PReD-Bench/PRed-Bench huggingface dataset:
Regenerative biomarkers for Duchenne muscular dystrophy
Authors: Simon Guiraud
Kay E Davies
Journal: Neural regeneration research (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: DMD; biomarkers; degeneration; embryonic myosin; methodologies
Affiliations: MDUK Oxford Neuromuscular Centre, Department of Physiology, Anatomy and Genetics, Oxford, UK.

Abstract:  Skeletal muscle has an extraordinary capacity to regenerate after injury and trauma. The muscle repair mechanism is a complex process orchestrated by multiple steps. In neuromuscular disorders such as Duchenne muscular dystrophy (DMD), the pathological consequences of the lack of dystrophin and the loss of the dystrophin-associated protein complex are dramatic, with a progressive cascade of events, such as continual influx of inflammation, repeated cycles of degeneration and impaired regeneration. Thus, muscle regeneration is a hallmark of the disease and careful monitoring of regenerative processes with robust markers should provide useful information to the field. Since decades, several indices of regeneration such as centronucleation and fibre size have been commonly used. In the present review, we discuss the impaired regenerative process in DMD, the common and new indices of regeneration and their associated methodologies. We notably highlight the regenerative marker embryonic myosin as a robust indicator of muscle regeneration. We also describe new quantitative methodologies offering the possibility of using a panel of translational regenerative biomarkers to obtain a more complete view of the regeneration processes. Upregulation of utrophin, an autosomal and functional paralogue of dystrophin, is one of the most promising therapeutic strategies as it targets the primary cause of the disease and is applicable to all DMD patients regardless their genetic defects. As utrophin is a regeneration associated protein increased in dystrophic muscle, we discuss the correlation of utrophin levels after drug treatment with regeneration markers. The recent advances in technologies and complementary markers of muscle regeneration described in this review, provide an unprecedented opportunity to develop more robust utrophin DMD based strategies for all DMD patients. 

Retracted: No

PubPeer comments:
 A question for the authors: should the images (or regions) marked below overlap as it appears they do? Signal strength is different and all are dark, which makes comparison difficult. ***  , 
 The images highlighted do indeed appear to overlap although the H E staining appear not to overlap. These are very difficult to exactly align. ,
Aegeline inspired synthesis of novel amino alcohol and thiazolidinedione hybrids with antiadipogenic activity in 3T3-L1 cells
Authors: Tadigoppula Narender
Ankita Srivastava
Sabbu Satish
Rakhi Choudhary
Salil Varshney
Vishal M Balaramnavar
Anil Nilkanth Gaikwad
Pragya Yadav
Journal: European Journal of Medicinal Chemistry (2018)
Discipline: CHEMISTRY
Keywords: Adipogenesis; Obesity; PPARŒ≥; Thiazolidinedione; Œ≤-amino alcohols.
Affiliations: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India., Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India., Global Institute of Pharmaceutical Education and Research, Jaspur Road, Kashipur, Uttarakhand, India., Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: ., Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: .

Abstract:  Excess adiposity is a hallmark of obesity, which is caused due to an imbalance between energy intake and energy consumed. Obesity is often associated with several metabolic disorders like dyslipidemia, cardiovascular diseases and type 2 diabetes. Earlier, our group had reported natural product Aegeline (amino-alcohol) isolated from the plant Aegle marmelos as an anti-diabetic and anti-dyslipidemic compound. With this background, we synthesized a series of novel amino alcohol and thiazolidinedione hybrid molecules and studied their antiadipogenic activity. As a result, we have identified a potent hybrid compound 12c as an inhibitor of adipocyte differentiation. The compound 12c inhibits lipid accumulation and adipogenesis in 3T3-L1 preadipocyte cell line. Exposure of compound 12c blocks mitotic clonal expansion and arrests cells in S-phase of cell cycle. Detailed analysis showed that compound 12c decreases expression of two major transcription factors that are involved in adipocyte differentiation, PPARŒ≥, C/EBPŒ±, and other adipogenesis associated genes like aP2 and FAS. Thus, we concluded that compound 12c shows potential ability to inhibit adipocyte differentiation which can be used therapeutically for the treatment of obesity and its associated metabolic disorders. 

Retracted: No

PubPeer comments:
 more similar than expected  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. ,
Retracted : Correlation of the expressions of IGF1R‚ÄêRACK1‚ÄêSTAT3 and Bcl‚Äêxl in nasopharyngeal carcinoma with the clinicopathological features and prognosis of nasopharyngeal carcinoma
Authors: Yong-Jian Wang
Xin Wen
Bin Hu
Chun-Hui Sun
Jun Lu
Shan Wang
Qiu-Mei Lei
Shao-Hua Fan
Qun Shan
Yuan-Lin Zheng
Dong-Mei Wu
Xin-Rui Han
Juan Zhuang
Min Shen
Meng-Qiu Li
Zi-Feng Zhang
Xia Ge
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Bcl-xl; IGF1R; RACK1; STAT3; nasopharyngeal carcinoma
Affiliations: Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, P.R. China., School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou, P.R. China., Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, School of Life Sciences, Huaiyin Normal University, Huaian, P.R. China., Department of Oncology, Linyi People's Hospital, Linyi, P.R. China.

