been shown to be critical in psoriasis, the initiation and maintenance of chronic skin inflammation has not been well understood. IL-25 (also called IL-17E), another IL-17 family cytokine, is well known to regulate allergic responses and type 2 immunity. Here we have shown that IL-25, also highly expressed in the lesional skin of psoriasis patients, was regulated by IL-17 in murine skin of a imiquimod (IMQ)-induced psoriasis model. IL-25 injection induced skin inflammation, whereas germline or keratinocyte-specific deletion of IL-25 caused resistance to IMQ-induced psoriasis. Via IL-17RB expression in keratinocytes, IL-25 stimulated the proliferation of keratinocytes and induced the production of inflammatory cytokines and chemokines, via activation of the STAT3 transcription factor. Thus, our data demonstrate that an IL-17-induced autoregulatory circuit in keratinocytes is mediated by IL-25 and suggest that this circuit could be targeted in the treatment of psoriasis patients. 

Retracted: No

PubPeer comments:
 The staining in Figure 1A and 3A, which represents different experiments, showed unexpected similar overlaps. Could the authors please explain? Figure 1A: ![file] Rotate: ![file] Figure 3A: ![file] , 
 #1 With regard to the similarities in the images of control mice in Figure 1E and 3A, they were from the same mouse (B6 control #1) and these two experiments were performed in the same time. So the B6#1 in Figure 1E was also used as a control in Figure 3A to indicate the successful psoriasis induction in IL-25f f and IL-25f fK5Cre mice. We also examined the other control mouse (B6 control #2) in the same experiment, which gave the same results. -Miao Xu and Chen Dong ![file] ,
Curcumin attenuates IR-induced myocardial injury by activating SIRT3
Authors: M Sun
R Wang
J-Y Zhang
M-G Zhai
Y-P Jia
M Zhang
Q-H Han
S-Y Di
H-L Liang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Ischemia-reperfusion injury; Curcumin; SIRT3; H9c2 cardiomyocytes; Apoptosis
Affiliations: Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, China. .

Abstract:  Objective: Ischemia-reperfusion (IR) injury remains an unresolved and complicated situation in clinical practice. In this study, H9c2 cardiomyocytes were subjected to curcumin (Cur) treatment in the absence or presence of the silent information regulator 3 (SIRT3) inhibitor 3-TYP and were then subjected to IR. Materials and methods: H9c2 cells and male Sprague-Dawley (SD) rats were cultured. MTT assay was performed to assess H9c2 cell viability. Cellular apoptosis was analyzed by TUNEL assay. The expressions of Bcl-2, Bax, SIRT3, and AcSOD2 were measured by Western-blotting. The activities of SOD, GSH-Px, and MDA were determined using commercially available kits. The myocardial infarct size was evaluated using TTC staining. Results: Cur significantly increased H9c2 cell viability, decreased the cell apoptotic index, and altered several biochemical parameters, including upregulation of the anti-apoptotic protein Bcl-2, downregulation of the proapoptotic protein Bax and AcSOD2, activation of SIRT3, increase in SOD and GSH-Px activity, and decrease in MDA content. In isolated rat hearts, Cur significantly improved cardiac function, decreased infarct size, and lowered lactate dehydrogenase levels. These protective effects induced by Cur were reversed by treatment with the SIRT3 inhibitor 3-TYP. Conclusions: These results demonstrate that Cur protects cardiomyocytes and that rat hearts were exposed to IRI by activating SIRT3. 

Retracted: No

PubPeer comments:
 Figure 2A shows: a. Control, b. IR, c. Cur + IR, d. Cur+3-TYP + IR, e. 3-TYP + IR. * Red boxes: In the bottom row (merged DAPI and TUNEL staining) the d and e panels appear to look the same. ![file] ,
Epigenetic suppression of human telomerase (hTERT) is mediated by the metastasis suppressor NME2 in a G-quadruplex–dependent fashion
Authors: Parashar Dhapola
Suman Sengupta
Ramesh Ummanni
Ankita Singh
Vishnu Dhople
Dhurjhoti Saha
Vivek Srivastava
Anirban Kar
Shantanu Chowdhury
Tabish Hussain
Journal: Journal of Biological Chemistry (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: G-quadruplex; NME2; REST repressor complex; chromatin modification; epigenetics
Affiliations: From the Genomics and Molecular Medicine Unit., Academy of Scientific & Innovative Research (AcSIR), CSIR-Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research (CSIR), Mathura Road, New Delhi 110025, India and., G.N.R. Knowledge Centre for Genome Informatics, and., Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India., From the Genomics and Molecular Medicine Unit, .

