PReD-Bench/PRed-Bench huggingface dataset:
Long Noncoding RNA MALAT1 Regulates Hepatocellular Carcinoma Growth Under Hypoxia via Sponging MicroRNA-200a
Authors: Zheng Bin Zhao
Xiao Fang Bai
Fei Chen
Journal: Yonsei Medical Journal (2019)
Discipline: CLINICAL MEDICINE
Keywords: HCC; MALAT1; hypoxic; miR-200a; proliferation.
Affiliations: Infection Department, The First Hospital of Lanzhou University, Lanzhou, China., Department of Ultrasound, The First Hospital of Lanzhou University, Lanzhou, China. ., Department of Ultrasound, The First Hospital of Lanzhou University, Lanzhou, China.

Abstract:  Purpose: Hepatocellular carcinoma (HCC) is a common cancer worldwide. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA), has been reported to be aberrantly expressed in hypoxic cancer cells. MALAT1 plays a significant role in many malignancies, including HCC. The aim of this study was to explore the role of MALAT1 in hypoxic HCC cells and its underlying regulatory mechanism. Materials and methods: Quantitative reverse transcription PCR (qRT-PCR) assay was performed to detect the mRNA levels of MALAT1 and microRNA-200a (miR-200a) in HCC cells. Cell invasion and migration ability were evaluated by Transwell assay. Starbase v2.0 and luciferase reporter assay were employed to identify the association between MALAT1 and miR-200a. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. Results: MALAT1 levels were significantly upregulated in HCC cells under hypoxia. Hypoxia promoted proliferation, migration, and invasion, and blocked apoptosis in Hep3B cells, which were weakened by knockdown of MALAT1. Starbase v2.0 showed that MALAT1 and miR-200a have a complementarity region, and luciferase reporter assay verified that MALAT1 interacted with miR-200a in Hep3B cells. Moreover, MALAT1 negatively regulated the expression of miR-200a. miR-200a levels were dramatically downregulated in HCC cells under hypoxia. Upregulation of miR-200a inhibited proliferation, migration, and invasion, and induced apoptosis in Hep3B cells under hypoxia. Interestingly, downregulation of miR-200a partially reversed the tumor-suppressive effect of knockdown of MALAT1 on Hep3B cells in hypoxic condition. Conclusion: LncRNA MALAT1 was involved in proliferation, migration, invasion, and apoptosis by interacting with miR-200a in hypoxic Hep3B cells, revealing a new mechanism of MALAT1 involved in hypoxic HCC progression. 

Retracted: No

PubPeer comments:
 Fig. 3.  Cell migration (A) and invasion (B) were evaluated by Transwell assay. Overlap marked. ![file] ,
Effect of Paclitaxel/etoposide co-loaded polymeric nanoparticles on tumor size and survival rate in a rat model of glioblastoma
Authors: Hossein Ghanbari
Masood Khosravani
Esmaeil Sadroddiny
Hassan Maleki
Mahdi Adabi
Mahmoud Reza Hadjighassem
Mohammad Reza Hosseini Najafabadi
Thomas J Webster
Journal: International Journal of Pharmaceutics (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Chemotherapy; Etoposide; Glioblastoma; Nanoparticle; Paclitaxel
Affiliations: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran., Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran., Chemical Engineering Department, Northeastern University, Boston, MA 02115, USA., Brain and Spinal Cord Injury research center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran., Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran., Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: .

Abstract:  The aim of this work is to co-load paclitaxel (PTX) and etoposide (ETP) in methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (mPEG-PLGA NPs) to overcome pharmacokinetics and physiological limitations and enhance therapeutic efficacy for treating intracranial glioblastoma. Both drugs were loaded into mPEG-PLGA NPs by a nano-precipitation method. The resultant NPs demonstrated an enhanced cytotoxic effect indicated by lower IC50 values and augmented cell apoptosis to U87 and C6 glioma cell lines compared to both free drugs. Additionally, blood compatibility assays showed that the PTX/ETP co-loaded mPEG-PLGA NPs did not induce blood hemolysis, blood clotting, or platelet aggregation. In vivo anti-glioma efficacy evaluation in rats bearingintracranialC6glioma revealed a superior anti-glioma activity for the treatment with PTX/ETP co-loaded mPEG-PLGA NPs compared to other formulations, particularly a significantly longer median survival, 76 days compared to 36 days for free PTX and 37 days for free ETP treatment, respectively, and higher tumor regression, proved by magnetic resonance imaging (MRI). 

Retracted: No

PubPeer comments:
 Figure 6 may have some repeated images, although they are cropped differently, suggesting that these (if accurately identified) were not merely errors during figure assembly. Could the authors please check? I will add the email addresses for the 2 corresponding authors. It is my understanding that Dr. Webster is no longer affiliated with Northeastern, so I am unsure what address to use for him. *** ![file] ,
Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms
Authors: Alexandre Blais
Guohong Li
Christopher L Woodcock
Brian D Dynlacht
Danny Reinberg
Kavitha Sarma
Raphael Margueron
Jiri Zavadil
Journal: Molecular Cell (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Polycomb group proteins; PRC2 complex; Ezh1; Ezh2; gene repression
Affiliations: Department of Biochemistry, New York University Medical School, 522 First Avenue, New York, NY 10016, USA.