Abstract:  The aim of this study was to investigate the correlation of expression of IGF1R-RACK1-STAT3 and Bcl-xl in nasopharyngeal carcinoma (NPC) with the clinicopathological features and the prognosis of NPC. Our study selected 215 NPC tissues and 178 chronic nasopharyngitis tissues (control group). Positive expression rates of IGF1R, RACK1, STAT3, and Bcl-xl were tested by immunohistochemical method, and expression of IGF1R, RACK1, STAT3, Bcl-xl, Bcl-2, and Bax by western blotting. Correlation of IGF1R, RACK1, STAT3, and Bcl-xl with the clinicopathological features of NPC was analyzed. The correlation among those four expression was analyzed by Spearman. The survival of NPC and independent factors of prognosis were tested by Kaplan-Meier and COX proportional hazards model respectively. The NPC group had higher positive expression rates of IGF1R, RACK1, STAT3, and Bcl-xl, and elevated expression of IGF1R, RACK1, STAT3, Bcl-xl, Bcl-2, and Bax. The lymph node metastasis (LNM) group had higher positive expression rates of IGF1R and RACK1 when compared with the non-LNM group. Patients with stage III and IV had higher positive expression rates of IGF1R, RACK1, STAT3, and Bcl-xl. There was positive correlation between expression of IGF1R and RACK1, STAT3. Such correlation was found between RACK1 and STAT3. Patients with negative expression of IGF1R, RACK1, STAT3, and Bcl-xl had higher survival rates. The risky factors of poor prognosis of NPC were positive expression of IGF1R, RACK1, STAT3 and Bcl-xl, and LNM. IGF1R-RACK1-STAT3 and Bcl-xl expression correlated with the clinicopathological features and poor prognosis of NPC. 

Retracted: Yes

PubPeer comments:
 Figure 4 * Blue boxes: The DMSO and TSA panels in  B appear to overlap.  ,
Taking care of the challenging tension headache patient
Authors: Treasa Mathew
Paul G Mathew
Journal: Current Pain and Headache Reports (2011)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Tension type headache; primary headache disorder; evaluation; diagnosis; treatment plan
Affiliations: Department of Neurology, John R. Graham Headache Center, Harvard Medical School, Brigham and Women's/Faulkner Hospital, Boston, MA 02130, USA. 

Abstract:  Tension type headache (TTH) is the most common primary headache disorder, but it is a diagnosis for which patients infrequently present for evaluation in the outpatient setting. Performing a thorough evaluation and establishing the correct diagnosis is essential in formulating an effective treatment plan. There are many complex issues that, although not causative, may play an exacerbating role in TTH. This article reviews the epidemiology, diagnosis, and pharmacologic treatment of TTH. In addition, nonpharmacologic treatment approaches, sleep dysfunction, and temporomandibular dysfunction are reviewed. 

Retracted: No

PubPeer comments:
 There is a big mistake on this article. The author authors ? (weird sentence) state:  In my experience, NSAIDs tend to be more effective than aspirin and acetaminophen.  Any reasonable process of peer-review would have seen that this sentence is problematic as aspirin is an NSAID. ,
Vascular endothelial growth factor receptor-2 couples cyclo-oxygenase-2 with pro-angiogenic actions of leptin on human endothelial cells
Authors: Graeme M Birdsey
Elena Garonna
Anna M Randi
Ruben R Gonzalez-Perez
Caroline P D Wheeler-Jones
Kathleen M Botham
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: leptin; endothelial cells; angiogenesis; inflammation; VEGFR2
Affiliations: Department of Basic Sciences, Royal Veterinary College, University of London, London, United Kingdom.

Abstract:  Background: The adipocyte-derived hormone leptin influences the behaviour of a wide range of cell types and is now recognised as a pro-angiogenic and pro-inflammatory factor. In the vasculature, these effects are mediated in part through its direct leptin receptor (ObRb)-driven actions on endothelial cells (ECs) but the mechanisms responsible for these activities have not been established. In this study we sought to more fully define the molecular links between inflammatory and angiogenic responses of leptin-stimulated human ECs. Methodology/principal findings: Immunoblotting studies showed that leptin increased cyclo-oxygenase-2 (COX-2) expression (but not COX-1) in cultured human umbilical vein ECs (HUVEC) through pathways that depend upon activation of both p38 mitogen-activated protein kinase (p38(MAPK)) and Akt, and stimulated rapid phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) on Tyr(1175). Phosphorylation of VEGFR2, p38(MAPK) and Akt, and COX-2 induction in cells challenged with leptin were blocked by a specific leptin peptide receptor antagonist. Pharmacological inhibitors of COX-2, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and p38(MAPK) abrogated leptin-induced EC proliferation (assessed by quantifying 5-bromo-2'-deoxyuridine incorporation, calcein fluorescence and propidium iodide staining), slowed the increased migration rate of leptin-stimulated cells (in vitro wound healing assay) and inhibited leptin-induced capillary-like tube formation by HUVEC on Matrigel. Inhibition of VEGFR2 tyrosine kinase activity reduced leptin-stimulated p38(MAPK) and Akt activation, COX-2 induction, and pro-angiogenic EC responses, and blockade of VEGFR2 or COX-2 activities abolished leptin-driven neo-angiogenesis in a chick chorioallantoic membrane vascularisation assay in vivo. Conclusions/significance: We conclude that a functional endothelial p38(MAPK)/Akt/COX-2 signalling axis is required for leptin's pro-angiogenic actions and that this is regulated upstream by ObRb-dependent activation of VEGFR2. These studies identify a new function for VEGFR2 as a mediator of leptin-stimulated COX-2 expression and angiogenesis and have implications for understanding leptin's regulation of the vasculature in both non-obese and obese individuals. 

