PReD-Bench/PRed-Bench huggingface dataset:
Mechanistic role of p38 MAPK in gastric cancer dissemination in a rodent model peritoneal metastasis
Authors: Stefano Fiorucci
Emanuel Cavazzoni
Giuseppe Palladino
Luigina Graziosi
Barbara Renga
Andrea Mencarelli
Chiara Santorelli
Sabrina Cipriani
Annibale Donini
Stefan Laufer
Michael Burnet
Journal: European journal of pharmacology (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Peritoneal dissemination; poorly differentiated gastric cancers; mitogen-activated protein kinases (MAPKs); p38 MAPK inhibition; mouse model
Affiliations: Dipartimento di Dipartimento di Scienze Chirurgiche, Radiologiche e Odontostomatologiche, Nuova Facoltà di Medicina e Chirurgia, Sant' Andrea delle Fratte, 06132 Perugia, Italy.

Abstract:  Peritoneal dissemination is a highly frequent complication of poorly differentiated gastric cancers for which no effective therapies are available. Constitutive activation of mitogen-activated protein kinases (MAPKs) signaling cascades is recognized as a causative factor in the malignant transformation of several carcinoma cell types. In the present study we provide evidence that p38 MAPK inhibition protects against gastric cancer cells dissemination in a mouse model of peritoneal carcinomatosis. Administering mice with ML3403 and SB203580, potent and selective p38 MAPK inhibitors, attenuate the formation of neoplastic foci induced by intraperitoneal inoculation of gastric cancer cells. By gene array analysis we found that such a protective effect correlates with a robust downregulation in the expression of CXC chemokine receptor-4, Fms-related tyrosine kinase 4 (FLT4), the non-receptor spleen tyrosine kinase (SYK) and the collagen α2(IV) (COL4A2) in neoplasic foci. Inhibition of p38 MAPK in vivo increased the sensitivity of tumor cells to cisplatin and associated with a robust downregulation in the expression of the multidrug resistance (MDR)-1, a well defined marker of resistance to chemotherapy. In summary, p38 MAPK inhibition by a small molecule is beneficial in preventing the peritoneal dissemination of poorly differentiated gastric cancer cells by acting at multiple check-points in the process of attachment and diffusion of tumor cells in the peritoneum. 

Retracted: No

PubPeer comments:
null, 
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 ![file] the second and third panel in figure 2G shoud represent different IHC stainings, but actually are overlapping parts of the same picture ,
YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators
Authors: Qili Fei
Ian A Roundtree
Zhongyu Zou
Chuan He
Hui-Lung Sun
Journal: PLoS Biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: m6A modification; YTHDF2; mRNA decay; cell cycle; WEE1
Affiliations: Department of Chemistry, The University of Chicago, Chicago, Illinois, United States of America., Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, United States of America., Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, China., Medical Scientist Training Program, The University of Chicago, Chicago, Illinois, United States of America., Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, United States of America., Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, United States of America.

Abstract:  The N6-methyladenosine (m6A) modification regulates mRNA stability and translation. Here, we show that transcriptomic m6A modification can be dynamic and the m6A reader protein YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) promotes mRNA decay during cell cycle. Depletion of YTHDF2 in HeLa cells leads to the delay of mitotic entry due to overaccumulation of negative regulators of cell cycle such as Wee1-like protein kinase (WEE1). We demonstrate that WEE1 transcripts contain m6A modification, which promotes their decay through YTHDF2. Moreover, we found that YTHDF2 protein stability is dependent on cyclin-dependent kinase 1 (CDK1) activity. Thus, CDK1, YTHDF2, and WEE1 form a feedforward regulatory loop to promote mitotic entry. We further identified Cullin 1 (CUL1), Cullin 4A (CUL4A), damaged DNA-binding protein 1 (DDB1), and S-phase kinase-associated protein 2 (SKP2) as components of E3 ubiquitin ligase complexes that mediate YTHDF2 proteolysis. Our study provides insights into how cell cycle mediators modulate transcriptomic m6A modification, which in turn regulates the cell cycle. 

Retracted: No

PubPeer comments:
 Fig4F: GAPDH in this blot is exactly the same for both siCUL1 and siCUL4A. ,
PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells
Authors: Renjun Peng
Hui Cao
Zigui Chen
Zhiming Ma
Xin Wan
Quan Cheng
Bing Jiang
Journal: Molecular Medicine Reports (2014)
Discipline: CLINICAL MEDICINE
Keywords: PAX6; glioma; microRNA; miR-335; invasion
Affiliations: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China., Department of Neurosurgery, Brain Hospital of Hunan Province, The Affiliated Hospital of Hunan Traditional Chinese Medicine University, Changsha, Hunan 410007, P.R. China.