Abstract:  Transcriptional activation of the human telomerase reverse transcriptase (hTERT) gene, which remains repressed in adult somatic cells, is critical during tumorigenesis. Several transcription factors and the epigenetic state of the hTERT promoter are known to be important for tight control of hTERT in normal tissues, but the molecular mechanisms leading to hTERT reactivation in cancer are not well-understood. Surprisingly, here we found occupancy of the metastasis suppressor non-metastatic 2 (NME2) within the hTERT core promoter in HT1080 fibrosarcoma cells and HCT116 colon cancer cells and NME2-mediated transcriptional repression of hTERT in these cells. We also report that loss of NME2 results in up-regulated hTERT expression. Mechanistically, additional results indicated that the RE1-silencing transcription factor (REST)-lysine-specific histone demethylase 1 (LSD1) co-repressor complex associates with the hTERT promoter in an NME2-dependent way and that this assembly is required for maintaining repressive chromatin at the hTERT promoter. Interestingly, a G-quadruplex motif at the hTERT promoter was essential for occupancy of NME2 and the REST repressor complex on the hTERT promoter. In light of this mechanistic insight, we studied the effects of G-quadruplex-binding ligands on hTERT expression and observed that several of these ligands repressed hTERT expression. Together, our results support a mechanism of hTERT epigenetic control involving a G-quadruplex promoter motif, which potentially can be targeted by tailored small molecules. 

Retracted: No

PubPeer comments:
 The Image 1i Gels do not match. Is it the control (b-actin) of the same sample that the authors have portrayed for the NME2? ![file] , 
 ![file] In the  Author contributions it is mentioned that  D. S. and A. S. performed ChIP-seq. . But the current manuscript has no ChIP-seq data. Without any experiments how it is exclusively introduced in the contribution list? , 
 ![file] The arrow marked inputs seems completely different compared to their respective IP lanes. Even the well size of the marked inputs are remarkably different. It appears that the two inputs are from different experiment. ,
Long non-coding RNA muscleblind like splicing regulator 1 antisense RNA 1 (LncRNA MBNL1-AS1) promotes the progression of acute myocardial infarction by regulating the microRNA-132-3p/SRY-related high-mobility-group box 4 (SOX4) axis
Authors: Wenyuan Lin
Weifeng Liu
Liangliang Yu
Journal: Bioengineered (2022)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: LncRNA MBNL1-AS1; SOX4; acute myocardial infarction; cell apoptosis; miR-132-3p.
Affiliations: Department of Cardiology, Yantai Yuhuangding Hospital, Qingdao Medical College, Qingdao University, Yantai, China

Abstract:  Long non-coding RNA muscleblind like splicing regulator 1 antisense RNA 1 (LncRNA MBNL1-AS1) exerts vital role in various physiological processes. However, its functions in acute myocardial infarction (AMI) are not elucidated. AMI model was constructed using Wistar rats and it was found that LncRNA MBNL1-AS1 was upregulated in AMI model according to the quantitative real-time polymerase chain reaction (qRT-PCR) results. The left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (±dp/dt max) were detected through hemodynamics test, which showed that knockdown of MBNL1-AS1 improved cardiac function in AMI model. Next, the myocardial infarction area was estimated by triphenyltetrazole chloride (TTC) staining, and the levels of cardiac troponin I (cTn-I) and creatine kinase-MB (CK-MB) were detected by enzyme-linked immunosorbent assay (ELISA) kit. The results revealed that silencing MBLN1-AS1 alleviated myocardial injury in AMI model. Additionally, MBNL1-AS1 knockdown inhibited apoptosis of myocardial cells and reduced the expression of apoptotic proteins. According to DIANA database and luciferase reporter assay, miR-132-3p was the direct target of MBNL1-AS1 and was negatively regulated by MBNL1-AS1. Furthermore, Targetscan database predicted that SRY-related high-mobility-group box 4 (SOX4) was the direct target of miR-132-3p and was regulated by MBNL1-AS1 through miR-132-3p. Moreover, overexpression of SOX4 partially eliminated effects of MBNL1-AS1 on myocardial cells. In conclusion, this investigation for the first time revealed that LncRNA MBNL1-AS1 was the potential target for treating AMI and expounded the underlying mechanisms of it. 

Retracted: No

PubPeer comments:
 Most of the qRT-PCR primer sequences listed in Table 1 appear to be incorrect (only forward primers were checked). In the text there are non-scientific and odd phrases. Eg. in the description of Western blotting, where they use unconjugated primary antibodies and directly detection of protein bands with infrared imaging system. According to the  Contribution of authors , none of the authors have performed any experiments. Furthermore, no funding is associated with this study. This is typical for many similar papermill papers affiliated with China. ![file] , 
 Since no response from the authors or papermill, I can add that one of the antibodies(anti-cleaved caspase 9) used in Western blotting (rat cells) is specific for humans. ,
Gastric microbes associated with gastric inflammation, atrophy and intestinal metaplasia 1 year after Helicobacter pylori eradication
Authors: Simson Tsz Yat Luk
Joseph J Y Sung
Olabisi Oluwabukola Coker
Jun Yu
Eagle Chu
Chun Ho Szeto
Harry Cheuk Hay Lau
Journal: Gut (2020)
Discipline: CLINICAL MEDICINE
Keywords: H. pylorieradication; atrophy; gastric inflammation; gastric microbes; intestinal metaplasia.
Affiliations: Department of Medicine and Therapeutics, Chinese University of Hong Kong, New Territories, Hong Kong ., Department of Medicine and Therapeutics, Chinese University of Hong Kong, New Territories, Hong Kong.