Abstract:  Polycomb group proteins are critical to maintaining gene repression established during Drosophila development. Part of this group forms the PRC2 complex containing Ez that catalyzes di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), marks repressive to transcription. We report that the mammalian homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting repressive roles. While PRC2-Ezh2 catalyzes H3K27me2/3 and its knockdown affects global H3K27me2/3 levels, PRC2-Ezh1 performs this function weakly. In accordance, Ezh1 knockdown was ineffectual on global H3K27me2/3 levels. Instead, PRC2-Ezh1 directly and robustly represses transcription from chromatinized templates and compacts chromatin in the absence of the methyltransferase cofactor SAM, as evidenced by electron microscopy. Ezh1 targets a subset of Ezh2 genes, yet Ezh1 is more abundant in nonproliferative adult organs while Ezh2 expression is tightly associated with proliferation, as evidenced when analyzing aging mouse kidney. These results might reflect subfunctionalization of a PcG protein during evolution. 

Retracted: No

PubPeer comments:
 Figure 3A. Much more similar than expected. ![file] , 
 Figure 6. * Some unexpected similarities between features within the same panel, as shown with boxes of the same color. ![file] Supported by ImageTwin on high-res partial screenshots from the PMC image. Colors do not correspond to my color choice above. ![file] , 
 #2 Agreed; these similarities are striking. Also, it is worth noting that the journal provides a very high quality image, if you click on the link labeled  Download Hi-res image . Finally, it is unfortunate that Chris Woodcock, the microscopist who might have been the one to have acquired these images, passed away earlier this year . This could complicate investigation of these isssues. ,
p38-MAPK signaling pathway is not involved in osteogenic differentiation during early response of mesenchymal stem cells to continuous mechanical strain
Authors: Peng Zhang
Bing Fang
Lingyong Jiang
Qinggang Dai
Yuqiong Wu
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mechanical stimuli; bone remodeling; orthodontic tooth movement; mechanical strain; bone mesenchymal stem cells
Affiliations: Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Shanghai 9th People's Hospital, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Abstract:  Mechanical stimuli play a significant role in the regulation of bone remodeling during orthodontic tooth movement. However, the correlation between mechanical strain and bone remodeling is still poorly understood. In this study, we used a model of continuous mechanical strain (CMS) on bone mesenchymal stem cells (BMSCs) to investigate the proliferation and osteogenic differentiation of BMSCs and the mechanism of mechano-transduction. A CMS of 10 % at 1 Hz suppressed the proliferation of BMSCs and induced early osteogenic differentiation within 48 h by activating Runx2 and increasing alkaline phosphatase (ALP) activity and mRNA expression of osteogenesis-related genes (ALP, collagen type I, and osteopontin). Regarding mitogen-activated protein kinase (MAPK) activation, CMS induced phased phosphorylation of p38 consisting of a rapid induction of p38 MAPK at 10 min and a rapid decay after 1 h. Furthermore, the potent p38 inhibitor SB203580 blocked the induction of p38 MAPK signaling, but had little effect on subsequent osteogenic events. These results demonstrate that mechanical strain may act as a stimulator to induce the differentiation of BMSCs into osteoblasts, which is a vital function for bone formation in orthodontic tooth movement. However, activation of the p38 signaling pathway may not be involved in this process. 

Retracted: No

PubPeer comments:
 Figure 5EF * Purple boxes: Panels E and F appear to look identical. It is not clear from the legend what they show, but the text in the results suggests they are different treatments. Maybe the authors can clarify if these two images are expected to look so similar. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. I would love to hear from the authors if the journal ever contacted them in the past five years. ![file] ,
MicroRNA-31 inhibits papillary thyroid carcinoma cell biological progression by directly targeting SOX11 and regulating epithelial-to-mesenchymal transition, ERK and Akt signaling pathways
Authors: C-X Zhou
B-G Liu
Y Wang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-31; SOX11; papillary thyroid carcinoma; PTC; cell proliferation
Affiliations: Department of Breast and Thyroid Surgery, Liaocheng People's Hospital, Liaocheng, China. .

Abstract:  Objective: The current study aimed to explore the roles of miR-31 and SOX11 in papillary thyroid carcinoma (PTC). Patients and methods: Fifty-four paired human PTC specimens and matched normal thyroid tissues were obtained. Meanwhile, human thyroid epithelial cell Nthy-ori3-1 and PTC cells were cultured. The effects of miR-31 on PTC cell proliferation, invasion and migration were detected by cell proliferation assays and transwell assay, respectively. SOX11 expression in tissue samples was examined by immunohistochemical staining analyses (IHC). The correlation between SOX11 and miR-31 was clarified by Dual-Luciferase reporter assay. The relative mRNA and protein expression were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. In addition, the xenograft model experiments were performed. Results: Declined miR-31 expressions were frequently identified in PTC, leading to poorer overall survival (OS) and worse clinicopathologic features of PTC patients. Moreover, functional assays indicated that miR-31 overexpression could notably repress PTC cell proliferation, invasion and migration abilities by regulating the extracellular regulated protein kinases (ERK) and protein kinase B (Akt) signaling pathways and epithelial-mesenchymal transition (EMT). In addition, the results of the Luciferase reporter assay demonstrated that SOX11 was a direct functional target of miR-31 in PTC cells. In vivo, miR-31 restoration significantly suppressed the tumor growth of xenograft PTC models. Conclusions: Our findings indicated that miR-31 exerted anti-PTC functions via targeting SOX11 and modulating the ERK and Akt signaling pathways and EMT. MiR-31 may potentially serve as a novel biomarker in future therapeutics of PTC. 