Abstract:  Paired box 6 (PAX6), a highly conserved transcription factor, is important in glioma. However, the molecular mechanisms involved remain unclear. The present study demonstrated that the expression of PAX6 was significantly reduced with the malignancy of glioma and also identified PAX6 as a novel target of microRNA (miR)‑335, which was significantly upregulated in glioma. The inhibition of miR‑335 increased the protein expression of PAX6, whereas the upregulation of miR‑335 suppressed its expression in human glioma U251 and U87 cells. Furthermore, upregulation of miR-335 promoted U251 cell proliferation, colony formation and invasion, which was reversed by the overexpression of PAX6. Furthermore, the present study demonstrated that the effect of miR‑335 on U251 cell invasion was via the modulation of matrix metalloproteinase (MMP)‑2 and MMP‑9 expression by targeting PAX6. In conclusion, the present study demonstrated that PAX6, as a novel target of miR‑335, has an anti‑oncogenic function in glioma, and thus PAX6 may serve as a therapeutic target for glioma. 

Retracted: Yes

PubPeer comments:
 Figure 2. * Red boxes: Panel B (0.7 mg ml) and panel C (0.5 mg ml) look remarkably similar. ![file] ,
STAT3 induces transcription of the DNA methyltransferase 1 gene (DNMT1) in malignant T lymphocytes
Authors: Qian Zhang
Anders Woetmann
Hong Y Wang
Niels Odum
Mariusz A Wasik
Puthiyaveettil N Raghunath
Journal: Blood (2006)
Discipline: CLINICAL MEDICINE
Keywords: STAT3; DNMT1; epigenetic gene silencing; oncogenic form; T lymphocytes
Affiliations: From the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Molecular Biology, University of Copenhagen, Copenhagen, Denmark.

Abstract:  In this study, we demonstrated that STAT3, a well-characterized transcription factor expressed in continuously activated oncogenic form in the large spectrum of cancer types, induces in malignant T lymphocytes the expression of DNMT1, the key effector of epigenetic gene silencing. STAT3 binds in vitro to 2 STAT3 SIE/GAS-binding sites identified in promoter 1 and enhancer 1 of the DNMT1 gene. STAT3 also binds to the promoter 1 region and induces its activity in vivo. Treatment of the malignant T lymphocytes with STAT3 siRNA abrogates expression of DNMT1, inhibits cell growth, and induces programmed cell death. In turn, inhibition of DNMT1 by a small molecule inhibitor, 5-aza-2-deoxy-cytidine, and 2 DNMT1 antisense DNA oligonucleotides inhibits the phosphorylation of STAT3. These data indicate that STAT3 may in part transform cells by fostering epigenetic silencing of tumor-suppressor genes. They also indicate that by inducing DNMT1, STAT3 facilitates its own persistent activation in malignant T cells. Finally, these data provide further rationale for therapeutically targeting STAT3 in T-cell lymphomas and, possibly, other malignancies. 

Retracted: No

PubPeer comments:
 Figure 4A. Much more similar than expected. ![file] ,
Variation in the group B Streptococcus CsrRS regulon and effects on pathogenicity
Authors: Manuela Puliti
Luciana Tissi
Sheng-Mei Jiang
Michael J Cieslewicz
Hervé Tettelin
Michael R Wessels
Nikhil Kumar
Julie Dunning Hotopp
Nadeeza Ishmael
Journal: Journal of Bacteriology (2008)
Discipline: MICROBIOLOGY
Keywords: CsrRS; CovRS; regulatory system; virulence factors; group B Streptococcus
Affiliations: Division of Infectious Diseases, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA., The J. Craig Venter Institute, Rockville, Maryland 20850, Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy, Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115

Abstract:  CsrRS (or CovRS) is a two-component regulatory system that controls expression of multiple virulence factors in the important human pathogen group B Streptococcus (GBS). We now report global gene expression studies in GBS strains 2603V/R and 515 and their isogenic csrR and csrS mutants. Together with data reported previously for strain NEM316, the results reveal a conserved 39-gene CsrRS regulon. In vitro phosphorylation-dependent binding of recombinant CsrR to promoter regions of both positively and negatively regulated genes suggests that direct binding of CsrR can mediate activation as well as repression of target gene expression. Distinct patterns of gene regulation in csrR versus csrS mutants in strain 2603V/R compared to 515 were associated with different hierarchies of relative virulence of wild-type, csrR, and csrS mutants in murine models of systemic infection and septic arthritis. We conclude that CsrRS regulates a core group of genes including important virulence factors in diverse strains of GBS but also displays marked variability in the repertoire of regulated genes and in the relative effects of CsrS signaling on CsrR-mediated gene regulation. Such variation is likely to play an important role in strain-specific adaptation of GBS to particular host environments and pathogenic potential in susceptible hosts. 

Retracted: No

PubPeer comments:
 **Please check these figure panels: Figure 4A, Figure 4B, and Figure 4C.** ![file] ![file] ![file] ,
Cellular interaction of folic acid conjugated superparamagnetic iron oxide nanoparticles and its use as contrast agent for targeted magnetic imaging of tumor cells
Authors: Uma Sharma
N R Jagannathan
Sameer Sapra
Amit K Dinda
Sujeet Mewar
Harpal Singh
Gurpal Singh
Vikas Arora
Manoj Kumar
Surender Kharbanda
Journal: International Journal of Nanomedicine (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: cancer-cell targeting ligand; cellular internalization; magnetic resonance imaging (MRI); superparamagnetic iron oxide nanoparticles (SPION).

