PReD-Bench/PRed-Bench huggingface dataset:
DANCR promotes HCC progression and regulates EMT by sponging miR-27a-3p via ROCK1/LIMK1/COFILIN1 pathway
Authors: Yarui Li
Yifei Chen
Dan Guo
Dan Zhang
Xin Wang
Guifang Lu
Mudan Ren
Xinlan Lu
Shuixiang He
Journal: Cell proliferation (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LIM domain kinase 1; differentiation antagonizing nonprotein coding RNA; epithelial-mesenchymal transition; hepatocellular carcinoma development; miR-27a-3p.
Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Abstract:  Objectives: This research aims to verify that the long non-coding RNA differentiation antagonizing nonprotein coding RNA (LncRNA DANCR) could modulate the proliferation and metastasis of hepatocellular carcinoma (HCC), and it thus may work as a novel biomarker to render new orientation for early diagnosis and clinical therapy of HCC. Materials and methods: Firstly, qRT-PCR was used to detect the expression of genes including LncRNA DANCR and miR-27a-3p. Next, MTT assay, Ethynyldeoxyuridine (EdU) analysis and clone formation assay were used for investigating cell growth and proliferation. Meanwhile, transwell assay and wound healing assay were applied to evaluate the capacity of cell metastasis and motility, respectively. In addition, bioinformatic analysis and dual-luciferase reporter assay were applied to analyse molecular interaction. Next, we conducted immunofluorescence and Western blot for mechanic investigation. Last but not the least, xenograft tumours in nude mice were built by subcutaneously injecting Hep3B cells stably transfected with sh-NC and sh-DANCR to detect proliferation and SMMC-7721 cells stably transfected with sh-NC and sh-DANCR to investigate metastasis. Results: The results of qRT-PCR and bioinformatic analysis revealed the high expression of DANCR in HCC. DANCR accelerated proliferation and metastasis of HCC cells and the knockdown of DANCR had the opposite effect. Meanwhile, xenograft tumours in sh-DANCR group grow slower and have smaller volumes compared with negative control group. Next, the antineoplastic effect of miR-27a-3p on cell growth and motility of HCC was confirmed. In addition, we clarified that DANCR acted as a ceRNA to decoy miR-27a-3p via mediating ROCK1/LIMK1/COFILIN1 pathway. In the end, we validated that DANCR/miR-27a-3p axis regulates EMT progression by cell immunofluorescence and Western blot. Conclusions: In a word, DANCR promotes HCC development and induces EMT by decoying miR-27a-3p to regulate ROCK1/LIMK1/COFILIN1 pathway. 

Retracted: No

PubPeer comments:
 Figure 2D. * Red boxes: Two of the SMMC-7721 panels appear to show a small area of overlap. ![file] , 
 Figure 3D. * Blue boxes: Two of the HepG2 panels appear to show a small area of overlap. ![file] , 
 Figure D6C. * Purple boxes: Two of the SMMC-7721 panels appear to show an area of overlap. ![file] ,
Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock
Authors: Raymond Kaempfer
Emmanuelle Supper
Adi Minis
Dalia Hillman
Iris Nasie
Ziv Rotfogel
Gila Arad
Uri Barash
Revital Levy
Tomer Shpilka
Journal: PLoS Biology (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bacterial superantigens; CD28; inflammatory cytokine storm; toxicity; peptide mimetics
Affiliations: Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Abstract:  Bacterial superantigens, a diverse family of toxins, induce an inflammatory cytokine storm that can lead to lethal shock. CD28 is a homodimer expressed on T cells that functions as the principal costimulatory ligand in the immune response through an interaction with its B7 coligands, yet we show here that to elicit inflammatory cytokine gene expression and toxicity, superantigens must bind directly into the dimer interface of CD28. Preventing access of the superantigen to CD28 suffices to block its lethality. Mice were protected from lethal superantigen challenge by short peptide mimetics of the CD28 dimer interface and by peptides selected to compete with the superantigen for its binding site in CD28. Superantigens use a conserved β-strand/hinge/α-helix domain of hitherto unknown function to engage CD28. Mutation of this superantigen domain abolished inflammatory cytokine gene induction and lethality. Structural analysis showed that when a superantigen binds to the T cell receptor on the T cell and major histocompatibility class II molecule on the antigen-presenting cell, CD28 can be accommodated readily as third superantigen receptor in the quaternary complex, with the CD28 dimer interface oriented towards the β-strand/hinge/α-helix domain in the superantigen. Our findings identify the CD28 homodimer interface as a critical receptor target for superantigens. The novel role of CD28 as receptor for a class of microbial pathogens, the superantigen toxins, broadens the scope of pathogen recognition mechanisms. 

