PReD-Bench/PRed-Bench huggingface dataset:
Allosteric potentiation of glycine receptor chloride currents by glutamate
Authors: Jun Liu
Yu Tian Wang
Dong Chuan Wu
Journal: Nature Neuroscience (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Neuronal excitability; CNS; synaptic excitation; inhibition; brainstem
Affiliations: Brain Research Centre and Department of Medicine, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract:  Neuronal excitability in the CNS is primarily controlled by a balance between synaptic excitation and inhibition. In the brainstem and spinal cord, synaptic excitation and inhibition are mediated by the excitatory transmitter glutamate acting on ionotropic glutamate receptor-gated cationic channels and the inhibitory transmitter glycine acting on glycine receptor (GlyR)-gated chloride channels. We found that glutamate and its analog ligands potentiated GlyR-mediated currents in both cultured spinal neurons and spinal cord slices of rats. This potentiation was not dependent on activation of any known glutamate receptor and manifested as an increase in single-channel open probability. Moreover, this glutamate potentiation was seen in HEK293 cells that transiently expressed GlyRs. Our data strongly suggest that glutamate allosterically potentiates GlyR-gated chloride channels, thereby blurring the traditional distinction between excitatory and inhibitory transmitters. Such a rapid homeostatic regulatory mechanism may be important for tuning functional balance between synaptic excitation and inhibition in the CNS. 

Retracted: No

PubPeer comments:
 A recent preprint (Aubrey et al., 2020, https: www.biorxiv.org content 10.1101 2020.03.08.982900v1.abstract ) calls into question the conclusions of this article. From the preprint:  Main conclusions **This study disputes the previously published finding that AP5, NMDA and glutamate act directly at GlyRs as positive allosteric modulators (Liu et al., 2010) and indicates that the finding that glutamate spill over onto inhibitory synapses interacts directly with GlyR to facilitate neurotransmitter crosstalk and help balance inhibitory and excitatory transmission in the spinal cord and hind brain is false**. This changes our understanding of how synapses function and are regulated. Neurobiological research is particularly susceptible to experimental confounds as the brain is designed to adapt and respond to subtle changes in input and is modulated by compounds that can have exceptionally high affinities (pM - u00b5M) for their biological target. This is significant because very low levels of contaminants can have profound biological effects. As unknown mechanisms of modulation are difficult to control for and brain function is highly dependent on physiological context, the publication of replication studies of key neurobiological findings by independent laboratories is essential to consolidating knowledge and more quickly advance understanding and development in the field of neurobiology ,
Vitamin D Modulation of TRAIL Expression in Human Milk and Mammary Epithelial Cells
Authors: Yuvaraj Sambandam
Sakamuri V Reddy
Carol L Wagner
Jennifer L Mulligan
Christina Voelkel-Johnson
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Vitamin D; TRAIL; Breast milk; Mammary epithelial cells; Rickets

Abstract:  The vitamin D levels in mothers affect the health status of both the mother and breastfeeding infant. Vitamin D deficient mothers' infants are prone to rickets. While tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has been implicated in cellular growth/apoptosis, immune cell function and bone-resorbing osteoclast formation, the expression of TRAIL in human milk as a function of vitamin D status in mothers remains unknown. We hypothesized that vitamin D deficiency alters TRAIL protein levels in human breast milk and mammary epithelial cells. Milk from vitamin D deficient mothers showed high levels of TRAIL (Œ± and Œ≤) proteins compared to milk from vitamin D replete women. Western blot analysis of total cell lysate obtained from normal human mammary epithelial (HME-1) cells treated with variable doses (0-20 nM) of vitamin D for 24 h demonstrated that low levels (0.5 to 5 nM) significantly increased the TRAIL Œ± but no change in Œ≤ expression. In contrast, vitamin D at 20 nM concentration suppressed the expression of both TRAIL Œ± and Œ≤ proteins. Consistently, vitamin D regulated TRAIL mRNA expression in HME-1 cells. Our results indicate that vitamin D status in mothers modulates TRAIL expression in breast milk, which may have implications for both mother and infant health. 

Retracted: No

PubPeer comments:
 The actin blots in Figure 3a and 3b initially appear to be different but when the image is compressed vertically and a bit horizontally they appear to be very similar. Could the authors explain? ***  ,
Treatment of recurrent symptomatic lymphocele after kidney transplantation with intraperitoneal Tenckhoff catheter
Authors: Vittorio Bresadola
Umberto Baccarani
Andrea Risaliti
Dino De Anna
Massimo Sponza
Daniele Gasparini
Gian Luigi Adani
Patrizia Tulissi
Domenico Montanaro
Journal: Urology (2007)
Discipline: CLINICAL MEDICINE
Keywords: lymphocele; kidney transplantation; intraperitoneal drainage; Tenckhoff catheter; outpatient basis
Affiliations: Department of Surgery and Transplantation, Udine University School of Medicine, Udine, Italy. 