Retracted: No

PubPeer comments:
 Figures 3C, 5E. Unexpected similarity between TFIID and beta-Actin loading controls.  , 
 Fig 3D:  The S28 blob is unexpectedly similar (apart from the lane labels) to ones from [de Ponti et al (2007)] , and Free Radic.Res (2006).  , 
 #1  For comparison: Fig 1A from [Tacchini et al (2008)] .  ,
Nuclear localization in the biology of the CD40 receptor in normal and neoplastic human B lymphocytes
Authors: Richard J Ford
Linda C Yoshimura
Archito T Tamayo
Lingchen Fu
Lan V Pham
Hai-Jun Zhou
Yen-Chiu Lin-Lee
Glenn L Decker
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CD40; TNF receptor; B-lymphocytes; nucleus; nuclear localization signal
Affiliations: Department of Hematopathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract:  CD40 is a tumor necrosis factor (TNF) receptor superfamily, (TNFR; TNFRSF-5) member, that initiates important signaling pathways mediating cell growth, survival, and differentiation in B-lymphocytes. Although CD40 has been extensively studied as a plasma membrane-associated growth factor receptor, we demonstrate here that CD40 is present not only in the plasma membrane and cytoplasm but also in the nucleus of normal and neoplastic B-lymphoid cells. Confocal microscopy showed that transfected CD40-green fluorescent fusion protein entered B-cell nuclei. The CD40 protein contains a nuclear localization signal sequence that, when mutated, blocks entry of CD40 into the nucleus through the classic karyopherins (importins-alpha/beta) pathway. Nuclear fractionation studies revealed the presence of CD40 protein in the nucleoplasm fraction of activated B cells, and chromatin immunoprecipitation assays demonstrated that CD40 binds to and stimulates the BLyS/BAFF promoter, another TNF family member (TNFSF-13B) involved in cell survival in the B cell lineage. Like other nuclear growth factor receptors, CD40 appears to be a transcriptional regulator and is likely to play a larger and more complex role than previously demonstrated in regulating essential growth and survival pathways in B-lymphocytes. 

Retracted: No

PubPeer comments:
  The three bands (in red boxes) in the left panel of CD 40 panels Figure 6A are very similar. The three bands (in green boxes) in the left panel of Actin panels Figure 6A are very similar. But they are of different groups. ,
Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression
Authors: Alexandre M√©jat
Laurent Schaeffer
Francis Ramond
Rhonda Bassel-Duby
Eric N Olson
Saadi Khochbin
Journal: Nature Neuroscience (2005)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Motor innervation; skeletal muscle; chromatin acetylation; histone deacetylase 9 (HDAC9); transcriptional response
Affiliations: Equipe Diff√©renciation Neuromusculaire, Institut F√©d√©ratif de Recherche 128, Unit√© Mixte de Recherche 5161, Centre National de la Recherche Scientifique/Ecole Normale Sup√©rieure, Ecole Normale Sup√©rieure 46, all√©e d'Italie, 69364 Lyon Cedex 07, France.

Abstract:  Electrical activity arising from motor innervation influences skeletal muscle physiology by controlling the expression of many muscle genes, including those encoding acetylcholine receptor (AChR) subunits. How electrical activity is converted into a transcriptional response remains largely unknown. We show that motor innervation controls chromatin acetylation in skeletal muscle and that histone deacetylase 9 (HDAC9) is a signal-responsive transcriptional repressor which is downregulated upon denervation, with consequent upregulation of chromatin acetylation and AChR expression. Forced expression of Hdac9 in denervated muscle prevents upregulation of activity-dependent genes and chromatin acetylation by linking myocyte enhancer factor 2 (MEF2) and class I HDACs. By contrast, Hdac9-null mice are supersensitive to denervation-induced changes in gene expression and show chromatin hyperacetylation and delayed perinatal downregulation of myogenin, an activator of AChR genes. These findings show a molecular mechanism to account for the control of chromatin acetylation by presynaptic neurons and the activity-dependent regulation of skeletal muscle genes by motor innervation. 

Retracted: No

PubPeer comments:
 Figure 2b. Much more similar than expected.  , 
 Figure 4c and 8e. Much more similar and different than expected.  , 
 #1 Well, the left-hand extremities of the bands in the yellow boxes in 2b are clearly not identical, even if the remaining 1.5 bands are rather similar. I guess that is what you meant. , 
 #3 What I mean is that the bands in the yellow boxes are very similar yet the bands in the red boxes are different. That would not fit with re-probing the same membrane. ,
MiR-145, a microRNA targeting ADAM17, inhibits the invasion and migration of nasopharyngeal carcinoma cells
Authors: Dan Zong
De-Jun Wang
Wen-Jie Guo
Jian-Feng Wu
Jing Wu
Kai Ding
Meng Chen
Jian-Zhong Wu
Jia-Jia Gu
Dan Chen
Li Yin
Nan Zhang
You-You Xia
Teng Huang
Xia He
Ning Jiang
Journal: Experimental Cell Research (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ADAM17; Invasion; MiR-145; Migration; Nasopharyngeal carcinoma.
Affiliations: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China., Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China., Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China. Electronic address: .

