PReD-Bench/PRed-Bench huggingface dataset:
Quinoxaline 1,4-dioxides: hypoxia-selective therapeutic agents
Authors: Pierre Yared
Mona Diab-Assef
Chafika Assaad
Makhluf J Haddadin
Hala U Gali-Muhtasib
Journal: Molecular Carcinogenesis (2002)
Discipline: CLINICAL MEDICINE
Keywords: clinicians; cancer; hypoxic tumors; chemotherapy; radiation therapy
Affiliations: Department of Biology, American University of Beirut, Beirut, Lebanon.

Abstract:  A problem that confronts clinicians in the treatment of cancer is the resistance of hypoxic tumors to chemotherapy and radiation therapy. Thus, the development of new drugs that are toxic to hypoxic cells found in solid tumors is an important objective for effective anticancer chemotherapy. We recently showed that the heterocyclic aromatic N-oxides, quinoxaline 1,4-dioxides (QdNOs), are cytotoxic to tumor cells cultured under hypoxia. In this study, we evaluated the hypoxia-selective toxicity of four diversely substituted QdNOs and determined their effect on the expression of hypoxia inducible factor (HIF) 1alpha in the human colon cancer cell line T-84. The various QdNOs were found to possess a 50- to 100-fold greater cytotoxicity to T-84 cells cultured under hypoxia compared with oxia. Interestingly, the hypoxia cytotoxicity ratio (HCR), the ratio of equitoxic concentrations of the drug under aerobic/anoxic conditions, was highly structure related and depended on the nature of the substituents on the QdNO heterocycle. The most cytotoxic 2-benzoyl-3-phenyl-6,7-dichloro derivative of QdNO (DCQ) was potent at a dose of 1 microM with an HCR of 100 and significantly reduced the levels of HIF-1alpha transcript and protein. The 2-benzoyl-3-phenyl derivative (BPQ) had a hypoxia potency of 20 microM and an HCR of 40. By contrast, the 2-aceto-3-methyl and the 2,3-tetramethylene (TMQ) derivatives of QdNO were much less cytotoxic under hypoxia (HCRs of 8.5 and 6.5, respectively) and reduced the expression of HIF-1alpha mRNA to a much lesser extent. Because the nonchlorinated analogue BPQ did not demonstrate behavior similar to that of DCQ, we hypothesize that the C-6, C-7-chlorine of DCQ might play a significant role in the selective hypoxic cytotoxicity of the drug. 

Retracted: No

PubPeer comments:
 Figure 4. * Green, red, and blue boxes: Some lanes look more similar than expected.  ,
TRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome
Authors: Linghui Zeng
Peifang Jiang
Xinyan Dong
Yicheng Xie
Weida Shen
Chen Chen
Shufen Li
Lifen Gong
Yu Shao
Zengxian Sun
Tao Zhu
Journal: Neurobiology of Disease (2021)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Cognitive dysfunction; Multiple sclerosis; NLRP3 inflammasome; Neuroinflammation; TRPM2 channel.
Affiliations: Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou 310052, China; Department of Pediatrics, Wenling First People's Hospital, Wenling 317500, China., Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou 310052, China., Department of Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China., Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou 310052, China; Department of Pediatrics, Lishui Central Hospital, Lishui 323000, China., Department of Pharmacy, Zhejiang University City College School of Medicine, Hangzhou 310015, China., Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou 310052, China. Electronic address: .

Abstract:  Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is characterized by demyelination, axonal injury and neurological deterioration. Few medications are available for progressive MS, which is associated with neuroinflammation confined to the CNS compartment. Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that plays pathological roles in a wide range of neuroinflammatory diseases; however, the underlying molecular mechanisms of TRPM2 remain elusive. Here, we established a cuprizone model that presents hallmark MS pathologies to investigate the role of TRPM2 in progressive MS. We demonstrated that genetic deletion of TRPM2 yields protection from the cuprizone-induced demyelination, synapse loss, microglial activation, NLRP3 inflammasome activation and proinflammatory cytokines production and ultimately leads to an improvement in cognitive decline. Furthermore, we showed that the pharmacological inhibition of NLRP3 ameliorated the demyelination, neuroinflammation and cognitive impairment in the model with no additive effects on the TRPM2 KO mice. Taken together, these results indicated that TRPM2 plays important roles in regulating neuroinflammation in progressive MS via NLRP3 inflammasome, and the results shed light on TRPM2's potential role as a therapeutic target for MS. 