Abstract:  The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8-10 nm), and relatively high T₂ relaxivity (R₂ = 222L · mmol⁻¹ · sec⁻¹). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T₂-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have two images which overlap, but are at different magnification. It seems that they are described as having been treated differently. *** ![file] ![file] ,
Identification of a Paracrine Signaling Mechanism Linking CD34high Progenitors to the Regulation of Visceral Fat Expansion and Remodeling
Authors: Aman Makaju
Maroua Ferhat
Sarah Franklin
Márcio Buffolo
Donald L Atkinson
Karla Maria Pires
Faith Bowman
Alan Achenbach
Bhagirath Chaurasia
Ez-Zoubir Amri
William L Holland
Olesya Ilkun
Sihem Boudina
Journal: Cell Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: adipose progenitors; cell sorting; fat expansion; transplantation; visceral fat.
Affiliations: Department of Nutrition and Integrative Physiology and Program in Molecular Medicine, University of Utah College of Health, Salt Lake City, UT 84112, USA., Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt Lake City, UT 84112, USA., Institut de Biologie Valrose, Université Nice Sophia Antipolis, 28, avenue de Valombrose, 06107 Nice Cedex 2, France., Department of Nutrition and Integrative Physiology and Program in Molecular Medicine, University of Utah College of Health, Salt Lake City, UT 84112, USA. Electronic address: .

Abstract:  Accumulation of visceral (VIS) is a predictor of metabolic disorders and insulin resistance. This is due in part to the limited capacity of VIS fat to buffer lipids allowing them to deposit in insulin-sensitive tissues. Mechanisms underlying selective hypertrophic growth and tissue remodeling properties of VIS fat are not well understood. We identified subsets of adipose progenitors (APs) unique to VIS fat with differential Cd34 expression and adipogenic capacity. VIS low (Cd34 low) APs are adipogenic, whereas VIS high (Cd34 high) APs are not. Furthermore, VIS high APs inhibit adipogenic differentiation of SUB and VIS low APs in vitro through the secretion of soluble inhibitory factor(s). The number of VIS high APs increased with adipose tissue expansion, and their abundance in vivo caused hypertrophic growth, fibrosis, inflammation, and metabolic dysfunction. This study unveils the presence of APs unique to VIS fat involved in the paracrine regulation of adipogenesis and tissue remodeling. 

Retracted: No

PubPeer comments:
 Figure 5(a). Much more similar than you would expect. https: imgur.com SRhJ1Zf ,
Plumbagin suppresses the migration and invasion of glioma cells via downregulation of MMP-2/9 expression and inaction of PI3K/Akt signaling pathway in vitro
Authors: Guanghui Chen
Jun Qin
Qing Ren
Xinping Xiao
Bin Xiao
Yan Yue
Journal: Journal of Pharmacological Sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Glioma; Invasion; Matrix metalloproteinase; Migration; Plumbagin.
Affiliations: Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China., Department of Obstetrics and Gynecology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China., Ultrasonic Imaging Division, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China. Electronic address: .

Abstract:  Plumbagin is a natural naphthoquinone constituent isolated from the roots of medicinal plant Plumbago zeylanica L., and has demonstrated anti-proliferative and anti-invasion activities in various cancer cells. However, its effect on the migration and invasion of glioma cells has not been elucidated. Therefore, human glioma U87 and U251 cells were treated with plumbagin at 1.0 and 2.0 μM for 24 h, and cell migration and invasion were assessed with scratch wound healing and invasion assays. The results showed that plumbagin significantly inhibited the migration and invasion of U87 and U251 cells, suppressed the activity and expression of MMP-2/-9, and inhibited the nuclear translocation of transcription factors Sp1 in the U87 and U251 cells. Moreover, plumbagin reduced the level of p-PI3K and p-Akt in these cells. The combined treatment with plumbagin and PI3K/Akt agonist insulin-like growth factor-1 (IGF-1) reversed plumbagin-mediated inhibitory effects on MMP-2/-9 expression, cell migration and invasion. These findings suggest that the plumbagin-induced inhibition of glioma cell migration and invasion is closely associated with the downregulation of MMP-2/-9 expression and activity, and suppression of PI3K/Akt signaling pathway activation. Thus, plumbagin might be a potential anti-invasive agent in the treatment of glioma. 

Retracted: No

PubPeer comments:
 *[left]* Fig. 3.  Effect of plumbagin on the invasion capacity of glioma cells in vitro. (A): The cells were treated with vehicle or plumbagin (1.0 and 2.0 u03bcM) for 24 h, and cell invasion was then tested by Matrigel-coated transwell system. Invasion cells on the bottom side of the membrane were fixed and stained with haematoxylin and eosin solution. *[right]* Figure 8 from [Wang et al (2019)] .  Transwell assay showing the effect of Evodiamine on the invasion of the SW480 cells. Evodiamine led to inhibition of cell invasion in SW480 cancer cells. ![] ,
The lncRNA SNHG3 accelerates papillary thyroid carcinoma progression via the miR‐214‐3p/PSMD10 axis
Authors: Feng Guo
Qiang Luo
Dan Fei
Butian Zhang
Guoqing Sui
Hui Wang
Journal: Journal of Cellular Physiology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PSMD10; SNHG3; miR-214-3p; papillary thyroid carcinoma.
Affiliations: Department of Ultrasonographic, China-Japan Union Hospital of Jilin University, Changchun, China., Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, China.