Abstract:  Objective: Helicobacter pylori is associated with gastric inflammation, precancerous gastric atrophy (GA) and intestinal metaplasia (IM). We aimed to identify microbes that are associated with progressive inflammation, GA and IM 1 year after H. pylori eradication. Design: A total of 587 H. pylori-positive patients were randomised to receive H. pylori eradication therapy (295 patients) or placebo (292 patients). Bacterial taxonomy was analysed on 404 gastric biopsy samples comprising 102 pairs before and after 1 year H. pylori eradication and 100 pairs before and after 1 year placebo by 16S rRNA sequencing. Results: Analysis of microbial sequences confirmed the eradication of H. pylori in treated group after 1 year. Principal component analysis revealed distinct microbial clusters reflected by increase in bacterial diversity (p&lt;0.00001) after H. pylori eradication. While microbial interactions remained largely unchanged after placebo treatment, microbial co-occurrence was less in treated group. Acinetobacter lwoffii, Streptococcus anginosus and Ralstonia were enriched while Roseburia and Sphingomonas were depleted in patients with persistent inflammation 1 year after H. pylori eradication. A distinct cluster of oral bacteria comprising Peptostreptococcus, Streptococcus, Parvimonas, Prevotella, Rothia and Granulicatella were associated with emergence and persistence of GA and IM. Probiotic Faecalibacterium praustznii was depleted in subjects who developed GA following H. pylori eradication. Functional pathways including amino acid metabolism and inositol phosphate metabolism were enriched while folate biosynthesis and NOD-like receptor signalling decreased in atrophy/IM-associated gastric microbiota. Conclusion: This study identified that gastric microbes contribute to the progression of gastric carcinogenesis after H. pylori eradication. 

Retracted: No

PubPeer comments:
 The authors explore a low biomass microbiome (gastric biopsies), due to their investigations of H. pylori eradication. Yet, they did apparently not include any negative control. Much of their actual data looks therefore like common contaminants (Stenotrophomonas, Methylobacterium, Halomonas, Cryocola, Massilia, Pseudomonas, Sphingomonas, Ralstonia, Erwinia, Brevundimonas), in combination with mouth microbiome (which might not be contamination, but biologically relevant). These gastric biopsies must be low on microbial biomass, therefore making the contaminations, especially after eradication, more prominent. ,
Time-course imaging of therapeutic functional tumor vascular normalization by antiangiogenic agents
Authors: Vytas Bindokas
Qingbei Zhang
H Rosie Xing
Jikun Shen
Hanli Fan
Robert M Hoffman
Journal: Molecular Cancer Therapeutics (2011)
Discipline: CLINICAL MEDICINE
Keywords: noninvasive imaging; tumor blood vessels; antiangiogenic agents; variable-magnification; in vivo-fluorescence imaging
Affiliations: Department of Pathology, The University of Chicago, 5841 South Maryland Avenue, AMB N339, MC1089, Chicago, IL 60637, USA.

Abstract:  We describe here new technology that enables noninvasive imaging of therapeutic functional normalization of tumor blood vessels by antiangiogenic agents. Noninvasive variable-magnification in vivo-fluorescence imaging as well as fluorescence tomography was used to visualize functional vessel normalization. Changes in the same vessel before and after drug treatment were imaged with high resolution in real time. Differences in vascular responses to the mTOR inhibitor rapamycin and to an anti-VEGF antibody were functionally imaged. Tumor vessel normalization was shown by significantly reduced leakiness and subsequent improved tumor delivery of Paclitaxel-BODPY as well as by normalized morphology. The tumor vascular pool agent, AngioSense(750), was retained only in tumors after either anti-VEGF antibody or rapamycin treatment, as visualized by noninvasive fluorescence tomography. The antiangiogenic therapy normalized vessels, which significantly enhanced the antitumor efficacy of paclitaxel because of increased drug penetration throughout the tumor. The optical imaging technology described here is thus a powerful, noninvasive, time-course imaging tool of functional tumor vessel normalization and its therapeutic consequences. 

Retracted: No

PubPeer comments:
 Identified by another reader. See also: *** ![file] , 
 https: retractionwatch.com 2013 11 27 cancer-researchers-retract-two-papers-in-the-jbc https: retractionwatch.com 2016 02 08 2014-ori-finding-results-in-retraction-of-cancer-paper-with-manipulated-images https: retractionwatch.com 2014 12 14 ori-sanctions-former-university-chicago-ucsf-scientists-faking-findings , 
 In fact, we know that Figure 2D iii and Figure 5B iii were indeed from one image, but were both clearly stated in each figure legend as HE staining images to demonstrate Mitotic Figures (MF) from anti-VEGF treated group. In Figure 2, anti-VEGF treatment was compared with Rapamycin treatment, while in Figure 5, anti-VEGF treatment was compared with Paclitaxel treatment. Both the labels in the figures and statements in figure legends clarified the image reuse. The reason we purposefully used the same representative image for anti-VEGF treatment group is in order to make it easier for the reader to compare the treatment efficacy of different treatment regimens when the results were presented in two Figures (Figure 2 and Figure 5). Nevertheless, we thanks this reader for raising the concern which gave us an opportunity to clarify. ,
Replication and episomal maintenance of Epstein-Barr virus-based vectors in mouse embryonal fibroblasts enable synthetic lethality screens
Authors: David W Melton
Dan Canaani
Michal Shenfeld
Elena Shistik
Yulia Einav
Arnold H Simons
Journal: Molecular Cancer Therapeutics (2003)
Discipline: CLINICAL MEDICINE
Keywords: chemical screen; genetic synthetic lethality; mouse embryonal fibroblasts (MEF); immortalized mammalian cell line; survival plasmid
Affiliations: Department of Biochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.