Retracted: No

PubPeer comments:
 Two sets of images in Figure 7A appear unexpectedly similar as they seem to be described as coming from two different groups. Could the authors please check? ***  ,
Leptospiral hemolysins induce proinflammatory cytokines through Toll-like receptor 2-and 4-mediated JNK and NF-Œ∫B signaling pathways
Authors: Chenglin Zhang
Jie Yan
Yifei Wu
David M Ojcius
Shibiao Ding
Huan Wang
Xu&#x27;ai Lin
X Frank Yang
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: Leptospira; hemolysins; proinflammatory cytokines; TLR2; TLR4
Affiliations: Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Abstract:  Background: Infection with pathogenic Leptospira species causes serious systemic inflammation in patients. Although a few leptospiral proinflammatory molecules have been identified, Leptospira likely encodes other unidentified strong inflammation stimulators. The pathogenic L. interrogans genome encodes numerous putative hemolysin genes. Since hemolysins from other bacteria can cause inflammatory reactions, we hypothesized that leptospiral hemolysins may function as proinflammatory stimulators that contribute to the strong inflammation associated with Leptospira infection. Methodology/principal findings: We first used cytokine protein microarrays for systematic analysis of serum cytokine profiles in leptospirosis patients and leptospire-infected mice. We found that IL-1Œ≤, IL-6 and TNF-Œ± were the main proinflammatory cytokines in the sera of both the patients and the mice. We then analyzed eight putative hemolysins in L. interrogans strain Lai. The results showed that five of them, Sph1, Sph2, Sph3, HlpA and TlyA were secreted and had hemolytic activity. More importantly, these five hemolysins induced the strong production of IL-1Œ≤, IL-6 and TNF-Œ± in human and mouse macrophages (although a bit lower in the latter). Furthermore, blockade of TLR2 or TLR4 with either antibodies or inhibitors of the NF-Œ∫B or JNK signaling pathways significantly reduced the production of hemolysin-induced IL-1Œ≤, IL-6 and TNF-Œ±. Macrophages isolated from TLR2-, TLR4-or double TLR2-and 4-deficient mice also confirmed that the leptospiral hemolysins that induce proinflammatory cytokines are both TLR2-and TLR4-dependent. Conclusions/significance: Our findings demonstrate that L. interrogans secretes many hemolysins that function as powerful inducers of proinflammatory cytokines through both TLR2-and TLR4-dependent JNK and NF-Œ∫B pathways. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than expected.  ,
Long non-coding RNA DLX6-AS1 regulates neuroblastoma progression by targeting YAP1 via miR-497-5p
Authors: Shan Wang
Chao Yang
Changchun Li
Journal: Life Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: DLX6-AS1; Long non-coding RNA; Neuroblastoma; YAP1; miR-497-5p.
Affiliations: Department of Pediatric surgical oncology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, PR China., Department of Pediatric surgical oncology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: .

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors with the approval of the Editor-in-Chief. The panel SK-N-SH/si-NC from Fig. 2F appears similar to the panel SH-SY5Y/si-NC (vertically flipped) and the panel SK-N-SH/si-DLX6-AS1 appears similar to the panel SH-SY5Y/si-DLX6-AS1 (vertically flipped). In addition, the authors were reportedly not able to retrieve the raw images of these panels. 

Retracted: Yes

PubPeer comments:
 Figure 2F appears to have some repeated images, flipped vertically. Common authors on this now-retracted paper: https: pubpeer.com publications 564771733E439A99701AA291C3DC46 ***  , 
 Retracted [15 February 2022] . -------------------- This article has been retracted at the request of the authors with the approval of the Editor-in-Chief. The panel SK-N-SH si-NC from Fig. 2F appears similar to the panel SH-SY5Y si-NC (vertically flipped) and the panel SK-N-SH si-DLX6-AS1 appears similar to the panel SH-SY5Y si-DLX6-AS1 (vertically flipped). In addition, the authors were reportedly not able to retrieve the raw images of these panels. ,
p53 promotes selection for Fas-mediated apoptotic resistance
Authors: C Koumenis
H L Maecker
A J Giaccia
Journal: Cancer research (2000)
Discipline: CLINICAL MEDICINE
Keywords: p53 inactivation; apoptotic response; oncogenic activation; DNA damage; Fas
Affiliations: Department of Radiation Oncology, Stanford University Medical Center, California 94305-5468, USA.

Abstract:  Although p53 inactivation is implicated as a mechanism to explain diminished apoptotic response, it is clear that tumor cells that possess transcriptionally functional p53 can also be resistant to diverse apoptotic stimuli. We hypothesize that oncogenic activation and DNA damage are sufficient stimuli to increase the p53-dependent transcription of Fas and thereby establish a situation in which cell to cell contact could be a selective pressure to either lose p53 function or inactivate components of the Fas death pathway. Examination of genetically matched tumor cell lines that possessed either wild-type or null p53 loci indicated that cells possessing functional p53 increased their surface levels of Fas and Fas ligand (FasL) in response to DNA damage. In contrast, stress induced by changes in the tumor microenvironment such as decreased oxygen did not up-regulate Fas or FasL. Cells with wild-type p53 underwent Fas-mediated killing in the presence of either FasL-expressing killer cells or activating Fas antibodies, whereas cells in which p53 was deleted or inactivated were protected from such killing. Furthermore, Fas and FasL expression and induction became transcriptionally repressed in transformed cells with wild-type p53 with increasing passage, whereas other p53 downstream targets and functions, such as p21 inducibility and cell cycle arrest, remained intact. Repression of the Fas locus could be reverted by treatment with the histone deacetylase inhibitor trichostatin A. These results support a model of tumor progression in which oncogenic transformation drives tumor cells to lose either p53 or their Fas sensitivity as a means of promoting their survival and evade immune surveillance. 