Abstract:  Small nucleolar RNA host gene 3 (SNHG3) is a long noncoding RNA (lncRNA), which is known to promote oncogenesis in many cancers but its role in human papillary thyroid carcinoma (PTC) remains poorly understood. We therefore assessed SNHG3 expression in PTC tissues via quantitative reverse transcription polymerase chain reaction. We additionally knocked down SNHG3 in PTC cells using short-hairpin RNAs (shRNAs) to explore its functional roles in PTC. The ability of SNHG3 to bind to specific microRNAs (miRNAs) was predicted using a bioinformatics tool, and this binding was confirmed via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. We then used a tumor xenograft model to assess the relevance of SNHG3 in vivo. We determined SNHG3 expression to be elevated in PTC tissues relative to controls, with advanced tumor-node-metastasis stage and lymph node metastasis being associated with this expression. Knocking down SNHG3 significantly reduced in vitro PTC cell migration, invasion, proliferation, and colony formation, and it further slowed the growth of tumors in vivo. We found that SNHG3 could bind to miR-214-3p as a competing endogenous RNA (ceRNA) for this miRNA, thereby regulating proteasome 26S subunit non-ATPase 10 (PSMD10) expression, a miR-214-3p target. These results thus indicate that SNHG3 is an oncogenic lncRNA in PTC, acting at least in part via the miR-214-3p/PSMD10 axis. 

Retracted: Yes

PubPeer comments:
 Fig 7(b).  Tumor tissues were imaged at the end of experiments. I assume from the variability of shadows here - sometimes present and sometimes not - that the image is a composite of tumors photographed separately. Could the authors confirm whether this is the case, or correct my error if I am mistaken? ![file] , 
 *[right]* Fig 2c.  Cell colony formation was determined in TPCu20101 cells transfected with shu2010NC or shu2010SNHG3 . *[left]* Fig 2C from [Fei et al (2020)] .  AFAP1-AS1 knockdown inhibited colony formation of U2OS cells . ![file] Different experiments; one panel is shared (with a 180-deg flip). , 
 Retracted [27 October 2021] . -------------------------- The above article, published online on 11 February 2020 in Wiley Online Library has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed after an investigation based on public allegations. The authors stated that unintentional errors occurred during the research process, and the experimental results cannot be verified. ,
The Effects of Omega-3 Fatty Acids Supplementation on Gene Expression Involved in the Insulin and Lipid Signaling Pathway in Patients with Polycystic Ovary Syndrome
Authors: Khadijeh Nasri
Esmat Aghadavod
Sedigheh Hantoushzadeh
Mohsen Taghizadeh
Zatollah Asemi
Journal: Hormone and Metabolic Research (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: omega-3 fatty acids; gene expression; insulin signaling pathway; lipid signaling pathway; polycystic ovary syndrome
Affiliations: Maternal-Fetal & Neonatal Research Center and Breast Feeding Research Center, Tehran University of Medical Sciences, Tehran, Iran, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran

Abstract:  Limited data are available evaluating the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid-signaling pathway in women with polycystic ovary syndrome (PCOS). This study was conducted to evaluate the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid signaling pathway in women with PCOS. This randomized double blind, placebo-controlled trial was done among 60 women aged 18-40 years old and diagnosed with PCOS according to the Rotterdam criteria. Participants were randomly assigned into 2 groups to receive either 1 000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid (n=30) or placebo (n=30) twice a day for 12 weeks. Gene expressions involved in the insulin and lipid-signaling pathway were quantified in blood samples of PCOS women with RT-PCR method. Quantitative results of RT-PCR demonstrated that compared with the placebo, omega-3 fatty acids supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) mRNA (p=0.005) in peripheral blood mononuclear cells of women with PCOS. In addition, compared to the placebo, omega-3 fatty acids supplementation downregulated expressed levels of oxidized low-density lipoprotein receptor (LDLR) mRNA (p=0.002) in peripheral blood mononuclear cells of women with PCOS. We did not observe any significant effect of omega-3 fatty acids supplementation on expressed levels of glucose transporter 1 (GLUT-1) and lipoprotein(a) [Lp(a)] genes in peripheral blood mononuclear cells. Overall, omega-3 fatty acids supplementation for 12 weeks in PCOS women significantly improved gene expression of PPAR-γ and LDLR. 

Retracted: No

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 A107 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 ,
A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5
Authors: Zhao Qingjie
Liu Chao
Cui Jin
Pan Panpan
Qin Longjuan
Zhang Zheng
Zhi Xin
Weng Weizong
Zhai Xiao
Su Jiacan
Chen Xiao
Cao Liehu
Hu Honggang
Journal: Frontiers in Pharmacology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: AKT pathway; RANKL; RPS5; matrine derivative; osteoclasts.

