PReD-Bench/PRed-Bench huggingface dataset:
α-Thrombin-mediated Phosphatidylinositol 3-Kinase Activation through Release of Gβγ Dimers from Gαqand Gαi2
Authors: Joseph J Baldassare
Reema Goel
Daniel M Raben
Polly J Phillips-Mason
Alice Gardner
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chinese hamster embryonic fibroblasts; Galpha subunits; alpha-thrombin; G proteins; membrane binding assay

Abstract:  Chinese hamster embryonic fibroblasts (IIC9 cells) express the Galpha subunits Galphas, Galphai2, Galphai3, Galphao, Galpha(q/11), and Galpha13. Consistent with reports in other cell types, alpha-thrombin stimulates a subset of the expressed G proteins in IIC9 cells, namely Gi2, G13, and Gq as measured by an in vitro membrane [35S]guanosine 5'-O-(3-thio)triphosphate binding assay. Using specific Galpha peptides, which block coupling of G-protein receptors to selective G proteins, as well as dominant negative xanthine nucleotide-binding Galpha mutants, we show that activation of the phosphatidylinositol 3-kinase/Akt pathway is dependent on Gq and Gi2. To examine the role of the two G proteins, we examined the events upstream of PI 3-kinase. The activation of the PI 3-kinase/Akt pathway by alpha-thrombin in IIC9 cells is blocked by the expression of dominant negative Ras and beta-arrestin1 (Phillips-Mason, P. J., Raben, D. M., and Baldassare, J. J. (2000) J. Biol. Chem. 275, 18046-18053, and Goel, R., Phillips-Mason, P. J., Raben, D. M., and Baldassare, J. J. (2002) J. Biol. Chem. 277, 18640-18648), indicating a role for Ras and beta-arrestin1. Interestingly, inhibition of Gi2 and Gq activation blocks Ras activation and beta-arrestin1 membrane translocation, respectively. Furthermore, expression of the Gbetagamma sequestrant, alpha-transducin, inhibits both Ras activation and membrane translocation of beta-arrestin1, suggesting that Gbetagamma dimers from Galphai2 and Galphaq activate different effectors to coordinately regulate the PI 3-kinase/Akt pathway. 

Retracted: No

PubPeer comments:
 It seems the six bands of Ras-GTP panel arenu2019t from the same blot. ![file] , 
 If I remember correctly we ran several plots of the same samples and then pasted them together. I might be mistaken. The lab has been closed for over 5 years and the data and samples lost so I can not check. ,
S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt
Authors: Alex I Lipovsky
Hui H Zhang
Mustafa Sahin
Brendan D Manning
Christian C Dibble
Journal: Molecular Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PI3K-Akt pathway; mTORC1; feedback inhibition; tumor syndromes; cancer
Affiliations: Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract:  Feedback inhibition of the PI3K-Akt pathway by the mammalian target of rapamycin complex 1 (mTORC1) has emerged as an important signaling event in tumor syndromes, cancer, and insulin resistance. Cells lacking the tuberous sclerosis complex (TSC) gene products are a model for this feedback regulation. We find that, despite Akt attenuation, the Akt substrate GSK3 is constitutively phosphorylated in cells and tumors lacking TSC1 or TSC2. In these settings, GSK3 phosphorylation is sensitive to mTORC1 inhibition by rapamycin or amino acid withdrawal, and GSK3 becomes a direct target of S6K1. This aberrant phosphorylation leads to decreased GSK3 activity and phosphorylation of downstream substrates and contributes to the growth-factor-independent proliferation of TSC-deficient cells. We find that GSK3 can also be regulated downstream of mTORC1 in a HepG2 model of cellular insulin resistance. Therefore, we define conditions in which S6K1, rather than Akt, is the predominant GSK3 regulatory kinase. 

Retracted: No

PubPeer comments:
 Figure 2C: More similar than expected. Could authors check please? ![file] , 
 Just come across this independently. ![file] , 
 Figure 4E. Much more similar than expected. ![file] ,
FNDC5/irisin is not only a myokine but also an adipokine
Authors: Lucía L Senin
Cecilia Castelao
María O Landrove
Luisa María Seoane
Arturo Roca-Rivada
Felipe F Casanueva
Javier Baltar
Ana Belén Crujeiras
María Pardo
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Exercise; FNDC5/irisin protein; muscle tissue; brown-fat development; thermogenesis
Affiliations: Grupo Obesidómica, Laboratorio de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.

Abstract:  Exercise provides clear beneficial effects for the prevention of numerous diseases. However, many of the molecular events responsible for the curative and protective role of exercise remain elusive. The recent discovery of FNDC5/irisin protein that is liberated by muscle tissue in response to exercise might be an important finding with regard to this unsolved mechanism. The most striking aspect of this myokine is its alleged capacity to drive brown-fat development of white fat and thermogenesis. However, the nature and secretion form of this new protein is controversial. The present study reveals that rat skeletal muscle secretes a 25 kDa form of FNDC5, while the 12 kDa/irisin theoretical peptide was not detected. More importantly, this study is the first to reveal that white adipose tissue (WAT) also secretes FNDC5; hence, it may also behave as an adipokine. Our data using rat adipose tissue explants secretomes proves that visceral adipose tissue (VAT), and especially subcutaneous adipose tissue (SAT), express and secrete FNDC5. We also show that short-term periods of endurance exercise training induced FNDC5 secretion by SAT and VAT. Moreover, we observed that WAT significantly reduced FNDC5 secretion in fasting animals. Interestingly, WAT of obese animals over-secreted this hormone, which might suggest a type of resistance. Because 72% of circulating FNDC5/irisin was previously attributed to muscle secretion, our findings suggest a muscle-adipose tissue crosstalk through a regulatory feedback mechanism. 

