PReD-Bench/PRed-Bench huggingface dataset:
Curcumin suppresses proliferation and induces apoptosis in human biliary cancer cells through modulation of multiple cell signaling pathways
Authors: Yusuke Hiraku
Bokyung Sung
Somchai Pinlaor
Ji Hye Kim
Subash C Gupta
Porntip Pinlaor
Bharat B Aggarwal
Sopit Wongkham
Banchob Sripa
Suksanti Prakobwong
Journal: Carcinogenesis (2011)
Discipline: CLINICAL MEDICINE
Keywords: Cholangiocarcinoma; Curcumin; Apoptosis; Proliferation; Cell signaling pathways
Affiliations: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

Abstract:  Cholangiocarcinoma (CCA) is a tumor with poor prognosis that is resistant to all currently available treatments. Whether curcumin, a nutraceutical derived from turmeric (Curcuma longa), has potential therapeutic activity against human CCA was investigated using three CCA cell lines (KKU100, KKU-M156 and KKU-M213). Examination of mitochondrial dehydrogenase activity, phosphatidylserine externalization, esterase staining, caspase activation and poly-adenosine diphosphate ribose polymerase cleavage demonstrated that curcumin inhibited proliferation of and induced apoptosis in these biliary cancer cells. Colony-formation assay confirmed the growth-inhibitory effect of curcumin on CCA cells. When examined for the mechanism, curcumin was found to activate multiple cell signaling pathways in these cells. First, all CCA cells exhibited constitutively active nuclear factor (NF)-Œ∫B, and treatment with curcumin abolished this activation as indicated by DNA binding, nuclear translocation and p65 phosphorylation. Second, curcumin suppressed activation of signal transducer and activator of transcription-3 as indicated by decreased phosphorylation at both tyrosine(705) and serine(727) and inhibition of janus kinase-1 phosphorylation. Third, curcumin induced expression of peroxisome proliferator-activated receptor gamma. Fourth, curcumin upregulated death receptors, DR4 and DR5. Fifth, curcumin suppressed the Akt activation pathway. Sixth, curcumin inhibited expression of cell survival proteins such as B-cell lymphoma-2, B-cell leukemia protein xL, X-linked inhibitor of apoptosis protein, c-FLIP, cellular inhibitor of apoptosis protein (cIAP)-1, cIAP-2 and survivin and proteins linked to cell proliferation, such as cyclin D1 and c-Myc. Seventh, the growth inhibitory effect of curcumin was enhanced in the IŒ∫B kinase-deficient cells, the enzyme required for nuclear factor-kappaB activation. Overall, our results indicate that curcumin mediates its antiproliferative and apoptotic effects through activation of multiple cell signaling pathways, and thus, its activity against CCA should be further investigated. 

Retracted: No

PubPeer comments:
 Identified by another reader. ***  ,
Age-dependent down-regulation of DNA polymerase Œ¥1 in human lymphocytes
Authors: Jin-Ling Wang
Chen-Geng Liu
Pei-Chang Wang
Hong-Lin Guo
Journal: Molecular and Cellular Biochemistry (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Aging progression; DNA repair potential; DNA polymerase Œ¥; genome stability; DNA replication
Affiliations: Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China.

Abstract:  Aging progress and degeneracy of functional activity are mainly attributed to the decreased DNA repair potential. DNA polymerase (pol) Œ¥ activity plays an essential role in genome stability by virtue of its crucial DNA replication and repair capacity. To order to clarify the role of DNA pol Œ¥ in aging progression, we firstly examined the expressions of its catalytic subunit named DNA pol Œ¥1 in human lymphocytes at different age stages, respectively, and then observed the effect of diseases on DNA pol Œ¥1 in vivo and of nutriture on its expressions in 2BS cells in vitro. Blood samples from the healthy subjects and patients with diabetes mellitus and coronary heart disease were collected, respectively, for analysis of transcription and protein expressions of DNA pol Œ¥1 by RT-PCR and western blot. 2BS cells of PD30 and PD47 were incubated in both normal medium and other mediums of different nutritures for verifying the differential expressions of DNA pol Œ¥1. Results showed that the mRNA expression of DNA pol Œ¥1 decreased substantially with age and the protein levels were well consistent with gene levels. Furthermore, there were no significant differences in DNA pol Œ¥1 expressions between the groups of healthy individuals and the age matched patients. In addition, DNA pol Œ¥1 gene expression levels were not affected by nutritional status in vitro. Our findings collectively confirmed that the down-regulations of DNA pol Œ¥1 are age-related and have little bearing on diseases and nutritures. DNA pol Œ¥1 has great potential for a new biomarker of aging. 

Retracted: No

PubPeer comments:
 Figure 1A and 3A * Red boxes: GAPDH panels look more similar than expected Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today.  , 
 I sent a note today as well. ,
Scalar implicature is not a default process: An ERP study of the scalar implicature processing under the effect of focus factor
Authors: Han, Zongliang
Dai, Xiaoxiao
Zhao, Ming
Liu, Xiufeng
Dong, Shuang
Journal: Brain Research (2021)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords:  according to whether participants could stably determine that the underinformative sentences were inappropriate
Affiliations: Language and Cognition Laboratory, School of Humanities and Arts, China University of Mining and Technology, Xuzhou, Jiangsu Province, China. Electronic address: ., Language and Cognition Laboratory, School of Humanities and Arts, China University of Mining and Technology, Xuzhou, Jiangsu Province, China., Department of Preschool and Special Education, Xuzhou Kindergarten Teachers College, Xuzhou, Jiangsu Province, China.