Abstract:  Objectives: The incidence of lymphocele after kidney transplantation ranges from 0.6% to 16%. The management of lymphocele is still controversial. Percutaneous needle aspiration and external drainage, with or without the injection of sclerosing solutions, are associated with high recurrence and complication rates. Open or laparoscopic intraperitoneal marsupialization requires hospital admission, general anesthesia, and, sometimes, extensive surgical dissection. Methods: We report our experience treating recurrent symptomatic lymphocele with intraperitoneal drainage using a Tenckhoff catheter on an outpatient basis in 7 consecutive patients. In all cases, the lymphocele was diagnosed by abdominal ultrasonography 26 to 90 days after kidney transplantation. The mean diameter of the lymphocele was 14 +/- 6 cm. Percutaneous drainage was the initial approach, which was also used to differentiate between urinoma and lymphocele and to rule out infection. The lymphocele recurred within 1 month in all cases. The recurrent lymphoceles were treated on an outpatient basis using intraperitoneal drainage with a Tenckhoff catheter inserted into the lymphocele under ultrasound guidance. After administration of local anesthesia, two 1-cm vertical incisions were performed: one to access the lymphocele and the other to access the peritoneal cavity. A Tenckhoff catheter was inserted in the lymphocele and tunneled into the peritoneal cavity. Results: All procedures were completed on an outpatient basis without any complications. The catheter was removed 6 months later with no evidence of recurrent lymphocele at ultrasound follow-up in all cases. Conclusions: This outpatient surgical approach using ultrasound-guided intraperitoneal drainage with a Tenckhoff catheter appears to be a simple, effective, and safe method for treating unilobular recurrent symptomatic lymphocele after renal transplantation. 

Retracted: No

PubPeer comments:
 This article reports the same results as another paper published by the same team: **Adani GL, Sponza M, Risaliti A, et al. Intraperitoneal Tenckhoff catheter for the treatment of recurrent lymphoceles after kidney transplantation: our early experience. Transplant Proc. 2007;39(6):1851-1852. doi:[10.1016 j.transproceed.2007.05.007] ** Did the authors inform the editors-in-chief of Transplantation Proceedings and Urology about submitting the same results in slightly different manuscripts to both journals which seems to be against their policies? Was potential self-plagiarism verified? ,
Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence
Authors: Tiziana Squillaro
Roberto De Rosa
Umberto Galderisi
Giovanni Di Bernardo
Nicola Alessio
Giovanni Galano
Gianfranco Peluso
Mariarosa A B Melone
Journal: eLife (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: SASP; human; human biology; medicine; mesenchymal stromal cells
Affiliations: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania "Luigi Vanvitelli,", Naples, Italy., ASL Napoli 1 Centro P.S.I. Napoli Est - Barra, Naples, Italy., Department of Medical, Surgical, Neurological, Metabolic Sciences, and Aging, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania 'Luigi Vanvitelli', Naples, Italy., Research Institute of Terrestrial Ecosystems (IRET), CNR, Naples, Italy., Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, United States.

Abstract:  Senescent cells secrete several molecules, collectively named senescence-associated secretory phenotype (SASP). In the SASP of cells that became senescent following several in vitro chemical and physical stress, we identified the IGFBP-4 protein that can be considered a general stress mediator. This factor appeared to play a key role in senescence-paracrine signaling. We provided evidences showing that genotoxic injury, such as low dose irradiation, may promote an IGFBP-4 release in bloodstream both in mice irradiated with 100 mGy X-ray and in human subjects that received Computer Tomography. Increased level of circulating IGFBP-4 may be responsible of pro-aging effect. We found a significant increase of senescent cells in the lungs, heart, and kidneys of mice that were intraperitoneally injected with IGFBP-4 twice a week for two months. We then analyzed how genotoxic stressors may promote the release of IGFBP-4 and the molecular pathways associated with the induction of senescence by this protein. 

Retracted: No

PubPeer comments:
 There appear to be some image overlaps between Figure 1c in this paper and one other paper among a set of three. The first and last author appears on all three papers that are involved. Some authors, Antonio Giordano, for example only appear on a single paper. Figure 1c, eLife (2020), doi: 10.7554 elife.54523, Received: 17 December 2019, https: pubpeer.com publications 8B51589E5BECC6E5EDBDE25B9F4EFE Figure 2, Neoplasia (2017), doi: 10.1016 j.neo.2017.06.005, Received 1 April 2017, https: pubpeer.com publications 128BEF59CE331E3BB55727E243FBA8 Figure 2 excerpt, Oncotarget (2015), doi: 10.18632 oncotarget.6277 Received: 10 September 10 2015, https: pubpeer.com publications C74A8C7AA46F3D00D393675E20A0C6 ***  ,
Antidepressant-like effects of paeoniflorin on post-stroke depression in a rat model
Authors: Yan-Bin Li
Xiang-Yan Chen
Ze-Yu Zhao
Bin Liu
Ming-Zhe Hu
An-Rong Wang
Journal: Neurological Research (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: BDNF; Post-stroke depression; fluoxetine; p-CREB; paeoniflorin.
Affiliations: The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China, Shandong University of Traditional Chinese Medicine, Jinan, China, School of Clinical Medicine, Weifang Medical University, Weifang, China, Department of Internal Medicine, Zibo City Hospital of Traditional Chinese Medicine, Zibo, China, Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China