Abstract:  Recently, we demonstrated the establishment of chemical and genetic synthetic lethality screens in cultured human cells. Here, we report the establishment of this method in mouse embryonal fibroblasts (MEF). The method employs an immortalized mammalian cell line, deficient in a gene of interest, which is complemented by an episomal survival plasmid expressing the wild-type cDNA for the gene of interest and the use of a novel green fluorescent protein (GFP)-based double-label fluorescence system. The crucial part in this endeavor has been the identification of a DNA replicon that could stably replicate in MEFs while under selection for survival and gets spontaneously lost relatively fast in the absence of such a pressure. Here, we show for the first time that EBV-based replicons but not polyoma virus-based ones can replicate and be stably maintained in MEFs. In the chemical screen, selective pressure imposed by synthetic lethal drugs prevented the spontaneous loss of the GFP-marked episome, enabling drug identification. Retention or spontaneous loss over time of the episomal survival plasmid could be sensitively detected in a large-scale blind test in the presence or absence of synthetic lethal chemicals, respectively. Establishing the synthetic lethality screen should thus permit high throughput screening for chemicals, which are synthetically lethal with any mouse mutant/knockout gene of interest. Moreover, it forms the basis for a genetic synthetic lethality screen in MEFs, an important new tool for mouse functional genomics. 

Retracted: No

PubPeer comments:
 Figure 2A. Much more similar than expected. ![file] , 
 Figure 2B. Much more similar than expected. ![file] ,
Parkinson&rsquo;s disease-associated melanin steal
Authors: Marty Hinz
Ted Cole
Alvin Stein
Journal: Neuropsychiatric Disease and Treatment (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: L-dopa; dopamine; fluctuations; melanocyte.
Affiliations: Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, USA., Stein Orthopedic Associates, Plantation, FL, USA., Cole Center for Healing, Cincinnati, OH, USA.

Abstract:  Urinary dopamine fluctuations in the competitive inhibition state were first documented in 2009. At that time, it was noted that progressively higher daily dosing values of L-tyrosine decreased the magnitude of these fluctuations. While extensive statistical analysis has been performed by the authors since 2004, it was not until 2012 that a plausible explanation was formulated. In the process, correlations with L-tyrosine administration and the on/off effect of Parkinson's disease were defined. This paper documents the current knowledge with regard to the management of retrograde phase 1 dopamine fluctuations and investigates the hypothesis that they are caused by a melanin steal phenomenon. 

Retracted: No

PubPeer comments:
 Copy pasted from https: doi.org 10.2147 NDT.S308261 :  Hinz M, Stein A, Cole T. Neuropsychiatr Dis Treat. 2014;10:2331u20132337. The Editor-in-chief and Publisher of Neuropsychiatric Disease and Treatment wish to retract the published article. This perspective article cites several original research articles published by the authors, which have recently been retracted. This article draws on the findings from those original research articles to form central arguments and discussion, and as a result of the research articlesu2019 retraction, the argument presented in this article is no longer valid and the editor has determined it should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. Published 3 March 2021 Volume 2021:17 Pages 733u2014734. See also https: retractionwatch.com 2021 03 12 supplement-selling-doctor-who-ran-afoul-of-fda-and-state-medical-board-up-to-20-retractions ,
Focal adhesion kinase is involved in the migration of human osteosarcoma cells
Authors: Sujia Wu
K E Ren
Sitan Feng
Xiaoliang Sun
Xin Shi
Journal: Oncology letters (2015)
Discipline: CLINICAL MEDICINE
Keywords: focal adhesion kinase; lamellipodia; migration; osteosarcoma; subclone cell lines.

Abstract:  The aim of the present study was to analyze the expression of focal adhesion kinase (FAK) in osteosarcoma (OS) cell lines with different migration abilities in order to determine the role of FAK in migration. A number of different 143B subclone cell lines (A1, A2, A3, A4 and A5) were obtained by a limiting dilution method, and the expression of FAK was detected using western blot analysis. The role of FAK in the migration of OS cells was investigated using small interfering RNA (siRNA), and the ratio of the number of lamellipodia was compared by immunofluorescence staining. The A2 and A3 OS 143B subclone cell lines demonstrated a stronger migration ability and exhibited higher FAK expression compared with the A1 cell line (P&lt;0.05). Following transfection with FAK-siRNA, the migration ability of the A3 cells was significantly decreased (P&lt;0.05), and the ratio of the number of lamellipodia formed was reduced from 35 to 11% (P&lt;0.05). In conclusion, the level of FAK expression was higher in the cell lines with a stronger migration ability. FAK affects the migration ability of OS cells by suppressing the formation of lamellipodia. 