Retracted: No

PubPeer comments:
  Fifty-four pairs of human PTC specimens and matched normal thyroid tissues were obtained from PTC patients who underwent thyroid cancer resection surgery at the Liaocheng Peopleu2019s Hospital from **May 2015 to October 2017**. According to Figs 1b and 5a, the authors followed their patients survival for five years after recruiting them, i.e. through to the date range **May 2020 to October 2022**. For a paper published in July 2019. Was a time machine involved? ![file] ,
Structural Characterization, Molecular Docking and Protective Effect on Coronary Artery Disease of a New Nanostructured Cu(II)-Coordination Polymer by Reducing the Inflammatory Level
Authors: Liu, Zhen
Li, Yi
Dong, Fengquan
Li, Haiying
Zhou, Lei
Journal: Journal of Inorganic and Organometallic Polymers and Materials (2020)
Discipline: CHEMISTRY
Keywords: Cu(II)-based coordination complexes; anticancer agents; coordination polymer; nano 1; coronary heart disease treatment

Abstract: The development of Cu(II)-based coordination complexes as potent anticancer agents has received increasing attention in recent years. In this study, a novel Cu(II) bearing coordination polymer formulated as [Cu2(bix)(aip)2(H2O)2]n (1, bix\u2009=\u20091,4‐bis(imidazol‐1‐ylmethyl)benzene, H2aip\u2009=\u20095‐aminoisophthalic acid) has been triumphantly prepared by the reaction of Cu(NO3)2·3H2O, bix and H2aip under the hydrothermal condition. Furthermore, the ultrasonic synthesis method was used to produce the nanoscale 1 (denoted as nano 1 hereafter) with the particle size in the range of 360&nbsp;nm. The protective effect of nano 1 on the coronary heart disease treatment was evaluated. Western blot was utilized to detect the relative expression of AMPK/SIRT1/NF-κB pathway, and the ROS detection was performed to measure the (reactive oxygen species) ROS level in the cells. Analysis further performed by molecular docking shows that Cu(II) complex possess the drug-like criteria indicating the anti-coronary heart disease potential.

Retracted: No

PubPeer comments:
 *[left]* Fig 2b,  The SEM diagram of 1 . *[right]* Fig 3d from [Lu et al (2020)] ,  The SEM diagrams of complexes 1 and 2 . ![file] , 
 Fig 2  c The SEM *[sic]* diagram of nano 1. d The DLS curve for the nano 1 ![file] Fig 3 of [Ma et al (2020)] . Many more manifestations are listed in [Zheng Yang (2020)] . ![] , 
 #1 Fig 2b again: ![] Another sighting! Supplementary Fig S1 from [Zhou Zhang (2021)] . ![] ,
MicroRNA-370 inhibits the proliferation, invasion and EMT of gastric cancer cells by directly targeting PAQR4
Authors: Yongjian Gao
Xuefeng Wang
Ye Feng
Yabo Yu
Tao Sun
Zhi Chen
Journal: Journal of Pharmacological Sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Gastric cancer; Invasion; MicroRNA-370; PAQR4; Proliferation.
Affiliations: Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Jilin, 130033, China., Department of Nephrology, First Hospital of Jilin University, Jilin, 130021, China., Department of Gastroenterology and Nephrology, General Hospital of Jilin Oilfield, Jilin, 130000, China., Department of Nephrology, First Hospital of Jilin University, Jilin, 130021, China. Electronic address: .

Abstract:  It has been reported that PAQR4 (Progestin and AdipoQ Receptor 4) expression is closely associated with progression of many cancers and microRNA (miRNA) processing. However, the effects and its precise mechanisms of PAQR4 in gastric cancer (GC) have not been well clarified. Our study aimed to explore the interaction between PAQR4 and miR-370 in GC. In our study, we found that the miR-370 level was significantly down-regulated in GC tissues and cell lines, and the expression of PAQR4 was dramatically increased. Interestingly, the low miR-370 level was closely associated with up-regulated PAQR4 expression in GC tissues. Moreover, introduction of miR-370 dramatically suppressed proliferation, invasion and EMT of GC cells. Whereas, miR-370 knockdown increased the proliferation, invasion and EMT in GC cells. We demonstrated that miR-370 could directly target PAQR4 by using both bioinformatics analysis and luciferase reporter assay. In addition, PAQR4 silencing had the similar effects with miR-370 overexpression on GC cells. Overexpression of PAQR4 in GC cells partially reversed the inhibitory effects of miR-370 mimic. miR-370 inhibited cell proliferation, invasion and EMT of GC cells by directly down-regulating PAQR4 expression, and miR-370 targeting PAQR4 was responsible for inhibition of the proliferation, invasion and EMT of GC cells. 