Abstract:  Background: Post-stroke depression (PSD) is one of the most prevalent emotional disorders after stroke and often results in poor outcomes. However, the underlying physiopathologic mechanism and effective treatment of PSD remain poorly elucidated. Objective: To investigate whether paeoniflorin has antidepressant-like activity in a rat model of PSD. Methods: Rats were randomly divided into four groups: sham-operated control (Sham), PSD, paeoniflorin (with PSD) and fluoxetine group(with PSD). PSD was developed by the right middle cerebral artery occlusion followed 21 days chronic unpredictable mild stress combined (CUMS) with raised alone. Tests of sucrose preference and open field were used to assess the depression-like behavior. Neurological function was evaluated by neurological deficit score and beam balance test. Expression of phosphorylated CREB (p-CREB) and brain-derived neurotrophic factor (BDNF) in the CA1 region of the hippocampal complex was evaluated by western blot and immunofluorescence. Results: Te depressive-like behaviors markedly improved after paeoniflorin and fluoxetine treatment. Furthermore, paeoniflorin treatment significantly increased BDNF and p-CREB expression in the CA1 region. Conclusions: Observed results suggested that paeoniflorin could ameliorate the symptoms and improve the functional capability of PSD rats, similar to the effect of fluoxetine. Abbreviations: PSD: post-stroke depression; CUMS: chronic unpredictable mild stress stimulation; MCAO: middle cerebral artery occlusion; OFT: open field test; SPT: sucrose preference test, NDS: neurological deficit score, BBT: beam balance test; BDNF: brain-derived neurotrophic factor protein; p-CREB: phosphorylated Cyclic-AMP responsive element binding protein. 

Retracted: No

PubPeer comments:
 There are duplications in the immunofluorescence images in Figure 6. The resolution is very low, so it is hard to say what is going on. But it looks like fluorescence intensity of DAPI changes, even when the BDNF does not, which is troubling. The authors should probably look into this.   ,
Homotypic versican G1 domain interactions enhance hyaluronan incorporation into fibrillin microfibrils
Authors: Koji Kimata
Yusuke Murasawa
Ken Watanabe
Zenzo Isogai
Masahiro Zako
Masahiko Yoneda
Lynn Y Sakai
Journal: Journal of Biological Chemistry (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ADAM ADAMTS; Dermis; Extracellular Matrix; Fibrillin; Hyaluronate
Affiliations: From the Department of Advanced Medicine and.

Abstract:  Versican G1 domain-containing fragments (VG1Fs) have been identified in extracts from the dermis in which hyaluronan (HA)-versican-fibrillin complexes are found. However, the molecular assembly of VG1Fs in the HA-versican-microfibril macrocomplex has not yet been elucidated. Here, we clarify the role of VG1Fs in the extracellular macrocomplex, specifically in mediating the recruitment of HA to microfibrils. Sequential extraction studies suggested that the VG1Fs were not associated with dermal elements through HA binding properties alone. Overlay analyses of dermal tissue sections using the recombinant versican G1 domain, rVN, showed that rVN deposited onto the elastic fiber network. In solid-phase binding assays, rVN bound to isolated nondegraded microfibrils. rVN specifically bound to authentic versican core protein produced by dermal fibroblasts. Furthermore, rVN bound to VG1Fs extracted from the dermis and to nondenatured versican but not to fibrillin-1. Homotypic binding of rVN was also seen. Consistent with these binding properties, macroaggregates containing VG1Fs were detected in high molecular weight fractions of sieved dermal extracts and visualized by electron microscopy, which revealed localization to microfibrils at the microscopic level. Importantly, exogenous rVN enhanced HA recruitment both to isolated microfibrils and to microfibrils in tissue sections in a dose-dependent manner. From these data, we propose that cleaved VG1Fs can be recaptured by microfibrils through VG1F homotypical interactions to enhance HA recruitment to microfibrils. 

Retracted: No

PubPeer comments:
 There are several undeclared splicing sites in Fig. 5A and C. It seems that the lanes were assembled together. ,
The Ku-dependent non-homologous end-joining pathway contributes to low-dose radiation-stimulated cell survival
Authors: Xiaoyan Yu
Ping Wang
Ya Wang
Hongyan Wang
Benjamin P C Chen
Journal: Journal of cellular physiology (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Low-dose radiation; adaptive responses; DNA double-strand breaks; repair pathway; homologous recombination repair
Affiliations: Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, USA.

Abstract:  Low-dose (‚â?.1 Gy) radiation-induced adaptive responses could protect cells from high-challenge dose radiation-induced killing. The protective role is believed to promote the repair of DNA double-strand breaks (DSBs) that are a severe threat to cell survival. However, it remains unclear which repair pathway, homologous recombination repair (HRR) or non-homologous end-joining (NHEJ), is promoted by low-dose radiation. To address this question, we examined the effects of low-dose (0.1 Gy) on high-challenge dose (2-4 Gy) induced killing in NHEJ- or HRR-deficient cell lines. We showed that 0.1 Gy reduced the high-dose radiation-induced killing for wild-type or HRR-deficient cells, but enhanced the killing for NHEJ-deficient cells. Interestingly, low-dose radiation also enhanced the killing for wild-type cells exposed to high-challenge dose radiation with high-linear energy transfer (LET). Because it is known that high-LET radiation induces an inefficient NHEJ, these results support that the low-dose radiation-stimulated protective role in reducing high-challenge dose (low-LET)-induced cell killing might depend on NHEJ. In addition, we showed that low-dose radiation activated the DNA-PK catalytic subunit (DNA-PKcs) and the inhibitor of DNA-PKcs destroyed the low-dose radiation-induced protective role. These results suggest that low-dose radiation might promote NHEJ through the stimulation of DNA-PKcs activity and; therefore, increase the resistance of cells to high-challenge dose radiation-induced killing. 