Abstract:  and a P200 effect and a sustained positivity effect according to the sentence-final words. In contrast

Retracted: No

PubPeer comments:
Xiufeng Liu
Zongliang Han
Xiaoxiao Dai
Shuang Dong
Ming Zhao
BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha
Authors: Peter Thielen
Fernanda Lisbona
Diego Rojas-Rivera
Alvaro Glavic
Christina Kress
Jonathan H Lin
John C Reed
Fabio Martinon
Laurie H Glimcher
Sebastian Zamorano
Peter Walter
Claudio Hetz
Derrick Todd
Journal: Molecular Cell (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Endoplasmic reticulum stress; Unfolded protein response; Bax inhibitor-1; IRE1alpha; X-box-binding protein-1
Affiliations: Institute of Biomedical Sciences, FONDAP Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile.

Abstract:  Adaptation to endoplasmic reticulum (ER) stress depends on the activation of an integrated signal transduction pathway known as the unfolded protein response (UPR). Bax inhibitor-1 (BI-1) is an evolutionarily conserved ER-resident protein that suppresses cell death. Here we have investigated the role of BI-1 in the UPR. BI-1 expression suppressed IRE1alpha activity in fly and mouse models of ER stress. BI-1-deficient cells displayed hyperactivation of the ER stress sensor IRE1alpha, leading to increased levels of its downstream target X-box-binding protein-1 (XBP-1) and upregulation of UPR target genes. This phenotype was associated with the formation of a stable protein complex between BI-1 and IRE1alpha, decreasing its ribonuclease activity. Finally, BI-1 deficiency increased the secretory activity of primary B cells, a phenomenon regulated by XBP-1. Our results suggest a role for BI-1 in early adaptive responses against ER stress that contrasts with its known downstream function in apoptosis. 

Retracted: No

PubPeer comments:
 Some of the gels in the supplement of this paper are spliced without acknowledgement. Not only that but the spliced image elements are still there in the pdf file. With the help of Inkscape, we can edit the pdf page. Here we go for Sup. Fig. 4F,H. Note that in one sF4H gel, two lanes are spliced in. In the accompanying gel only one lane. Does not compute.  , 
 Another surreptitiously assembled gel slice appears in Fig. s1B. Left image showing selection in Preview. Right side showing deconstruction in Inkscape.  ,
Effects of Coenzyme Q10 Supplementation on Gene Expressions Related to Insulin, Lipid, and Inflammation Pathways in Patients With Diabetic Nephropathy
Authors: Esmat Aghadavod
Alireza Soleimani
Zatollah Asemi
Gholamali Hamidi
Akbar Heidari
Journal: Iranian journal of kidney diseases (2018)
Discipline: CLINICAL MEDICINE
Keywords: Coenzyme Q10; gene expression; insulin; lipid; inflammation
Affiliations: Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran. .

Abstract:  Introduction: Data on the effects of coenzyme Q10 (CQ10) on gene expression related to insulin, lipid, and inflammation in patients with diabetic nephropathy (DN) are scarce. This study aimed to determine the effects of CQ10 supplementation on gene expression related to insulin, lipid, and inflammation pathways in patients with DN. Materials and methods: Forty patients with DN, aged 40 to 85 years old, were randomly assigned into 2 groups to receive either 100 mg/d of CQ10 supplements (n = 20) or placebo (n = 20), for 12 weeks. Gene expression related to signaling pathway of insulin, lipid, and inflammation were determined in blood samples using a reverse transcriptase polymerase chain reaction method. Results: Quantitative results of reverse transcriptase polymerase chain reaction demonstrated that compared with the placebo, CQ10 administration upregulated gene expression of peroxisome proliferator-activated receptor-Œ≥ (P = .02) in peripheral blood mononuclear cells of the patients with DN. In addition, compared with the placebo, CQ10 supplementation downregulated gene expression of interleukin-1 (P = .003) and tumor necrosis factor-Œ± (P = .02). No significant effects were observed on gene expression of oxidized low-density lipoprotein, lipoprotein(a), glucose transporter-1, transforming growth factor-Œ≤ in the CQ10 group. Conclusions: Overall, CQ10 supplementation for 12 weeks in DN patients significantly improved gene expression of peroxisome proliferator-activated receptor-Œ≥, interleukin-1, and tumor necrosis factor-Œ±. 

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 A134 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. 18 publications have an expression of concern, and 6 have been retracted. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
Mechanisms of antimicrobial and antiendotoxin activities of a triazine‚Äêbased amphipathic polymer
Authors: Song Yub Shin
Eun Young Kim
S Dinesh Kumar
Jeong Kyu Bang
Journal: Biotechnology and Bioengineering (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: antiendotoxic activity; antimicrobial peptides; drug resistance; protease stability; triazine-based amphipathic polymer.
Affiliations: Department of Biomedical Science, Graduate SchoolChosun UniversityGwangju Republic of Korea, Division of Magnetic ResonanceKorea Basic Science Institute (KBSI)Ochang Republic of Korea, Department of Cellular &amp; Molecular Medicine, School of MedicineChosun UniversityGwangju Republic of Korea