Retracted: No

PubPeer comments:
 Figure 8A. Much more similar than you would expect. https: imgur.com 0pLwQ2P , 
 Figure 3B. Much more similar than you would expect. https: imgur.com NAtGyZu ,
Ex Vivo Stromal Cell-Derived Factor 1-Mediated Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells into Hepatocytes Is Enhanced by Chinese Medicine Yiguanjian Drug-Containing Serum
Authors: Ying Zhu
Hailong Chen
Ling Wang
Linlin Fu
Bingyao Pang
Aijing Leng
Journal: Evidence-based Complementary and Alternative Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: Yiguanjian; liver diseases; liver fibrosis; traditional Chinese medicine; Stromal Cell-Derived Factor 1 (SDF-1)
Affiliations: Department of Infectious Disease, The First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Xigang District, Dalian 116011, China, Department of Digestive Disease, Gansu Provincial Hospital, Lanzhou 730000, China, Department of Chinese Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China

Abstract:  Yiguanjian is administered in traditional Chinese medicine for liver diseases and has been demonstrated to reduce liver fibrosis. This study investigated the effect of Yiguanjian drug-containing serum (YGJ) with Stromal Cell-Derived Factor 1 (SDF-1) and Hepatocyte Growth Factor (HGF) on the differentiation of murine bone-marrow-derived mesenchymal cells (BM-MSCs) into hepatocytes in vitro. Adherent MSCs were isolated from murine bone marrow. Differentiation was induced by 20 ng/mL HGF, 50 ng/mL SDF-1, and 20% Yiguanjian drug-containing serum for 7 to 28 days, and mature hepatocytes' marker albumin (ALB) and cholangiocytes' marker cytokeratin-18 (CK-18) were assessed by immunocytochemistry and western blot. BM-MSCs exhibited homogeneous spindle shape growth after subculture and stained positive for CD90 and negative for CD34. After induction with HGF + normal serum or YGJ for 14 days, HGF + SDF-1 + normal serum for 7 days, or HGF + SDF-1 + YGJ for 5 days, MSCs' morphology changed gradually and begun to resemble hepatocyte-like cells. Cultures supplemented with HGF + SDF-1 + YGJ contained significantly higher proportions of ALB and CK-18 positive cells than cultures supplemented with HGF + SDF-1 + normal serum at day 7. These observations corroborated the results of western blot. In conclusion, Yiguanjian drug-containing serum could facilitate the differentiation of murine BM-MSCs into hepatocytes in vitro and has a synergistic effect with SDF-1 and HGF. 

Retracted: No

PubPeer comments:
 The images in figure 1e and 3a appear to be the same. I am not sure that this is intentional. Could the authors comment? Indicated with red boxes. *** Close up, contrast enhanced; Figure 1 (3a below): ![file] *** Figure 1 ![file] *** Figure 3 ![file] , 
 What about these two image areas? ![file] ,
Overexpression of kinesins mediates docetaxel resistance in breast cancer cells
Authors: George R Stark
Rocky Cipriano
Sarmishtha De
Mark W Jackson
Journal: Cancer research (2009)
Discipline: CLINICAL MEDICINE
Keywords: chemotherapy resistance; docetaxel resistance; breast cancer; insertional mutagenesis; proteins
Affiliations: Department of Genetics and Pathology, Case Western Reserve University, Case Comprehensive Cancer Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Abstract:  Resistance to chemotherapy remains a major barrier to the successful treatment of cancer. To understand mechanisms underlying docetaxel resistance in breast cancer, we used an insertional mutagenesis strategy to identify proteins whose overexpression confers resistance. A strong promoter was inserted approximately randomly into the genomes of tumor-derived breast cancer cells, using a novel lentiviral vector. We isolated a docetaxel-resistant clone in which the level of the kinesin KIFC3 was elevated. When KIFC3 or the additional kinesins KIFC1, KIF1A, or KIF5A were overexpressed in the breast cancer cell lines MDA-MB231 and MDA-MB 468, the cells became more resistant to docetaxel. The binding of kinesins to microtubules opposes the stabilizing effect of docetaxel that prevents cytokinesis and leads to apoptosis. Our finding that kinesins can mediate docetaxel resistance might lead to novel therapeutic approaches in which kinesin inhibitors are paired with taxanes. 

Retracted: No

PubPeer comments:
 Figure 5. Much more similar and different than you would expect. https: imgur.com zuYb4S8 ,
Folic acid rivals methylenetetrahydrofolate reductase (MTHFR) gene-silencing effect on MEPM cell proliferation and apoptosis
Authors: Min Wu
Bing Shi
Wen-Lin Xiao
Journal: Molecular and Cellular Biochemistry (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: environmental factors; orofacial clefting; candidate genes; periconceptional folic acid supplementation; methylenetetrahydrofolate reductase (MTHFR) gene
Affiliations: Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu, The People's Republic of China.