Retracted: No

PubPeer comments:
 Figure 5A. Much more similar than you might expect. https: imgur.com ymltjE7 ,
Mild cold induced thermogenesis: are BAT and skeletal muscle synergistic partners?
Authors: Srinivas Patnaik
Sarita Das
Chanakya N Kundu
Chinmayee Sethy
Ananya Banerjee
Sunil Pani
Naresh C Bal
Santosh K Maurya
Journal: Bioscience Reports (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Core body temperature; brown adipose tissue; cold adaptation; cytokines; skeletal muscle
Affiliations: School of Biotechnology, KIIT University, Campus-11, Bhubaneswar, Odisha 751024, India ., Department of Physiology and Cell Biology, The Ohio State University, College of Medicine, Columbus, OH 43210, U.S.A., Sanford Burnham Prebys Medical Discovery Institute, Lake Nona, Orlando, FL 32827, U.S.A., School of Biotechnology, KIIT University, Campus-11, Bhubaneswar, Odisha 751024, India.

Abstract:  There are two well-described thermogenic sites; brown adipose tissue (BAT) and skeletal muscle, which utilize distinct mechanisms of heat production. In BAT, mitochondrial metabolism is the molecular basis of heat generation, while it serves only a secondary role in supplying energy for thermogenesis in muscle. Here, we wanted to document changes in mitochondrial ultrastructure in these two tissue types based upon adaptation to mild (16¬∞C) and severe (4¬∞C) cold in mice. When reared at thermoneutrality (29¬∞C), mitochondria in both tissues were loosely packed with irregular cristae. Interestingly, adaptation to even mild cold initiated ultrastructural remodeling of mitochondria including acquisition of more elaborate cristae structure in both thermogenic sites. The shape of mitochondria in the BAT remained mostly circular, whereas the intermyofibrilar mitochondria in the skeletal muscle became more elongated and tubular. The most dramatic remodeling of mitochondrial architecture was observed upon adaptation to severe cold. In addition, we report cold-induced alteration in levels of humoral factors: fibroblast growth factor 21 (FGF21), IL1Œ±, peptide YY (PYY), tumor necrosis factor Œ± (TNFŒ±), and interleukin 6 (IL6) were all induced whereas both insulin and leptin were down-regulated. In summary, adaptation to cold leads to enhanced cristae formation in mitochondria in skeletal muscle as well as the BAT. Further, the present study indicates that circulating cytokines might play an important role in the synergistic recruitment of the thermogenic program including cross-talk between muscle and BAT. 

Retracted: No

PubPeer comments:
 Data seems to have been duplicated in figure 1B (green square).  , 
 April 7, 2021 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. ,
Upregulation of microRNA-375 increases the cisplatin-sensitivity of human gastric cancer cells by regulating ERBB2
Authors: Yong Tang
Ning Zhou
Chunlei Xu
Yanli Qu
Journal: Experimental and therapeutic medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: DDP sensitivity; ERBB2; SGC7901 human gastric cancer cells; SGC7901/DDP cells; microRNA-375.

Abstract:  Resistance to chemotherapy is a major challenge in the effective treatment of patients with gastric cancer; however, the mechanisms underlying chemoresistance in gastric cancer cells are yet to be elucidated. MicroRNAs (miRNAs) have previously been associated with cancer progression and sensitivity to chemotherapy; therefore, the present study aimed to identify miRNAs that may influence the sensitivity of human gastric cancer cells to cisplatin (DDP) treatment. Initially, miRNAs that were differentially expressed between the DDP-sensitive SGC7901 human gastric cancer cell line and DDP-resistant SGC7901/DDP cell line were identified using high-throughput sequencing technology. miRNA-375 (miR-375), which was shown to be downregulated in the SGC7901/DDP cells, has previously been associated with numerous types of cancer; however, to the best of our knowledge, a role for miR-375 in the DDP-sensitivity of gastric cancer cells has yet to be explored. In the present study, the expression levels of miR-375 were significantly downregulated in the SGC7901/DDP cells, as compared with the SGC7901 cells, as demonstrated by reverse transcription-quantitative polymerase chain reaction. In addition, upregulation of miR-375 significantly enhanced the anti-proliferative and apoptosis-inducing effects of DDP, whereas downregulation of miR-375 decreased these effects. Subsequently, western blot analysis demonstrated that upregulation of miR-375 in the SGC7901/DDP cells increased their sensitivity to DDP treatment via regulating the protein expression levels of erb-b2 receptor tyrosine kinase 2 and phosphorylated-Akt. The results of the present study indicate that the expression levels of miR-375 may influence the sensitivity of human gastric cancer cells to the effects of DDP; thus suggesting that a combination of miR-375 regulation and DDP may be considered a novel strategy in the treatment of patients with chemoresistant gastric cancer. 

Retracted: No

PubPeer comments:
 This paper was found during a systematic search of papers in this journal with possible duplicated images. About 10% of the papers in this journal (n=169 examined) were found to contain inappropriately duplicated images. These papers have all been reported to the journal publisher in 2017. The editors promised to  investigate promptly but no action has been taken as of today. Figure 6. Unexpected similarities between bands in different panels representing different proteins or experiments. A Forensically analysis appears to agree with the visual inspection.  ,
Macrophage‚ÄìNLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes
Authors: Wen-Bin Liang
Hong-Bin Lin
Zhi-Jian You
Qian-Qian Zhang
Guan-Shan Wei
Ya-Qian Weng
Pu Hong
Hong-Fei Zhang
Wen-Jing Guo
Shi-Yuan Xu
Feng-Xian Li
Journal: Neuroscience Bulletin (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Cardiac dysfunction; Diabetes mellitus; Ischemic stroke; Macrophage; NLRP3 inflammasome.
Affiliations: Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510220, China., Department of Anesthesiology, Shenzhen SAMII Medical Center, Shenzhen, 518118, China., Department of Anesthesiology, The Second Affiliated Hospital, Shantou University Medical College, Shantou, 515041, China., University of Ottawa Heart Institute and Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, K1N, Canada., Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510220, China. .