Abstract:  MiR-145 is downregulated and functions as a tumor suppressor in many malignancies. In this study, the biological function, molecular mechanism, and direct target genes of miR-145 in nasopharyngeal carcinoma (NPC) cells were investigated. Cell survival was detected by cell viability assay, and cell cycle was determined through flow cytometry. Invasion and migration of NPC cells were examined using cell invasion and wound healing assays, respectively. A disintegrin and metalloproteinase 17 (ADAM17) was verified as the target of miR-145 through luciferase reporter assay, qRT-PCR, and Western blot analysis. In NPC cell lines, miR-145 expression was significantly downregulated and ADAM17 protein expression was upregulated. ADAM17 was downregulated at the post-transcriptional level by miR-145 via the binding site of ADAM17-3'UTR. Transfection with miR-145 mimic suppressed cell growth and induced cell cycle arrest in the G0/G1 phase by upregulating key G0/G1 phase regulators, namely, p53 and p21. MiR-145 also inhibited cellular migration and invasion through targeting ADAM17 involving the regulation of EGFR and E-cadherin. Knockdown of ADAM17 elicited similar effects to that of miR-145 on NPC cells. This study reveals that miR-145 suppressed the invasion and migration of NPC cells by targeting ADAM17. Thus, miR-145 could be a therapeutic target for NPC. 

Retracted: No

PubPeer comments:
 A possible image duplication in figure 6A  , 
 #1 Figs 5D, 6A.  ,
Calcium signaling in lymphocytes and ELF fields Evidence for an electric field metric and a site of interaction involving the calcium ion channel
Authors: R P Liburdy
Journal: FEBS Letters (1992)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Calcium influx; Mitogen-activated signal transduction; Thymic lymphocytes; Magnetic field; Electric field

Abstract:  Calcium influx increased during mitogen-activated signal transduction in thymic lymphocytes exposed to a 22 mT, 60 Hz magnetic field (E induced = 1.7 mV/cm, 37 degrees C, 60 min). To distinguish between an electric or a magnetic field dependence a special multi-ring annular cell culture plate based on Faraday's Law of Induction was employed. Studies show a dependence on the strength of the induced electric field at constant magnetic flux density. Moreover, exposure to a pure 60 Hz electric field or to a magnetically-induced electric field of identical strength resulted in similar changes in calcium transport. The first real-time monitoring of [Ca2+]i during application of a 60 Hz electric field revealed an increase in [Ca2+]i observed 100 s after mitogen stimulation; this suggests that the plateau phase rather than the early phase of calcium signaling was influenced. The hypothesis was tested by separating, in time, the early release of calcium from intracellular stores from the influx of extracellular calcium. In calcium-free buffer, 60 Hz field exerted little influence on the early release of calcium from intracellular stores. In contrast, addition of extracellular calcium during exposure enhanced calcium influx through the plasma membrane. Alteration of the plateau phase of calcium signaling implicates the calcium channel as a site of field interaction. In addition, an electric field exposure metric is mechanistically consistent with a cell-surface interaction site. 

Retracted: No

PubPeer comments:
 Su C, Han Y, Zhang H, et al. CiRS-7 targeting miR-7 modulates the progression of non-small cell lung cancer in a manner dependent on NF-u03baB signalling. J Cell Mol Med. 2018;22(6):3097-3107. doi:10.1111 jcmm.13587  Figure 4F , Same transwell images (pcDNA group) has been used in different cell line(A549,H1299). ,
Protective properties of Huperzine A through activation Nrf2/ARE-mediated transcriptional response in X-rays radiation-induced NIH3T3 cells
Authors: Peng-Wei Yan
Yan-Xin Fan
Ya-Tian Liu
Jing Wen
Qian Zhang
Li-Jun Wang
Huan-Feng Zhu
Yan-Hong Luo
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Huperzine A; NIH3T3 cells; Nrf2; X-rays radiation; protective effect.
Affiliations: Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China.

Abstract:  Huperzine A (HupA), derived from Huperzia Serrata, has exhibited a variety of biological actions, in particular neuroprotective effect. However, the protective activities of HupA on murine embryonic fibroblast NIH3T3 cells after X-rays radiation have not been fully elucidated. Herein, HupA treatment dramatically promoted cell viability, abated a G0/G1 peak accumulation, and ameliorated increase of cell apoptosis in NIH3T3 cells after X-rays radiation. Simultaneously, HupA notably enhanced activities of anti-oxidant enzymes, inhibited activity of lipid peroxide, and efficiently eliminated production of reactive oxygen species in NIH3T3 cells after X-rays radiation. Dose-dependent increase of antioxidant genes by HupA were associated with up-regulated Nrf2 and down-regulated Keap-1 expression, which was confirmed by increasing nuclear accumulation, and inhibiting of degradation of Nrf2. Notably, augmented luciferase activity of ARE may explained Nrf2/ARE-mediated signaling pathways behind HupA protective properties. Moreover, expression of Nrf2 HupA-mediated was significant attenuated by AKT inhibitor (LY294002), p38 MAPK inhibitor (SB202190) and ERK inhibitor (PD98059). Besides, HupA-mediated cell viability, and ROS production were dramatically bated by LY294002, SB202190, and PD98059. Taken together, HupA effectively ameliorated X-rays radiation-induced damage Nrf2-ARE-mediated transcriptional response via activation AKT, p38, and ERK signaling in NIH3T3 cells. 