Retracted: No

PubPeer comments:
 Correction, August 2015: https: journals.plos.org plosbiology article?id=10.1371 journal.pbio.1002237  The authors would like to clarify that for some of the actin RNA loading control panels in Figure 2A and those in Figure 6A, a temporary placeholder was left in inadvertently. In Figure 2A, actin RNA was not assayed for pc9, as this phage display peptide was used as a negative control that failed to inhibit cytokine mRNA induction by SEB. Since equal amounts of RNA were loaded for electrophoretic analysis, the conclusion remains valid. Figure 6A now displays the actual actin RNA panels. tk2 mutant SEB is impaired in its ability to induce cytokine gene expression; reduced cytokine mRNA levels are reflected by reduced protein levels. Here is the original Figure 2A, with red, green, and blue boxes marking some panels that looked very similar. ![file] ,
MiR-21-mediated Metabolic Alteration of Cancer-associated Fibroblasts and Its Effect on Pancreatic Cancer Cell Behavior
Authors: Wanrun Lin
Shuo Chen
Jiancang Ma
Xi Chen
Tao Shan
Ya&#x27;an Kang
Wei Li
Journal: International Journal of Biological Sciences (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: cancer-associated fibroblasts; glycolysis; metabolic alteration; miR-21.
Affiliations: Department of General Surgery, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004 China., Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032 China., Graduate School, Fourth Military Medical University, Xi'an 710033, China., Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Abstract:  In this study, we investigated whether the metabolic alteration of cancer-associated fibroblasts (CAFs) occurs via miR-21 remodeling and the effect of this alteration on pancreatic cancer cells. CAFs and normal fibroblasts (NFs) were isolated and cultured. Glucose consumption and lactic acid production were tested, and lactate dehydrogenase (LDHA), pyruvate kinase m2 (PKM2), and miR-21 expression were examined. The level of glycolysis in CAFs was determined after treatment with a miR-21 inhibitor. Primary miR-21-NC CAFs and miR-21-inhibitor CAFs were indirectly co-cultured with BxPc-3 in vitro, and the invasion capacity of these cells was determined. The aerobic oxidation index of cancer cells and the expression of succinodehydrogenase (SDH) and fumarate hydratase (FH) were assessed. Compared with NFs, CAFs showed enhanced glucose uptake capacity, lactic acid production, and elevated LDHA, PKM2, and miR-21 expression. After miR-21 inhibitor treatment, the extent of glycolysis in CAFs was reduced. After indirect co-culture with CAFs, oxidative phosphorylation and SDH, FH, and MCT expression increased in BxPc-3 cells. After co-culture with miR-21-inhibitor-CAFs, oxidative phosphorylation and invasion ability of the pancreatic cancer cells decreased. MiR-21 was involved in metabolic alteration of CAFs and affected the development of cancer cells. This metabolic alteration may be an important mechanism by which the microenvironment promotes tumor progression in a nonvascular manner. 

Retracted: No

PubPeer comments:
 In Figure 2, alpha-tubulin bands of A) and C) are identical as are alpha-tubulin bands in B) and D) (although it is also not clear how densitometry was performed when the bands are not clearly distinguishable!): ![file] ,
Interaction of Akt-phosphorylated SRPK2 with 14-3-3 Mediates Cell Cycle and Cell Death in Neurons
Authors: Manuel Yepes
Sung-Wuk Jang
Keqiang Ye
Howard Rees
Xia Liu
Haian Fu
Allan Levey
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: neurons; cell cycle; apoptosis; SRPK2; cyclin D1
Affiliations: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Abstract:  Terminally differentiated neurons are unable to reenter the cell cycle. Aberrant cell cycle activation provokes neuronal cell death, whereas cell cycle inhibition elevates neuronal survival. However, the molecular mechanism regulating the cell cycle and cell death in mature neurons remains elusive. Here we show that SRPK2, a protein kinase specific for the serine/arginine (SR) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin D1. Akt phosphorylates SRPK2 on Thr-492 and promotes its nuclear translocation leading to cyclin D1 up-regulation, cell cycle reentry, and neuronal apoptosis. In addition, SRPK2 phosphorylates SC35 and, thus, inactivates p53, resulting in cyclin D1 up-regulation. 14-3-3 binding to SRPK2, regulated by Akt phosphorylation, inhibits these events. We find that SRPK2 is phosphorylated in ischemia-attacked brain, correlating with the observed increase in cyclin D1 levels. Hence, phosphatidylinositol 3-kinase/Akt mediates the cell cycle and cell death machinery in the nervous system through phosphorylation of SRPK2. 

Retracted: No

PubPeer comments:
 Figures 3B and 5C. Much more similar than you would expect. https: imgur.com 5TAcFr8 ,
Distinctive neural signatures for negative sentences in Hindi: an fMRI study
Authors: Ramesh K Mishra
Uttam Kumar
Prakash Padakannaya
C L Khetrapal
Journal: Brain Imaging and Behavior (2013)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: fMRI; Hindi readers; semantic judgment task; affirmative sentences; negative sentences
Affiliations: Neuroimaging, Centre of Biomedical Magnetic Resonance, Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Lucknow, India. 

Abstract:  We examined cortical activations using functional magnetic resonance imaging (fMRI) technique in skilled native Hindi readers while they performed a 'target-probe' semantic judgment task on affirmative and negative sentences. Hindi, an Indo-Aryan language widely spoken in India, follows subject-object-verb (SOV) order canonically but allows free word order. The common cortical regions involved in affirmative and negative sentence conditions included bilateral inferior frontal gyrus (IFG), left parietal cortex (BA 7/40), left fusiform (BA 37), bilateral supplementary motor area (SMA) (BA 6), bilateral middle temporal gyrus (BA 21), and bilateral occipital area (BA 17/18). While no distinct region was activated for affirmative sentences, we observed activations in the region of bilateral anterior temporal pole for negative sentence. The behavioral results showed no significant mean difference for reaction times (RT) and accuracy measures between affirmative and negative sentences. However, the imaging results suggest the recruitment of anterior temporal pole in processing of negative sentences. Region of interest (ROI) analysis for selected regions showed higher signal intensity for negative sentences possibly indicating the associated inherent difficulty level of processing, especially when integrating information related to negations. 