Retracted: No

PubPeer comments:
 Figure 2. * Red boxes: Panel a-2 b-2 c-2 appears to look very similar to panel b-1. ![file] ,
Long non-coding RNA THRIL promotes LPS-induced inflammatory injury by down-regulating microRNA-125b in ATDC5 cells
Authors: Qiao Zhang
Guangyao Liu
Yongkun Wang
Mingran Zhang
Journal: International immunopharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cell inflammation; JAK1/STAT3 and NF-κB pathways; Lipopolysaccharide; Long non-coding RNA THRIL; MicroRNA-125b
Affiliations: Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun 130033, China., Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun 130033, China. Electronic address: .

Abstract:  Background: Osteoarthritis is an age-related disorder of bone-joint that causes pain and disability in middle and older people. This study aimed to investigate the potential effects of long non-coding RNA (lncRNA) THRIL on lipopolysaccharide (LPS)-induced osteoarthritis cell injury model (ATDC5 cell inflammatory injury), as well as the possible internal molecular mechanisms. Methods: Cell viability and apoptosis were assessed using CCK-8 assay and Guava Nexin assay, respectively. Cell transfection was conducted to change the expression of THRIL and microRNA-125b (miR-125b) in ATDC5 cells. qRT-PCR was performed to detect the expression of THRIL, miR-125b and pro-inflammatory cytokines IL-6, TNF-α and monocyte chemotactic protein 1 (MCP-1) in ATDC5 cells. ELISA was used to measure the concentrations of IL-6, TNF-α and MCP-1 in culture supernatant of ATDC5 cells. Finally, the protein expression of key factors involved in cell apoptosis, inflammatory response, JAK1/STAT3 and NF-κB pathways were evaluated using western blotting. Results: LPS significantly induced ATDC5 cell inflammatory injury and up-regulated the expression of THRIL. Overexpression of THRIL aggravated the LPS-induced ATDC5 cell inflammatory injury. Suppression of THRIL had opposite effects. Moreover, THRIL negatively regulated the expression of miR-125b in ATDC5 cells. miR-125b participated in the effects of THRIL overexpression on LPS-induced ATDC5 cell inflammatory injury. Furthermore, overexpression of THRIL enhanced the LPS-induced JAK1/STAT3 and NF-κB pathways activation by down-regulating miR-125b. Conclusion: THRIL exerted pro-inflammatory roles in LPS-induced osteoarthritis cell injury model. Overexpression of THRIL promoted LPS-induced ATDC5 cell inflammatory injury by down-regulating miR-125b and then activating JAK1/STAT3 and NF-κB pathways. 

Retracted: No

PubPeer comments:
 This article appears to be computer-generated with [SCIgen] . ![file] --- This comment was written by Guillaume Cabanac and Cyril Labbu00e9. Contact: [SeekAndBlastn-Operators@univ-grenoble-alpes.fr](mailto:SeekAndBlastn-Operators@univ-grenoble-alpes.fr). ,
No raw data, no science: another possible source of the reproducibility crisis
Authors: Tsuyoshi Miyakawa
Journal: Molecular brain (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Data fabrication; Misconduct; Open data; Open science; Raw data
Affiliations: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, 470-1192, Japan. .

Abstract:  A reproducibility crisis is a situation where many scientific studies cannot be reproduced. Inappropriate practices of science, such as HARKing, p-hacking, and selective reporting of positive results, have been suggested as causes of irreproducibility. In this editorial, I propose that a lack of raw data or data fabrication is another possible cause of irreproducibility.As an Editor-in-Chief of Molecular Brain, I have handled 180 manuscripts since early 2017 and have made 41 editorial decisions categorized as "Revise before review," requesting that the authors provide raw data. Surprisingly, among those 41 manuscripts, 21 were withdrawn without providing raw data, indicating that requiring raw data drove away more than half of the manuscripts. I rejected 19 out of the remaining 20 manuscripts because of insufficient raw data. Thus, more than 97% of the 41 manuscripts did not present the raw data supporting their results when requested by an editor, suggesting a possibility that the raw data did not exist from the beginning, at least in some portions of these cases.Considering that any scientific study should be based on raw data, and that data storage space should no longer be a challenge, journals, in principle, should try to have their authors publicize raw data in a public database or journal site upon the publication of the paper to increase reproducibility of the published results and to increase public trust in science. 