Retracted: No

PubPeer comments:
null, 
  , 
null, 
null, 
null, 
 #2 Figure 10B. Much more similar than you would expect. https: imgur.com FLTy3o5 , 
 #3 I disagree. These look quite similar to me. ***  ,
MicroRNA-378 inhibits cell growth and enhances L-OHP-induced apoptosis in human colorectal cancer
Authors: Kai-Yu Wang
Ji-Shan Xue
Ming-Jun Yu
Fu-Xi Zhang
Jun Ma
Ji-Sheng Zhao
Journal: IUBMB life (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CDC40; chemoresistance; colorectal cancer; miR-378; microRNA.
Affiliations: Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China; Department of General Surgery, Affiliated Hospital of Beihua University, Jilin, China., Department of Radiology; Affiliated Hospital of Beihua University; Jilin China, Department of General Surgery; Affiliated Hospital of Beihua University; Jilin China, Department of Gastroenterology; Affiliated Hospital of Beihua University; Jilin China, Department of General Surgery; General Hospital of Jilin Chemical Group Company; Jilin China, Department of Gastrointestinal Surgery; China-Japan Union Hospital of Jilin University; Changchun China

Abstract:  MicroRNAs (miRNAs) are small noncoding RNAs that participate in a variety of biological processes, and dysregulation of miRNAs is widely associated with cancer development and progression. MiR-378 is frequently downregulated in colorectal cancer (CRC) and colorectal cell lines; however, it has high serum levels. Bioinformatics analysis further deduced that CDC40 is a potential target of miR-378, and luciferase reporter assays confirmed the direct regulation of CDC40 by miR-378. CDC40 plays a key role in cell cycle progression through G1/S and G2/M and pre-mRNA splicing. Subsequently, we determined that miR-378 inhibits cell growth and the G1/S transition in CRC cells and that these effects were CDC40-dependent. Finally, miR-378 increased cell apoptosis induced by the chemotherapeutic drug L-OHP. Our data highlight the potential application of miR-378 as a tumor suppressor for CRC therapy and overcoming chemoresistance, and it may also be a potential tumor marker for CRC prognosis. 

Retracted: No

PubPeer comments:
 A set of images has been duplicated in Figure 3. Note however that the fluorescence intensity changes slightly between the two sets. The authors should consult their original images and contact the journal for a correction.  , 
 These papers refer to the micro RNA as miR-378, which does not exist! What they are actually studying is miR-378a-3p, which they should use the correct terminology for ,
Immunocompatibility and Toxicity Studies of Poly‚ÄêL‚ÄêLysine Nanocapsules in Sprague‚ÄìDawley Rats for Drug‚ÄêDelivery Applications
Authors: Dhanya Chandrasekharan Rajalekshmi
Haider Sami
Janeesh Plakkal Ayyappan
Annie Abraham
Sri Sivakumar
Journal: Chemical Biology & Drug Design (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Poly-L-Lysine nanocapsules; immunocompatibility; immunomodulatory genes; inflammatory markers.
Affiliations: Department of Biochemistry, University of Kerala, Kariavattom campus, Trivandrum, 695 581, Kerala, India., Department of Biological Sciences and Bioengineering Indian Institute of Technology (IIT) Kanpur Kanpur Uttar Pradesh India, Department of Biochemistry University of Kerala Kariavattom campus Trivandrum 695 581 Kerala India, Unit of Excellence on Soft Nanofabrication Department of Chemical Engineering Indian Institute of Technology Kanpur (IIT) Kanpur Uttar Pradesh India

Abstract:  Poly-L-Lysine (PLL) nanocapsules are the emerging drug-delivery vehicle for the therapeutics of targeted diseases. The study was designed for the synthesis and characterization of PLL nanocapsules and to know its immunocompatibility and toxicity behavior for in vivo drug-delivery applications. Alteration in hematologic parameters, immunomodulatory gene expression by RT-PCR studies, toxicity markers status, immunoblotting of major inflammatory marker proteins, and histopathologic studies from major tissues of rat after intravenous administration of PLL nanocapsules after 30 days were assessed. In vivo toxicity markers activity, hematologic parameters alteration, and RT-PCR analysis of important immunomodulatory genes such as monocyte chemotactic protein-1(MCP 1), tumor necrosis factor-alpha (TNF-Œ±), Intercellular adhesion molecule-1 (ICAM-1), and interleukin-6 (IL-6) showed least changes when compared with control. The immunoblotting of major inflammatory markers such as cyclooxygenase-2 (COX-2), lipo-oxygenase-15 (LOX-15), and nitric oxide synthase (NOS) found have least expression showing the immunocompatibility of PLL nanocapsules. Histopathologic studies of important tissues showed almost normal architecture after treatment using different concentration of PLL nanocapsules after the experimental period. The results showed a promising outcome and further confirmed the immunocompatibility and non-toxicity of PLL nanocapsules in vivo for drug-delivery applications. 

Retracted: No

PubPeer comments:
 Could the authors clarify this image duplication in the same publication?  , 
 Could the authors clarify this too?  , 
 Could the authors clarify this too?  , 
 Tissue images in Figure 4 appear to be used multiple times, with rotation and resizing.  ,
The effects of folate supplementation on inflammatory factors and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial
Authors: Fereshteh Bahmani
Hossein Shakeri
Maryam Karamali
Zatollah Asemi
Journal: Clinical Endocrinology (2014)
Discipline: CLINICAL MEDICINE
Keywords: folate supplementation; polycystic ovary syndrome; inflammatory factors; oxidative stress; clinical trial
Affiliations: Research Center for Biochemistry and Nutrition in Metabolic Diseases; Kashan University of Medical Sciences; Kashan Iran, Department of Gynecology and Obstetrics; School of Medicine; Arak University of Medical Sciences; Arak Iran