Abstract:  Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke. 

Retracted: No

PubPeer comments:
null, 
 Identified by another reader. ***  , 
 https: retractionwatch.com 2014 01 06 fourth-retraction-results-from-cardiff-investigation ,
Activation of cannabinoid receptors by the pentacyclic triterpene Œ±,Œ≤-amyrin inhibits inflammatory and neuropathic persistent pain in mice
Authors: Flavia C Meotti
Allisson Freire Bento
Ana F Paszcuk
Giselle F Passos
Kathryn A B Sim√£o da Silva
Eduardo S Silva
Jo√£o B Calixto
Journal: Pain (2011)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Œ±,Œ≤-amyrin; cannabinoid receptors; antinociception; anti-inflammatory properties; cytokines
Affiliations: Departamento de Farmacologia, Centro de Ci√™ncias Biol√≥gicas, Universidade Federal de Santa Catarina, Campus Universit√°rio Trindade, Bloco D, CCB, Caixa Postal 476, CEP 88049-900, Florian√≥polis, Santa Catarina, Brazil.

Abstract:  In this study, we report that Œ±,Œ≤-amyrin, a plant-derived pentacyclic triterpene, reduced persistent inflammatory and neuropathic hyperalgesia in mice by a direct activation of the CB(1) and CB(2) cannabinoid receptors (CB(1)R and CB(2)R). The oral treatment with Œ±,Œ≤-amyrin (30 mg/kg) significantly reduced mechanical and thermal hyperalgesia and inflammation induced by complete Freund's adjuvant (CFA) and by partial sciatic nerve ligation (PSNL). The pretreatment with either CB(1)R or CB(2)R antagonists and the knockdown gene of the receptors significantly reverted the antinociceptive effect of Œ±,Œ≤-amyrin. Of note, binding studies showed that Œ±,Œ≤-amyrin directly bound with very high affinity to CB(1)R (K(i)=0.133 nM) and with a lower affinity to CB(2)R (K(i)=1989 nM). Interestingly, Œ±,Œ≤-amyrin, ACEA (CB(1)R agonist), or JWH-133 (CB(2)R agonist), at doses that caused antinociception, failed to provoke any behavioral disturbance, as measured in the tetrad assay. In addition, Œ±,Œ≤-amyrin largely decreased interleukin-1Œ≤ (IL-1Œ≤), tumor necrosis factor Œ± (TNF-Œ±), keratinocyte-derived chemokine (KC) and interleukin 6 (IL-6) levels, and myeloperoxidase activity. Likewise, Œ±,Œ≤-amyrin prevented the activation of the transcriptional factors: nuclear factor Œ∫B (NF-Œ∫B) and cyclic adenosine monophosphate response element binding (CREB) and the expression of cyclooxygenase 2 in mice footpads and spinal cords. The present results demonstrated that Œ±,Œ≤-amyrin exhibits long-lasting antinociceptive and anti-inflammatory properties in 2 models of persistent nociception via activation of cannabinoid receptors and by inhibiting the production of cytokines and expression of NF-Œ∫B, CREB and cyclooxygenase 2. 

Retracted: No

PubPeer comments:
 Supplementary Figure 1. More similar than expected after rotating the image. Could authors check please?  , 
 Thank you for identifying and bringing this matter to our attention. We are currently retrieving the original data to review the figure, and we are in contact with the Editorial Board to solve the issue. ,
C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1
Authors: J M√ºller
T Copeland
D K Morrison
S Ory
H Piwnica-Worms
Journal: Molecular cell (2001)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Kinase suppressor of Ras; KSR1; Cdc25C-associated kinase 1; C-TAK1; MEK
Affiliations: Regulation of Cell Growth Laboratory, Center for Cancer Research, NCI-Frederick, Frederick, MD 21702, USA.

Abstract:  Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway that interacts directly with MEK and MAPK. Here we show that KSR1 translocates from the cytoplasm to the cell surface in response to growth factor treatment and that this process is regulated by Cdc25C-associated kinase 1 (C-TAK1). C-TAK1 constitutively associates with mammalian KSR1 and phosphorylates serine 392 to confer 14-3-3 binding and cytoplasmic sequestration of KSR1 in unstimulated cells. In response to signal activation, the phosphorylation state of S392 is reduced, allowing the KSR1 complex to colocalize with activated Ras and Raf-1 at the plasma membrane, thereby facilitating the phosphorylation reactions required for the activation of MEK and MAPK. 

Retracted: No

PubPeer comments:
 Figure 2. Much more similar than you would expect. https: imgur.com wsbDy1N ,
NF-kappaB activation represses tumor necrosis factor-alpha-induced autophagy
Authors: Manuela Amelotti
G√©rard Pierron
Julie Mathieu
Mojgan Djavaheri-Mergny
Patrice Codogno
Sylvie Souqu√®re
Fran√ßoise Besan√ßon
Chantal Bauvy
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NF-kappaB; autophagy; cell death; regulation; cross-talk
Affiliations: INSERM U756, Facult√© de Pharmacie, Universit√© Paris-Sud 11, 5 Rue Jean-Baptiste Cl√©ment, 92296 Ch√¢tenay-Malabry, France. 