Retracted: No

PubPeer comments:
 Highly recommended for readers and contributors of Pubpeer. , 
 #1 Thank you. #factfreescience , 
 This is an interesting editorial , 
 Interesting editorial point of view. I strongly support appreciate the effort. But I have a serious concern: Is it really safe to provide all the raw data before the manuscript is accepted for publication ? Requisition of raw data before manuscript publishing seems good must initiative. Requisition of raw data before review process can be dangerous as you never know it can be scooped. Editors reviewers are not GOD, they too are scientists , 
 #4 Thanks for the comment. In the case of Molecular Brain, we mandate the deposition of raw data before publication of the paper but not at the time of submission, which would address the concern you raised. , 
 #5 Thanks for your clearance. Such an editorial policy is highly appreciating must be adopted by all the journals to curb the data falsification. Thanks for making scientific community aware about it. good for healthy science. Cheers ,
Docosahexaenoic acid attenuates hypoxic pulmonary vasoconstriction by activating the large conductance Ca2+-activated K+ currents in pulmonary artery smooth muscle cells
Authors: Yuchun Gu
Jinchuan Yan
Peijing Liu
Rui Chen
Journal: Pulmonary Pharmacology & Therapeutics (2014)
Discipline: CLINICAL MEDICINE
Keywords: BK(Ca) channel; Docosahexaenoic acid; Hypoxia; Pulmonary arterial smooth muscle cell.
Affiliations: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, China. Electronic address: ., Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, China., Institute of Molecular Medicine, Peking University, Beijing 100871, China.

Abstract:  Background: The inhibition of potassium (K(+)) channels plays an important role in pulmonary circulation for its close relationship with hypoxic pulmonary vasoconstriction (HPV). Docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, is well known for its prevention and treatment of cardiovascular diseases. However the role which DHA plays in HPV remains unclear. Here, we tested the hypothesis that DHA contributes to pulmonary vascular tone by activating the large conductance Ca(2+)-activated K(+) (BKCa) channels via calcium sparks. Methods and results: Isolated resistance pulmonary artery preparation was used to study the vasomotor response to DHA. Pulmonary artery smooth muscle cells (PASMCs) were isolated from third- to fourth order branches of pulmonary arteries by collagenase digestion method. BKCa and the voltage-dependent potassium channel (Kv) currents in PASMCs were measured by the whole-cell patch-clamp technique. Fluo-8 was used as a fluorescence indicator for the real-time measurement of calcium dynamics in PASMCs. DHA dilated resistance pulmonary arteries in a dose-dependent manner in hypoxic or normoxic solution, and the effects of DHA were abolished after pre-treatment with heparin (100 μg/ml), a 1,4,5-triphosphate (IP3) receptor (IP3R) inhibitor or iberiotoxin (100 nmol/L), a specific inhibitor of BKCa channel. DHA activated BKCa channels in a dose-dependent manner, however, the activation induced by DHA was not seen in PASMCs pre-incubated with heparin. While the Kv currents decreased from 102.6 ± 5.4 to 36.5 ± 6.7 pA/pF by addition of 10 μmol/L DHA. DHA also caused calcium sparks in PASMCs. Moreover, hypoxia inhibited BKCa currents in PASMCs, but this inhibition was reversed by DHA. Conclusion: Our findings suggest that DHA is a novel BKCa opener in PASMCs, which may indicate a potential therapeutic role in HPV. 

Retracted: Yes

PubPeer comments:
 ![file] ,
LIM mineralization protein-1 inhibits the malignant phenotypes of human osteosarcoma cells
Authors: Huiwen Liu
Zhanming Zhang
Min Dai
Yong Shu
Zhimin Han
Zhongzu Zhang
Zhuo Chen
Lu Huang
Kai Cao
Xiang Chen
Dong Yang
Yongping Zen
Zhiming Yu
Journal: International journal of molecular sciences (2014)
Discipline: CHEMISTRY
Keywords: Osteosarcoma; LIM mineralization protein-1 (LMP-1); tumor suppressor; cell proliferation; invasion
Affiliations: Department of Orthopedics, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China. ., Department of Children Health and Care, Jiangxi Maternal and Child Health Hospital, Nanchang 330006, China. ., Department of Oncology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China. .

Abstract:  Osteosarcoma (OS), also known as osteogenic sarcoma, is the most common primary malignancy of bone tumor in children and adolescents. However, its underlying molecular pathogenesis is still only vaguely understood. Recently, LIM mineralization protein-1 (LMP-1) was reported to be an essential positive regulator of osteoblast differentiation. In the present study, we found that the expression of LMP-1 is downregulated in OS tissues compared with adjacent normal tissues. Moreover, we restored the expression of LMP-1 through a recombinant adenovirus. Overexpression of LMP-1 inhibited cell proliferation and invasion, arrested cell cycle progression, and induced apoptosis in vitro. Finally, ectopic LMP-1 expression suppressed the expression of Runx2 and BMP-2 in OS cells. These data demonstrate that LMP-1 is an essential tumor suppressor in the OS pathological process, which will provide a new opportunity for discovering and identifying novel effective treatment strategies. 

Retracted: No

PubPeer comments:
 Figure 4A. * Red boxes: In the SaOS-2 AdLMP1 panel, a narrow strip of cells appears to be visible two times. ![file] , 
 #1 A second concern with Fig 4A: ![file] The panel marked with a blue box had previously appeared in Fig 2a of  miR-137 impairs the proliferative and migratory capacity of human non-small cell lung cancer cells by targeting paxillin ([Bi et al 2014] ). ![file] ![file] ,
Efficient Cholera Toxin B Subunit-Based Nanoparticles with MRI Capability for Drug Delivery to the Brain Following Intranasal Administration
Authors: Chen Xu
Bingran Yu
Wenli Hu
Yiming Chen
Huimin Fan
Journal: Macromolecular Bioscience (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: blood-brain barrier; brain drug delivery; cholera toxin B subunit; intranasal administration; magnetic resonance imaging.
Affiliations: State Key Laboratory of Chemical Resource EngineeringKey Laboratory of Carbon Fiber and Functional Polymers (Ministry of Education)Beijing Laboratory of Biomedical MaterialsBeijing Advanced Innovation Center for Soft Matter Science and EngineeringBeijing University of Chemical Technology Beijing 100029 China, Department of NeurologyBeijing Chaoyang HospitalCapital Medical University Beijing 100043 China