Abstract:  Objective: This study was conducted to determine the effects of folate supplementation on inflammatory factors and biomarkers of oxidative stress among women with polycystic ovary syndrome (PCOS). Design, patients and measurements: This randomized, double-blind, placebo-controlled clinical trial was conducted among 69 women diagnosed with PCOS and aged 18-40 year old. Participants were randomly assigned to three groups receiving the following: (1) folate-1: 1 mg/d folate supplements (N = 23); (2) folate-5: 5 mg/d folate supplements (N = 23) and (3) placebo (N = 23) for 8 weeks. Fasting blood samples were taken at the beginning of the study and after 8 weeks to measure homocysteine (Hcy), inflammatory factors including high-sensitivity C-reactive protein (hs-CRP), nitric oxide (NO), biomarkers of oxidative stress including total antioxidant capacity (TAC), glutathione (GSH), malondialdehyde (MDA) and homoeostatic model assessment-beta cell function (HOMA-B). Results: Supplementation with 5 mg/d folate resulted in reduced plasma Hcy (-2¬∑23 vs -1¬∑86 and 1¬∑16 Œºm, respectively, P &lt; 0¬∑05), HOMA-B (-7¬∑63 vs 1¬∑43 and 13¬∑66, respectively, P &lt; 0¬∑05), serum hs-CRP (-212¬∑2 vs -262¬∑4 and 729¬∑8 Œºg/l, respectively, P &lt; 0¬∑05) and plasma MDA concentrations (-0¬∑48 vs -0¬∑24 and 0¬∑69 Œºm, respectively, P &lt; 0¬∑01) compared with folate-1 and placebo groups. Furthermore, a significant rise in plasma TAC (0¬∑64 vs -3¬∑53 and -215¬∑47 mm, respectively, P &lt; 0¬∑01) and GSH levels (162¬∑1 vs 195¬∑8 and -158¬∑2 Œºm, respectively, P &lt; 0¬∑01) was also observed following the administration of 5 mg/d folate supplements compared with folate-1 and placebo groups. Conclusions: In conclusion, folate supplementation (5 mg/d) in women with PCOS had beneficial effects on inflammatory factors and biomarkers of oxidative stress. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A18 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
Polyethylene glycol improves current methods for circulating extracellular vesicle-derived DNA isolation
Authors: H Peinado
R N√∫√±ez-Torres
G Rackov
V Gonz√°lez-Rumayor
S Esteban-Rubio
J Carri√≥n-Navarro
C Belda-Iniesta
A Ayuso-Sacido
A Gonz√°lez-Neira
I Palac√≠n-Aliana
A Asensi-Puig
N Garc√≠a-Romero
R Madurga
Journal: Journal of Translational Medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: ExoQuick¬Æ; Extracellular vesicles; Liquid biopsy; Polyethylene glycol; PureExo¬Æ
Affiliations: Fundaci√≥n de Investigaci√≥n HM Hospitales, HM Hospitales, C/O√±a 10, 28050, Madrid, Spain., IMDEA Nanoscience, Madrid, Spain., Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain., Atrys Health, Barcelona, Spain., Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain., Fundaci√≥n de Investigaci√≥n HM Hospitales, HM Hospitales, C/O√±a 10, 28050, Madrid, Spain. ., Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain. .

Abstract:  Background: Extracellular vesicles (EVs) are small membrane-bound vesicles which play an important role in cell-to-cell communication. Their molecular cargo analysis is presented as a new source for biomarker detection, and it might provide an alternative to traditional solid biopsies. However, the most effective approach for EV isolation is not yet well established. Results: Here, we study the efficiency of the most common EV isolation methods-ultracentrifugation, Polyethlyene glycol and two commercial kits, Exoquick¬Æ and PureExo¬Æ. We isolated circulating EVs from the bloodstream of healthy donors, characterized the size and yield of EVs and analyzed their protein profiles and concentration. Moreover, we have used for the first time Digital-PCR to identify and detect specific gDNA sequences, which has several implications for diagnostic and monitoring many types of diseases. Conclusions: Our findings present Polyethylene glycol precipitation as the most feasible and less cost-consuming EV isolation technique. 

Retracted: No

PubPeer comments:
 This article featured an interesting data by comparing different exisitng methods to isolate extracellular vesicles. Of interest, the authors mentioned using 10% PEG 8000 with Ref. ID: (Sigma Aldrich, 3015). However, this Ref.ID showed that PEG used is 200 and not 8000. The authors are kindly asked to clarify which PEG has been used in the study. ,
Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer‚Äôs phenotype
Authors: Salim Merali
Carlos Barrero
Domenico Pratic√≤
Jian-Guo Li
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Alzheimer's disease; environmental factors; genetic factors; homocysteine; ALOX5 gene
Affiliations: Department of Pharmacology and Center for Translational Medicine, Lewis Katz School of Medicine, Temple University Philadelphia, PA 19140, USA., Department of Pharmaceutical Sciences, Temple University Philadelphia, PA 19140, USA.