Retracted: No

PubPeer comments:
null, 
 As it is already mentioned in comment that  these are not definitive results and require manual inspection the reported and recalculated value as described above does not differ even manual inspection does not shows any changes. It is also specified above that  The errors that may affect the computed p-value (but not the statistical significance) were reported as so the above calculation does not have impact on article. ,
Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway
Authors: Kai Zhou
Minglei Shao
Dongwei Lv
Haijun Sun
Zhitao Wang
Journal: Pharmaceutical Biology (2022)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Chondrocytes; IL-1β; anabolic; catabolic; nigericin.
Affiliations: Department of Orthopedics, Dongying People’s Hospital, Dongying, PR China, Department of Joint Surgery, Dongying People’s Hospital, Dongying, PR China, Department of Orthopedics, Dongying District People’s Hospital, Dongying, PR China

Abstract:  Context: Osteoarthritis (OA) is a degenerative disease. Senkyunolide A (SenA) is an important phthalide from Ligusticum chuanxiong Hort (Umbelliferae) with anti-spasmodic and neuroprotective effects. Objective: We explored the effect of SenA on IL-1β-stimulated chondrocytes and OA mice. Materials and methods: Chondrocytes were stimulated by IL-1β (10 ng/mL) to establish an OA model in vitro. Cells were treated with SenA (20, 40, 80 and 160 μg/mL) for 48 h. The in vivo OA model was established by cutting off the medial meniscus tibial ligament (MMTL) at right knee incision of male C57BL/6 mice. One week after surgery, mice were injected with SenA (intraperitoneally one week) and divided into four groups (n = 6 per group): Sham, OA, OA + SenA 20 mg/kg and OA + SenA 40 mg/kg. The OA progression was examined by haematoxylin and eosin (H&amp;E) staining. Results: SenA treatment increased cell viability (33%), proliferation (71%), inhibited apoptosis (21%), decreased levels of catabolic marker proteins (MMP13, 23%; ADAMTS4, 31%; ADAMTS5, 19%), increased levels of anabolic marker proteins (IGF-1, 57%; aggrecan, 75%; Col2a1, 48%), reduced levels of inflammation cytokines (TNF-α, 31%; IL-6, 19%; IL-18, 20%) and decreased levels of NLRP3 (21%), ASC (20%) and caspase-1 (29%) of chondrocytes. However, NLRP3 agonist nigericin increased levels of MMP13 (55%), ADAMTS4 (70%), ADAMTS5 (53%), decreased levels of IGF-1 (36%), aggrecan (26%), Col2a1 (25%), inhibited proliferation (61%) and promoted apoptosis (76%). Discussion and conclusions: SenA alleviates OA progression by inhibiting NLRP3 signalling pathways. These findings provide an experimental basis for the clinical application of drugs in the treatment of OA. 

Retracted: No

PubPeer comments:
 https: twitter.com jonaslindeloev status 1353834264756965377 , 
 https: lindeloev.net new-pnas-paper-income-is-a-poor-way-to-improve-well-being , 
 https: twitter.com kjhealy status 1353829809252610049?s=19 , 
 A defence. https: twitter.com rlucas11 status 1354123127568130048 ,
Secretome of Differentiated PC12 Cells Restores the Monocrotophos-Induced Damages in Human Mesenchymal Stem Cells and SHSY-5Y Cells: Role of Autophagy and Mitochondrial Dynamics
Authors: A Srivastava
A Pandey
D Kumar
V K Khanna
S Singh
P Srivastava
A B Pant
C S Rajpurohit
Journal: NeuroMolecular Medicine (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Autophagy; Conditioned medium; Mesenchymal stem cells; Mitochondrial dynamics; PC12 cells
Affiliations: System Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), MG Marg, Lucknow, Uttar Pradesh, 226001, India., Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow, India., System Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), MG Marg, Lucknow, Uttar Pradesh, 226001, India. ., Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow, India. .

Abstract:  A perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell-cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many health hazards. We, therefore, explored the protective efficacy of the secretome of differentiated PC12 cells with emphasis on induction of autophagy and mitochondrial biogenesis. Monocrotophos (MCP), a widely used neurotoxic organophosphate, was used as the test compound at sublethal concentration. The conditioned medium (CM) of differentiated PC12 cells comprising of their secretome restored the cell viability, oxidative stress and apoptotic cell death in MCP-challenged human mesenchymal stem cells and SHSY-5Y, a human neuroblastoma cell line. Delving further to identify the underlying mechanism of this restorative effect we observed a marked increase in the expression of autophagy markers LC3, Beclin-1, Atg5 and Atg7. Exposure to autophagy inhibitor, 3-methyladenine, led to a reduced expression of these markers with a concomitant increase in the expression of pro-apoptotic caspase-3. Besides that, the increased mitochondrial fission in MCP-exposed cells was balanced with increased fusion in the presence of CM facilitated by AMPK/SIRT1/PGC-1α signaling cascade. Mitochondrial dysfunctions are strongly associated with autophagy activation and as per our findings, cellular secretome too induces autophagy. Therefore, connecting these three potential apices can be a major breakthrough in repair and rescue of xenobiotic-damaged tissues and cells. 