Abstract:  Alzheimer's disease (AD) is an incurable neurodegenerative brain disorder that exhibits clear pathologic changes in the hippocampus. Traditional drug delivery systems are ineffective due to the existence of the blood-brain barrier (BBB). In this study, an efficient, stable, and easily constructed nanosystem (CB-Gd-Cy5.5) based on the cholera toxin B subunit (CB) is designed to improve the efficiency of drug delivery to the brain, especially the hippocampus. Through intranasal administration, CB-Gd-Cy5.5 is easily delivered to the brain without intervention by the BBB. The CB in CB-Gd-Cy5.5 is used for specifically combining with the monosialoganglioside GM1, which is widely found in the hippocampus. This nanosystem exhibits impressive performance in accumulating in the hippocampus. In addition, the good magnetic resonance imaging (MRI) capability of CB-Gd-Cy5.5 can satisfy the monitoring of AD in the different stages. 

Retracted: No

PubPeer comments:
 In this paper, Figure 5d and Figure 5f are two slices from one sample. However, the authors declared they belonged to different groups. ![file] , 
 We truly apologize for our mistake in this paper. Thank you for pointing out our mistake. We published a correction in the Macromolecular Bioscience . ,
Soluble Epoxide Hydrolase Pharmacological Inhibition Ameliorates Experimental Acute Pancreatitis in Mice
Authors: Bruce D Hammock
Fawaz G Haj
Samah Chahed
Ahmed Bettaieb
Stephen Griffey
Santana Bachaalany
Journal: Molecular Pharmacology (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Acute pancreatitis; sEH; pharmacological inhibition; inflammatory cytokines; cerulein
Affiliations: Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California., Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California .

Abstract:  Acute pancreatitis (AP) is an inflammatory disease, and is one of the most common gastrointestinal disorders worldwide. Soluble epoxide hydrolase (sEH; encoded by Ephx2) deficiency and pharmacological inhibition have beneficial effects in inflammatory diseases. Ephx2 whole-body deficiency mitigates experimental AP in mice, but the suitability of sEH pharmacological inhibition for treating AP remains to be determined. We investigated the effects of sEH pharmacological inhibition on cerulein- and arginine-induced AP using the selective sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), which was administered before and after induction of pancreatitis. Serum amylase and lipase levels were lower in TPPU-treated mice compared with controls. In addition, circulating levels and pancreatic mRNA of the inflammatory cytokines tumor necrosis factor-α, interleukin Il-1β, and Il-6 were reduced in TPPU-treated mice. Moreover, sEH pharmacological inhibition before and after induction of pancreatitis was associated with decreased cerulein- and arginine-induced nuclear factor-κB inflammatory response, endoplasmic reticulum stress, and cell death. sEH pharmacological inhibition before and after induction of pancreatitis mitigated cerulein- and arginine-induced AP. This work suggests that sEH pharmacological inhibition may be of therapeutic value in acute pancreatitis. 

Retracted: No

PubPeer comments:
 Figure 4B. * Red boxes: The left Tubulin panel might look similar to the first three lanes of the right Tubulin panel, but vertically flipped. Can the authors please check? ![file] , 
 Figure 5A. * Pink boxes: The pPERKT980 panel looks unexpectedly similar to the pIre1aS721 panel. ![file] ,
Dynein and dynactin leverage their bivalent character to form a high-affinity interaction
Authors: Amanda E Siglin
Martin Poenie
John C Williams
Jeffrey K Moore
Shangjin Sun
James D Lear
Sarah Tan
Tatyana Polenova
John A Cooper
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Cytoplasmic dynein; dynactin; retrograde transport; organelles; checkpoint signaling
Affiliations: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA.

Abstract:  Cytoplasmic dynein and dynactin participate in retrograde transport of organelles, checkpoint signaling and cell division. The principal subunits that mediate this interaction are the dynein intermediate chain (IC) and the dynactin p150(Glued); however, the interface and mechanism that regulates this interaction remains poorly defined. Herein, we use multiple methods to show the N-terminus of mammalian dynein IC, residues 10-44, is sufficient for binding p150(Glued). Consistent with this mapping, monoclonal antibodies that antagonize the dynein-dynactin interaction also bind to this region of the IC. Furthermore, double and triple alanine point mutations spanning residues 6 to 19 in the yeast IC homolog, Pac11, produce significant defects in spindle positioning. Using the same methods we show residues 381 to 530 of p150(Glued) form a minimal fragment that binds to the dynein IC. Sedimentation equilibrium experiments indicate that these individual fragments are predominantly monomeric, but admixtures of the IC and p150(Glued) fragments produce a 2:2 complex. This tetrameric complex is sensitive to salt, temperature and pH, suggesting that the binding is dominated by electrostatic interactions. Finally, circular dichroism (CD) experiments indicate that the N-terminus of the IC is disordered and becomes ordered upon binding p150(Glued). Taken together, the data indicate that the dynein-dynactin interaction proceeds through a disorder-to-order transition, leveraging its bivalent-bivalent character to form a high affinity, but readily reversible interaction. 