Abstract:  TZP4 is a triazine-based amphipathic polymer designed to mimic the amphipathic structure found in antimicrobial peptides. TZP4 showed potent antimicrobial activity comparable to melittin against antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. TZP4 showed high resistance to proteolytic degradation and low tendency to develop drug resistance. The results from membrane depolarization, SYTOX Green uptake, flow cytometry, and gel retardation revealed that the mechanism of antimicrobial action of TZP4 involved an intracellular target rather than the bacterial cell membrane. Furthermore, TZP4 suppressed the messenger RNA levels of inducible nitric oxide synthase and tumor necrosis factor-Œ± (TNF-Œ±) and inhibited the release of nitric oxide and TNF-Œ± in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. BODIPY-TR-cadaverine displacement and dissociation of fluorescein isothiocyanate (FITC)-labeled LPS assays revealed that TZP4 strongly bound to LPS and disaggregated the LPS oligomers. Flow cytometric analysis demonstrated that TZP4 inhibits the binding of FITC-conjugated LPS to RAW264.7 cells. These observations indicate that TZP4 may exert its antiendotoxic activity by directly binding with LPS and inhibiting the interaction between LPS and CD14+ cells. Collectively, TZP4 is a promising drug candidate for the treatment of endotoxic shock and sepsis caused by Gram-negative bacterial infections. 

Retracted: No

PubPeer comments:
 Issues with flow cytometry in Fig 6A, lower two panels. Despite different treatment groups (TZP4 vs Buforin-2), the traces overlay near perfectly with each other. Similar issue with Figure 9B with the red dotted lines representing untreated cells while green is FITC-LPS. In this case, I would guess the authors are purposefully displaying the same data twice - however the percentage of cells binding FITC-LPS for the controls are slightly different (by 0.3%) implying two different control experiments.   ,
WITHDRAWN: Therapeutic potential of metabotropic glutamate receptor 4-positive allosteric modulator TAS-4 in rodent models of movement disorders
Authors: Chandrashekhar Devidas Upasani
Aakanksha Dube
Sumit Chaudhary
Tanaji Mengawade
Journal: Journal of the Neurological Sciences (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: 6-OHDA (6-hydroxydopamine); Abnormal involuntary movements; Metabotropic glutamate receptor 4-positive allosteric modulator (mGluR4 PAM); Parkinson's disease (PD); TAS-4
Affiliations: Department of Pharmacology, Faculty of Pharmacy, SNJB's Shriman Sureshdada Jain College of Pharmacy, Jain Gurukul, Chandwad, Nashik, India., Department of Pharmacology, Faculty of Pharmacy, SNJB's Shriman Sureshdada Jain College of Pharmacy, Jain Gurukul, Chandwad, Nashik, India. Electronic address: .

Abstract:  Parkinson's disease (PD) is a very serious neurological disorder, and current methods of treatment fail to achieve long-term control. Previous studies suggest that stimulation of the metabotropic glutamate receptor 4 (mGluR4) represents a promising new approach to the symptomatic treatment of Parkinson's disease (PD). Preclinical models using both agonists and positive allosteric modulators of mGluR4 have demonstrated the potential for this receptor for the treatment of PD. In the present study, we describe the pharmacological characterization of an mGluR4 PAM, N-(2, 4-dichlorophenyl) pyridine-2-carboxamide (TAS-4), in several rodent PD models. TAS-4 is a potent and selective mGluR4 PAM of the human mGluR4 receptor (EC50- 287.8nM). TAS-4 showed efficacy alone or when administered in combination with l-DOPA. When administered alone, TAS-4 exhibited efficacy in reversing haloperidol-induced catalepsy. In addition, acute TAS-4 dose-dependently potentiated contralateral turning behavior induced by a threshold dose of l-3,4-dihydroxyphenylalanine (l-DOPA, 4mg/kg i.p.), a classical test for antiparkinson drug screening. Subchronic (28days, twice a day) TAS-4 (10mg/kg i.p.)+l-DOPA (4mg/kg i.p.) did not induce sensitization to turning behavior or abnormal involuntary movements during the course of treatment. Moreover, subchronic administration of a fully effective dose of l-DOPA (8mg/kg i.p.) significantly induces sensitization to turning behavior or abnormal involuntary movements. Results showed that TAS-4, in association with a low dose of l-DOPA, displayed antiparkinsonian activity similar to that produced by a full dose of l-DOPA without exacerbating abnormal motor side effects. 

Retracted: No

PubPeer comments:
  This article has been withdrawn at the request of the author(s) and or editor. The Publisher apologizes for any inconvenience this may cause. ,
MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway
Authors: S Yang
J-H Fu
D-Q Lu
C-J Nan
C-C Zhou
S Li
H-Q Mu
Journal: European Review for Medical and Pharmacological Sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: PI3K/AKT/mTOR signaling pathway; tumorigenesis; renal cancer; MiR-182; mTOR expression
Affiliations: Department of Urology, Dongyang People's Hospital, Dongyang, Zhejiang, China. .