Abstract:  Activation of NF-kappaB and autophagy are two processes involved in the regulation of cell death, but the possible cross-talk between these two signaling pathways is largely unknown. Here, we show that NF-kappaB activation mediates repression of autophagy in tumor necrosis factor-alpha (TNFalpha)-treated Ewing sarcoma cells. This repression is associated with an NF-kappaB-dependent activation of the autophagy inhibitor mTOR. In contrast, in cells lacking NF-kappaB activation, TNFalpha treatment up-regulates the expression of the autophagy-promoting protein Beclin 1 and subsequently induces the accumulation of autophagic vacuoles. Both of these responses are dependent on reactive oxygen species (ROS) production and can be mimicked in NF-kappaB-competent cells by the addition of H2O2. Small interfering RNA-mediated knockdown of beclin 1 and atg7 expression, two autophagy-related genes, reduced TNFalpha- and reactive oxygen species-induced apoptosis in cells lacking NF-kappaB activation and in NF-kappaB-competent cells, respectively. These findings demonstrate that autophagy may amplify apoptosis when associated with a death signaling pathway. They are also evidence that inhibition of autophagy is a novel mechanism of the antiapoptotic function of NF-kappaB activation. We suggest that stimulation of autophagy may be a potential way bypassing the resistance of cancer cells to anti-cancer agents that activate NF-kappaB. 

Retracted: No

PubPeer comments:
  Fig. (6). TEM photomicrographs of (A) Plain SLNs Much could be said about these solid lipid nanoparticles, but I would prefer to focus on the support membrane used in the transmission electron microscopy, and in particular, on its peculiarly repetitive nature. Emphasised at the right with increased contrast.  , 
  Fig (13). Fluorescent microscopy of qualitative uptake in the HNGC1 Tumor Cell Lines (A) Plain FITC; (B) FITC labeled plain SLNs and (C) FITC labeled CBSA conjugated SLNs.  Reviewers and editors looked at the successive enlargements in (B) and (C) and thought  Yes, that s exactly what random clumps of tumor cells should look like after taking up fluorescein-isothiocyanate-labeled nanoparticles! UPDATE: Unexpected similarities to the random cell pairs of Fig. 11 from [Agarwal et al (2011)] ,  Fluorescent photomicrographs of DOX uptake in the HNGC 1 cells from Plain DOX, SLN-DOX, CBSA-SLN-DOX and CBSA+ CBSA-SLN-DOX.  There, (C) and (D) are rotationally symmetrical. , 
 #1 Fig 6,  TEM photomicrographs of ... (B) CBSA conjugated SLNs. The repeating background is smeared out in some places.  ,
MiR-566 protects the malignant progression of breast cancer by negatively regulating WNT6
Authors: T Li
L-P Wang
M-M Zhang
Y-Q Du
X-C Hu
B-Y Wang
M-C Zhao
Z-H Tao
J Zhang
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-566; prognosis; breast cancer; WNT6; tumor size
Affiliations: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Fudan University School of Medicine, Shanghai, China. .

Abstract:  Objective: To elucidate the relationship between microRNA-566 (miR-566) and prognosis in breast cancer (BC) and to clarify the influences of miR-566 and WNT6 in its locus region on BC progression. Patients and methods: MiR-566 and WNT6 levels in 44 pairs of BC samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The influences of miR-566 on clinical features and prognosis in BC patients were analyzed. According to the differential expressions of miR-566 in the tested BC cell lines, MDA-MB-231 and MCF-7 cells were selected for generating miR-566 knockdown and overexpression models, respectively. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assays were conducted to explore the role of miR-566 in BC cell functions. Besides, the regulatory interaction between miR-566 and its downstream gene WNT6 was assessed by performing Dual-Luciferase reporter assay. Finally, the co-regulation of miR-566 and WNT6 in BC cell functions was examined. Results: MiR-566 was downregulated in BC tissues. BC patients with a low expression level of miR-566 were prone to suffering a large tumor size, advanced tumor grade, high incidence of lymphatic metastasis and poor prognosis. Overexpression of miR-566 weakened proliferative and migratory abilities in MCF-7 cells, whereas knockdown of miR-566 produced the opposite results in MDA-MB-231 cells. WNT6 was the target gene binding to miR-566, and they displayed a negative expression correlation in BC tissues. Regulatory effects of miR-566 on BC progression could be reversed by WNT6. Conclusions: MiR-566 is closely related to tumor size, tumor grade, lymphatic metastasis and prognosis in BC. It protects the malignant progression of BC by negatively regulating WNT6. 

Retracted: No

PubPeer comments:
 probably mixed up clone 2 and 3  ,
Sodium arsenite accelerates TRAIL-mediated apoptosis in melanoma cells through upregulation of TRAIL-R1/R2 surface levels and downregulation of cFLIP expression
Authors: Vladimir N Ivanov
Tom K Hei
Journal: Experimental cell research (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AP-1/cJun; NF-kappaB; STAT3; sodium arsenite; apoptosis
Affiliations: Center for Radiological Research, Columbia University College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. 