Abstract:  Environmental and genetic risk factors are implicated in the pathogenesis of Alzheimer's disease (AD). However, how they interact and influence its pathogenesis remains to be investigated. High level of homocysteine (Hcy) is an AD risk factor and associates with an up-regulation of the ALOX5 gene. In the current paper we investigated whether this activation is responsible for the Hcy effect on the AD phenotype and the mechanisms involved. Triple transgenic mice were randomized to receive regular chow diet, a diet deficient in folate and B vitamins (Diet), which results in high Hcy, or the Diet plus zileuton, a specific ALOX5 inhibitor, for 7 months. Compared with controls, Diet-fed mice had a significant increase in Hcy levels, memory and learning deficits, up-regulation of the ALOX5 pathway, increased AŒ≤ levels, tau phosphorylation, and synaptic pathology, which were absent in mice treated with zileuton. In vivo and vitro studies demonstrated that the mechanism responsible was the hypomethylation of the ALOX5 promoter. Our findings demonstrate that the up-regulation of the ALOX5 is responsible for the Hcy-dependent worsening of the AD phenotype in a relevant mouse model of the disease. The discovery of this previously unknown cross-talk between these two pathways could afford novel therapeutic opportunities for treating or halting AD. 

Retracted: No

PubPeer comments:
 Figure 3D and 4D two row of blots seems similar.  , 
 Figure 5C (below) appears unexpectedly similar to an image from another paper: https: pubpeer.com publications 3C3B301A0B70EE3C9D9F34D040364A I must admit I am getting a bit confused, although perhaps not as much as the authors appear to be. Update: u201dThis work was in part supported by grants from National Institute of Health, HL112966 and AG51684 and the Wanda Simone Endowment for Neuroscience.u201d  , 
  The white bars in these two papers appear identical. Please review raw data if available. , 
 Reported to journal and institution in October 2020. , 
 A PLoS ONE paper seems to be involved too. ***  ,
Isolation of extracellular vesicle with different precipitation-based methods exerts a tremendous impact on the biomarker analysis for clinical plasma samples
Authors: Weibin Zhang
Jizhuang Wang
Cheng Peng
Qiyuan Bao
Jun Wang
Yuhui Shen
Zhuochao Liu
Junxiang Wen
Journal: Cancer Biomarkers (2020)
Discipline: CLINICAL MEDICINE
Keywords: Extracellular vesicles; commercial kits; osteosarcoma; the extracellular RNA; ultracentrifugation.
Affiliations: Department of Orthopaedics, Ruijin Hospital, Shanghai, China, Shanghai Institute of Orthopaedics and Traumatology, Shanghai, China

Abstract:  Background: Extracellular vesicles(EVs) is an emerging approach of cancer liquid biopsy. Although the precipitation-based method with commercial kits has gained popularity as the second most commonly used technique, these protocols vary tremendously with many included reagents still unknown to the community. Methods: In this study, we assigned each of the 3 clinical plasma samples into 6 aliquots to assess five commercial EV isolation kits, in comparison with ultracentrifugation(UC). We implemented a standardized EV preparation and transcriptome analysis workflow except the EV isolation methods used. The metrics of EVs and its RNA cargo (evRNA) were compared to assess the technical variations versus the biological variations in the clinical setting. Results: Although the size range of the isolated EVs demonstrated a similar distribution, we found significant technical variability among these methods, in terms of EV amount, purity, subpopulations and RNA integrity. Such variabilities were further relayed to a drastic divergence of evRNA expression on a transcriptome-wide fashion. Conclusions: Our study demonstrated a highly variable result from polymeric precipitation-based EV isolation methods, making EVs based biomarker analysis difficult to interpret and reproduce. We highlighted the importance of benchmarking and transparent reporting of the precipitation-based protocols in the liquid biopsy research. 

Retracted: No

PubPeer comments:
 The findings of this study are interesting, not least because extracellular vesicles (EVs) cannot be isolated by precipitation. Polymer precipitation (or  salting out ) yields a wide variety of extracellular particles (EPs), especially from complex samples such as blood plasma in which EVs are outnumbered by other EPs by several orders of magnitude. It is not unexpected that biomarker analysis of precipitated material might vary widely with variations in the exact protocol. However, these differences should not be attributed to EVs, a small minority of the precipitated EPs. ,
WITHDRAWN: Association of uncoupling protein 2 and 3 gene polymorphisms with type 2 diabetes in Asian Indians
Authors: M R S Rao
P P Majumder
S Ghosh
K S Vimaleswaran
V Mohan
V Radha
Journal: Journal of endocrinological investigation (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Withdrawn article; Publisher; Ahead of Print
Affiliations: Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, Chennai, India.

Abstract:  Ahead of Print article withdrawn by publisher. 

Retracted: No

PubPeer comments:
 J Endocrinol Invest. 2009 Sep 30. [Epub ahead of print] WITHDRAWN: Association of uncoupling protein 2 and 3 gene polymorphisms with type 2 diabetes in Asian Indians. Vimaleswaran KS1, Radha V, Ghosh S, Majumder PP, Rao MR, Mohan V. Author information 1Madras Diabetes Research Foundation and Dr. Mohan s Diabetes Specialities Centre, Chennai, India. Abstract Ahead of Print article withdrawn by publisher. PMID:19794301 DOI: 10.3275 6523 ,
Heat shock transcription factor 1 opens chromatin structure of interleukin-6 promoter to facilitate binding of an activator or a repressor
Authors: Akira Nakai
Sachiye Inouye
Tamami Nakamura
Eiichi Takaki
Tsonwin Hai
Mitsuaki Fujimoto
Naoki Hayashida
Journal: Journal of Biological Chemistry (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Heat shock transcription factor 1; HSF1; IL-6 promoter; LPS stimulation; NF-kappaB
Affiliations: Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube, Japan.