Retracted: No

PubPeer comments:
 Figure 2B. * Red boxes: Two lanes appear to look very similar if one of the two is rotated 180 degrees. Reported in 2015 to the journal, with a friendly reminder in 2016, but no action yet. ![file] ,
Cytotoxic indole alkaloids against human leukemia cell lines from the toxic plant Peganum harmala
Authors: Chunhua Wang
Zhenxue Zhang
Yihai Wang
Xiangjiu He
Journal: Toxins (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Peganum harmala; anti-leukemia; cytotoxicity; indole alkaloids; mitochondrial pathway.
Affiliations: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. ., College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China. .

Abstract:  Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The cytotoxicity against human leukemia cells was assayed for the alkaloids and some of them showed potent activity. Harmalacidine (compound 8, HMC) exhibited the highest cytotoxicity against U-937 cells with IC50 value of 3.1 ± 0.2 μmol/L. The cytotoxic mechanism of HMC was targeting the mitochondrial and protein tyrosine kinase signaling pathways (PTKs-Ras/Raf/ERK). The results strongly demonstrated that the alkaloids from Peganum harmala could be a promising candidate for the therapy of leukemia. 

Retracted: No

PubPeer comments:
 The p-Raf band in Figure 3B appears unexpectedly similar to the Bax band in Figure 2E when flipped horizontally and vertically. *** Here are the 2 images, shown in inverse. Top 2E Bottom 3B ![file] *** 2 bands, isolated ![file] *** False color via ImageJ ![file] ,
WITHDRAWN: Can quantitative RT-PCR for SARS-coV-2 help in better management of patients and control of coronavirus disease 2019 pandemic
Authors: Ashok Rattan
Hafiz Ahmad
Journal: Indian Journal of Medical Microbiology (2020)
Discipline: IMMUNOLOGY
Keywords: Article withdrawal; Author; Editor; Publisher; Elsevier Policy
Affiliations: All India Institute of Medical Sciences, Delhi, India; Pathkind Labs, Gurgaon, Haryana, India., Department of Medical Microbiology and Immunology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, United Arab Emirates; RAK Hospital, Ras Al Khaimah, United Arab Emirates.

Abstract:  This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal. 

Retracted: No

PubPeer comments:
 **Withdrawn** (unknown date): https: doi.org 10.1016 j.ijmmb.2020.10.016  *This article has been withdrawn at the request of the author(s) and or editor. The Publisher apologizes for any inconvenience this may cause.* *The full Elsevier Policy on Article Withdrawal can be found at https: www.elsevier.com about our-business policies article-withdrawal* ,
Inhibition of lymphoma cell proliferation by peroxisomal proliferator-activated receptor-γ ligands via Wnt signaling pathway
Authors: Pei-Qing Liu
Xiao-Dan Liu
Dong-Jun Lin
Ruo-Zhi Xiao
Ren-Wei Huang
Zhi-Gang Fang
He-Qing Huang
Jia-Jun Liu
Xue-Jun Dai
Yan Xu
Yong Zhang
Journal: Cell Biochemistry and Biophysics (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PPARγ; Wnt/β-catenin signaling; apoptosis; GSK-3β; Raji cells
Affiliations: Department of Hematology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China. 

Abstract:  Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in regulating energy balance, glucose and lipid metabolisms and inflammation. PPARγ also exerts multiple anti-cancer effects including tumor growth and angiogenesis inhibition, induction of cell differentiation, and apoptosis. Perturbed Wnt/β-catenin signaling likely plays a key role in tumorigenesis and the interaction between PPARγ and the transcriptional regulator β-catenin maybe important in this process. Phosphorylation of β-catenin by GSK-3β inactivates it and suppresses tumor cell proliferation and self-renewal of tumor stem cells. In combination with Frizzled, Wnt suppresses GSK-3β and causes degradation of β-catenin and activation of many tumor proliferation factors. In the present study, we investigated the effects of PPARγ agonist rosiglitazone (RGZ) and PPARγ antagonist GW9662 on the growth, mitotic cycle, and apoptosis of human lymphoma cell line, Raji cells. We also studied the influence of PPARγ ligands on the expression of β-catenin and GSK-3β in Raji cells to reveal whether Wnt/GSK-3β/β-catenin signaling pathways are involved in PPARγ ligands triggered Raji cell apoptosis. Results showed that both RGZ and GW9662 can inhibit the growth of Raji cells by inducing apoptosis and arresting cell cycle; however, there was no correlation between these effects and expression of PPARγ. Both the PPARγ ligands, RGZ and GW9662, appear to reciprocally regulate the mRNA and protein expressions of GSK-3β, which promotes apoptosis, and of β-catenin, which blocks apoptosis. These results suggest that PPARγ ligands mediate their effects via Wnt/GSK-3β/β-catenin signaling on Raji cell proliferation and survival. 

Retracted: No

PubPeer comments:
 Figure 2 seems to contain images with repetitive internal features. Some appear to have been resized. *** False color ![file] *** Original ![file] ,
Cellular FLICE-like inhibitory protein protects against cardiac hypertrophy by blocking ASK1/p38 signaling in mice
Authors: Jian Wu
Ying Huang
Lianpin Wu
Yumei Li
Lili Hou
Journal: Molecular and Cellular Biochemistry (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cellular FLICE-like inhibitory protein; Flip; nuclear factor κB signaling; cardiac hypertrophy; knockout
Affiliations: Department of Oncology and nursing, Shanghai Pulmonary Hospital of Tongji University, 507 Zhengmin Rd, Yangpu, Shanghai, 200433, China.