Retracted: No

PubPeer comments:
 Fig. 1a u2013 possible duplication  ,
Roux-en-Y gastric bypass enhances energy expenditure and extends lifespan in diet-induced obese rats
Authors: Lee M Kaplan
Alison G Hoppin
Nicholas Stylopoulos
Journal: Obesity (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Gastrointestinal weight-loss surgery; Roux en-Y gastric bypass; weight loss; physiology; energy balance
Affiliations: Gastrointestinal Unit and MGH Weight Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Abstract:  Gastrointestinal weight-loss surgery (GIWLS) is currently the most effective treatment for severe obesity, with Roux en-Y gastric bypass (RYGB) among the best of the available surgical options. Despite its widespread clinical use, the mechanisms by which RYGB induces its profound weight loss remain largely unknown. This procedure effects weight loss by altering the physiology of weight regulation and eating behavior rather than by simple mechanical restriction and/or malabsorption as previously thought. To study how RYGB affects the physiology of energy balance, we developed a rat model of this procedure. In this report, we demonstrate that RYGB in diet-induced obese (DIO) rats induces a 25% weight loss, prolongs mean survival by 45%, and normalizes glucose homeostasis and lipid metabolism. RYGB induced a 19% increase in total and a 31% increase in resting energy expenditure (REE). These effects, along with a 17% decrease in food intake and a 4% decrease in nutrient absorption account for the normalization of body weight after this procedure. These effects indicate that surgery acts by altering the physiology of weight regulation and help to explain the effectiveness of RYGB in comparison to restrictive dieting and other forms of dietary and pharmacological therapies for obesity. The clinical effectiveness of RYGB and its physiological effects on body weight regulation and energy expenditure (EE) suggest that this operation provides a unique opportunity to explore the mechanisms of energy homeostasis and to identify novel therapies for obesity and related metabolic diseases. 

Retracted: No

PubPeer comments:
 I suspect that in Fig 3a, the legend is wrong and that Sham should eat more than bypassed animals. , 
 #1 I agree - the legend is correct but the labels are clearly switched (apparently inadvertently) ,
Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells
Authors: R M Medford
P E Tummala
M T Olbrych
R W Alexander
X L Chen
Journal: Circulation Research (1998)
Discipline: CLINICAL MEDICINE
Keywords: Monocyte infiltration; Atherosclerosis; Hypertension; Renin-angiotensin system; MCP-1
Affiliations: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., From the Division of Cardiology, Department of Medicine, Emory University School of Medicine (X.C., P.E.T., M.T.O., R.W.A., R.M.M.), Atlanta, Ga, and AtheroGenics, Inc (R.M.M.), Norcross, Ga.

Abstract:  Monocyte infiltration into the vessel wall, a key initial step in the process of atherosclerosis, is mediated in part by monocyte chemoattractant protein-1 (MCP-1). Hypertension, particularly in the presence of an activated renin-angiotensin system, is a major risk factor for the development of atherosclerosis. To investigate a potential molecular basis for a link between hypertension and atherosclerosis, we studied the effects of angiotensin II (Ang II) on MCP-1 gene expression in rat aortic smooth muscle cells. Rat smooth muscle cells treated with Ang II exhibited a dose-dependent increase in MCP-1 mRNA accumulation that was prevented by the AT1 receptor antagonist losartan. Ang II also activated MCP-1 gene transcription. Inhibition of NADH/NADPH oxidase, which generates superoxide and H2O2, with diphenylene iodonium or apocynin decreased Ang II-induced MCP-1 mRNA accumulation. Induction of MCP-1 gene expression by Ang II was inhibited by catalase, suggesting a second messenger role for H2O2. The tyrosine kinase inhibitor genistein and the mitogen-activated protein kinase kinase inhibitor PD098059 inhibited Ang II-induced MCP-1 gene expression, consistent with a mitogen-activated protein kinase-dependent signaling mechanism. Ang II may thus promote atherogenesis by direct activation of MCP-1 gene expression in vascular smooth muscle cells. 

Retracted: No

PubPeer comments:
 Figure 2. https: imgur.com jw2lTTO Figure 5A https: imgur.com KDetG9k Figure 6. https: imgur.com EpbJtaq ,
Branched Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Protect against Colitis by Regulating Gut Innate and Adaptive Immune Responses
Authors: Christopher Vickers
Oren Parnas
Eric U Yee
Jennifer Lee
Cynthia J Donaldson
Pratik Aryal
Alan Saghatelian
Angela Castoldi
Pedro M Moraes-Vieira
Barbara B Kahn
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Paneth cell; T helper cells; anti-inflammatory lipids; branched fatty acid esters of hydroxy fatty acids; colitis
Affiliations: From the Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and., Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215., the Clayton Foundation Laboratories for Peptide Biology, Helmsley Center for Genomic Medicine, Salk Institute for Biological Studies, La Jolla, California 92037, and., the Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142., From the Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and .

Abstract:  We recently discovered a structurally novel class of endogenous lipids, branched palmitic acid esters of hydroxy stearic acids (PAHSAs), with beneficial metabolic and anti-inflammatory effects. We tested whether PAHSAs protect against colitis, which is a chronic inflammatory disease driven predominantly by defects in the innate mucosal barrier and adaptive immune system. There is an unmet clinical need for safe and well tolerated oral therapeutics with direct anti-inflammatory effects. Wild-type mice were pretreated orally with vehicle or 5-PAHSA (10 mg/kg) and 9-PAHSA (5 mg/kg) once daily for 3 days, followed by 10 days of either 0% or 2% dextran sulfate sodium water with continued vehicle or PAHSA treatment. The colon was collected for histopathology, gene expression, and flow cytometry. Intestinal crypt fractions were prepared for ex vivo bactericidal assays. Bone marrow-derived dendritic cells pretreated with vehicle or PAHSA and splenic CD4+ T cells from syngeneic mice were co-cultured to assess antigen presentation and T cell activation in response to LPS. PAHSA treatment prevented weight loss, improved colitis scores (stool consistency, hematochezia, and mouse appearance), and augmented intestinal crypt Paneth cell bactericidal potency via a mechanism that may involve GPR120. In vitro, PAHSAs attenuated dendritic cell activation and subsequent T cell proliferation and Th1 polarization. The anti-inflammatory effects of PAHSAs in vivo resulted in reduced colonic T cell activation and pro-inflammatory cytokine and chemokine expression. These anti-inflammatory effects appear to be partially GPR120-dependent. We conclude that PAHSA treatment regulates innate and adaptive immune responses to prevent mucosal damage and protect against colitis. Thus, PAHSAs may be a novel treatment for colitis and related inflammation-driven diseases. 