Retracted: No

PubPeer comments:
 ![file] , 
 ![file] ![file] ,
Autophagic Turnover of Inactive 26S Proteasomes in Yeast Is Directed by the Ubiquitin Receptor Cue5 and the Hsp42 Chaperone
Authors: Richard D Vierstra
Fionn McLoughlin
Richard S Marshall
Journal: Cell Reports (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: 26S proteasome; autophagy; insoluble protein deposit (IPOD); nitrogen starvation; proteaphagy
Affiliations: Department of Genetics, University of Wisconsin, 425 Henry Mall, Madison, WI 53706, USA; Department of Biology, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, USA., Department of Biology, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, USA., Department of Genetics, University of Wisconsin, 425 Henry Mall, Madison, WI 53706, USA; Department of Biology, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, USA. Electronic address: .

Abstract:  The autophagic clearance of 26S proteasomes (proteaphagy) is an important homeostatic mechanism within the ubiquitin system that modulates proteolytic capacity and eliminates damaged particles. Here, we define two proteaphagy routes in yeast that respond to either nitrogen starvation or particle inactivation. Whereas the core autophagic machineries required for Atg8 lipidation and vesiculation are essential for both routes, the upstream Atg1 kinase participates only in starvation-induced proteaphagy. Following inactivation, 26S proteasomes become extensively modified with ubiquitin. Although prior studies with Arabidopsis implicated RPN10 in tethering ubiquitylated proteasomes to ATG8 lining the autophagic membranes, yeast proteaphagy employs the evolutionarily distinct receptor Cue5, which simultaneously binds ubiquitin and Atg8. Proteaphagy of inactivated proteasomes also requires the oligomeric Hsp42 chaperone, suggesting that ubiquitylated proteasomes are directed by Hsp42 to insoluble protein deposit (IPOD)-type structures before encapsulation. Together, Cue5 and Hsp42 provide a quality control checkpoint in yeast directed at recycling dysfunctional 26S proteasomes. 

Retracted: No

PubPeer comments:
 Figure 2. Much more similar than you would expect. https: imgur.com BPIOVTi ,
DNA Methylation on N6-Adenine in C. elegans
Authors: L Aravind
Yang Shi
Chih-Hung Hsu
Eric Lieberman Greer
Erdem Sendinc
David Aristizábal-Corrales
Lei Gu
Chuan He
Jianzhao Liu
Mario Andres Blanco
Journal: Cell (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DNA methylation; epigenetic mark; C. elegans; adenine N(6)-methylation; trans-generationally
Affiliations: Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ., Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Department of Chemistry and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA., National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 208943, USA.

Abstract:  In mammalian cells, DNA methylation on the fifth position of cytosine (5mC) plays an important role as an epigenetic mark. However, DNA methylation was considered to be absent in C. elegans because of the lack of detectable 5mC, as well as homologs of the cytosine DNA methyltransferases. Here, using multiple approaches, we demonstrate the presence of adenine N(6)-methylation (6mA) in C. elegans DNA. We further demonstrate that this modification increases trans-generationally in a paradigm of epigenetic inheritance. Importantly, we identify a DNA demethylase, NMAD-1, and a potential DNA methyltransferase, DAMT-1, which regulate 6mA levels and crosstalk between methylations of histone H3K4 and adenines and control the epigenetic inheritance of phenotypes associated with the loss of the H3K4me2 demethylase spr-5. Together, these data identify a DNA modification in C. elegans and raise the exciting possibility that 6mA may be a carrier of heritable epigenetic information in eukaryotes. 

Retracted: No

PubPeer comments:
 Lead authors of Cell paper published a study suggesting that detection of DNA 6mA in the C. elegans was artifact of bacteria contamination https: bmcgenomics.biomedcentral.com articles 10.1186 s12864-019-5754-6 , 
 #1 Perhaps the authors should check out this recent study showing severe limitations and artifacts in standard 6mdA detection methods, and suggesting that there is no evidence to support the presence of 6mdA in higher organisms https: www.ncbi.nlm.nih.gov pubmed 32206710 , 
 This Cell paper should not continue to float around in the literature and be cited by others as valid science. The leading authors themselves (Dr. Eric Greer, Dr. Yang Shi, Dr. Chuan He) were unable to reliably detect 6mA in the worm and other multicellular organisms after controlling for experimental artifacts. The new study was published in BMC genomics - https: bmcgenomics.biomedcentral.com articles 10.1186 s12864-019-5754-6. It is admirable that the authors have attempted to correct their mistakes, but that is no substitute for a formal retraction of the flawed science. ,
Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat
Authors: Arnold G Coran
Jacob Bejar
Tal Koppelmann
Igor Sukhotnik
Jorge Mogilner
Yulia Pollak
Journal: BMC gastroenterology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Arginine; nitric oxide; intestine; methotrexate; supplementation
Affiliations: The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of intestinal adaptation and recovery, Haifa, Israel.