Retracted: No

PubPeer comments:
 Figs 3B and 4. A band seems to have been repeated, differently labeled. Could the authors check? ![file] , 
 Fig 1F.  Pearson s correlation analysis of the relative expression levels of miR-370 and the relative PAQR4 mRNA levels in GC tissues. ![file] In a subset of human samples, the expression of miR-370 and the relative PAQR4 mRNA levels display a linear relationship. Perhaps this phenomenon deserves further study. ,
Fasting inhibits the growth and reproductive axes via distinct Y2 and Y4 receptor-mediated pathways
Authors: Dana Boey
Katy Slack
En-Ju D Lin
Matthew J During
Amanda Sainsbury
Nicola J Lee
Herbert Herzog
Shu Lin
Journal: Endocrinology (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Neuropeptide Y; hypothalamo-pituitary-somatotropic axis; hypothalamo-pituitary-gonadotropic axis; Y2 receptor; Y4 receptor
Affiliations: Neuroscience Research Program (S.L., E.-J.D.L., D.B., N.J.L., K.S., A.S., H.H.), Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia, Comprehensive Cancer Center (M.J.D.), The Ohio State University, Columbus, Ohio 43210

Abstract:  Neuropeptide Y, a neuropeptide abundantly expressed in the brain, has been implicated in the regulation of the hypothalamo-pituitary-somatotropic axis and the hypothalamo-pituitary-gonadotropic axis. Elevated hypothalamic neuropeptide Y expression, such as that occurs during fasting, is known to inhibit both of these axes. However, it is not known which Y receptor(s) mediate these effects. Here we demonstrate, using Y receptor knockout mice, that Y2 and Y4 receptors are separately involved in the regulation of these axes. Fasting-induced inhibition of hypothalamic GHRH mRNA expression and reduction of circulating IGF-I levels were observed in wild-type and Y4(-/-) mice but not Y2(-/-) or Y2(-/-)Y4(-/-) mice. In contrast, fasting-induced reduction of GnRH expression in the medial preoptic area and testis testosterone content were abolished in the absence of Y4 receptors. Colocalization of Y2 receptors and GHRH in the arcuate nucleus (Arc) suggests that GHRH mRNA expression in this region might be directly regulated by Y2 receptors. Indeed, hypothalamic-specific deletion of Y2 receptors in conditional knockout mice prevented the fasting-induced reduction in Arc GHRH mRNA expression. On the other hand, fasting-induced decrease in GnRH mRNA expression in the medial preoptic area is more likely indirectly influenced by Y4 receptors because no Y4 receptors could be detected on GnRH neurons in this region. Together these data show that fasting inhibits the somatotropic axis via direct action on Y2 receptors in the Arc and indirectly inhibits the gonadotropic axis via Y4 receptors. 

Retracted: No

PubPeer comments:
 Figure 4C and 4D appear to overlap, after rotation and resizing. *** ![file] ,
Entropy-based model for interpreting life systems in traditional chinese medicine
Authors: Ji-Feng Zhang
Guo-Lian Kang
Shao Li
Journal: Evidence-based Complementary and Alternative Medicine (2008)
Discipline: CLINICAL MEDICINE
Keywords: Cold and Hot; Entropy; Yin and Yang; life systems; qi
Affiliations: Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100080, China, Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China

Abstract:  Traditional Chinese medicine (TCM) treats qi as the core of the human life systems. Starting with a hypothetical correlation between TCM qi and the entropy theory, we address in this article a holistic model for evaluating and unveiling the rule of TCM life systems. Several new concepts such as acquired life entropy (ALE), acquired life entropy flow (ALEF) and acquired life entropy production (ALEP) are propounded to interpret TCM life systems. Using the entropy theory, mathematical models are established for ALE, ALEF and ALEP, which reflect the evolution of life systems. Some criteria are given on physiological activities and pathological changes of the body in different stages of life. Moreover, a real data-based simulation shows life entropies of the human body with different ages, Cold and Hot constitutions and in different seasons in North China are coincided with the manifestations of qi as well as the life evolution in TCM descriptions. Especially, based on the comparative and quantitative analysis, the entropy-based model can nicely describe the evolution of life entropies in Cold and Hot individuals thereby fitting the Yin-Yang theory in TCM. Thus, this work establishes a novel approach to interpret the fundamental principles in TCM, and provides an alternative understanding for the complex life systems. 

Retracted: No

PubPeer comments:
  Moreover, a real data-based simulation shows life entropies of the human body with different ages, Cold and Hot constitutions and in different seasons in North China are coincided with the manifestations of qi as well as the life evolution in TCM descriptions This is simply spirituality masquerading as science ,
Stress-induced spine loss in the medial amygdala is mediated by tissue-plasminogen activator
Authors: S Chattarji
S Bennur
R Pawlak
S Strickland
B S Shankaranarayana Rao
B S McEwen
Journal: Neuroscience (2007)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: amygdala; stress; tPA; spine density; structural plasticity
Affiliations: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bangalore 560065, India.

Abstract:  The amygdala, which exerts a regulatory influence on the stress response, is itself affected by stress. It has been reported that the serine protease tissue-plasminogen activator (tPA), a key mediator of spine plasticity, is required for stress-induced facilitation of anxiety-like behavior. Importantly, tPA is also involved in stress-induced activation of molecular signals that have the potential to contribute to neuronal remodeling in the medial amygdala (MeA). However, little is known about the precise nature of, and specific role played by tPA in, stress-induced structural plasticity in the MeA. Hence, we compared the impact of chronic restraint stress on spine density of medium spiny stellate neurons in MeA in wild-type mice with mice in which the tPA gene is disrupted (tPA-/-). In wild-type mice, chronic stress caused significant reduction in MeA spine density, which was in contrast to enhanced spine density in the neighboring basolateral amygdala (BLA). Strikingly, tPA-/- mice exhibited significant attenuation of stress-induced spine retraction in the MeA, but BLA spinogenesis was not affected. Therefore, tPA-dependence of stress-induced modulation in spine density was restricted to the MeA. Further, MeA neurons in tPA-/- mice, even when challenged with repeated stress, were able to maintain levels of spine density that were comparable to that of wild-type mice without stress. Our findings provide novel evidence for a permissive role for tPA in amygdalar spine plasticity elicited by behavioral stress. 