Abstract:  Cellular FLICE-like inhibitory protein (Flip) is a negative regulator of nuclear factor κB signaling which has been shown previously to complicate with cardiac hypertrophy. In the present study, we tested the hypothesis that the knockout of Flip would increase cardiac hypertrophy in vivo and in vitro. The effects of Flip knockout on cardiac hypertrophy were investigated using in vitro and in vivo models. Flip was downregulated in transverse aortic constriction (TAC)-induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 1 h. An in vivo, heart hypertrophy model, was performed by TAC in Flip knockdown and sham mice. The extent of hypertrophy of heart was quantitated by echocardiography, and further confirmed by pathological and molecular examination of heart tissue samples. Conditional knockout of Flip in the murine heart increases the hypertrophic response induced by TAC, whereas cardiac function was preserved with reduced Flip levels in response to hypertrophic stimuli. Western blot experiments further showed Flip knockout activated markedly ASK1/P38 signaling cascades in vivo and in vitro. In conclusion, Flip preserves cardiac functions and inhibits cardiac hypertrophy partially by blocking ASK1/P38 signaling. 

Retracted: No

PubPeer comments:
 Figures 1 and 2. * Red boxes: Three lanes in the right BNP panel in Figure 1 look similar to three lanes in the Flip panel in Figure 2A. Figure 4. * Blue boxes: The left GAPDH panel looks similar to the right P38 panel. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. I would love to hear from the authors if the journal ever contacted them in the past five years. ![file] ,
Increased ATP release and CD73-mediated adenosine A2A receptor activation mediate convulsion-associated neuronal damage and hippocampal dysfunction
Authors: Jiang-Fan Chen
Elisabete Augusto
Paula M Canas
Nélio Gonçalves
Marco Matos
Daniela Pochmann
Joana E Real
Francisco Q Gonçalves
Tiago S Silva
Ângelo R Tomé
Rodrigo A Cunha
Henrique B Silva
Journal: Neurobiology of Disease (2021)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: A(2A) receptors; ATP; Astrocytes; CD73; Ecto-nucleotidases
Affiliations: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA., CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Portugal., CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal., Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA; Molecular Neuropharmacology Lab, School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China., CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal. Electronic address: .

Abstract:  Extracellular ATP is a danger signal to the brain and contributes to neurodegeneration in animal models of Alzheimer's disease through its extracellular catabolism by CD73 to generate adenosine, bolstering the activation of adenosine A2A receptors (A2AR). Convulsive activity leads to increased ATP release, with the resulting morphological alterations being eliminated by A2AR blockade. However, it is not known if upon convulsions there is a CD73-mediated coupling between ATP release and A2AR overactivation, causing neurodegeneration. We now show that kainate-induced convulsions trigger a parallel increase of ATP release and of CD73 and A2AR densities in synapses and astrocytes of the mouse hippocampus. Notably, the genetic deletion of CD73 attenuates neuronal degeneration but has no impact on astrocytic modifications in the hippocampus upon kainate-induced convulsions. Furthermore, kainate-induced convulsions cause a parallel deterioration of hippocampal long-term potentiation (LTP) and hippocampal-dependent memory performance, which is eliminated by knocking out CD73. This demonstrates the key role of the ATP release/CD73/A2AR pathway to selectively control synaptic dysfunction and neurodegeneration following an acute brain insult, paving the way to consider CD73 as a new therapeutic target to prevent neuronal damage upon acute brain damage. 

Retracted: No

PubPeer comments:
 Western blots in Fig 1, panels G and H appear to be duplicated from G to H with a vertical flip: ![file] ,
Effects of OX40–OX40L Interaction on the Nuclear Factor of Activated T Cells c1 in ApoE-Deficient Mice
Authors: Zhong-qun Wang
Cui-ping Wang
Jin-chuan Yan
Liang-jie Xu
Journal: Inflammation (2014)
Discipline: IMMUNOLOGY
Keywords: OX40-OX40L interaction; NFATc1; atherosclerosis; ApoE(-/-) mice; inflammation
Affiliations: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, 212001, China, .

Abstract:  We previously reported the emerging role of OX40-OX40L interaction in inflammation and atherosclerosis. However, the mechanism by which OX40-OX40L interaction contributes to pathogenesis is poorly understood. This study investigated the effects of OX40-OX40L interaction on the nuclear factor of activated T cells c1 (NFATc1) in ApoE(-/-) mice. Atherosclerotic plaque was induced via rapid perivascular carotid collar placement in ApoE(-/-) mice. The expression levels of OX40, OX40L, and NFATc1 in the lymphocytes were measured via real-time polymerase chain reaction and flow cytometry. The presence of NFATc1 in the atherosclerotic plaque was detected via immunohistochemistry, and the level of IL-4 was measured via enzyme-linked immunosorbent assay. The expression level of NFATc1 significantly increased in atherosclerotic lesion and in the leukocytes from the ApoE(-/-) mice. After stimulating OX40-OX40L interaction, the mRNA and protein expression levels of NFATc1 in the lymphocytes significantly increased. Meanwhile, anti-OX40LmAb significantly suppressed the expression of NFATc1 in the leukocytes and substantially elevated the level of IL-4. NFATc1 inhibitor markedly suppressed IL-4 production. This study suggests that OX40-OX40L interaction regulates the expression of NFATc1, which may play a critical role in atherosclerotic plaque formation, and may therefore have implications with pathophysiology of atherosclerosis. 