Abstract:  Background: Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat. Methods: Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression. Results: MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels. Conclusions: Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat. 

Retracted: No

PubPeer comments:
 The micrographs in Figure 4A are unusual compared to what I am used to see. The structures are lined up in one direction. Why? ![file] ,
Effect of zinc(II) doping on thermal and optical properties of potassium hydrogen phthalate (KHP) crystals
Authors: Parthiban, S.
Murali, S.
Madhurambal, G.
Meenakshisundaram, S. P.
Mojumdar, S. C.
Journal: Journal of Thermal Analysis and Calorimetry (2010)
Discipline: CHEMISTRY
Keywords: doping; transition metal; Zn(II); potassium hydrogen phthalate; KHP crystals

Abstract: The influence of doping the transition metal Zn(II) on potassium hydrogen phthalate (KHP) crystals has been studied. A close observation of FT-IR and XRD profiles of doped and undoped samples reveals some minor structural variations. It appears that the crystal undergoes considerable lattice stress as a result of doping the bivalent zinc. Furthermore, the possibility of cation vacancies aroused owing to the substitution of K1+ by Zn2+ could result in a defective crystal system. Energy dispersive spectra reveal the incorporation of Zn(II) in the crystalline matrix of KHP crystals. Differential scanning calorimetry (DSC) and TG-DTA studies reveal the purity of the sample and no decomposition is observed below the melting point. Small quantity additions of Zn(II) enhance the fluorescence intensity of KHP crystals. The doping results in morphological changes and significantly improves the second harmonic generation (SHG) efficiency of the host crystal.

Retracted: No

PubPeer comments:
 In this paper authors describe the effect of zinc(II) doping on thermal and optical properties of potassium hydrogen phthalate (KHP) crystals. According to authors  A small quantity of dopant, Zn(II) (0.0005u20130.012 mol dmu22123) in the form of ZnSO4 was used for doping.  By use of Zn(II) authors claim to have grown so called Zn(II) doped KHP crystal. Unfortunately authors have not taken into consideration that Zn(II) is dication unlike K+ which is monopositive. It is not clear how the charge balance can be maintained. In addition authors have not taken into consideration that reaction of ZnSO4.7H2O with KHP can also result in the formation of the four coordinate ZN(II) compound [Zn(phth)2(H2O)2] (phth = o-phthalate) the structure of which was reported by Wen et al in 2007 in Analytical Sciences. It is not clear why these authors are not getting this four coordinate compound but zinc doped KHP. Authors may like to clarify this especially the charge imbalance between the dopant metal zinc and the host potassium ,
Inhibition of HUVEC tubulogenesis by hederacolchiside-A1 is associated with plasma membrane cholesterol sequestration and activation of the Ha-Ras/MEK/ERK cascade
Authors: Chantal Barthomeuf
Dominique Boivin
Richard Béliveau
Journal: Cancer Chemotherapy and Pharmacology (2004)
Discipline: CLINICAL MEDICINE
Keywords: Neoangiogenesis; HCol-A1; Endothelial cells; Triterpenoid saponin; Matrigel-induced angiogenesis
Affiliations: Laboratoire de Pharmacognosie et Biotechnologies, Faculté de Pharmacie, UMR-INSERM U-484-UdA-CJP, Place H Dunant, Rue Montalembert, BP 184, 63001, Clermont-Fd Cedex, France. 

Abstract:  Purpose: Neoangiogenesis is critical to cancer proliferation and metastasis and constitutes an attractive target for cancer therapy. It has previously been demonstrated that hederacolchiside-A1 (HCol-A1), a triterpenoid saponin from Hedera colchica Koch, has antimelanoma potential. The goal of this study was to evaluate, in vitro, if in addition to its tumoricidal effect on melanoma cells, HCol-A1 might affect endothelial cell network formation. Methods: We investigated whether HCol-A1 affects matrigel-induced tubulogenesis and inhibits the viability (WST-1 assay) of human umbilical vein endothelial cells (HUVECs). To provide structure-activity relationships (SAR), studies were conducted on HCol-A1, oleanolic acid and hederacolchiside A (HCol-A), a triterpenoid saponin which possess the same sugar sequence as Hcol-A1. Plasma membrane cholesterol sequestration was studied by labelling with [3H]cholesterol and assayed with HCol-A1-cholesterol complexes. HCol-A1 signalling was investigated using immunoassays. Results: In contrast to HCol-A and oleanolic acid, HCol-A1 inhibited matrigel-induced angiogenesis at micromolar concentration. Plasma membrane cholesterol sequestration was found to be critical for this activity. Activation of the Ras/MEK/ERK cascade appears to be one of the mechanisms by which Hcol-A1 affects HUVEC network formation. The predominant activation of the Ha-Ras isoform, which decreases HUVEC-tolerance to apoptosis, might contribute to the high susceptibility of this cell line to HCol-A1. Conclusion: Since cholesterol sequestration affects cell confluence-dependent remodelling of endothelial membranes and vascular endothelial growth factor receptor-2 activity, these results raise the possibility that Hcol-A1 might slow-down cancer proliferation and metastasis in vivo by inhibiting critical aspects of neoangiogenesis. Further in vivo studies are needed to verify this hypothesis. 