Abstract:  It's clear that environmental factors play a role in the aetiology of orofacial clefting (OFC) and an important area of future research will be to unravel interactions that occur between candidate genes and environmental factors during early development of the embryo. Periconceptional folic acid supplementation may reduce the risk of OFC. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methylenetetrahydrofolate, the predominant circulating form of folic acid. To determine the effect of MTHFR gene mutation on murine embryonic palatal mesenchymal (MEPM) cells and the interaction with folic acid supplement, we used RNAi study in the primary cultures of MEPM cells. The cells of MTHFR gene silencing grew slower and the apoptosis cell number was more than the cells of control. Supplement with 20 microg/ml folic acid was the best to preventing teratogenic effect of MTHFR gene silencing. By flow cytometry analysis of cell cycle, results were shown that the MEPM cells were retarded in G(0)/G(1) after MTHFR gene silencing. While using 20 microg/ml folic acid supplements could make cell transit the G(1)/S restriction point and the cells growth was close to normal level. 

Retracted: No

PubPeer comments:
 This paper has a 2007 Erratum that reads:  The B graph was incomplete in Fig. 6. The bottom of B graph was covered partially by C graph. The correct picture is herewith reprinted. There is also a possible duplication in Figure 2, where two b-actin panels look very similar. Marked with blue boxes. Reported to the journal in October 2015, but no response as of today. ![file] ,
Influence of various lipid core on characteristics of SLNs designed for topical delivery of fluconazole against cutaneous candidiasis
Authors: Madhu Gupta
Suresh P Vyas
Shailja Tiwari
Journal: Pharmaceutical Development and Technology (0)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Dermal delivery; fluconazole; solid lipid nanoparticles; drug release; therapeutic efficacy
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical sciences, Dr. H. S. Gour Viswavidyalaya, Sagar-470003, MP, India.

Abstract:  Dermal delivery of fluconazole (FLZ) is still a major limitation due to problems relating to control drug release and achieving therapeutic efficacy. Recently, solid lipid nanoparticles (SLNs) were explored for their potential of topical delivery, possible skin compartments targeting and controlled release in the skin strata. The retention and accumulation of drug in skin is affected by composition of SLNs. Hence, the aim of this study was to develop FLZ nanoparticles consisted of various lipid cores in order to optimize the drug retention in skin. SLNs were prepared by solvent diffusion method and characterized for various in vitro and in vivo parameters. The results indicate that the SLNs composed of compritol 888 ATO (CA) have highest drug encapsulation efficiency (75.7 ± 4.94%) with lower particle size (178.9 ± 3.8 nm). The in vitro release and skin permeation data suggest that drug release followed sustained fashion over 24 h. The antifungal activity shows that SLNs made up of CA lipid could noticeably improve the dermal localization. In conclusion, CA lipid based SLNs are represents a promising carrier means for the topical treatment of skin fungal infection as an alternative to the systemic delivery of FLZ. 

Retracted: No

PubPeer comments:
 The authors write that  They observe an excess of 53 u00b1 15 events (a 3.5u03c3 Poisson significance) over the known background in the energy bins between (1u20137) keV with a peak between (2u20133) keV. It should be noted that the statistical significance depends on the specified alternate H_1. In this case, 3.5u03c3 is the significance of an axion detection, assuming the background B_0 as null. ,
Comparative proteomics analysis suggests that placental mitochondria are involved in the development of pre-eclampsia
Authors: Hongjuan Ding
Wei Long
Rong Shen
Chun Zhao
Zhonghua Shi
Xirong Guo
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Pre-eclampsia; Mitochondria; Proteins; iTRAQ analysis; LC-MS/MS
Affiliations: State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.

Abstract:  Introduction: Pre-eclampsia (PE), a severe pregnancy-specific disease characterized by the new onset of hypertension, proteinuria, edema, and a series of other systematic disorders, is a state of widespread mitochondrial dysfunction of the placenta. Methods: We compared the morphology of mitochondria in pre-eclamptic and normotensive placentae using electron microscopy. To reveal the systematic protein expression changes of placental mitochondria that might explain the pathogenesis of PE, we performed iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on differentially expressed placental mitochondria proteins from 4 normotensive and 4 pre-eclamptic pregnancies. Bioinformatics analysis was used to find the relative processes that these differentially expressed proteins were involved in. Three differentially expressed proteins were chosen to confirm by Western blotting and immunohistochemistry. Results: Morphological data demonstrated degenerative and apoptotic changes in the mitochondria of pre-eclamptic placentae. We found four proteins were upregulated and 22 proteins were downregulated in pre-eclamptic placentae compared with normotensive placentae. Bioinformatics analysis showed that these proteins were involved in many critical processes in the development of pre-eclampsia such as apoptosis, fatty acid oxidation, the respiratory chain, reactive oxygen species generation, the tricarboxylic acid cycle and oxidative stress. Conclusions: This preliminary work provides a better understanding of the proteomic alterations of mitochondria from pre-eclamptic placentae and may aid in our understanding of the importance of mitochondria in the development of pre-eclampsia. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: In the SPE row, the PRDX3 and TFRC panels appear to show an overlap * Green boxes: In the Control row, the HSPE1 and PRDX3 panels appear to show an overlap ![file] ,
Long noncoding RNA SNHG14 promotes breast cancer cell proliferation and invasion via sponging miR-193a-3p
Authors: L-D Jin
J Shen
W-H Zhao
C Qin
Y-X Chen
S-D Xie
J-C Zhou
L-B Wang
A-H Huang
Q-C Wang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Breast cancer; lncRNA SNHG14; development; metastasis; RT-qPCR
Affiliations: Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. .