Retracted: No

PubPeer comments:
 Figure 1 shows the presence of Chloroflexi, Cyanobacteria and Planctomycetes, which are all normally environmental bacteria. These contaminations seem to be minor, and can probably be attributed to the lack of negative control. , 
 #1 Hi Hornung, Thanks for good suggestion. We will pay attention to this issue and set negative control in the future study. , 
 Glad to hear this :). To be honest, normally I d not even expect that contamination would be visible in gut data, since there is normally so much biomass that it just doesn t show up. I wouldn t know why it is visible here, but it s definitely better to use a negative control, to filter it out (although there are also challenges, but nevertheless). Luckily it doesn t impact the overall result, so this is good :). ,
<p>Effects of Atypical Protein Kinase C Inhibitor (DNDA) on Lung Cancer Proliferation and Migration by PKC-ι/FAK Ubiquitination Through the Cbl-b Pathway</p>
Authors: Tracess Smalley
Rekha Patel
Mildred Acevedo-Duncan
Raja Reddy BommaReddy
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: FAK; NSCLC; aPKC inhibitor; migration; ubiquitination.
Affiliations: Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.

Abstract:  Purpose: The options for treating lung cancers are limited, as diagnosis typically occurs during the late stages of the disease. There is a dire need to develop aPKC (atypical Protein Kinase C) inhibitors due to aPKC overexpression and contributions to lung cancer malignancies. In this study, we investigate the role of atypical PKCs (aPKCs) in cell proliferation and migration in lung cancer cell lines and the effect of the novel aPKC inhibitor DNDA (3,4-amino-2,7 napthalene disulfonic acid). Methods: The normal and lung cancer cells were treated with various concentrations of DNDA. We used a WST assay to determine lung cell viability, then analyzed cell apoptosis through Annexin V/PI staining and flow cytometry. Immunoprecipitation determined the proteins' associations, and Western blot allowed testing of the expression of interest proteins. We also employed the UbiTest to identify the ubiquitination of the FAK. The scratch and transwell assays measured cell migration and invasion of lung cancer cells. Results: Our data from cell viability and flow cytometry showed a significant reduction in cell proliferation and induction of apoptosis with DNDA treatment in lung cancer cells, as well as no toxic effect on normal BEAS-2B lung cells. Western blot results showed that the phosphorylation of PKC-iota and phosphorylation of FAK decreased in A549 lung cancer cells upon DNDA treatment. Immunoprecipitation (IP) data revealed an association of PKC-ι with FAK and FAK with Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b). UbiTest results suggest that PKC-ι regulates FAK cleavage through its ubiquitination by Cbl-b, thereby inhibiting A549 lung cancer cells' migration. This was evident from scratch, invasion, and migration assays. Conclusion: Our study data suggest that DNDA inhibits cell proliferation and induces apoptosis in lung cancer cells. Moreover, DNDA inhibit A549 lung cancer cells' migration by PKC- ι/FAK ubiquitination via Cbl-b. 

Retracted: No

PubPeer comments:
 I have concerns about some of the Western blots presented in this paper. *** Possible splice in Figure 4A ![file] *** Possible splice in Figure 4A (Inverse) ![file] *** Possible splice in Figure 5A ![file] *** Possible splice in Figure 5A (Inverse) ![file] *** Possible band reuse in 7A D; unexpectedly similar ![file] *** Possible band reuse in 7A D; unexpectedly similar (False color) ![file] ,
Adverse health effects of 5G mobile networking technology under real-life conditions
Authors: Aristides Tsatsakis
Ronald N Kostoff
Paul Heroux
Michael Aschner
Journal: Toxicology Letters (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 5G; Adverse health effects; Combined effects; Electromagnetic fields; Mobile networking technology
Affiliations: Research Affiliate, School of Public Policy, Georgia Institute of Technology, Georgia, United States. Electronic address: ., Toxicology and Health Effects of Electromagnetism, McGill University, Canada., Molecular Pharmacology, Einstein Center of Toxicology, Albert Einstein College of Medicine, United States., Laboratory of Toxicology, Medical School, University of Crete, Voutes, 71409 Heraklion, Crete, Greece; Department of Analytical, Toxicology, Pharmaceutical Chemistry and Pharmacognosy, Sechenov University, 119991 Moscow, Russia. Electronic address: .

Abstract:  This article identifies adverse effects of non-ionizing non-visible radiation (hereafter called wireless radiation) reported in the premier biomedical literature. It emphasizes that most of the laboratory experiments conducted to date are not designed to identify the more severe adverse effects reflective of the real-life operating environment in which wireless radiation systems operate. Many experiments do not include pulsing and modulation of the carrier signal. The vast majority do not account for synergistic adverse effects of other toxic stimuli (such as chemical and biological) acting in concert with the wireless radiation. This article also presents evidence that the nascent 5G mobile networking technology will affect not only the skin and eyes, as commonly believed, but will have adverse systemic effects as well. 