Retracted: No

PubPeer comments:
 Figure 2 and 3: * Red boxes: The 3 ug ml Hcol-A1 panel in Figure 2B looks similar to the 5 ug ml Hcol-A1 panel in Figure 3, albeit shown at different exposures. ![file] Figure 6A. * Blue ellipses: Both Total Ras panels look similar to each other. * Red ellipses: The same lane appears to be visible three times. ![file] All these concerns were reported to the journal in June 2015, but no action was taken. ,
Cardamonin sensitizes tumour cells to TRAIL through ROS- and CHOP-mediated up-regulation of death receptors and down-regulation of survival proteins
Authors: Bharat B Aggarwal
Sahdeo Prasad
Vivek R Yadav
Journal: British Journal of Pharmacology (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: TRAIL; Cardamonin; Apoptosis; Cancer; DR5
Affiliations: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract:  Background and purpose: TNF-related apoptosis-inducing ligand (TRAIL) is currently in clinical trials as a treatment for cancer, but development of resistance is a major drawback. Thus agents that can overcome resistance to TRAIL are urgently needed. Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) has been shown to affect cell growth by modulating various cell signalling pathways. Hence, we investigated the effect of cardamonin on the actions of TRAIL. Experimental approach: The effect of cardamonin on TRAIL was measured by plasma membrane integrity, phosphatidylserine exposure, mitochondrial activity, and activation of caspase-8, caspase-9, and caspase-3 in human colon cancer cells. Key results: Cardamonin potentiated TRAIL-induced apoptosis and this correlated with up-regulation of both the TRAIL death receptor (DR) 4, 5 at mRNA and protein levels. TRAIL-decoy receptor DcR1 was down-regulated by cardamonin. Induction of DRs by cardamonin occurred in a variety of cell types. Gene silencing of the DRs by small interfering RNA (siRNA) abolished the effect of cardamonin on TRAIL-induced apoptosis, suggesting that sensitization was mediated through the DR. Induction of the DR by cardamonin was p53-independent but required CCAAT/enhancer binding protein homologous protein (CHOP); cardamonin induced CHOP, and its silencing by siRNA eliminated the induction of DR5. Cardamonin increased the production of reactive oxygen species (ROS) and quenching ROS abolished its induction of receptors and enhancement of TRAIL-induced apoptosis. Cardamonin also decreased the expression of various cell survival proteins. Conclusions and implications: Cardamonin potentiates TRAIL-induced apoptosis through ROS-CHOP-mediated up-regulation of DRs, decreased expression of decoy receptor and cell survival proteins. Thus, cardamonin has the potential to make TRAIL more effective as an anticancer therapy. 

Retracted: No

PubPeer comments:
 Retracted [6 December 2021] . Part of a collection on  [Big Data and Intelligent Computing Techniques in Geosciences]  , edited by Ahmed Farouk.  The Editor-in-Chief and the Publisher have retracted this article because the content of this article is nonsensical. The peer review process was not carried out in accordance with the Publisher s peer review policy. The author has not responded to correspondence regarding this retraction. ,
Tidal stretches differently regulate the contractile and cytoskeletal elements in intact airways
Authors: Kenneth R Lutchen
Erzsébet Bartolák-Suki
Béla Suki
Adam S LaPrad
Brian C Harvey
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Tidal stretches; Airway constriction; Cytoskeletal structure; Integrin receptors; Transmural pressure
Affiliations: Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America.

Abstract:  Recent reports suggest that tidal stretches do not cause significant and sustainable dilation of constricted intact airways ex vivo. To better understand the underlying mechanisms, we aimed to map the physiological stretch-induced molecular changes related to cytoskeletal (CSK) structure and contractile force generation through integrin receptors. Using ultrasound, we measured airway constriction in isolated intact airways during 90 minutes of static transmural pressure (Ptm) of 7.5 cmH2O or dynamic variations between Ptm of 5 and 10 cmH20 mimicking breathing. Integrin and focal adhesion kinase activity increased during Ptm oscillations which was further amplified during constriction. While Ptm oscillations reduced β-actin and F-actin formation implying lower CSK stiffness, it did not affect tubulin. However, constriction was amplified when the microtubule structure was disassembled. Without constriction, α-smooth muscle actin (ASMA) level was higher and smooth muscle myosin heavy chain 2 was lower during Ptm oscillations. Alternatively, during constriction, overall molecular motor activity was enhanced by Ptm oscillations, but ASMA level became lower. Thus, ASMA and motor protein levels change in opposite directions due to stretch and contraction maintaining similar airway constriction levels during static and dynamic Ptm. We conclude that physiological Ptm variations affect cellular processes in intact airways with constriction determined by the balance among contractile and CSK molecules and structure. 