Abstract:  Objective: Breast cancer (BC) is one of the most ordinary fatal cancers. Recent studies have identified the vital role of long noncoding RNAs (lncRNAs) in the development and progression of BC. In this research, lncRNA SNHG14 was studied to identify how it functioned in the development and metastasis of BC. Patients and methods: SNHG14 expression of tissues was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) in 50 paired patients with BC. And cell proliferation assay, colony formation assay, and transwell assay were enrolled to observe the biological behavior changes of BC cells through gain or loss of SNHG14. In addition, luciferase assays and RNA immunoprecipitation assay (RIP) were performed to discover the potential targets of SNHG14 in BC cells. Results: SNHG14 expression level of BC samples was higher than that of adjacent ones. Besides, cell growth ability and cell invaded ability of BC cells were inhibited after SNHG14 was silenced, while cell growth ability and cell invaded ability of BC cells were promoted after SNHG14 was overexpressed. In addition, miR-193a-3p was upregulated after silence of SNHG14 in BC cells, while miR-193a-3p was downregulated after overexpression of SNHG14 in BC cells. Furthermore, luciferase assays and RNA immunoprecipitation assay (RIP) showed that miR-193a-3p was a direct target of SNHG14 in BC. Conclusions: Our study uncovers a new oncogene in BC and suggests that SNHG14 could enhance BC cell proliferation and invasion via sponging miR-193a-3p, which provided a novel therapeutic target for BC patients. 

Retracted: Yes

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A91 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
CircUSP45 inhibited osteogenesis in glucocorticoid-induced osteonecrosis of femoral head by sponging miR-127-5p through PTEN/AKT signal pathway: Experimental studies
Authors: Dachuan Wang
Jian-Xiong Ma
Fei Xing
Ming-Jie Kuang
Lei Sun
Xin-Long Ma
Journal: Biochemical and Biophysical Research Communications (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Glucocorticoid-induced osteonecrosis of femoral head; circRNAs; miRNA.
Affiliations: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 300052, People's Republic of China., Tianjin Hospital, Tianjin, 300211, People's Republic of China., Department of Orthopedics, The Provincial Hospital Affiliated to Shandong University, Shandong, 250014, People's Republic of China., Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 300052, People's Republic of China. Electronic address: .

Abstract:  Purpose: large doses of glucocorticoids (GCs) are the most common cause of glucocorticoid-induced osteonecrosis of femoral head (GIONFH). Although awareness of GIONFH among patients with GCs history has increased over recent years, several studies indicate that its mechanism remains unclear. Methods: To evaluate the function of circUSP45 in GIONFH, femoral heads in GIONFH patients or femoral heads in fracture patients were collected. In vitro, RT-PCR, FISH, RNA pull down and Western blotting assay were used to evaluate the function of circUSP45. In addition, we also verified the effects of circUSP45 on osteogenesis using alizarin red staining. In vivo, we used HE staining and microCT analysis to evaluate the bone mass. Moreover, the mechanism of circUSP45 regulating osteogenesis through the miR-127-5p/PTEN/AKT pathway was also investigated. Results: The results showed that expression of circUSP45 increased in GIONFH patients. The overexpression of circUSP45 decreases osteogenic gene expression and inhibits the proliferation of BMSCs. Furthermore, circUSP45 was located mainly in the cytoplasm and directly interacted with miR-127-5p. MiR-127-5p acts with its targets PTEN to regulate the osteogenesis. MicroCT and HE staining verify the function of circUSP45 in GIONFH rat model. Conclusion: CircUSP45 decreases osteogenesis in bone GIONFH by sponging miR-127-5p through PTEN/AKT signal pathway. 