Retracted: No

PubPeer comments:
 ![file] ,
Endogenous Nerve Growth Factor Regulates Collagen Expression and Bladder Hypertrophy through Akt and MAPK Pathways during Cystitis
Authors: Qing L Zhang
Chul-Won Chung
Li-Ya Qiao
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Type I collagen; cyclophosphamide; cystitis; bladder weight; bladder wall thickness

Abstract:  Type I collagen forms the main constituent of the extracellular matrix in visceral organs. We reported here that cyclophosphamide (CYP)-induced cystitis significantly increased the production of type I collagen in the inflamed bladder leading to increases in the bladder weight and the thickness of the bladder wall. The endogenous nerve growth factor (NGF) in the urinary bladder regulated type I collagen expression because the neutralizing NGF antibody attenuated cystitis-induced type I collagen up-regulation in the inflamed bladder. Neutralizing NGF antibody also subsequently reversed cystitis-induced increases in bladder weight. Further studies on the intermediate signaling pathways mediating NGF-induced type I collagen expression in the inflamed bladder during cystitis revealed that Akt, JNK, and ERK1/2 activities were increased in the inflamed bladder, whereas p38 MAPK remained unchanged. Suppression of endogenous NGF level with neutralizing NGF antibody significantly blocked the increased activity of Akt, JNK, and ERK1/2 in the inflamed bladder during cystitis. These results indicate that endogenous NGF plays an important role in the activation of Akt and MAPK in the urinary bladder and in bladder hypertrophy during cystitis. 

Retracted: No

PubPeer comments:
 undeclared splice site in Figure 7A. ![file] ,
Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli
Authors: Randal S Tibbetts
Shigeki Miyamoto
Yuling Shi
Zhao-Hui Wu
Journal: Science (2006)
Discipline: Multidisciplinary
Keywords: NF-kappaB; NEMO; ATM; IKK; DNA double-strand breaks
Affiliations: Department of Pharmacology, University of Wisconsin-Madison, 301 SMI, 1300 University Avenue, Madison, WI 53706, USA., Department of Pharmacology, University of Wisconsin–Madison, 301 SMI, 1300 University Avenue, Madison, WI 53706, USA.

Abstract:  The transcription factor NF-kappaB modulates apoptotic responses induced by genotoxic stress. We show that NF-kappaB essential modulator (NEMO), the regulatory subunit of IkappaB kinase (IKK) (which phosphorylates the NF-kappaB inhibitor IkappaB), associates with activated ataxia telangiectasia mutated (ATM) after the induction of DNA double-strand breaks. ATM phosphorylates serine-85 of NEMO to promote its ubiquitin-dependent nuclear export. ATM is also exported in a NEMO-dependent manner to the cytoplasm, where it associates with and causes the activation of IKK in a manner dependent on another IKK regulator, a protein rich in glutamate, leucine, lysine, and serine (ELKS). Thus, regulated nuclear shuttling of NEMO links two signaling kinases, ATM and IKK, to activate NF-kappaB by genotoxic signals. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: On my quest finding NEMO in Figure 4E, I noticed that lanes 8 and 9 appeared to look unexpectedly similar to each other, with one of the two in mirror image. Lane 10 might show some repetitive features too. ![file] * Blue boxes: In the a-GST panel, lanes 1-2 look similar to lanes 5 and 6. ![file] Shared with the journal in 2015, and still waiting. , 
 Figure S2A: * Red ellipses: In the right 32P panel, the same area appears to be visible twice around lane 7. ![file] , 
 Copy pasted from https: science.sciencemag.org content 371 6533 1002.1 :  Editorial Expression of Concern, Science, 05 Mar 2021, Vol. 371, Issue 6533, pp. 1002. On 24 February 2006, Science published the Report u201cMolecular linkage between the kinase ATM and NF-u03baB signaling in response to genotoxic stimuliu201d by Z.-H. Wu et al. (1). Concerns about Figs. 4E and 4F and fig. S2A were posted to PubPeer in 2020 (2). Because of the age of the paper, we no longer had original files to examine. We have now learned that relevant institutions have completed investigations and have concluded that there was figure manipulation. We are contacting the institutions to obtain further clarification but in the meantime are notifying readers of our concern about the paper s data integrity. References and Notes [1]. Z.-H. Wu, Y. Shi, R. S. Tibbetts, S. Miyamoto, Science 311, 1141 (2006). [2] E. M. Bik, Comment on u201cMolecular linkage between the kinase ATM and NF-u03baB signaling in response to genotoxic stimuli,u201d PubPeer (2020); https: pubpeer.com publications 7D3169F9D6FD50088CCCF35361A4E4  ,
A model of ischemia and reperfusion increases JNK activity, inhibits the association of BAD and 14-3-3, and induces apoptosis of rabbit spinal neurocytes
Authors: Guangxu Xu
Guoyong Yin
Ning Zhang
Jin Fan
David J Nagel
Zhengzhe Hua
Journal: Neuroscience Letters (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: protein BAD; c-Jun N-terminal kinase (JNK) pathway; spinal cord injury; rabbit model; apoptosis
Affiliations: The First Affiliated Hospital of Nanjing Medical University, Jiangsu 210029, China.