Abstract:  Heat shock transcription factor 1 (HSF1) not only regulates expression of heat shock genes in response to elevated temperature, but is also involved in developmental processes by regulating genes such as cytokine genes. However, we did not know how HSF1 regulates non-heat shock genes. Here, we show that constitutive HSF1 binding to the interleukin (IL)-6 promoter is necessary for its maximal induction by lipopolysaccharide (LPS) stimulation in mouse embryo fibroblasts and peritoneal macrophages. Lack of HSF1 inhibited LPS-induced in vivo binding of an activator NF-kappaB and a repressor ATF3 to IL-6 promoter. Neither NF-kappaB nor ATF3 binds to the IL-6 promoter in unstimulated HSF1-null cells even if they were overexpressed. Treatment with histone deacetylase inhibitor or a DNA methylation inhibitor restored LPS-induced IL-6 expression in HSF1-null cells, and histone modification enzymes were recruited on the IL-6 promoter in the presence of HSF1. Consistently, chromatin structure of the IL-6 promoter in the presence of HSF1 was more open than that in its absence. These results indicate that HSF1 partially opens the chromatin structure of the IL-6 promoter for an activator or a repressor to bind to it, and provides a novel mechanism of gene regulation by HSF1. 

Retracted: No

PubPeer comments:
            ,
IL-37 is increased in brains of children with autism spectrum disorder and inhibits human microglia stimulated by neurotensin
Authors: Irene Tsilioni
Susan E Leeman
Theoharis C Theoharides
Harry Pantazopoulos
Pio Conti
Arti B Patel
Sabina Berretta
Journal: Proceedings of the National Academy of Sciences of the United States of America (2019)
Discipline: Multidisciplinary
Keywords: IL-37; autism spectrum disorder; brain; inflammation; neurotensin.
Affiliations: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology, Tufts University School of Medicine, Boston, MA 02111., Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111., Translational Neuroscience Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA 02478., Immunology Division, Postgraduate Medical School, University of Chieti, 65100 Pescara, Italy., Department of Pharmacology, Boston University School of Medicine, Boston, MA 02118;  ., Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology, Tufts University School of Medicine, Boston, MA 02111;  ., Department of Internal Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, MA 02111.

Abstract:  Autism spectrum disorder (ASD) does not have a distinct pathogenesis or effective treatment. Increasing evidence supports the presence of immune dysfunction and inflammation in the brains of children with ASD. In this report, we present data that gene expression of the antiinflammatory cytokine IL-37, as well as of the proinflammatory cytokines IL-18 and TNF, is increased in the amygdala and dorsolateral prefrontal cortex of children with ASD as compared to non-ASD controls. Gene expression of IL-18R, which is a receptor for both IL-18 and IL-37, is also increased in the same brain areas of children with ASD. Interestingly, gene expression of the NTR3/sortilin receptor is reduced in the amygdala and dorsolateral prefrontal cortex. Pretreatment of cultured human microglia from normal adult brains with human recombinant IL-37 (1 to 100 ng/mL) inhibits neurotensin (NT)-stimulated secretion and gene expression of IL-1Œ≤ and CXCL8. Another key finding is that NT, as well as the proinflammatory cytokines IL-1Œ≤ and TNF increase IL-37 gene expression in cultured human microglia. The data presented here highlight the connection between inflammation and ASD, supporting the development of IL-37 as a potential therapeutic agent of ASD. 

Retracted: No

PubPeer comments:
 Pannel A and B of Figure 3 (see below) appear to have identical datapoint spread and axis. Possibly an error.  ,
LKB1 is necessary for Akt-mediated phosphorylation of proapoptotic proteins
Authors: Paula M Vertino
Wei Zhou
Xiuju Liu
Diansheng Zhong
Shi-Yong Sun
Fadlo R Khuri
Journal: Cancer research (2008)
Discipline: CLINICAL MEDICINE
Keywords: LKB1; tumor suppressor; Akt; mammalian target of rapamycin; AMP-activated protein kinase
Affiliations: The Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Abstract:  LKB1 plays the role of tumor suppressor, opposite to Akt, by negatively regulating mammalian target of rapamycin through the activation of AMP-activated protein kinase and TSC signaling. We have discovered a novel, potentially oncogenic role for LKB1 as a supporter of Akt-mediated phosphorylation of proapoptotic proteins. We found that Akt activation led to increased phosphorylation of FoxO3a at Thr(32) in LKB1 wild-type cells but not in LKB1-null cells. Depletion of LKB1 in the cells with wild-type LKB1 resulted in attenuation of that phosphorylation of FoxO3a by activated Akt, whereas the restoration of LKB1 function in LKB1-null cells reestablished Akt-mediated FoxO3a phosphorylation. On expanding our analysis to other Akt targets, using isogenic LKB1 knockdown cell line pairs and a phospho-specific antibody microarray, we observed that there was a requirement for LKB1 in the phosphorylation of other Akt downstream targets, including Ask1 (Ser(83)), Bad (Ser(136)), FoxO1 (Ser(319)), FoxO4 (Ser(197)), and glycogen synthase kinase 3beta (GSK3beta; Ser(9)). Because the phosphorylation of these sites by Akt suppresses apoptosis, the requirement of LKB1 suggests that LKB1 may have an antiapoptotic role in tumor cells with constitutively active Akt. Indeed, we found that the suppression of LKB1 expression led to apoptosis in three cell lines in which Akt is constitutively active but not in two cell lines without Akt activation. This observation may explain the lack of LKB1 somatic mutations in brain, breast, and colon cancers, where Akt is frequently activated due to mutations in phosphatidylinositol 3-kinase, PTEN, or Akt itself. 