Retracted: No

PubPeer comments:
  This article also presents evidence that the nascent 5G mobile networking technology will affect not only the skin and eyes, as commonly believed, but will have adverse systemic effects as well.  This is simply not true as 5g waves have less energy then green visible light waves do. IMAGE SOURCE IS FROM BBC UK: ![file] , 
 The corresponding author: ![file] , 
 Concerns about the editorial process of this journal, this paper is mentioned. https: blogs.harvard.edu sj 2021 09 30 journal-level-fraud-elsevier-fakes-peer-review-of-covid-click-bait ,
The molecular and biochemical insight view of grape seed proanthocyanidins in ameliorating cadmium-induced testes-toxicity in rat model: implication of PI3K/Akt/Nrf-2 signaling
Authors: Kalist Shagirtha
Nazima Bashir
Vaikundam Manoharan
Selvaraj Miltonprabu
Journal: Bioscience Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Nrf2/HO-1; antioxidant; cadmium; grape seed proanthocyanidins; oxidative stress
Affiliations: Department of Zoology, Annamalai University, Chidambaram 608002, India., Department of Biochemistry, St. Joseph's College, Cuddalore 607001, India., Department of Zoology, Faculty of Science, University of Madras, Chennai 600025, India  .

Abstract:  The present study aims to evaluate the protective effect of grape seed proanthocyanidins (GSP) on cadmium (Cd)-induced testicular apoptosis, inflammation, and oxidative stress in rats. A total of 24 male Wistar rats were divided into four groups, namely control, GSP (100 mg/kg BW), Cd (5 mg/kg BW), and Cd+GSP. Cd-treated rat testes exhibited a significant increment in oxidative stress mediated inflammation and apoptosis. Pre-administration of GSP exhibit significant protection against the apoptotic and inflammatory damages elicited by Cd and uphold the intercellular antioxidant status in testes. Histological changes were studied and the immunohistochemical staining for caspase 3, HSP70, and eNOS protein expressions were also analyzed to justify the protective action of GSP. Furthermore, GSP prevented DNA damage, and enhanced the expression of antioxidant responsive elements Nrf2/HO-1 by PI3K/Akt-dependent pathway. Therefore, our results suggest that GSP acts as a multipotent antioxidant entity against Cd-induced oxidative testicular toxicity in rats. 

Retracted: No

PubPeer comments:
 Figure 10. Some unexpected repetitive elements within the same photo - in all four of the phots in this figure. Could the authors please explain what happened here? ![file] , 
 #1 Another echo in 10B. ![file] , 
 Fig 8:  Effect of GSP and Cd on Immunohistochemical staining of iNOS, caspase-3, eNOS, HSP70 in rat testis ![file] The iNOS and HSP70 panels tend to overlap. ![] If adjacent slices of tissue had been stained, I would expect more differences in morphology, whereas the actual differences seem to be artefacts of image expansion and aspect ratio. ![file] ![file] , 
 https: doi.org 10.1042 BSR-20180515_EOC 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. ,
The Effects of Vitamin D Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Maryam Chamani
Maryam Maktabi
Zatollah Asemi
Journal: Hormone and Metabolic Research (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: vitamin D supplementation; metabolic status; polycystic ovary syndrome (PCOS); randomized trial; insulin resistance
Affiliations: Department of Gynecology and Obstetrics, Endocrinology and Metabolism Research Center, School of Medicine, Arak University of Medical Sciences, Arak, I. R. Iran, Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, I. R. Iran, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I. R. Iran

Abstract:  Data on the effects of vitamin D supplementation on metabolic status of patients with polycystic ovary syndrome (PCOS) are scarce. The current study was conducted to evaluate the effects of vitamin D supplementation on metabolic status of patients with PCOS. This randomized double-blind, placebo-controlled trial was performed on 70 vitamin D-deficient (serum concentrations&lt;20 ng/ml) women with phenotype B-PCOS according to the Rotterdam criteria aged 18-40 years old. Participants were randomly allocated into 2 groups to take either 50 000 IU vitamin D (n=35) or placebo (n=35) every 2 weeks for 12 weeks. Metabolic, endocrine, inflammation, and oxidative stress biomarkers were quantified at the beginning of the study and after 12-week intervention. After the 12-week intervention, compared to the placebo, vitamin D supplementation significantly decreased fasting plasma glucose (FPG) (-3.1±7.3 vs. +0.5±6.3 mg/dl, p=0.02), insulin (-1.4±3.6 vs. +2.6±7.0 μIU/ml, p=0.004), homeostasis model of assessment-estimated insulin resistance (-0.3±0.8 vs. +0.6±1.6, p=0.003), homeostasis model of assessment-estimated B cell function (-4.9±13.4 vs. +9.9±26.9, p=0.005), and increased quantitative insulin sensitivity check index (+0.01±0.01 vs. -0.02±0.05, p=0.007). Supplementation with vitamin D also led to significant reductions in serum high-sensitivity C-reactive protein (hs-CRP) (-0.7±1.4 vs. +0.5±2.1 μg/mL, p=0.009) and plasma malondialdehyde (MDA) levels (-0.1±0.5 vs. +0.9±2.1 μmol/l, p=0.01) compared to the placebo. Overall, vitamin D supplementation for 12 weeks in vitamin D-deficient women with phenotype B-PCOS had beneficial effects on glucose homeostasis parameters, hs-CRP, and MDA. 

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 A103 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 ,