Abstract:  AP-1/cJun, NF-kappaB and STAT3 transcription factors control expression of numerous genes, which regulate critical cell functions including proliferation, survival and apoptosis. Sodium arsenite is known to suppress both the IKK-NF-kappaB and JAK2-STAT3 signaling pathways and to activate the MAPK/JNK-cJun pathways, thereby committing some cancers to undergo apoptosis. Indeed, sodium arsenite is an effective drug for the treatment of acute promyelocytic leukemia with little nonspecific toxicity. Malignant melanoma is highly refractory to conventional radio- and chemotherapy. In the present study, we observed strong effects of sodium arsenite treatment on upregulation of TRAIL-mediated apoptosis in human and mouse melanomas. Arsenite treatment upregulated surface levels of death receptors, TRAIL-R1 and TRAIL-R2, through increased translocation of these proteins from cytoplasm to the cell surface. Furthermore, activation of cJun and suppression of NF-kappaB by sodium arsenite resulted in upregulation of the endogenous TRAIL and downregulation of the cFLIP gene expression (which encodes one of the main anti-apoptotic proteins in melanomas) followed by cFLIP protein degradation and, finally, by acceleration of TRAIL-induced apoptosis. Direct suppression of cFLIP expression by cFLIP RNAi also accelerated TRAIL-induced apoptosis in these melanomas, while COX-2 suppression substantially increased levels of both TRAIL-induced and arsenite-induced apoptosis. In contrast, overexpression of permanently active AKTmyr inhibited TRAIL-mediated apoptosis via downregulation of TRAIL-R1 levels. Finally, AKT overactivation increased melanoma survival in cell culture and dramatically accelerated growth of melanoma transplant in vivo, highlighting a role of AKT suppression for effective anticancer treatment. 

Retracted: No

PubPeer comments:
 Figure 1C. It is supposed to be a time series. There are only 4 lanes.  , 
 Different concentration of PAG were used for protein separation: 8% for PARP, 10% for caspase-8, 12% for caspase-3. , 
 #1 We would like to thank Cortinarius Rufolatus for his comment on Fig.1C of Exp. Cell Res 2006, 312:4120-4138. The central lane in the upper blot for Caspase-8 has indeed removed from the scan this blot. The boundary between the left and right parts is now indicated by a solid line. The updated Fig.1C is shown below this note.  , 
 #3 What about the other panels in figure 1C? Are they spliced in the middle? Should they be presented alongside the Casp8 panel? , 
 #4 No, they were not spliced in the middle. ,
GATA1-mediated transcriptional regulation of the Œ≥-secretase activating protein increases AŒ≤ formation in Down syndrome
Authors: Thomas Wisniewski
Jin Chu
Domenico Pratic√≤
Journal: Annals of Neurology (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Down syndrome; AŒ≤ peptides; Alzheimer disease; amyloidosis; Œ≥-secretase activating protein (GSAP)
Affiliations: Department of Pharmacology and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA., Departments of Neurology, Psychiatry, and Pathology, and Center for Cognitive Neurology, New York University School of Medicine, New York, NY.

Abstract:  Because of an extra copy of the AŒ≤ precursor protein gene on chromosome 21, Down syndrome (DS) individuals develop high levels of AŒ≤ peptides and Alzheimer disease-like brain amyloidosis early in life. Here we show that the Œ≥-secretase activating protein (GSAP), a key enzyme in amyloidogenesis, is increased in DS brains and specifically regulated at the transcriptional level by GATA1 transcription factor. The discovery of this novel pathway has translational implications for DS, because pharmacological inhibition of GSAP is an attractive and viable AŒ≤-lowering therapeutic strategy for this disorder. 

Retracted: No

PubPeer comments:
 [Retracted] (as yet, no date or pagination). The authors are to be applauded, although it is a pity that they do not specify the  other agencies [who] partly contributed data to this article . ----------------------------------------------------------- The authors of the article ... have requested retraction on the following basis: Because other agencies have partly contributed data to this article, there is also a risk for data fraud in this article. After collecting more new data and materials through recent experiments, the authors cannot guarantee the uniqueness of their data anymore and have decided to retract the manuscript due to scientific rigor. The authors would like to apologize for the troubles brought to readers and colleagues. ,
Suppression of TGF-Œ≤1 enhances chemosensitivity of cisplatin-resistant lung cancer cells through the inhibition of drug-resistant proteins
Authors: Yunqing Chen
Fenggang Xiang
Min Li
Hong Li
Jinghua Chi
Jin Wang
Keyu Ren
Journal: Artificial Cells Nanomedicine and Biotechnology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Epithelial‚Äìmesenchymal transition (EMT); TGF-Œ≤1; chemoresistance; non-small cell lung cancer (NSCLC).
Affiliations: Department of Pathology, Medical School of Qingdao University, Qingdao, China;, Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China;, The Affiliated Hospital of Qingdao University, Qingdao, China

Abstract:  Cisplatin-based chemotherapy is the first-line treatment for non-small cell lung cancer (NSCLC), but drug resistance occurs in most patients, leading to treatment failure. Recent studies have shown that epithelial-mesenchymal transition (EMT) is associated with drug resistance. However, the underlying mechanism is not entirely clear. In this study, first we showed significant positive correlation between the expression of ERCCl and vimentin, and significant negative correlation between the ERCCl and E-cadherin in the neoadjuvant chemotherapy group and the simple surgery group. Second, we showed that cisplatin-resistant A549 cells (A549/DDP) acquire EMT phenotype with high expression of drug-resistant proteins, P-gp and ERCC1. Knockdown of TGF-Œ≤1 may reverse EMT and significantly reduce the expression of P-gp and ERCC1. Moreover, A549/DDP cells become more sensitive to cisplatin. In summary, our results globally confirm a molecular and phenotypic association between chemoresistance and EMT of resistant tumour cells under a histological and cellular level. More importantly, silence of TGF-Œ≤1 may enhance sensitivity to cisplatin of A549/DDP through inducing the reversal of EMT and inhibiting the expression of resistance-associated proteins. Hence, inhibition of TGF-Œ≤1 could be considered as an effective strategy for eliminating resistant lung cancer. 