Retracted: No

PubPeer comments:
 Figure 1A. Much more similar than you wuld expect. https: imgur.com bvUAmjq , 
 Figure 1A. Much more similar than you would expect. https: imgur.com qe1gIHS ,
Silver(I) Coordination Polymers: Photocatalytic Properties and Enhanced Treatment Activity of Haloperidol on Children Tic Disorder by Regulating Neurotransmitter Content
Authors: Guo-Feng Liu
Hui-Li Qian
Xin Yu
Journal: Journal of Fluorescence (2020)
Discipline: CHEMISTRY
Keywords: Coordination polymer; Photocatalysis; Single crystal X-ray; Tic disorder.
Affiliations: Department of Pediatrics (II), Cangzhou Central Hospital, Cangzhou, Hebei, China. ., Department of Rehabilitation, Jining Medical University, Jining, Shandong, China., Maternal and Child Health Hospital, Jining, Shandong, China.

Abstract:  In this article, the characterization, synthesis, as well as the photocatalysis dye degradation performance of two novel silver(I) coordination polymers, namely, [Ag(L)(Hbdc)]n (1, L = 1,4-Bis(5,6-dimethylbenzimidazol-1-yl)butane, H2bdc = 1,4-Benzenedicarboxylic acid) and [Ag2(L)(hip)]n (2, H2hip = 5-Hydroxyisophthalic acid), were investigated. Fascinatingly, the photocatalytic performance of Complexes 1 and 2 have been investigated, wherein Complex 2 is considered an excellent photocatalyst for degrading Rhodamine B/methyl violet/methylene blue mixed organic dyes. Furthermore, the treatment activities of Complexes 1 and 2 on Tic disorder (TD) were assessed when used with haloperidol, and biochemical studies were conducted to reveal the mechanism in detail. Initially, the enzyme-linked immunosorbent assay was carried out to determine the dopamine and high vanillic acid contents in the striatum of the TD animal model. Subsequently, the reverse transcription-polymerase chain reaction was utilized to determine the relative expression of dopamine 1 and 2 receptor. 

Retracted: No

PubPeer comments:
 The authors refer repeatedly to a mouse model of TD (tic disorder), which they induce, then treat with various combinations of haloperidol and freshly synthesised silver(I) compounds. - After the construction of the TD model, - . In short, the animal model of TD was established as described formerly - The TD animal model was constructed - The ELISA results show that the dopamine and HVA content in the striatum of TD animal model was significantly reduced after being treated by Compound 1 + haloperidol, but compound 2 + haloperidol showed no activities. However, they provide no information about how this condition is induced, nor any References to such a model, robbing the paper of any value. The reader is free to conclude that no experiments were performed. , 
 Then there are the nonsensical Refs [8,9].  The multifarious structures of CPs have confirmed their great latent capacity when applied in the fields of electrochemistry, heterogeneous catalysis, gas separation and storage, luminescence, ion exchange, magnetism, as well as drug delivery [8u201312]. - [8]. Liu W, Li H, Zhu H, Xu P (2020) Materials 13:1180 ** The Interfacial Adhesion Performance and Mechanism of a Modified Asphaltu2013Steel Slag Aggregate ** - [9]. Wang Z, Zhang X, Jiang S, Qu Y, Ou D, Wang J (2020) J Alloy Compd 828:154412 ** Arc Erosion Dynamic of Island-and Skeleton-Restricted Microstructure Evolution Modes in Agu2013CuO Contact Materials ** ,
Bartonella vinsonii subsp. arupensis as an agent of blood culture-negative endocarditis in a human
Authors: St√©phane Sire
Didier Raoult
Florence Fenollar
Journal: Journal of clinical microbiology (2005)
Discipline: MICROBIOLOGY
Keywords: Endocarditis; Bartonella; Antibodies; Immunofluorescence; Western blotting
Affiliations: Unit√© des Rickettsies, CNRS UMR 6020, IFR 48, Facult√© de M√©decine, Universit√© de la M√©diterran√©e, 27 Boulevard Jean Moulin, 13385 Marseille cedex 05, France.

Abstract:  We report the case of a patient hospitalized with endocarditis. The etiological diagnosis of Bartonella was suggested by detection of high titers of antibodies by immunofluorescence and Western blotting. Two different nested PCRs performed on sera identified Bartonella vinsonii subsp. arupensis by sequencing. 

Retracted: No

PubPeer comments:
 This article has an erratum, which reads: *Page 945: The article byline and affiliation line should read as given above. Page 947, Acknowledgments: u201cNathalie Wilhelm andu201d should be deleted.* , 
 Could the authors please have a look at Figure 1? * Red boxes: Panels B (B. vinsonii subsp. arupensis-adsorbed serum) and C (B. vinsonii subsp. berkhoffii-adsorbed serum) appear to look very similar. Note the presence of a lighter stripe in lane 3, and some dots in lanes 1 and 2. * Blue boxes: Lanes 1-3 in panel D (B. quintana-adsorbed serum) and E (B. henselae-adsorbed serum) appear to look similar to each other * Green boxes: Lanes 4 and 5 in panel D (B. quintana-adsorbed serum) look similar to each other albeit at a different exposure. They also look similar to lane 4 in panel E (B. henselae-adsorbed serum). A sharp vertical background transition is visible between lanes 4 and 5 in panel D.  , 
 As pointed out by a reader, the top part of lane 4 in panel E (and of lane 5 of panel D) looks a bit more  smudged as lane 4 in panel D. Here is a detailed view.  , 
 Elisabeth, Think an image convolution filter can be used on D and then pattern-matched to E? I can try something and post. , 
 (removed comment based on being out of my element, but thanks) ,
Functional cooperation between TrkA and p75(NTR) accelerates neuronal differentiation by increased transcription of GAP-43 and p21(CIP/WAF) genes via ERK1/2 and AP-1 activities
Authors: Giovanni Perini
Jean-Marc Herbert
Daniel Diolaiti
Roberto Bernardoni
Stefania Trazzi
Giuliano Della Valle
Antonella Papa
Fran√ßoise Bono
Antonio Porro
Journal: Experimental cell research (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: NGF action; neurotrophin receptors; TrkA; p75(NTR); intracellular signaling
Affiliations: Department of Biology, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.