Abstract:  Objective: PI3K/AKT/mTOR signaling pathway plays a crucial role in tumorigenesis and development. It was shown that mTOR overexpression was associated with the pathogenesis of renal cancer. Down-regulation of MiR-182 was found in renal carcinoma tissue. This study thus aims to investigate the influence of miR-182 in regulating mTOR expression and renal carcinoma cell proliferation, invasion, and apoptosis. Patients and methods: The targeted regulatory relationship between miR-182 and mTOR was tested by dual luciferase assay. Renal carcinoma tissue and benign renal tissue were collected to detect miR-182 and mTOR expressions. MiR-182, mTOR, p-mTOR, and Survivin levels were compared between HK-2 and A498 cells. Renal carcinoma A498 cells were divided into four groups, including miR-NC, anti-miR-182 mimic, si-NC, and si-mTOR groups. Cell apoptosis and proliferation were evaluated by flow cytometry. Cell invasion was determined by transwell assay. Results: Bioinformatics analysis revealed the complementary relationship between miR-182 and the 3'-UTR of mTOR mRNA. The level of miR-182 was significantly reduced, while mTOR expression was upregulated in renal carcinoma tissue compared with that in benign lesion, which was associated with TNM stage. MiR-182 expression was markedly declined, whereas mTOR, p-mTOR, and Survivin levels were apparently upregulated in A498 cells compared with that in HK-2 cells. The treatment of miR-182 mimic or si-mTOR transfection significantly downregulated mTOR, p-mTOR, and Survivin expressions, restrained cell proliferation and invasion, and enhanced cell apoptosis. Conclusions: The decreasing level of miR-182 plays a role in enhancing mTOR expression and promoting renal carcinoma pathogenesis. Overexpression of miR-182 inhibited mTOR expression and weakened cell proliferation and invasion, which provides leads to the future therapy of renal cancer. 

Retracted: Yes

PubPeer comments:
 Theu00a0entireu00a0section on coherence domains has been copy pastedu00a0from this paper;-https: www.semanticscholar.org paper Quantum-Coherent-Water-%2C-Non-thermal-EMF-Effects-%2C-Ho 071e91e34a1245ee505888d9bca715d7e8facdde u00a0 A few tweaks to the wordings have been made to avoid suspicion. Similarly many parts of the paper are just pasted from other articles without appropriate citations. ,
The DNA Damage Transducer RNF8 Facilitates Cancer Chemoresistance and Progression through Twist Activation
Authors: Hong-Jen Lee
Patricia A Thompson
Diane Ruan
Michael A Frohman
Chien-Feng Li
Chia-Hsin Chan
Scott Powers
Journal: Molecular cell (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Twist; K63-linked ubiquitination; RNF8; E3 ligase; activation
Affiliations: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA., National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan; Department of Pathology, Chi-Mei Foundational Medical Center, Tainan 710, Taiwan., Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA., Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA; Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA., Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA., Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: .

Abstract:  Twist has been shown to cause treatment failure, cancer progression, and cancer-related death. However, strategies that directly target Twist are not yet conceivable. Here we reveal that K63-linked ubiquitination is a crucial regulatory mechanism for Twist activation. Through an E3 ligase screen and biochemical studies, we unexpectedly identified that RNF8 functions as a direct Twist activator by triggering K63-linked ubiquitination of Twist. RNF8-promoted Twist ubiquitination is required for Twist localization to the nucleus for subsequent EMT and CSC functions, thereby conferring chemoresistance. Our histological analyses showed that RNF8 expression is upregulated and correlated with disease progression, EMT features, and poor patient survival in breast cancer. Moreover, RNF8 regulates cancer cell migration and invasion and cancer metastasis, recapitulating the effect of Twist. Together, our findings reveal a previously unrecognized tumor-promoting function of RNF8 and provide evidence that targeting RNF8 is an appealing strategy to tackle tumor aggressiveness and treatment resistance. 

Retracted: No

PubPeer comments:
 Figure 1b. https: imgur.com MkcOIMg , 
 Figure 5d. https: imgur.com GPaWVxw ,
Spectroscopic Studies on Photoelectron Transfer from 2-(furan-2-yl)-1-phenyl-1H-phenanthro[9,10-d]imidazole to ZnO, Cu‚Äîdoped ZnO and Ag‚Äîdoped ZnO
Authors: J Jayabharathi
V Thanikachalam
A Arunpandiyan
P Ramanathan
C Karunakaran
Journal: Journal of fluorescence (2014)
Discipline: CHEMISTRY
Keywords: FPI; fluorescent sensor; nanoparticulate ZnO; photoelectron transfer; PET
Affiliations: Department of Chemistry, Annamalai University, Annamalainagar, 608 002, Tamilnadu, India.

Abstract:  The 2-(furan-2-yl)-1-phenyl-1H-phenanthro[9,10-d]imidazole [FPI] has been designed and synthesized as fluorescent sensor for nanoparticulate ZnO. The present work investigates the photoelectron transfer (PET) from FPI to ZnO, Cu-doped ZnO and Ag- doped ZnO nanoparticles using electronic and life time spectral measurements. Broad absorption along with red shift indicates the formation of charge-transfer complex [FPI-Nanoparticles]. The photophysical studies indicate lowering of HOMO and LUMO energy levels of FPI on adsorption on ZnO due to FPI- ZnO interaction. The obtained binding constant implies that the binding of FPI with nanoparticles was influenced by the surface modification of ZnO nanoparticles with Cu and Ag. 