Retracted: No

PubPeer comments:
 Concern about GAPDH panels (loading control,  LC ) in Figures 2A, 2C, 3A, 7C, and 7D. The same three bands appear to be visible multiple times, but representing different experiments, albeit sometimes flipped either horizontally or vertically, or stretched compressed. Boxes and arrows of the same colors depict bands that look similar, as well as their orientation. ![file] , 
 Concern about GAPDH panels (loading control,  LC ) in Figures 2B, 3B, and 7B. The same two bands appear to be visible multiple times. Although they might represent the same experiments, the 2 bands are sometimes visible in mirror image. Shown with blue boxes and arrows. ![file] ,
The lncRNA RHPN1-AS1 downregulation promotes gefitinib resistance by targeting miR-299-3p/TNFSF12 pathway in NSCLC
Authors: Su Cui
Shun Xu
Xuehao Li
Qiming Shen
Chunlu Yang
Xin Zhang
Journal: Cell Cycle (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: NSCLC; RHPN1-AS1; gefitinib.
Affiliations: Department of Thoracic Surgery, the First Hospital of China Medical University, Shenyang City, P.R. China

Abstract:  Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has exhibited notable clinical efficacy in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is ultimately limited by the development of gefitinib resistance. The present study aimed to investigate the effects of the long non-coding RNA, RHPN1-AS1 on gefitinib resistance in NSCLC and explore the underlying mechanisms. In this study, RHPN1-AS1 was observed to be downregulated in gefitinib resistant patients and NSCLC cell lines. Besides, decreased expression of RHPN1-AS1 was found to be associated with poor prognosis of NSCLC patients. RHPN1-AS1 knockdown conferred gefitinib resistance to gefitinib sensitive NSCLC cells, whereas the overexpression of RHPN1-AS1 sensitized gefitinib resistant NSCLC cells to gefitinib treatment. Mechanistically, RHPN1-AS1 was found to positively regulate the expression of TNFSF12 by directly interacting with miR-299-3p. Collectively, RHPN1-AS1 modulates gefitinib resistance through miR-299-3p/TNFSF12 pathway in NSCLC. Our findings indicate that RHPN1-AS1 may serve as not only a prognostic biomarker for gefitinib resistance but also as a promising therapeutic biomarker and target for the treatment of NSCLC patients. 

Retracted: No

PubPeer comments:
 Due to the randomly organization of data and presentation in several Figures and the characteristic artificial looking Western blots, it all looks like a product from a Chinese paper mill. Microscopy data in Figure 2D, 3D and 6C are heavily contaminated by duplications and manipulations. A rather unusual duplication of a tumor is also seen in Figure 3e. The Western blots in Figure 5G are of the typical Chinese style, with artificial look. ![file] , 
 Fig 6C.  Transwell migration assay of PC9GR (left) and HCC827GR (right) cells transfected with miR-Control, miR-299-3p mimics or miR-299-3p mimics + pcDNA-TNFSF12 6h prior to the stimulation with 0.1 u03bcM gefitinib for 24h. I have concerns. ![] , 
 In addition to the above concerns, with which I agree, there seems to be at least two images which appear on a previously published paper in Oncotarget. I did not look further. Figure 6A, Oncotarget (2015), doi: 10.18632 oncotarget.5004, discussed here: https: pubpeer.com publications 294B425C9C17F448DDCFDBF666A965 *** ![file] ,
MiR-127-3p inhibits cell growth and invasiveness by targeting ITGA6 in human osteosarcoma
Authors: Kai Wang
Dong Wang
Liang Tang
Huihui Wu
Dongyun Gu
Journal: IUBMB Life (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ITGA6; miR-127-3p; osteosarcoma.
Affiliations: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200011, China., Engineering Research Center of Digital Medicine and Clinical Translation, Ministry of Education of P.R. China, Shanghai, China.

Abstract:  Osteosarcoma (OS) is one of the most universal malignant bone tumors that occur mostly in children and adolescents. This study aimed to investigate the roles of miR-127-3p and integrin subunit-α 6 (ITGA6) in OS proliferation, apoptosis, invasion and migration, and to explore the possible molecular mechanism and target relationship. By conducting quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, the microRNA (miRNA) and protein expressions of miR-127-3p and ITGA6 in both tissues and cells were determined. The expression of apoptosis and migration related were also detected by western blot. The target relationship between miR-127-3p and ITGA6 was predicted by TargetScan and verified by dual-luciferase reporter assay. The biological functions of miR-127-3p and ITGA6 in OS were investigated by following experiments: cell counting kit 8 (CCK-8) and colony formation assays to inspect cell proliferation, flow cytometry, and caspase 3 activity assay to examine apoptosis, and transwell and wound healing assays to analyze invasion and migration. Significant down-regulation of miR-127-3p and up-regulation of ITGA6 was found out in OS tissues and cells. ITGA6 was proved to be the downstream target gene of miR-127-3p and functioned as a tumor promotor in OS, while miR-127-3p restrained deterioration of OS by suppressing cell viability, reducing migration and invasion, and promoting apoptosis. MiR-127-3p suppressed proliferation, invasion, and migration while stimulated apoptosis of OS cells through knocking down ITGA6. © 2018 IUBMB Life, 70(5):411-419, 2018. 