Retracted: No

PubPeer comments:
 Figure 4C: More similar than expected. Could authors check please?  ,
Author Correction: Structural insights into Œº-opioid receptor activation
Authors: Brian K Kobilka
Hideaki E Kato
Jan Steyaert
William I Weis
Peter Gmeiner
Aashish Manglik
Ralf C Kling
Stephen M Husbands
Kathryn E Livingston
Adrian L Sanborn
Weijiao Huang
John R Traynor
Toon Laeremans
Evan N Feinberg
S√©bastien Granier
Ron O Dror
A J Venkatakrishnan
Thor S Thorsen
Journal: Nature (2020)
Discipline: Multidisciplinary
Keywords: amendment; published; link; paper
Affiliations: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California, USA., Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California, USA. ., Department of Computer Science, Stanford University, Stanford, California, USA., Institute for Computational and Mathematical Engineering, Stanford University, Stanford, California, USA., Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium., Structural Biology Research Center, VIB, Brussels, Belgium., Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA., Department of Chemistry and Pharmacy, Friedrich Alexander University, Erlangen, Germany., Institut de G√©nomique Fonctionnelle, CNRS UMR-5203 INSERMU1191, University of Montpellier, Montpellier, France., Department of Pharmacy and Pharmacology, University of Bath, Bath, UK., Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA.

Abstract:  An amendment to this paper has been published and can be accessed via a link at the top of the paper. 

Retracted: No

PubPeer comments:
 My arguments for the revised structure of BU72 endorsed in this correction can be found in: Revised (u03b2-phenyl) stereochemistry of ultrapotent u03bc opioid BU72. *bioRxiv* 2020. https: doi.org dq7s ,
Interleukin-17 Reduces Œ≤ENaC via MAPK Signaling in Vascular Smooth Muscle Cells
Authors: Jeremy W Duncan
Joey P Granger
Michael J Ryan
Heather A Drummond
Journal: International journal of molecular sciences (2020)
Discipline: CHEMISTRY
Keywords: IL-17; JNK; NFŒ∫B; VSMCs; beta-ENaC
Affiliations: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39206, USA.

Abstract:  Degenerin proteins, such as the beta epithelial Na+ channel (Œ≤ENaC), are essential in the intracellular signaling of pressure-induced constriction, an important vascular smooth muscle cell (VSMC) function. While certain cytokines reduce ENaC protein in epithelial tissue, it is unknown if interleukin-17 (IL-17), a potent pro-inflammatory cytokine, directly mediates changes in membrane-associated Œ≤ENaC in VSMCs. Therefore, we tested the hypothesis that exposure to IL-17 reduces Œ≤ENaC in VSMCs through canonical mitogen-activated protein kinase (MAPK) signaling pathways. We treated cultured rat VSMCs (A10 cell line) with IL-17 (1-100 ng/mL) for 15 min to 16 h and measured expression of Œ≤ENaC, p38MAPK, c-jun kinase (JNK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFŒ∫B). IL-17 reduced Œ≤ENaC protein expression in a concentration-dependent fashion and increased phosphorylation of p38MAPK by 15 min and JNK by 8 h. NFŒ∫B was unaffected by IL-17 in VSMCs. IL-17 treatment reduced VSMC viability but had no effect on cell death. To determine the underlying signaling pathway involved in this response, VSMCs were treated before and during IL-17 exposure with p38MAPK or JNK inhibitors. We found that JNK blockade prevented IL-17-mediated Œ≤ENaC protein suppression. These data demonstrate that the pro-inflammatory cytokine IL-17 regulates VSMC Œ≤ENaC via canonical MAPK signaling pathways, raising the possibility that Œ≤ENaC-mediated loss of VSMC function may occur in inflammatory disorders. 

Retracted: No

PubPeer comments:
 Where is the evidence that beta ENaC exists in these cells? A blot that shows something being recognized around 150Kda? A micrograph showing something fluoresces and is blocked by the immunizing antigen. An effect of pharmacological doses of amiloride? This is just descriptive and lacks proper validation. Even the original 2005 manuscript does not show that the antibody recognizes beta ENaC- just shows it recognizes a partial and tagged fusion protein. I suspect that the reason commercial antibody is used for alpha but not beta (in 2020 where so many places have beta antibodies) is that these available ones do not show something at 150KDa. ,
Downregulation of canonical Wnt signaling in hippocampus of SAMP8 mice
Authors: Paolo Felice
Antoni Camins
Anna-Maria Canudas
Paolo Rosa
Sergi Bayod
Merc√® Pall√†s
Pol Andr√©s
Journal: Neurobiology of Aging (2015)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Aging; Alzheimer's disease; DKK-1; Hippocampus; SAMP8
Affiliations: Unitat de Farmacologia i Farmacogn√≤sia, Facultat de Farm√†cia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain; Centros de Investigaci√≥n Biom√©dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain., Unitat de Farmacologia i Farmacogn√≤sia, Facultat de Farm√†cia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain; Centros de Investigaci√≥n Biom√©dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Electronic address: .