Abstract:  Post-menopausal osteoporosis (PMOP) is a metabolic bone disorder characterized by low bone mass and micro-architectural deterioration of bone tissue. The over-activated osteoclastogenesis, which plays an important role in osteoporosis, has become an important therapeutic target. M54 was a bioactive derivative of the Chinese traditional herb matrine. We found that M54 could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells and RAW264.7 cells through suppressing NF-κB, PI3K/AKT, and MAPKs pathways activity in vitro, and prevent ovariectomy-induced bone loss in vivo. Our previous study has proved that ribosomal protein S5 (RPS5) was a direct target of M19, based on which M54 was synthesized. Thus we deduced that M54 also targeted RPS5. During osteoclastogenesis, the RPS5 level in RAW264.7 cells was significantly down-regulated while M54 could maintain its level. After RPS5 was silenced, the inhibitory effects of M54 on osteoclastogenesis were partially compromised, indicating that M54 took effects through targeting RPS5. In summary, M54 was a potential clinical medicine for post-menopause osteoporosis treatment, and RPS5 is a possible key protein in PMOP. 

Retracted: No

PubPeer comments:
 Figures 2A and 3A. Much more similar than expected after 50% vertical stretch. https: imgur.com ypmA4a7 , 
 #1 Figure 3A. p130cas panel. Splicing between rightmost 2 lanes. https: i.imgur.com k3a3o1q.jpg ,
The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation
Authors: Hongyue Xu
Wenjing Luan
Yang Wang
Xinhua Cui
Jinyang Shi
Hong Zhou
Yuli Song
Keshu Shen
Yunxiao Ma
Lu Yu
Xudong Tang
Journal: International Journal of Biological Macromolecules (2022)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cloxacillin (CXN); Combination therapy; Staphylococcus aureus (S. aureus); Tetracycline (TC); Thioridazine (TZ)

Abstract:  Staphylococcus aureus (S. aureus) infection is difficult to fight, previous experimental reports have demonstrated thioridazine (TZ) and tetracycline (TC) is an inhibitor of S. aureus efflux pump NorA and autolysin Atl, respectively, here, by means of molecular docking and molecular dynamics simulation, we observed that thioridazine (TZ) and tetracycline (TC) blocked the binding of substrates to NorA and Atl, respectively, and reduced their activities, and our antibacterial susceptibility test and three-dimensional checkerboard method showed that the three-drug combination of antibiotic cloxacillin (CXN), TZ and TC had a synergistic anti-Staphylococcal activity in vitro, and α-Hemolysin tests and scanning electron microscopy showed that the three-drug combination and the subinhibitory concentration of the combination significantly inhibited the secretion of α-hemolysin relative to the number of membrane-derived vesicles produced by S. aureus. Whereas Western blot and pharmacological inhibition assays showed that the three-drug combination significantly inhibited the expression of MAPK/NF-κB/NLRP3 proteins in macrophages induced with S. aureus α-hemolysin. In vivo, the drug combination significantly reduced bacterial colony-forming unit counts in the viscera of a mouse peritonitis model of S. aureus infection, therapy reduced the primary inflammatory pathology and the bacteria-stimulated release of cytokines such as IL-1β and TNF-α, and inhibited the expression of MAPK/NF-κB/NLRP3 proteins in peritoneal macrophages. Thus, the combination of efflux pump inhibitor, autolysis inhibitor and antibiotic, is a novel anti-Staphylococcal and anti-inflammatory strategy who owning good antibacterial activity and significant inhibiting staphylococcal α-hemolysin and inflammation. 

Retracted: No

PubPeer comments:
 The image quality of western blot bands in fig 6, 7 and 9 are surprisingly poor, in sharp contrast with the clear text and plots. In addition, the original images of these bands seem to have strong heterogeneity. ![file] ![file] ![file] ,
Stretchable impedance sensor for mammalian cell proliferation measurements
Authors: Xudong Zhang
William Wang
Fang Li
Ioana Voiculescu
Journal: Lab on a Chip (2017)
Discipline: CHEMISTRY
Keywords: fabrication; testing; stretchable electric cell-substrate impedance sensing (ECIS); lab on a chip device; ECIS electrodes
Affiliations: The City College of New York, Mechanical Engineering Department, USA, Amity Regional High School, New York Institute of Technology

Abstract:  This paper presents the fabrication and testing of a novel stretchable electric cell-substrate impedance sensing (ECIS) lab on a chip device. This is the first time that ECIS electrodes were fabricated on a stretchable polydimethylsiloxane (PDMS) substrate and ECIS measurements were performed on mammalian cells exposed to cyclic strain. The stretchable ECIS biosensors simulate in vitro the dynamic environment of organisms, such as pulsation, bending and stretching, which enables investigations on cell behavior that undergoes mechanical stimuli in biological tissue. Usually cell-based assays used in cell mechanobiology rely on endpoint cell tests, which provide a limited view on dynamic cellular mechanisms. The ECIS technique is a label-free, real-time and noninvasive method to monitor the cellular response to mechanical stimuli. Bovine aortic endothelial cells (BAECs) have been used in this research because the BAECs are exposed in vivo to cyclic physiologic elongation produced by blood circulation in the arteries. These innovative stretchable ECIS biosensors were used to analyze the proliferation of BAECs under different cyclic mechanical stimulations. The results of fluorescence based cell proliferation assays confirmed that the stretchable ECIS sensors were able to analyze in real-time the BAEC proliferation. The novel stretchable ECIS sensor has the ability to analyse cell proliferation, determine the cell number and density, and apply mechanical stimulation at the same time. 