Retracted: No

PubPeer comments:
 Figure 4 shows fluorescence graphs obtained with mixing nanoparticles doped with different compounds. Although the black graph is probably the control in each of these 3 panels, some other graphs, representing different nanoparticles, appear to look unexpectedly similar. Some examples: * The red line in FPI-ZnO panel looks similar to the green line in the FPI-Ag-doped panel * The green line in the FPI-ZnO panel looks similar to the blue line in the FPI-Ag-doped panel and to the turquise line in the FPI-Cu-doped ZnO panel * The blue line in the FPI-ZnO panel looks similar to the turquoise line in the FPI-Ag-doped panel It is almost as if some lines have been removed and others have been added, while recoloring the lines. Could the authors please clarify if these graphs are supposed to look this similar?  ,
Arginyltransferase knockdown attenuates cardiac hypertrophy and fibrosis through TAK1-JNK1/2 pathway
Authors: Kanika Singh
Ankit Gupta
Ashish Sarkar
Santanu Rana
Sagartirtha Sarkar
Ishita Gupta
Sameena Khan
Journal: Scientific Reports (2020)
Discipline: Multidisciplinary
Keywords: Myocardial hypertrophy; Arginyltransferase; ATE1; cardiac fibrosis; apoptosis
Affiliations: Drug Discovery Research Centre, Translational Health Science and Technology Institute, Faridabad, Haryana, India., Structural Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, Delhi, India., Department of Zoology, University of Calcutta, Kolkata, India., Drug Discovery Research Centre, Translational Health Science and Technology Institute, Faridabad, Haryana, India. .

Abstract:  Myocardial hypertrophy, an inflammatory condition of cardiac muscles is a maladaptive response of the heart to biomechanical stress, hemodynamic or neurohormonal stimuli. Previous studies indicated that knockout of Arginyltransferase (ATE1) gene in mice and embryos leads to contractile dysfunction, defective cardiovascular development, and impaired angiogenesis. Here we found that in adult rat model, downregulation of ATE1 mitigates cardiac hypertrophic, cardiac fibrosis as well as apoptosis responses in the presence of cardiac stress i.e. renal artery ligation. On contrary, in wild type cells responding to renal artery ligation, there is an increase of cellular ATE1 protein level. Further, we have shown the cardioprotective role of ATE1 silencing is mediated by the interruption of TAK1 activity-dependent JNK1/2 signaling pathway. We propose that ATE1 knockdown in presence of cardiac stress performs a cardioprotective action and the inhibition of its activity may provide a novel approach for the treatment of cardiac hypertrophy. 

Retracted: No

PubPeer comments:
 Fig 6 GAPDH is duplicated. Quantification is a concern because of high intensity in the first lane. Can authors clarify?  Also, which lane is your sham operated rat in Fig C and D? , 
 Fig 5 D and E Again, GAPDH is duplicated.  Can authors explain why p-ERK 1 2 and ERK 1 2 are looked similar? It is generally noted that ERK 1 2 show two bands at 44 42 kDa region. Here, one band is always missing. Is it a mistake? , 
 17 January 2020 (predating the concerns above) This Article contains errors. In Figure 5A, the orientation of GADPH blot for P-TAK1 is incorrect. In addition, width of Figure 5B has been adjusted. The correct Figure 5 appears below, as Figure 1.  ,
Bilateral downregulation of Nav1.8 in dorsal root ganglia of rats with bone cancer pain induced by inoculation with Walker 256 breast tumor cells
Authors: Zhi-Jie Lu
Zhang-Xiang Huang
Cheng He
Xiao-Fei Gao
Wei-Feng Yu
Jing-Xiang Wu
Xue-Rong Miao
Xiao-Qing Li
Journal: BMC Cancer (2010)
Discipline: CLINICAL MEDICINE
Keywords: cancer-induced bone pain; Nav1.8; nociceptor function; rat model; Walker 256 cells
Affiliations: Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Abstract:  Background: Rapid and effective treatment of cancer-induced bone pain remains a clinical challenge and patients with bone metastasis are more likely to experience severe pain. The voltage-gated sodium channel Nav1.8 plays a critical role in many aspects of nociceptor function. Therefore, we characterized a rat model of cancer pain and investigated the potential role of Nav1.8. Methods: Adult female Wistar rats were used for the study. Cancer pain was induced by inoculation of Walker 256 breast carcinosarcoma cells into the tibia. After surgery, mechanical and thermal hyperalgesia and ambulation scores were evaluated to identify pain-related behavior. We used real-time RT-PCR to determine Nav1.8 mRNA expression in bilateral L4/L5 dorsal root ganglia (DRG) at 16-19 days after surgery. Western blotting and immunofluorescence were used to compare the expression and distribution of Nav1.8 in L4/L5 DRG between tumor-bearing and sham rats. Antisense oligodeoxynucleotides (ODNs) against Nav1.8 were administered intrathecally at 14-16 days after surgery to knock down Nav1.8 protein expression and changes in pain-related behavior were observed. Results: Tumor-bearing rats exhibited mechanical hyperalgesia and ambulatory-evoked pain from day 7 after inoculation of Walker 256 cells. In the advanced stage of cancer pain (days 16-19 after surgery), normalized Nav1.8 mRNA levels assessed by real-time RT-PCR were significantly lower in ipsilateral L4/L5 DRG of tumor-bearing rats compared with the sham group. Western-blot showed that the total expression of Nav1.8 protein significantly decreased bilaterally in DRG of tumor-bearing rats. Furthermore, as revealed by immunofluorescence, only the expression of Nav1.8 protein in small neurons down regulated significantly in bilateral DRG of cancer pain rats. After administration of antisense ODNs against Nav1.8, Nav1.8 protein expression decreased significantly and tumor-bearing rats showed alleviated mechanical hyperalgesia and ambulatory-evoked pain. Conclusions: These findings suggest that Nav1.8 plays a role in the development and maintenance of bone cancer pain. 