Retracted: No

PubPeer comments:
 Correction of the wrong figure 1. , 
 Dear Dr Spinosa, Thank you for your comment. The figure has been already corrected. It will be available soon in the new version of the review. Bests. Daria ,
Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland
Authors: Kristian Helin
Diego Pasini
Eros Lazzerini Denchi
Claire Attwooll
Journal: Molecular and Cellular Biology (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RB1; E2F transcription factors; pituitary tumors; transgenic mice; inducible E2F3 protein
Affiliations: Biotech Research and Innovation Center, Fruebjergvej 3, 2100 Copenhagen, Denmark., Department of Experimental Oncology, European Institute of Oncology, Milan, Italy, Biotech Research &amp; Innovation Center, Copenhagen, Denmark

Abstract:  The retinoblastoma gene, RB1, is one of the most frequently mutated genes in human cancer. Rb heterozygous mice develop pituitary tumors with 100% incidence, and the E2F transcription factors are required for this. To assess whether deregulated E2F activity is sufficient to induce pituitary tumors, we generated transgenic mice expressing an inducible E2F3 protein in the intermediate lobe of the pituitary gland. We found that short-term deregulation of E2F activity, similar to the earliest stages of Rb loss, is able to induce abnormal proliferation of otherwise quiescent melanotrophs. However, while long-term exposure to deregulated E2F activity results in hyperplasia of the intermediate lobe, it did not lead to tumor formation. In fact, melanotrophs become insensitive to sustained E2F stimulation and enter an irreversible senescence-like state. Thus, although deregulated E2F activity results in hyperproliferation, it is not sufficient to mimic loss of Rb, sustain proliferation of melanotrophs, and ultimately induce pituitary tumors. Similarly, we found that primary cells in tissue culture become insensitive to sustained E2F3 activation and undergo premature senescence in a pRB-, p16Ink4a-, and p19Arf-dependent manner. Thus, we conclude that deregulated E2F activity is not sufficient to fully mimic loss of Rb due to the engagement of a senescence response. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than expected. ![file] ,
miR-34a modulates angiotensin II-induced myocardial hypertrophy by direct inhibition of ATG9A expression and autophagic activity
Authors: Longgen Xiong
Benrong Liu
Shiming Liu
He Huang
Chuanfang Cheng
Jing Ye
Xiangyu You
Wen Sun
Jionghua Huang
Yun Zhong
Wei Pan
Journal: PloS one (2014)
Discipline: Multidisciplinary
Keywords: Cardiac hypertrophy; miRNA expression; autophagic activity; ATG9A; LC3 II/I
Affiliations: Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Cardiovascular Disease, Guangzhou, China.

Abstract:  Cardiac hypertrophy is characterized by thickening myocardium and decreasing in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. This study investigated altered miRNA expression and autophagic activity in pathogenesis of cardiac hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by heart morphology, induction of cardiomyocyte autophagy, altered expression of autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a expression. The in vitro data showed that in hypertrophic cardiomyocytes induced by Ang II, miR-34a expression was downregulated, whereas ATG9A expression was up-regulated. Moreover, miR-34a was able to bind to ATG9A 3'-UTR, but not to the mutated 3'-UTR and inhibited ATG9A protein expression and autophagic activity. The latter was evaluated by autophagy-related LC3 II/I and p62 levels, TEM, and flow cytometry in rat cardiomyocytes. In addition, ATG9A expression induced either by treatment of rat cardiomyocytes with Ang II or ATG9A cDNA transfection upregulated autophagic activity and cardiomyocyte hypertrophy in both morphology and expression of hypertrophy-related genes (i.e., ANP and β-MHC), whereas knockdown of ATG9A expression downregulated autophagic activity and cardiomyocyte hypertrophy. However, miR-34a antagonized Ang II-stimulated myocardial hypertrophy, whereas inhibition of miR-34a expression aggravated Ang II-stimulated myocardial hypertrophy (such as cardiomyocyte hypertrophy-related ANP and β-MHC expression and cardiomyocyte morphology). This study indicates that miR-34a plays a role in regulation of Ang II-induced cardiomyocyte hypertrophy by inhibition of ATG9A expression and autophagic activity. 

Retracted: No

PubPeer comments:
 Figures 3, 4, and 5. * Blue boxes: An ATG9A band in Figure 3D looks similar to n ATG9A band in Figure 5D * Red boxes: A GAPDH band in Figure 4D looks similar a GAPDH band in Figure 5C Reported to the journal in October 2015, but no update yet. ![file] ,
Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells
Authors: S H Hanissian
R S Geha
Journal: Immunity (1997)
Discipline: IMMUNOLOGY
Keywords: CD40; B lymphocytes; tyrosine phosphorylation; Jak3; STAT3
Affiliations: Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract:  CD40 is a receptor that is critical for the survival, growth, differentiation, and isotype switching of B lymphocytes. Although CD40 lacks intrinsic tyrosine kinase activity, its ligation induces protein tyrosine phosphorylation, which is necessary for several CD40-mediated events. We show that engagement of CD40 induces tyrosine phosphorylation and activation of Jak3 as well as of STAT3. Jak3 is constitutively associated with CD40, and this interaction requires a proline-rich sequence in the membrane-proximal region of CD40. Deletion of this sequence abolishes the capacity of CD40 to induce expression of CD23, ICAM-1, and lymphotoxin-alpha genes in B cells. These results indicate that signaling through Jak3 is activated by CD40 and plays an important role in CD40-mediated functions. 

Retracted: No

PubPeer comments:
 Figure 2A. Much more similar than expected. ![file] ,