Retracted: No

PubPeer comments:
 This paper is mathematically erroneous. The correct solution to Stokes second problem for the second grade fluid can be found there: https: www.sciencedirect.com science article pii S002072251100228X?via%3Dihub [preprint at http: arxiv.org abs 1111.4464] ,
Three-dimensional periodontal tissue regeneration using a bone-ligament complex cell sheet
Authors: Otto Baba
Yoshizo Matsuka
Arief Waskitho
Masahisa Inoue
Resmi Raju
Masamitsu Oshima
Yan Huijiao
Tsuyoshi Morita
Miho Inoue
Journal: Scientific Reports (2020)
Discipline: Multidisciplinary
Keywords: Periodontal tissue; Cell sheet technology; Tissue regeneration; Stem/progenitor cells; Three-dimensional structure
Affiliations: Department of Stomatognathic Function and Occlusal Reconstruction, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, 770-8503, Japan., Department of Oral and Maxillofacial Anatomy, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, 770-8503, Japan., Laboratories for Structure and Function Research, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, 770-8055, Japan., Department of Stomatognathic Function and Occlusal Reconstruction, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, 770-8503, Japan. .

Abstract:  Periodontal tissue is a distinctive tissue structure composed three-dimensionally of cementum, periodontal ligament (PDL) and alveolar bone. Severe periodontal diseases cause fundamental problems for oral function and general health, and conventional dental treatments are insufficient for healing to healthy periodontal tissue. Cell sheet technology has been used in many tissue regenerations, including periodontal tissue, to transplant appropriate stem/progenitor cells for tissue regeneration of a target site as a uniform tissue. However, it is still difficult to construct a three-dimensional structure of complex tissue composed of multiple types of cells, and the transplantation of a single cell sheet cannot sufficiently regenerate a large-scale tissue injury. Here, we fabricated a three-dimensional complex cell sheet composed of a bone-ligament structure by layering PDL cells and osteoblast-like cells on a temperature responsive culture dish. Following ectopic and orthotopic transplantation, only the complex cell sheet group was demonstrated to anatomically regenerate the bone-ligament structure along with the functional connection of PDL-like fibers to the tooth root and alveolar bone. This study represents successful three-dimensional tissue regeneration of a large-scale tissue injury using a bioengineered tissue designed to simulate the anatomical structure. 

Retracted: No

PubPeer comments:
 ![file] ,
Modulation of endothelial cell morphogenesis in vitro by MMP-9 during glial-endothelial cell interactions
Authors: S Jasti
F Ali-Osman
W C Olivero
W K Alfred-Yung
S Mohanam
J S Rao
N Chandrasekar
D H Dinh
A P Kyritsis
G L Nicolson
M Gujrati
Journal: Clinical & Experimental Metastasis (2000)
Discipline: CLINICAL MEDICINE
Keywords: matrix metalloproteinase-9 (MMP-9); tissue inhibitor of metalloproteinase-1 (TIMP-1); capillary structures; brain microvascular endothelial cells; SNB19 glioblastoma cells
Affiliations: Department of Biomedical and Therapeutic Sciences, UIC College of Medicine at Peoria, Illinois 61656, USA.

Abstract:  The purpose of this study was to investigate the roles of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the formation of capillary structures by human brain microvascular endothelial cells cocultured with SNB19 glioblastoma cells. Unstimulated cocultures did not form capillaries and produce MMP-9 but stimulation with the protein kinase C (PKC) activator 4-phorbol-12-myristate 13-acetate (PMA) produced MMP-9 and capillary networks. Addition of recombinant MMP-9 increased capillary formation. Anti-MMP-9 antibodies, TIMP-1, the synthetic MMPs inhibitor Batimastat (BB-94), and the PKC inhibitor calphostin-C all reduced MMP-9 activity and capillary network formation in these cocultures. Cytochalasin-D in the presence of PMA suppressed MMP-9 expression and capillary formation, but colchicine-B had no such effect. Finally, PMA-induced MMP-9 expression and capillary formation were inhibited by the MEKK-specific inhibitor PD98059. These results suggest that MMP-9 is important in endothelial cell morphogenesis and the formation of capillaries in glial/endothelial cocultures in vitro. 