Retracted: No

PubPeer comments:
 image duplication, reversed  Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Association between circulating 25-hydroxyvitamin D levels and psoriasis, and correlation with disease severity: a meta-analysis
Authors: G G Song
Y H Lee
Journal: Clinical and Experimental Dermatology (2018)
Discipline: CLINICAL MEDICINE
Keywords: Psoriasis; 25-hydroxy vitamin D; Meta-analysis; Circulating levels; Severity
Affiliations: Division of Rheumatology; Department of Internal Medicine; Korea University College of Medicine; Seoul Korea

Abstract:  Background: Psoriasis is a chronic, autoimmune, inflammatory skin disorder. 25-hydroxy vitamin D [25(OH)D] deficiency may contribute to the pathogenesis of psoriasis through reduction in antiproliferative, anti-inflammatory and antiangiogenic activities. Aim: To evaluate the relationship between circulating 25(OH)D levels and psoriasis, and to determine the correlation between serum/plasma 25(OH)D levels and psoriasis severity. Methods: We performed a meta-analysis to compare serum/plasma 25(OH)D levels between patients with psoriasis and healthy controls (HCs), and to determine the correlation coefficients between circulating 25(OH)D levels and psoriasis severity as assessed by Psoriasis Area and Severity Index (PASI). Results: Ten articles with a total of 571 patients with psoriasis and 496 HCs were included. The 25(OH)D level was significantly lower in the psoriasis group than in the HC group. Subgroup analysis by sample size revealed a significantly lower level of 25(OH)D in the psoriasis group for large (N &gt; 80) but not for small (N &lt; 80) sample sizes. Stratification by adjustment for age and/or sex or sample type revealed a significantly lower 25(OH)D level in the psoriasis group after adjustment for serum but not after nonadjustment for plasma. Meta-analysis of the correlation coefficients revealed a small but statistically significant positive correlation between circulating 25(OH)D levels and PASI. Conclusions: This meta-analysis demonstrated that circulating 25(OH)D levels are lower in patients with psoriasis, and that a small but statistically significant negative correlation exists between 25(OH)D levels and psoriasis severity. 

Retracted: No

PubPeer comments:
 The abstract contains contradictory statements regarding the correlation between 25(OH)D levels and psoriasis severity (see yellow marking). The same happens in the Results section of the full text (2nd picture).   , 
 One more comment regards marking of the Horizontal axis of the forest plots. Based on the results the Psoriasis and Control markings must have been misplaced.  ,
Xiao Tan He Wei Decoction reverses MNNG-induced precancerous lesions of gastric carcinoma in vivo and vitro: Regulation of apoptosis through NF-Œ∫B pathway
Authors: Dazhi Sun
Jingyu Xu
Wei Shen
Xuan Zhang
Ye Lu
LiJuan Xiu
Xiaowei Wang
Yongjin Li
Bei Pei
Xuan Liu
XiaoQiang Yue
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Chinese traditional medicine; Gastric cancer; Gastric precancerous lesions; NF-kB; Xian Tan He Wei Decoction.
Affiliations: Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China., Changjiang Road Community Health Service Center, NO. 639, Tonghe Road, Zhangmiao Street, Baoshan Qv, Shanghai, 200431, China., Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China. Electronic address: .

Abstract:  In recent years, Chinese medicine has played an important role in the prognosis of gastric cancer. Precancerous lesions of gastric carcinoma (PLGC) is a class of gastric cancer which is closely related to the gastric mucosal pathology changes in the role of carcinogenic incentives, and plays key role in the progression of normal gastric mucosal cells into gastric cancerous cells. In current experiment, we explore the relationship between Chinese traditional medicine (Xiao Tan He Wei Decoction) and gastric cancer in the PLGC rat animal models and epithelial-mesenchymal transitioned GES-1 cells which were induced useing 1- Methyl-3-nitro-1-nitrosoguanidine (MNNG). PLGC rat model showed significant deterioration in the gastric mucosa with terrible growth rate in body weight and more atypical hyperplasia in gastric mucosa. MC cells, MNNG induced GES-1 cells which epithelial- mesenchymal-transition (EMT)-related proteins have a great change compare with normal GES-1 cells. The cells had characteristics of malignant cells including proliferation, invasion and metastasis ability. Our research founds that Xiao Tan He Wei Decoction could inhibit cell proliferation and increased apoptosis by increase the level of pro-apoptotic proteins like Bax and caspase-3 and decreased the level of anti-apoptotic protein Bcl-2, block the cells in G0/G1 phase simultaneously. Furthermore, Xiao Tan He Wei Decoction could inhibit nuclear factor kappa-light-chain-enhancer (NF-kB) activity and inhibit its transfer from the cytoplasm to the nucleus. However, when we incubated with NF-Œ∫B activator PMA, the effect of Xiao Tan He Wei Decoction was reversed. These results suggested that Xiao Tan He Wei Decoction could be used as a method for the treatment of gastric precancerous lesions, and possibly provide a theoretical basis for the clinical treatment of gastric cancer and gastric precancerous lesions. 