Retracted: No

PubPeer comments:
 Overlap images Left: this study, Fig 6A, ITGA6 group Right: [Tang 2018] , Fig 3A, control group ![file] these two research shared the same authors (Dong Wang, Liang Tang), maybe it was a mistake ,
A Trial on The Effects of Magnesium-Zinc-Calcium-Vitamin D Co-Supplementation on Glycemic Control and Markers of Cardio-Metabolic Risk in Women with Polycystic Ovary Syndrome
Authors: Mehri Jamilian
Maryam Maktabi
Zatollah Asemi
Journal: Archives of Iranian Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: magnesium; zinc; calcium; vitamin D; co-supplementation
Affiliations: Endocrinology and Metabolism Research Center, Department of Gynecology and Obstetrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran., Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R. Iran.

Abstract:  Background: There is scarce data on the effects of magnesium-zinc-calcium-vitamin D co-supplementation on glycemic control and markers of cardio-metabolic risk among women with polycystic ovary syndrome (PCOS). The objective of this study was to assess the effects of magnesium-zinc-calcium-vitamin D co-supplementation on glycemic control and markers of cardio-metabolic risk in women with PCOS. Methods: Sixty PCOS women were randomized into two groups and treated with 100 mg of magnesium, 4 mg of zinc, 400 mg of calcium plus 200 IU of vitamin D supplements (n = 30) or placebo (n = 30) twice a day for 12 weeks. Glycemic control and markers of cardio-metabolic risk were assessed at baseline and at the end of trial. Results: After the 12-week intervention, compared with the placebo, magnesium-zinc-calcium-vitamin D co-supplementation supplementation resulted in significant reductions in serum insulin levels (-1.9 ± 4.6 vs. +0.4 ± 2.8 µIU/mL, P = 0.01), and homeostatic model of assessment for insulin resistance (-0.4 ± 1.0 vs. +0.1 ± 0.6, P = 0.02), as well as a significant increase in quantitative insulin sensitivity check index (+0.01 ± 0.02 vs. -0.0003 ± 0.01, P = 0.02). In addition, magnesium-zinc-calcium-vitamin D co-supplementation significantly decreased serum triglycerides (-26.5 ± 42.9 vs. +8.9 ± 17.9 mg/dL, P &lt; 0.001), VLDL-cholesterol concentrations (-5.3 ± 8.6 vs. +1.8 ± 3.6 mg/dL, P &lt; 0.001), total cholesterol (-4.2 ± 30.7 vs. +11.1 ± 28.4 mg/dL, P = 0.04) and total-/HDL-cholesterol ratio (-0.04 ± 0.6 vs. +0.3 ± 0.9, P = 0.04) compared with the placebo. Conclusion: Overall, the results of this study demonstrated that magnesium-zinc-calcium-vitamin D co-supplementation for 12 weeks among patients with PCOS had beneficial effects on insulin metabolism and markers of cardio-metabolic risk. 

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 A98 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 ,
v-Jun overrides the mitogen dependence of S-phase entry by deregulating retinoblastoma protein phosphorylation and E2F-pocket protein interactions as a consequence of enhanced cyclin E-cdk2 catalytic activity
Authors: E J Black
U Kruse
P K Vogt
N LaThangue
A MacLaren
W Clark
D A Gillespie
Journal: Molecular and Cellular Biology (2000)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: v-Jun; G(1) progression; Myc; E2F; E1A
Affiliations: <!--label omitted: 1-->Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, Garscube Estate, Bearsden, Glasgow G61 1BD, Scotland, United Kingdom

Abstract:  v-Jun accelerates G(1) progression and shares the capacity of the Myc, E2F, and E1A oncoproteins to sustain S-phase entry in the absence of mitogens; however, how it does so is unknown. To gain insight into the mechanism, we investigated how v-Jun affects mitogen-dependent processes which control the G(1)/S transition. We show that v-Jun enables cells to express cyclin A and cyclin A-cdk2 kinase activity in the absence of growth factors and that deregulation of cdk2 is required for S-phase entry. Cyclin A expression is repressed in quiescent cells by E2F acting in conjunction with its pocket protein partners Rb, p107, and p130; however, v-Jun overrides this control, causing phosphorylated Rb and proliferation-specific E2F-p107 complexes to persist after mitogen withdrawal. Dephosphorylation of Rb and destruction of cyclin A nevertheless occur normally at mitosis, indicating that v-Jun enables cells to rephosphorylate Rb and reaccumulate cyclin A without exogenous mitogenic stimulation each time the mitotic "clock" is reset. D-cyclin-cdk activity is required for Rb phosphorylation in v-Jun-transformed cells, since ectopic expression of the cdk4- and cdk6-specific inhibitor p16(INK4A) inhibits both DNA synthesis and cell proliferation. Despite this, v-Jun does not stimulate D-cyclin-cdk activity but does induce a marked deregulation of cyclin E-cdk2. In particular, hormonal activation of a conditional v-Jun-estrogen receptor fusion protein in quiescent, growth factor-deprived cells stimulates cyclin E-cdk2 activity and triggers Rb phosphorylation and DNA synthesis. Thus, v-Jun overrides the mitogen dependence of S-phase entry by deregulating Rb phosphorylation, E2F-pocket protein interactions, and ultimately cyclin A-cdk2 activity. This is the first report, however, that cyclin E-cdk2, rather than D-cyclin-cdk, is likely to be the critical Rb kinase target of v-Jun. 

Retracted: No

PubPeer comments:
 Figure 7b. cdk2 and p27 KIP1 panels do not look like they come from the same blot. ![file] ,