Abstract:  The biological complexity of NGF action is achieved by binding two distinct neurotrophin receptors, TrkA and p75(NTR). While several reports have provided lines of evidence on the interaction between TrkA and p75(NTR) at the plasma membrane, much fewer data are available on the consequence of such an interaction in terms of intracellular signaling. In this study, we have focused on how p75(NTR) may affect TrkA downstream signaling with respect to neuronal differentiation. Here, we have shown that cooperation between p75(NTR) and TrkA results in an increased NGF-mediated TrkA autophosphorylation, leads to a sustained activation of ERK1/2 and accelerates neurite outgrowth. Interestingly, neurite outgrowth is concomitant with a selective enhancement of the AP-1 activity and the transcriptional activation of genes such as GAP-43 and p21(CIP/WAF), known to be involved in the differentiation process. Collectively, our results unveil a functional link between the specific expression profile of neurotrophin receptors in neuronal cells and the NGF-mediated regulation of the differentiation process possibly through a persistent ERKs activation and the selective control of the AP-1 activity. 

Retracted: No

PubPeer comments:
 Unexpected similarities. Solid line - potentially duplicated bands. Dashed line - potentially duplicated and horizontally flipped bands.  , 
 Unexpected similarities. Solid line - potentially duplicated bands. Dashed line - potentially duplicated and horizontally flipped bands.  , 
 Unexpected similarities. Potentially duplicated and horizontally flipped bands.  ,
Baicalein induces apoptosis in esophageal squamous cell carcinoma cells through modulation of the PI3K/Akt pathway
Authors: Hong-Bo Zhang
Zhen-Hua Zhang
Xiang-Yu Meng
Qing-Yin Guo
Ping Lu
Journal: Oncology Letters (2013)
Discipline: CLINICAL MEDICINE
Keywords: PI3K/Akt signaling pathway; baicalein; cell apoptosis; esophageal squamous cell carcinoma.
Affiliations: Department of Anatomy and Cell Biology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001;

Abstract:  Baicalein, a flavone present in Scutellaria baicalensis Georgi, has been demonstrated to possess antitumor activity in a variety of cancer cells in vitro. However, its effects on the growth inhibition and induction of apoptosis in human esophageal carcinoma cells remain unclear. The aims of this study were to determine whether cultured EC-109 esophageal squamous cell carcinoma (ESCC) cells undergo apoptosis when treated with baicalein and to investigate the underlying mechanisms in vitro. Cell growth was measured using MTT and plate colony formation assays. Induction of apoptosis was examined using Hoechst 33258 staining, flow cytometry analysis and a DNA fragmentation assay. The mechanisms underlying the observed growth suppression were examined using western blot analysis. The results demonstrated that treatment of EC-109 cells with baicalein for 48 h markedly decreased the rate of cell viability. Colony formation was almost fully suppressed at 40 ŒºM baicalein. EC-109 cells underwent apoptosis in response to baicalein treatment, demonstrated by an increase in the percentage of cells stainable with Hoechst 33258 and Annexin V-FITC/PI, increased DNA fragmentation and activation of the intrinsic (mitochondrial) pathway for cell death. The latter was characterized by increased expression of the cleaved forms of caspase-9 and -3, and poly (ADP-ribose) polymerase (PARP). Additionally, baicalein was found to downregulate anti-apoptotic components and upregulate apoptotic components of the PI3K/Akt pathway. In conclusion, baicalein induces apoptosis in EC-109 cells through modulation of the PI3K/Akt pathway, thus providing further understanding of the molecular mechanisms of baicalein action in esophageal carcinoma. Therefore, the present study revealed that baicalein significantly inhibits growth and induces apoptosis in EC-109 human ESCC cells in vitro. 

Retracted: No

PubPeer comments:
 Fig 3B.  Induction of apoptosis in ECu2011109 cells by baicalein. ... (B) ECu2011109 cells were treated for 48 h with baicalein at 0 (lane 1), 10 (lane 2), 20 (lane 3), and 40 u00b5M (lane 4). Lane M shows the migration of D2000 markers (100, 250, 500, 750, 1,000 and 2,000 bp).  Reappeared, with the 4th lane repeated as the 6th, as Figure 5 from [Bin et al (2018)] .  Pterostilbene induced DNA fragmentation in HeLa cancer cells. HeLa cells were treated with increasing doses of the drug, harvested using trypsinization, DNA was extracted and then analyzed using 1.5% agarose gel electrophoresis. The Figure proves that pterostilbene triggers DNA damage in HeLa cells.  ,