Retracted: No

PubPeer comments:
 Figure 2, 3, and 4. * Shown in red: The first two lanes in the TIMP-1 panels of Figure 2A, 2B, 3B, and 4B all appear to look similar, while the adjacent lanes are different in each panel. The lanes could show the same conditions, but that means that the other lanes might actually not have run adjacent or even in the same gel. This makes it hard to judge if lanes are of the same size or exposure. * Shown in yellow: Two lanes in the MMP panels of Figure 2A, 3A, and 4A all appear to look similar, while the adjacent lanes are different in each panel. The lanes could show the same conditions, but that means that the other lanes might actually not have run adjacent or even in the same gel. This makes it hard to judge if lanes are of the same size or exposure. ![file] , 
 In addition to the above concerns, with which I agree, there appear to be two images in Figure 1 that overlap, after 90-degree rotation. *** ![file] ,
Minocycline attenuates hypoxia-inducible factor-1α expression correlated with modulation of p53 and AKT/mTOR/p70S6K/4E-BP1 pathway in ovarian cancer: in vitro and in vivo studies
Authors: Parvin Ataie-Kachoie
Mohammad H Pourgholami
Samina Badar
Farnaz Bahrami-B
David L Morris
Journal: American journal of cancer research (2015)
Discipline: CLINICAL MEDICINE
Keywords: AKT; HIF-1; Minocycline; VEGF; mTOR
Affiliations: Department of Surgery, St George Hospital Sydney, Australia., University of New South Wales Department of Surgery, St George and Sutherland Clinical School Sydney, Australia., Department of Surgery, St George Hospital Sydney, Australia ; University of New South Wales Department of Surgery, St George and Sutherland Clinical School Sydney, Australia.

Abstract:  Hypoxia-inducible factor (HIF)-1α is the key cellular survival protein under hypoxia, and is associated with tumor progression and angiogenesis. We have recently shown the inhibitory effects of minocycline on ovarian tumor growth correlated with attenuation of vascular endothelial growth factor (VEGF) and herein report a companion laboratory study to test if these effects were the result of HIF-1α inhibition. In vitro, human ovarian carcinoma cell lines (A2780, OVCAR-3 and SKOV-3) were utilized to examine the effect of minocycline on HIF-1 and its upstream pathway components to elucidate the underlying mechanism of action of minocycline. Mice harboring OVCAR-3 xenografts were treated with minocycline to assess the in vivo efficacy of minocycline in the context of HIF-1. Minocycline negatively regulated HIF-1α protein levels in a concentration-dependent manner and induced its degradation by a mechanism that is independent of prolyl-hydroxylation. The inhibition of HIF-1α was found to be associated with up-regulation of endogenous p53, a tumor suppressor with confirmed role in HIF-1α degradation. Further studies demonstrated that the effect of minocycline was not restricted to proteasomal degradation and that it also caused down-regulation of HIF-1α translation by suppressing the AKT/mTOR/p70S6K/4E-BP1 signaling pathway. Minocycline treatment of mice bearing established ovarian tumors, led to suppression of HIF-1α accompanied by up-regulation of p53 protein levels and inactivation of AKT/mTOR/p70S6K/4E-BP1 pathway. These data reveal the therapeutic potential of minocycline in ovarian cancer as an agent that targets the pro-oncogenic factor HIF-1α through multiple mechanisms. 

Retracted: No

PubPeer comments:
 Figure 6 appears to have a repeated band. Could the authors please post the original images? As the first author appears to have left this lab, perhaps Dr. Morris could investigate that authoru2019s papers. I have found issues which each I have reviewed. *** ![file] ,
A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis
Authors: B A Croy
A Champagne
E D Lightbody
F Pouliot
Y Hao
A Ghaffari
B Neveu
X Yang
C J B Nicol
V R Kay
H J Janse van Rensburg
B Yeung
H Shen
K L Guan
J Zhang
T Azad
Journal: Nature communications (2018)
Discipline: Multidisciplinary
Keywords: Hippo pathway; LATS kinase; VEGFR; VEGF; PI3K/MAPK signaling
Affiliations: Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada, K7L3N6., Department of Surgery (Urology), CHU de Québec-Université Laval Research Center, Laval University, Quebec, Ontario, Canada, G1V 0A6., Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada, K7L 3N6., Department of Cancer Genetics and Genomics, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA., Department of Pharmacology, University of California at San Diego, La Jolla, CA, 92093, USA., Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada, K7L3N6. .

Abstract:  The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ. We further show that the Hippo pathway is a critical mediator of VEGF-induced angiogenesis and tumor vasculogenic mimicry. Thus, our work offers a biosensor tool for the study of the Hippo pathway and suggests a role for Hippo signaling in regulating blood vessel formation in physiological and pathological settings. 

Retracted: No

PubPeer comments:
 The conclusion of this article is challenged by a recent study in Developmental Cell. https: www.cell.com developmental-cell fulltext S1534-5807(20)30007-1 Azad et al. demonstrated that Yap is required for vascular formation in vivo. On the other hand, Lundin et al. indicated that loss of Yap did not show any change in vascular formation in vivo. While the models are different, Azad used mouse neonate and Lundin used zebrafish embryo, could the authors explain the difference in their observations? , 
 #1 ![file] ,
Sevoflurane attenuates brain damage through inhibiting autophagy and apoptosis in cerebral ischemia‑reperfusion rats
Authors: Ke-Zhong Li
Teng Song
Jia-Hai Ma
Xue-Qin Wang
Jin Jin
Guang-Hong Li
Cun-Xian Shi
Journal: Molecular Medicine Reports (2019)
Discipline: CLINICAL MEDICINE
Keywords: sevoflurane; cerebral ischemia-reperfusion injury; autophagy; apoptosis; Toll-like receptor-4-nuclear factor-κB.
Affiliations: Department of Anesthesiology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China., Department of Anesthesiology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China., Department of Neurosurgery, Heze Municipal Hospital, Heze, Shandong 274000, P.R. China.