Retracted: No

PubPeer comments:
 Two panels with PCR data have apparently been reused in Figure 3B and D).  , 
 Dear Pubpeer, We apologize for the delay in responding to your comment. After a lot of searching, itu2019s difficult for us to find raw data of PCR, because we made this experiment in 2014. However, we checked these PCR results many times, although they are similar, we find they have difference after we regulated and returned to the same size and shape. Now we will continue to search the raw data, at the same time, if you have any question, please contact me. Sincerely yours, Keyu Ren ,
5-Aminolevulinic acid photodynamic therapy stimulates local immunity in patients with condylomata acuminata via activation of T lymphocytes
Authors: X-N Lu
F Li
J-F Wu
Z Zhang
Q Cheng
J Du
S-Y Chen
Y-L Wang
J-H Xu
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 5-Aminolevulinic acid; photodynamic therapy; local immunity; condylomata acuminata; T lymphocytes

Abstract:  The article "5-Aminolevulinic acid photodynamic therapy stimulates local immunity in patients with condylomata acuminata via activation of T lymphocytes" by J. Du, Q. Cheng, Z. Zhang, J.-F. Wu, F. Li, S.-Y. Chen, Y.-L. Wang, X.-N. Lu, J.-H. Xu, published in Eur Rev Med Pharmacol Sci 2017; 21 (5): 1125-1135 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,
Id2 drives differentiation and suppresses tumor formation in the intestinal epithelium
Authors: Anna Lasorella
Robert G Russell
Antonio Iavarone
Luis E Dettin
Journal: Cancer Research (2004)
Discipline: CLINICAL MEDICINE
Keywords: Oncogenic signals; Id2; tumor suppressor proteins; retinoblastoma; p107
Affiliations: Lombardi Cancer Center, Department of Oncology, Georgetown University, Washington, D. C., USA.

Abstract:  Oncogenic signals elevate expression of Id2 in multiple tumor types. When deregulated, Id2 inactivates the tumor suppressor proteins retinoblastoma, p107, and p130. Here, we report a novel and unexpected tumor inhibitory function of Id2 in the intestinal epithelium. First, genetic ablation of Id2 in the mouse prevents differentiation and cell cycle arrest of enterocytes at the time of formation of the crypt-villus unit. Later, these developmental abnormalities evolve toward neoplastic transformation with complete penetrance. Id2-null tumors contain severe dysplastic and metaplastic lesions and express aberrant amounts of beta-catenin. Thus, our data are the first to establish a direct requirement of basic helix-loop-helix inhibitors in driving differentiation and define an unexpected role for the retinoblastoma-binding protein Id2 in preventing tumor formation. 

Retracted: No

PubPeer comments:
 Figure 4G. Beta-catenin panel. Much more similar than you would expect. No background. https: imgur.com tzo8bhB ,
Characterization, biorecognitive activity and stability of WGA grafted lipid nanostructures for the controlled delivery of Rifampicin
Authors: Ramakrishna Sistla
Bharathi B Reddy
Lakshmi Tunki
Deep Pooja
Hitesh Kulhari
Journal: Chemistry and physics of lipids (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Biorecognition; Rifampicin; Solid-lipid nanoparticles; Stability; Wheat germ agglutinin.
Affiliations: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India., Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Health Innovations Research Institute, RMIT University, Melbourne, Australia., Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: .

Abstract:  Targeted nanomedicines improve the delivery of drugs by increasing the drug concentration at target site, protecting the premature degradation and releasing the encapsulated drug in controlled manner. To make rifampicin (RFN) delivery more effective, we designed and characterized wheat germ agglutinin (WGA) conjugated, RFN loaded solid-lipid nanoparticles (WRSN). Nanoparticles were prepared by solvent emulsification/evaporation and conjugated with fluorescein isothiocyanate-labeled WGA. Important characteristics, such as particle size, zeta potential, encapsulation efficiency, conjugation efficiency and in vitro drug release behavior, were investigated. WGA conjugation to the nanoparticles was confirmed by Fourier Transform Infrared (FTIR) analysis. Conjugation efficiency was determined by fluorescent spectroscopy and Bradford assay. RFN was released from nanoparticles via the diffusion-controlled, non-fickian and supercase II mechanism. A haemaglutination test confirmed that WGA retained its bio-recognition activity and sugar-binding specificity after it was coupled with the nanoparticles. In vitro experiments demonstrated that WRSN interacted more than non-conjugated nanoparticles with porcine mucin. WRSN were stable in the presence of electrolytes up to 1M concentration. Therefore, WGA-conjugated solid lipid nanoparticles could be a promising tool for the controlled delivery of RFN or other anti-tubercular drugs. 

Retracted: No

PubPeer comments:
 Figure 4,  baemagglutination test (sic). * Blue boxes: The row with the positive control looks very similar to the row with the WRSN samples.  , 
 Correction, December 2021: https: www.sciencedirect.com science article pii S0009308421001158  The authors regret that, in Fig. 4, a row was repeated during the rearrangement of the rows in sequence to the text discussed. This happened because for three samples, we used n = 9 and for two samples, we used n = 3. Hence, we tried to represent n = 3 for all the samples. After verifying with the original raw files, Fig. 4 is now replaced with correct figure. I thank the authors for correcting this duplication. ,