Abstract:  In the adult brain, canonical Wnt (Wnt/Œ≤-catenin) signaling modulates neuronal function, hippocampal neurogenesis, and synaptic plasticity. Indeed, growing evidence suggests that downregulation of Wnt signaling could be involved in the cognitive decline associated with aging and also with the physiopathology of Alzheimer's disease (AD). However, the molecular basis remains unknown. At present, SAMP8 is an experimental model that has been proposed for studying age-related neurodegenerative changes associated with aging and the pathogenesis of AD. Here, we examined Wnt signaling in the hippocampus of SAMP8 mice at 9 and 12 months of age, as well as in its control-strain SAMR1 mice. Our results showed increased Dickkopf-1 protein levels in SAMP8 with age, in addition to GSK-3 Œ±/Œ≤ activation and hyperphosphorylated tau. Consequently, higher Œ≤-catenin phosphorylation at Ser(33,37) and Thr(41), which promotes its degradation, along with a decrease in active Œ≤-catenin (ABC) in the nucleus, were observed in SAMP8, mainly at the age of 12 months. Moreover, nuclear levels of Dvl3 were lower in 9- and 12-month-old SAMP8 mice. Related to these findings, SAMP8 showed an increase in neuronal loss in the hippocampus that was associated with lower protein levels of the antiapoptotic protein and the Wnt target gene, Bcl-2, in addition to an increase in the proapototic protein Bax. Our results suggest a relationship between age-related downregulation of canonical Wnt signaling and neuronal loss observed in the hippocampus of SAMP8 mice. Thus, enhancing Wnt signaling may represent a novel neuroprotective strategy aimed at counteracting the cognitive decline that is associated not only with aging but also with AD. 

Retracted: No

PubPeer comments:
 An image in Figure 4 appears to have 2 regions with substantially similar features. *** Enhanced brightness  ,
HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF
Authors: Julie de Saintignon
Roger Ferreira
Zohair Mishal
Annick Harel-Bellan
Marion Mathieu
Anne Chauchereau
Linda L Pritchard
Anne Dejean
Journal: Oncogene (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PLZF; transcriptional repressor; development; acute leukaemias; chromosomal translocation
Affiliations: UPR 9079 CNRS-Ligue Nationale Contre le Cancer, Institut Andr√© Lwoff, 7 rue Guy M√¥quet, 94800 Villejuif, France.

Abstract:  PLZF, the promyelocytic leukaemia zinc-finger protein, is a transcriptional repressor essential to development. In some acute leukaemias, a chromosomal translocation fusing the PLZF gene to that encoding the retinoic acid receptor RARalpha gives rise to a fusion protein, PLZF-RARalpha, thought to be responsible for constitutive repression of differentiation-associated genes in these cells. Repression by both PLZF and PLZF-RARalpha is sensitive to the histone deacetylase inhibitor TSA, and PLZF was previously shown to interact physically with HDAC1, a class I histone deacetylase. We here asked whether class II histone deacetylases, known to be generally involved in differentiation processes, participate in the repression mediated by PLZF and PLZF-RARalpha, and found that PLZF interacts with HDAC4 in both GST-pull-down and co-immunoprecipitation assays. Furthermore, HDAC4 is indeed involved in PLZF and PLZF-RARalpha-mediated repression, since an enzymatically dead mutant of HDAC4 released the repression, as did an siRNA that blocks HDAC4 expression. Taken together, our data indicate that recruitment of HDAC4 is necessary for PLZF-mediated repression in both normal and leukaemic cells. 

Retracted: No

PubPeer comments:
 Figure 1. Much more similar than expected. https: imgur.com JLTecSy ,
Differential effects of growth hormone and alpha calcidol on trabecular and cortical bones in hypophysectomized rats
Authors: John F Aloia
Mariano Castro-Magana
James K Yeh
Afshan A Chaudhry
Journal: Pediatric research (2009)
Discipline: CLINICAL MEDICINE
Keywords: Growth hormone deficiency; Alfacalcidol; Bone formation; Hypophysectomized rats; Body weight
Affiliations: Department of Pediatric Endocrinology, Winthrop University Hospital, Mineola, New York 11501, USA. 

Abstract:  Growth hormone (GH) deficiency in children causes severe growth retardation, vitamin D deficiency, and osteopenia. We investigated whether alfacalcidol (1OHD) alone or in combination with GH can improve bone formation. Forty hypophysectomized female rats (HX) at the age of 8 wk were divided into HX, HX + 1OHD (oral 0.25 microg/kg daily), HX+GH (0.666 mg/0.2 mL SC daily) and HX+GH + 1OHD groups for a 4-wk study. Results showed that GH increased body weight, bone area, bone mineral content (BMC), and bone mineral density (BMD), whereas 1OHD only increased BMC and BMD. In cortical bone, GH increased both periosteal and endocortical bone formation resulting in a significant increase in cortical size and area in percentage, whereas 1OHD suppressed endocortical erosion surface per bone surface (ES/BS) without a significant effect on bone formation rate per bone surface (BFR/BS). In trabecular bone, GH mitigated the bone loss by increasing BFR/BS, whereas the 1OHD effect was by suppression of trabecular bone turnover in the HX rats. The combination of GH and 1OHD had no additive effect on increasing trabecular bone mass. In conclusion, GH activates new bone formation and increases bone turnover whereas 1OHD suppresses bone turnover. The combination intervention does not seem to provide any additive benefit. 