Abstract:  The present study aimed to investigate the effects of sevoflurane post‑conditioning in a rat brain cerebral ischemia‑reperfusion (I/R) model and examine its possible mechanism. Rats were randomly divided into six groups: Sham control group (Sham), I/R group, sevoflurane group (Se), Toll‑like receptor‑4 (TLR4) inhibitor group (Tak‑242), nuclear factor (NF)‑κB inhibitor group (QNZ) and Sevoflurane post‑conditioning combined with TLR4‑NF‑κB signaling pathway inhibitor group (Se + Tak‑242). Morris water maze test and tetrazolium chloride staining were used to investigate the I/R injury. The nerve cell apoptosis and autophagy in cortical tissue were detected by TUNEL and transmission electron microscopy, respectively. The expression of TLR4 protein in cortical tissue was observed by immunohistochemical staining. The expression of autophagy and apoptotic associated proteins in cortical tissues and the activity of TLR4‑NF‑κB signaling pathway were assayed by western blot analysis. Sevoflurane post‑conditioning improved the learning and memory dysfunction caused by cerebral I/R injury. The cerebral infarction area, nerve cell apoptosis and formation of autophagic vacuoles were reduced after sevoflurane administration. The expression of light chain 3II/I, Beclin‑1, Bad and Cleaved‑Caspase‑3 proteins were inhibited and the expression of Bcl‑2 protein was upregulated after sevoflurane administration. Sevoflurane post‑conditioning also inhibited the TLR4 protein and NF‑κB phosphorylation, and increased inhibitor of kBα phosphorylation. The treatment effect of Tak‑242 and QNZ groups were not significantly different compared with the Se group (P&gt;0.05), and the Se + Tak‑242 group had the best results. The present study demonstrated that sevoflurane post‑conditioning could protect middle cerebral artery occlusion‑induced brain injury rats by inhibiting autophagy and apoptosis, and that its mechanism is related to the TLR4‑NF‑κB signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 4A. * Marked in red: The Tak-242 and the Se+Tak-242 panels appear to show an overlap. ![file] , 
 Figure 6A and 7A. * Marked in green: The beta-actin panel from Figure 6A looks remarkably similar to the NF-kB panel in Figure 7A. ![file] ,
Cell surface-associated Tat modulates HIV-1 infection and spreading through a specific interaction with gp120 viral envelope protein
Authors: Serena Marchiò
Enrico De Vivo
Luca Primo
Massimo Alfano
Daniela Gramaglia
Luisa Gennero
Federico Bussolino
Mauro Giacca
Renata Pasqualini
Wadih Arap
Luca Butini
Journal: Blood (2005)
Discipline: CLINICAL MEDICINE
Keywords: HIV-1; Tat; extracellular; heparan sulfate proteoglycans; cell surface
Affiliations: Division of Molecular Angiogenesis, Department of Oncological Sciences, University of Turin Medicine School, Institute for Cancer Research and Treatment, Sp 142, km 3.95-10060 Candiolo (TO) Italy. 

Abstract:  Human immunodeficiency virus-1 (HIV-1) Tat, a nuclear transactivator of viral gene expression, has the unusual property of being released by infected cells. Recent studies suggest that extracellular Tat is partially sequestered by heparan sulfate proteoglycans. As a consequence, Tat is concentrated on the cell surface and protected from proteolytic degradation, thus remaining in a biologically active form. We show that Tat binds the surfaces of both HIV-1-infected and surrounding uninfected cells. We provide evidence for a specific interaction between Tat and the HIV-1 glycoprotein 120 (gp120) envelope protein, which enhances virus attachment and entry into cells. We map the interacting sites of both Tat and gp120 and show that synthetic peptides mimicking the gp120 site inhibit HIV-1 infection. Our data demonstrate that membrane-associated Tat is a novel modulator of virus entry and suggest that the Tat-gp120 interaction represents a critical step in HIV-1 spreading during the course of infection. 

Retracted: No

PubPeer comments:
 Figure 4A. Much more similar than you would expect. https: imgur.com Tns7DH7 , 
 Thank you for appreciating the reproducibility of GAPDH, our loading control!!! , 
 #2 RE: * Thank you for appreciating the reproducibility of GAPDH, our loading control!!! * This has nothing to do with  reproducibility . Those two images are clearly duplicates, not just similar. Yet they are supposed to be different samples (from infections with two different HIV-1 strains). Thus, it is inescapable that one (or both) of these images must be erroneous. , 
 #2 Surely you want a control after the cells have been infected? The cells infected with either III B, or Ba-L, are different. https: imgur.com WzUIwo7 , 
 Perhaps this will encourage the authors to correct this paper. *** False color ![file] ,