Abstract:  It is now well established that the protein BAD (a pro-apoptotic Bcl-2 family protein) plays a pivotal role in determining cell death and survival. The c-Jun N-terminal kinase (JNK) pathway has been hypothesized to be involved in regulation of BAD. To clarify the role of BAD within the JNK pathway, a randomized, controlled study was designed using a rabbit model of ischemic spinal cord injury [5,8]. Forty-five white adult New England rabbits were randomly assigned to one of the three groups: sham-operation group (n=5), vehicle group (n=20), and JNK inhibitor group (n=20). We examined alterations in spinal tissue morphology, local concentration and cellular locations of key regulatory proteins, and protein-protein interactions. Changes in spinal cord morphology were observed with hematoxylin and eosin (H&amp;E) staining and electron microscopy. In the vehicle group, the amount of JNK phosphorylation, cytochrome c release, and the interaction between BAD and Bcl-XL or Bcl-2 were increased compared with the JNK inhibitor group. Similarly, the phosphorylation of BAD (Ser136) and the interaction between BAD and 14-3-3 were decreased in the vehicle group. Immunohistochemical studies showed that cytoplasmic location of 14-3-3 and p-BAD (Ser136) were decreased in the vehicle group compared with the JNK inhibitor group. In addition, mitochondrial morphology was better preserved and the percentage of apoptosis was lower when JNK was inhibited. These results indicate that the JNK pathway has a critical role in the survival of neurocytes by regulating the interaction between BAD and 14-3-3. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 2A. * Red arrows: In the 14-3-3 panel, the topic of this paper, lanes 3-4-5 look very similar to lanes 6-7-8. * Blue arrows: In the BCL-2 pannel, lanes 1-2-3 look very similar to lanes 7-8-9. * Some panels have splices visible between lanes 5 and 6 while other panels do not. ![file] ,
Molecular analysis of the methylprednisolone-mediated inhibition of NK-cell function: evidence for different susceptibility of IL-2– versus IL-15–activated NK cells
Authors: Chiara Vitale
Lorenzo Moretta
Sara Moretti
Laura Chiossone
Maria Cristina Mingari
Bruno Azzarone
Francesca Cottalasso
Journal: Blood (2007)
Discipline: CLINICAL MEDICINE
Keywords: Steroids; NK cells; IL-15; IL-2; Methylprednisolone
Affiliations: Instituto Scientifico Giannina Gaslini, Genoa, Italy., Dipartimento Medicina Sperimentale, Università di Genova, Genova, Italy;, Istituto Scientifico Giannina Gaslini, Genova, Italy;, U542 Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Paul Brousse, Villejuif, France;, Centro di Eccellenza per le Ricerche Biomedicali, Università di Genova, Genova, Italy;, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy

Abstract:  Steroids have been shown to inhibit the function of fresh or IL-2-activated natural killer (NK) cells. Since IL-15 plays a key role in NK-cell development and function, we comparatively analyzed the effects of methylprednisolone on IL-2- or IL-15-cultured NK cells. Methylprednisolone inhibited the surface expression of the major activating receptors NKp30 and NKp44 in both conditions, whereas NK-cell proliferation and survival were sharply impaired only in IL-2-cultured NK cells. Accordingly, methylprednisolone inhibited Tyr phosphorylation of STAT1, STAT3, and STAT5 in IL-2-cultured NK cells but only marginally in IL-15-cultured NK cells, whereas JAK3 was inhibited under both conditions. Also, the NK cytotoxicity was similarly impaired in IL-2- or IL-15-cultured NK cells. This effect strictly correlated with the inhibition of ERK1/2 Tyr phosphorylation, perforin release, and cytotoxicity in a redirected killing assay against the FcRgamma(+) P815 target cells upon cross-linking of NKp46, NKG2D, or 2B4 receptors. In contrast, in the case of CD16, inhibition of ERK1/2 Tyr phosphorylation, perforin release, and cytotoxicity were not impaired. Our study suggests a different ability of IL-15-cultured NK cells to survive to steroid treatment, thus offering interesting clues for a correct NK-cell cytokine conditioning in adoptive immunotherapy. 

Retracted: No

PubPeer comments:
 The problem is solved. ,
Synergistic anti-tumor effects of liraglutide with metformin on pancreatic cancer cells
Authors: Jingjing Zhang
Tianpei Hong
Qing Tian
Ran Lu
Jing Ke
Fei Yu
Junling Liu
Rui Wei
Jin Yang
Journal: PLoS ONE (2018)
Discipline: Multidisciplinary
Keywords: metformin; liraglutide; pancreatic cancer; anti-tumor effects; combination treatment
Affiliations: Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China.

Abstract:  Either metformin or liraglutide has been reported to have anti-tumor effects on pancreatic cancer cells. However, it is not clear whether their combined treatment has additive or synergistic anti-tumor effects on pancreatic cancer cells. In this study, the human pancreatic cancer cell line MiaPaca-2 was incubated with liraglutide and/or metformin. The cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and wound-healing and transwell migration assays were used to detect cell viability, clonogenic survival, cell cycle and cell migration, respectively. RT-PCR and western blot analyses were used to determine the mRNA and protein levels of related molecules. Results showed that combination treatment with liraglutide (100 nmol/L) and metformin (0.75 mmol/L) significantly decreased cell viability and colony formation, caused cell cycle arrest, upregulated the level of pro-apoptotic proteins Bax and cleaved caspase-3, and inhibited cell migration in the cells, although their single treatment did not exhibit such effects. Combination index value for cell viability indicated a synergistic interaction of liraglutide and metformin. Moreover, the combined treatment with liraglutide and metformin could activate the phosphorylation of AMP-activated protein kinase (AMPK) more potently than their single treatment in the cells. These results suggest that liraglutide in combination with metformin has a synergistic anti-tumor effect on the pancreatic cancer cells, which may be at least partly due to activation of AMPK signaling. Our study provides new insights into the treatment of patients with type 2 diabetes and pancreatic cancer. 