Retracted: No

PubPeer comments:
 The authors claim to have acquired a sample of pancreatic carcinoma cells of the PAN-C strain (provenance unknown), to have cultured them in a growth medium, and to have reduced their survival and their invasive and migratory tendencies by exposing them to a suspension of the present material (in pulverised form).  Briefly, in **logical growth** stage, PANC-1 pancreatic cancer cells could be collected and then they were inoculated into plates of 96 well at 10^5 cells well **ultimate destiny**. After incubating for twelve hours at 5%CO2 and 37u2103 in the incubator, the treatment was conducted after adding the compound into well with various concentration. Subsequently, discarding culture medium l and add the fresh medium having the reagent of CCK-8 (10 u03bcL) to further culture. Finally, for each well, the absorbance was measured by the microplate reader at least three times. Some curious terms are often found within [the products of a prolific papermill] . ,
LncRNA ANRIL promotes NLRP3 inflammasome activation in uric acid nephropathy through miR-122-5p/BRCC3 axis
Authors: Zhijie Yang
Hao Wu
Junjun Dong
Jiacai Hu
Daochun Wang
Journal: Biochimie (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ANRIL; BRCC3; NLRP3; Uric acid nephropathy; miR-122-5p.
Affiliations: Department of Traditional Chinese Medicine, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: ., Department of Traditional Chinese Medicine, Renmin Hospital of Wuhan University, Wuhan, China., Department of Acupuncture and Moxibustion, Renmin Hospital of Wuhan University, Wuhan, China.

Abstract:  This study is designed to explore the mechanism by which long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) plays a pathogenic role in uric acid nephropathy (UAN). The expressions of ANRIL, miR-122-5p, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and NOD-like receptor protein 3 (NLRP3) were determined in UAN patients and uric acid-treated HK-2 cells by qRT-PCR. Protein levels of BRCC3 and NLRP3 were examined by western blot. The levels of inflammatory cytokines were quantified by ELISA. CCK-8 assay was used to assess cell viability. Apoptosis was detected by Annexin V-FITC/PI double-labeled flow cytometry and TUNEL assay. The interaction between ANRIL, miR-122-5p and BRCC3 were studied using luciferase reporter assay. The role of ANRIL in renal injury was evaluated in experimental rats. ANRIL and BRCC3 were highly expressed while miR-122-5p was down-regulated in serum of UAN patients and uric acid-treated tubular epithelial cells. Luciferase reporter assay and in vitro rescue experiment confirmed that ANRIL promoted NLRP3 inflammasome activation by up-regulating BRCC3 expression via sponging miR-122-5p. Furthermore, in vivo experiment validated that knockdown of ANRIL alleviated renal injury of UAN rats. ANRIL exerted pathogenic effect in UAN to promote NLRP3 inflammasome activation via miR-122-5p/BRCC3 axis. 

Retracted: No

PubPeer comments:
 Possibly an error in Figure 7(A):  Effect of ANRIL on renal pathological features and cell apoptosis in experimental UAN rats Renal histopathological observation using **HE staining (A)**; Assessment of renal interstitial fibrosis using Massonu2019s trichrome staining (B); Detection of cell apoptosis of kidney tissue using TUNEL staining (C) .  Two panels are the same. ,
The laxative effect of emodin is attributable to increased aquaporin 3 expression in the colon of mice and HT-29 cells
Authors: Chun-Fang Liu
Na Lin
Yan-Fang Zheng
Zuan-Fang Li
Wen-Fang Lai
Qing Xiang
Hui Wang
Journal: Fitoterapia (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Aquaporin 3; Colon; Emodin; Laxative.
Affiliations: Fujian University of Traditional Chinese Medicine, No. 1, Huatuo Road, Minhoushangjie, Fuzhou 350122, China., Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China., Fujian University of Traditional Chinese Medicine, No. 1, Huatuo Road, Minhoushangjie, Fuzhou 350122, China; Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China., Fujian University of Traditional Chinese Medicine, No. 1, Huatuo Road, Minhoushangjie, Fuzhou 350122, China; Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China. Electronic address: .

Abstract:  Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a stimulant laxative and used to treat constipation. Aquaporin 3 (AQP3) plays an important role in regulating water transfer in the colon. In the study, we investigated whether the laxative effect of emodin is associated with the regulation of AQP3 in the colon. Our results showed that treatment with emodin increased the fecal water content in the colon of mice and evaluation index of defecation in a dose-dependent manner. More interestingly, emodin significantly increased the AQP3 protein and mRNA expression both in the colon of mice and in human intestinal epithelial cells (HT-29). Mechanistically, emodin obviously up-regulated the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A catalytic subunits Œ± (PKA C-Œ±) and phosphorylated cAMP response element-binding protein (p-CREB Ser133) expression in HT-29 cells. These results suggest that the laxative effect of emodin is associated with the increased expression of AQP3 by up-regulating PKA/p-CREB signal pathway. 

Retracted: No

PubPeer comments:
 Figures 5 and 6. * Red boxes: Lanes 1-4 of the GAPDH panel in Figure 5A (Emodin time series) look similar to lanes 1-4 of the GAPDH panel in Figure 6A (Emodin Forskolin concentration series). * Blue boxes: the GAPHD panels of Figures 5B and 6B look similar, but this is expected because they show the same experiments.  , 
 The GAPDH panels marked in blue and red in comment #1 also look similar to GAPDH panels in Figures 4 and 6 of another paper by the same research group, i.e. Liu C et al. BioMed Research International (2014), DOI: 10.1155 2014 619465. See: https: pubpeer.com publications 93476E7A88E2A9DD3EDE52DB4AD893 .  ,