Retracted: No

PubPeer comments:
 A TCM paper with questionable data? No surprise. Figure 3A (red boxes) and 4B (green boxes). While the authors are looking for original data, would they be able to upload the original uncropped Western blots as well? ***  ***  ,
The sulfated laminarin triggers a stress transcriptome before priming the SA- and ROS-dependent defenses during grapevine's induced resistance against Plasmopara viticola
Authors: Victor Flors
David Wendehenne
Sophie Trouvelot
Patrick Frettinger
Jani Kelloniemi
Adrien Gauthier
Jean-Marie Joubert
Alberto Ferrarini
Benoit Poinssot
Massimo Delledonne
Xavier Daire
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Grapevine; Pathogens; Resistance; Elicitors; Laminarin
Affiliations: UMR 1347 Agro√©cologie, Universit√© de Bourgogne, Dijon, France., UMR 1347 Agro√©cologie, INRA, Dijon, France., Laboratoires Go√´mar, Saint Malo, France., Dipartimento di Biotecnologie, Universit√† degli Studi di Verona, Verona, Italy., Plant Physiology Section, University of Jaume I, Castell√≥n, Spain.

Abstract:  Grapevine (Vitis vinifera) is susceptible to many pathogens which cause significant losses to viticulture worldwide. Chemical control is available, but agro-ecological concerns have raised interest in alternative methods, especially in triggering plant immunity by elicitor treatments. The Œ≤-glucan laminarin (Lam) and its sulfated derivative (PS3) have been previously demonstrated to induce resistance in grapevine against downy mildew (Plasmopara viticola). However, if Lam elicits classical grapevine defenses such as oxidative burst, pathogenesis-related (PR)-proteins and phytoalexin production, PS3 triggered grapevine resistance via a poorly understood priming phenomenon. The aim of this study was to identify the molecular mechanisms of the PS3-induced resistance. For this purpose we studied i) the signaling events and transcriptome reprogramming triggered by PS3 treatment on uninfected grapevine, ii) grapevine immune responses primed by PS3 during P. viticola infection. Our results showed that i) PS3 was unable to elicit reactive oxygen species (ROS) production, cytosolic Ca(2+) concentration variations, mitogen-activated protein kinase (MAPK) activation but triggered a long lasting plasma membrane depolarization in grapevine cells, ii) PS3 and Lam shared a common stress-responsive transcriptome profile that partly overlapped the salicylate- (SA) and jasmonate-(JA)-dependent ones. After P. viticola inoculation, PS3 specifically primed the SA- and ROS-dependent defense pathways leading to grapevine induced resistance against this biotroph. Interestingly pharmacological approaches suggested that the plasma membrane depolarization and the downstream ROS production are key events of the PS3-induced resistance. 

Retracted: No

PubPeer comments:
 Corrected in March 2018. The correction reads:  *The Adj + Gli panel in Fig 5C incorrectly appears as a duplicate of the Adj + DPI panel in Figure 4D. This error arose during the construction of Fig 5. Please see the corrected Fig 5 here. * Here is the duplication between Figure 4 and 5, as reported in October 2015.  ,
Consumption of synbiotic bread decreases triacylglycerol and VLDL levels while increasing HDL levels in serum from patients with type-2 diabetes
Authors: Navid Mazroii
Yaser Ghandi
Maryam Tajabadi-Ebrahimi
Zatollah Asemi
Fatemeh Abedi
Haleh Hadaegh
Hossein Shakeri
Journal: Lipids (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: synbiotic bread; blood lipid profiles; type 2 diabetes mellitus; probiotic; Lactobacillus sporogenes
Affiliations: Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.

Abstract:  To our knowledge, no reports are available indicating the favorable effects of synbiotic bread consumption on blood lipid profiles among patients with type 2 diabetes mellitus (T2DM). This study was conducted to evaluate the effects of the daily consumption of synbiotic bread on blood lipid profiles of patients with T2DM. This randomized double-blinded controlled clinical trial was performed with 78 diabetic patients, aged 35-70 years. After a 2-week run-in period, subjects were randomly assigned to consume either synbiotic (n = 26), probiotic (n = 26) or control bread (n = 26) for 8 weeks. The synbiotic bread contained viable and heat-resistant probiotic Lactobacillus sporogenes (1 √ó 10(8) CFU) and 0.07 g inulin (HPX) as prebiotic per 1 g. The probiotic bread contained L. sporogenes (1 √ó 10(8) CFU) per 1 g. Patients were asked to consume the synbiotic, probiotic and control breads three times a day in a 40 g package for a total of 120 g/day. Biochemical measurements including blood lipid profiles were conducted before and after 8 weeks of intervention. Consumption of the synbiotic bread, compared to the probiotic and control breads, led to a significant decrease in serum TAG (P = 0.005), VLDL-C (P = 0.005), TC/HDL-C (P = 0.002) and a significant increase in serum HDL-C levels (P = 0.01). No significant effect of synbiotic bread consumption on FPG, TC, LDL-C and non-HDL-C levels was seen compared to the probiotic and control breads (P &gt; 0.05). Trial registry code: http://www.irct.ir IRCT201311215623N13. 

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 A19 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 ,
Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105
Authors: Danying Chen
Zhiqin Li
Jingbo Zhang
Hong-Bing Shu
Journal: Biochemical and Biophysical Research Communications (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Casper; c-FLIP; apoptosis; NF-kappaB; p105
Affiliations: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 10005, China.