Retracted: No

PubPeer comments:
 ![file] , 
 #1 ![file] , 
 We highly appreciate for pointing out this error. We apologise for this inadvertent mistake. We are contacting the respective journal office to retract the article Asian Pacific J Cancer Prev, 12 1989-1993. , 
 Authors have failed to retract paper as claimed by them a year ago. ,
Sinomenine hydrochloride inhibits the progression of plasma cell mastitis by regulating IL-6/JAK2/STAT3 pathway
Authors: Yu Ren
Yang Liu
Ke Wang
Jianjun He
Yushi Sun
Yuhui Zhou
Xiaojiang Tang
Journal: International immunopharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: IL-6/JAK2/STAT3 pathway; Plasma cell mastitis; Sinomenine hydrochloride.
Affiliations: Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an 710061, Shaanxi Province, China., Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an 710061, Shaanxi Province, China., Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an 710061, Shaanxi Province, China. Electronic address: .

Abstract:  Plasma cell mastitis (PCM) is a special form of mastitis characterized by periductal inflammation and large-scale plasma cell infiltration. At present, the recurrence rate of PCM after excision is quite high, making PCM a major problem for mammary surgeons. However, no effective drug exists for the treatment of PCM. Numerous studies have demonstrated that Sinomenine hydrochloride (SH) has potent anti-inflammatory and immunoregulatory properties. However, the efficacy and the underlying mechanisms of SH in the treatment of PCM remain unclear. In the present study, we first investigated the therapeutic effects of SH in the PCM mouse model and clarified the possible mechanisms. We found that the levels of plasmocytes and lymphocytes infiltration were alleviated significantly in the 100 mg/kg SH group compared to the control group. In addition, few CD138+ plasma cells were found in the mammary glands of the 100 mg/kg SH group. The levels of Bcl-2 in the 100 mg/kg SH group were dramatically decreased compared with those in the saline group. Mechanistically, we demonstrated that SH inhibited the progression of PCM mainly through downregulating IL-6/JAK2/STAT3 levels. Collectively, our results suggested that SH could inhibit the progression of PCM by suppressing IL-6/JAK2/STAT3 cascades and ultimately achieve a therapeutic effect in PCM. This study provides theoretical support for the clinical application of SH in the treatment of PCM. 

Retracted: No

PubPeer comments:
 In Figure 4, a micrograph has been duplicated and presented as something else (b vs c). ![file] ,
Aryl hydrocarbon receptor- and calcium-dependent induction of the chemokine CCL1 by the environmental contaminant benzo[a]pyrene
Authors: Claudine Rauch
Dominique Lagadic-Gossmann
Olivier Fardel
Monique N&#x27;Diaye
Valérie Lecureur
Marie-Dominique Galibert
Patricia Monteiro
Eric Le Ferrec
Sébastien Corre
David Gilot
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Polycyclic aromatic hydrocarbons; PAHs; immunotoxic; environmental contaminants; pro-inflammatory cytokines
Affiliations: INSERM U620, Unité Mixte de Recherche 6061, Laboratoire de Génétique et Développement, Facultéde Médecine, Université de Rennes 1, IFR140, 35043 Rennes Cedex.

Abstract:  Polycyclic aromatic hydrocarbons (PAHs) are widely distributed immunotoxic environmental contaminants well known to regulate expression of pro-inflammatory cytokines such as interleukine-1beta and tumor necrosis factor-alpha. In the present study, we demonstrated that the chemokine CCL1, notably involved in cardiovascular diseases and inflammatory or allergic processes, constitutes a new molecular target for PAHs. Indeed, exposure to PAHs such as benzo[a]pyrene (BP) markedly increased mRNA expression and secretion of CCL1 in primary human macrophage cultures. Moreover, intranasal administration of BP to mice enhanced mRNA levels of TCA3, the mouse orthologue of CCL1, in lung. CCL1 induction in cultured human macrophages was fully prevented by targeting the aryl hydrocarbon receptor (AhR) through chemical inhibition or small interfering RNA-mediated down-modulation of its expression. In addition, BP and the potent AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin were found to enhance activity of a CCL1 promoter sequence containing a consensus xenobiotic-responsive element known to specifically interact with AhR. Moreover, 2,3,7,8-tetrachlorodibenzo-p-dioxin triggered AhR binding to this CCL1 promoter element as revealed by chromatin immunoprecipitation experiments and electrophoretic mobility shift assays. In an attempt to further characterize the mechanism of CCL1 induction, we demonstrated that BP was able to induce an early and transient increase of intracellular calcium concentration in human macrophages. Inhibition of this calcium increase, using the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester or the calcium store-operated channel inhibitor 2-aminoethoxydiphenyl borate, fully blocked CCL1 up-regulation. Taken together, these results bring the first demonstration that PAHs induce expression of the chemokine CCL1 in an AhR- and calcium-dependent manner. 

Retracted: No

PubPeer comments:
 The immunoblots in Figure 5B were very similar in red boxes or green boxes. ![file] ,
Mitochondrial protein UCP1 mediates liver injury induced by LPS through EKR signaling pathway
Authors: G-J Shi
P Zhang
Z-Y Chen
P Liu
J Yang
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: research misconduct; mitochondrial protein UCP1; liver injury; LPS; EKR signaling pathway
Affiliations: Department of Cadre Health Care, Qingdao Municipal Hospital, Qingdao, Shandong, China.

Abstract:  Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Mitochondrial protein UCP1 mediates liver injury induced by LPS through EKR signaling pathway, by P. Liu, J. Yang, Z.-Y. Chen, P. Zhang, G.-J. Shi, published in Eur Rev Med Pharmacol Sci 2017; 21 (16): 3674-3679-PMID: 28925474" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13284. 

Retracted: No

PubPeer comments:
 This is a retraction notice for pubmed: 28925474, see: https: pubpeer.com publications 34697230A12EA45BA57644580EE8FC The journal writes:  *Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, u201cMitochondrial protein UCP1 mediates liver injury induced by LPS through EKR signaling pathway, by P. Liu, J. Yang, Z.-Y. Chen, P. Zhang, G.-J. Shi, published in Eur Rev Med Pharmacol Sci 2017; 21 (16): 3674-3679u2013PMID: 28925474u201d has been withdrawn. *  *The Publisher apologizes for any inconvenience this may cause. * ,
Simultaneous Determination of 13 Constituents of Radix Polygoni Multiflori in Rat Plasma and Its Application in a Pharmacokinetic Study
Authors: Wenhao Cheng
Wei Yang
Yang Gao
Shuofeng Zhang
Yingfei Li
Mengmeng Wei
Siyang Wu
Yinghui Li
Chen Kang
Journal: International Journal of Analytical Chemistry (2020)
Discipline: CHEMISTRY
Keywords: Radix Polygoni Multiflori; stilbenes; anthraquinones; hepatotoxicity; UPLC-MS/MS
Affiliations: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China, Center for DMPK Research of Herbal Medicines, Institute of Chinese Materia Medica, China Academy of Chinese, Beijing 100700, China

Abstract:  Radix Polygoni Multiflori (RPM) has been widely used to treat various diseases in Asian countries for many centuries. Although, stilbenes and anthraquinones, two major components of RPM, show various bioactive effects, it has been speculated that the idiosyncratic hepatotoxicity induced by RPM may be related to these constituents. However, information on the pharmacokinetics of stilbenes and anthraquinones at a subtoxic dose of RPM is limited. A simple and sensitive UPLC-MS/MS bioanalytical method for the simultaneous determination of 13 ingredients of RPM, including chrysophanol, emodin, aloe-emodin, rhein, physcion, questin, citreorosein, questinol, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside, torachrysone-8-O-glucoside, chrysophanol-8-O-β-D-glucoside, emodin-8-O-β-D-glucoside, and physcion-8-O-β-D-glucoside, in rat plasma was established. Acetonitrile was employed to precipitate the plasma with appropriate sensitivity and acceptable matrix effects. Chromatographic separation was performed using a waters HSS C18 column with a gradient elution using water and acetonitrile both containing 0.025% formic acid within a run time of 9 min. The constituents were detected in negative ionization mode using multiple reaction monitoring. The method was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects, and stability. The lower limit of quantitation of the analytes was 0.1-1 ng/mL. The intrabatch and interbatch accuracies were 87.1-109%, and the precision was within the acceptable limits. The method was applied to a pharmacokinetic study after oral administration of RPM extract to rats at a subtoxic dose of 36 g/kg. 

Retracted: No

PubPeer comments:
 Could the authors check figure 2? A chromatogram appears to be repeated. *** ![file] *** Full figure ![file] ,
Role of protease activated receptor-2 in lymph node metastasis of uterine cervical cancers
Authors: Israt Jahan
Jiro Fujimoto
Syed Mahfuzul Alam
Teruhiko Tamaya
Eriko Sato
Journal: BMC Cancer (2008)
Discipline: CLINICAL MEDICINE
Keywords: Protease activated receptor-2; PAR-2; lymph node metastasis; uterine cervical cancers; histoscores
Affiliations: Department of Obstetrics and Gynecology, Gifu University School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Japan. 

Abstract:  Background: Protease activated receptor-2 (PAR-2) has been implicated in cellular proliferation, invasion and metastasis in various tumors. Lymph node metastasis is an important patient prognostic factor for uterine cervical cancers. This prompted us to study the role of PAR-2 in lymph node metastasis of uterine cervical cancers. Methods: Thirty patients underwent surgery for uterine cervical cancers. PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. Patient prognosis was analyzed with a 48-month survival rate. Results: PAR-2 histoscores and mRNA levels significantly (P &lt; 0.05) increased in 12 of 30 metastatic lymph node lesions from the corresponding primary tumor. The 48-month survival rate of the 12 patients with increased PAR-2 levels in metastatic lymph nodes was 42%, while the rate of the other 18 patients with no change in PAR-2 levels was 82%, regardless of histopathological type. Conclusion: PAR-2 might work on lymph node metastasis of uterine cervical cancers, and is considered to be a novel prognostic indicator for uterine cervical cancers. 

Retracted: No

PubPeer comments:
 tumor and controls should be more different ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,