Abstract:  Casper/c-FLIP is a caspase-8-related molecule critically involved in regulation of death receptor-induced apoptosis. It has been shown that Casper can either promote or antagonize apoptosis and can activate the transcription factor NF-kappaB. The exact functions of Casper are controversial. To further understand how Casper signals, we searched Casper-interacting proteins by yeast two-hybrid screening. This effort identified NF-kappaB1 (p105), an atypical IkappaB molecule and the precursor of NF-kappaB subunit p50. Co-immunoprecipitation experiments indicated that Casper interacted with p105 in 293 cells and this interaction was mediated through the C-terminal IkappaB-like domain (IkappaBgamma). Overexpression of p105 and IkappaBgamma inhibited Casper-induced NF-kappaB activation and potentiated Casper-induced apoptosis. Furthermore, Casper and its C-terminal caspase-like domain inhibited p105 processing into p50. Our findings suggest that p105 is involved in Casper-mediated regulation of apoptosis and NF-kappaB activation. 

Retracted: No

PubPeer comments:
 Fig. 1B tsNSCs 3d shares a portion with Fig. 1A P0 day 5 of [another paper Xiong, et al. 2018] from the same group. I put the two images side-by-side with dimension adjusted to match their scale bars, demonstrating the apparent manipulation of the magnification after cropping a piece of the image to use for a different experiment.  ,
Cooperative Subnetworks of Molecularly Similar Interneurons in Mouse Neocortex
Authors: Rafael Yuste
Jesse Jackson
Mahesh M Karnani
Inbal Ayzenshtat
William G Snider
Jason Tucciarone
Kasra Manoocheri
Journal: Neuron (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: neocortical neurons; brain computations; excitatory principal cells; inhibitory interneurons; somatostatin
Affiliations: Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: ., Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA., Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; MSTP/Neuroscience Graduate Program, Stony Brook University, Stony Brook, NY 11790, USA.

Abstract:  Simultaneous co-activation of neocortical neurons is likely critical for brain computations ranging from perception and motor control to memory and cognition. While co-activation of excitatory principal cells (PCs) during ongoing activity has been extensively studied, that of inhibitory interneurons (INs) has received little attention. Here, we show in vivo and in vitro that members of two non-overlapping neocortical IN populations, expressing somatostatin (SOM) or vasoactive intestinal peptide (VIP), are active as populations rather than individually. We demonstrate a variety of synergistic mechanisms, involving population-specific local excitation, GABAergic disinhibition and excitation through electrical coupling, which likely underlie IN population co-activity. Firing of a few SOM or VIP INs recruits additional members within the cell type via GABAergic and cholinergic mechanisms, thereby amplifying the output of the population as a whole. Our data suggest that IN populations work as cooperative units, thus generating an amplifying nonlinearity in their circuit output. 

Retracted: No

PubPeer comments:
 VIP and SOM interneurons in V1 and S1 form cooperative within-class teams: the more a few nearby SOM neurons fire, the more other nearby SOMs will fire. Same for VIPs. Mechanisms are broadly the same for both populations: sparse and weak electrical coupling through gap-junctions, and disinhibition of team members through the strong mutual inhibition between VIPs and SOMs. Also, VIP cooperativity was reduced by the nAChR blocker mecamylamine. Also, SOMs and VIPs are driven by mostly non-overlapping nearby pyramidals, and at different synaptic dynamics - so their input from nearby pyramidal cell ensembles can drive VIP and SOM teams at different times, and team members at the same time. The limitation of this study is the low number of neurons recorded simultaneously - in slice recordings only 4 and in vivo only up to 19 VIPs or 12 SOMs in a square field of view of approximately 300um on each side, and in just one plane, meaning many nearby team members were not recorded. So there is not enough information to say how many more than 4-19 neurons are in a team. This interesting experiment would be quite simple with a 3d scanning 2p rig which are common these days. ,
Network pharmacology-based analysis of the role of traditional Chinese herbal medicines in the treatment of COVID-19
Authors: Junwu Wang
Haitao Shen
Shengwei Yu
Journal: Annals of Palliative Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: COVID-19; Novel coronavirus; network pharmacology; traditional Chinese herbal medicines (traditional CHM).
Affiliations: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China., Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China. .

Abstract:  Background: The novel coronavirus named COVID-19, which originated in Wuhan, China, has spread to many countries around the world. Currently, no effective medical treatment exists to combat this disease. Traditional Chinese herbal medicines (CHM) have unique roles in the treatment of viral infections. In this article we analyzed the effectiveness and possible molecular mechanisms of CHM formulas for the prevention of COVID-19. Methods: The active ingredients and action targets of CHM formulas were obtained from the TCMSP database. Genes related to severe acute respiratory syndromes (SARS) and Middle East respiratory syndrome (MERS) were queried on the GeneCards database. The action mechanisms of these genes were predicted using a Gene Ontology (GO)-based functional enrichment and annotation tool and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: CHM formulas played a positive role in preventing COVID-19 and warrant further application. Conclusions: Our research provides new evidence to support the possible value of CHM formulas for the prevention of COVID-19. However, further clinical studies with large sample sizes are required to verify their effectiveness. 

Retracted: No

PubPeer comments:
 Traditional chinese medicine (TCM) or Chinese Herbal Medicine (CHM) which it s termed here, is based on pseudoscience.  In summary, a network pharmacology method was used in our current study to investigate the effectiveness of CHM for COVID-19. Although the results were promising, more clinical trials are warranted for our findings to be confirmed. No, you need to prove that CHM actually works by solid scientifically experiments with proper controls, before any clinical studies. Otherwise it is wasted time and resources and may set patients at risk. ,