PReD-Bench/PRed-Bench huggingface dataset:
The Noonan syndrome-associated D61G variant of the protein tyrosine phosphatase SHP2 prevents synaptic down-scaling
Authors: Wen Lu
Fusheng Xue
Bin Zhang
Yifei Luan
Heng Ai
Journal: Journal of Biological Chemistry (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: SHP2; Src homology 2 domain (SH2 domain); phosphatase; phosphorylation; phosphotyrosine signaling
Affiliations: Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, China., Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, China., Department of Physiology, Hangzhou Medical College, Hangzhou, Zhejiang, China., Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Life Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China., Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Life Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China .

Abstract:  Homeostatic scaling of the synapse, such as synaptic down-scaling, has been proposed to offset deleterious effects induced by sustained synaptic strength enhancement. Proper function and subcellular distribution of Src homology 2 domain-containing nonreceptor protein tyrosine phosphatase (SHP2) are required for synaptic plasticity. However, the role of SHP2 in synaptic down-scaling remains largely unknown. Here, using biochemical assays and cell-imaging techniques, we found that synaptic SHP2 levels are temporally regulated during synaptic down-scaling in cultured hippocampal neurons. Furthermore, we observed that a Noonan syndrome-associated mutation of SHP2, resulting in a D61G substitution, prevents synaptic down-scaling. We further show that this effect is due to an inability of the SHP2-D61G variant to properly disassociate from postsynaptic density protein 95, leading to impaired SHP2 dispersion from synaptic sites after synaptic down-scaling. Our findings reveal a molecular mechanism of the Noonan syndrome-associated genetic variant SHP2-D61G that contributes to deficient synaptic down-scaling. 

Retracted: No

PubPeer comments:
 Noticed that data points are found behind error bars and in front of error bars in this graph. Do graphing programs work like that?  Arrangement of lower data points on the darker bars in each set are nearly identical.  , 
 By symmetry considerations I suspect that the bottom dark blue bar isn t plotted at the mean. , 
 #1 It seems this is completely normal (if odd): https: twitter.com OKalliokoski status 1271039778448969728 The pattern of dots would be predictable - if the data are same. How unlikely is it that the 6 lowest values would repeat so closely? #2 A data point has been cut off from the figure shown, so the mean is probably correct. ,
<p><em>SNHG1</em> Promotes Malignant Progression of Glioma by Targeting miR-140-5p and Regulating PI3K/AKT Pathway</p>
Authors: Li-Li Xie
Jian-Long Chen
Ren-Duan Cai
Chao-Cai Zhang
Peng-Cheng Wang
Hong-Tao Lv
Chui-Xue Huang
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: PI3K/AKT pathway; SNHG1; glioma; miR-140-5p.

Abstract:  Purpose: To explore the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) in glioma. Materials and methods: The expression of SNHG1 and miR-140-5p in glioma tissues and glioma cell lines (LN-18, KNS-81, and KALS-1) was determined, and the effect of the two on cell proliferation, invasion, and PI3K/AKT pathway was analyzed. Results: SNHG1 was overexpressed in glioma tissues, while miR-140-5p was underexpressed in them, and there was a significant negative correlation between SNHG1 and miR-140-5p. In addition, both down-regulation of SNHG1 and up-regulation of miR-140-5p significantly inhibited the malignant proliferation and invasion of glioma, intensified the apoptosis, and also significantly suppressed the activation of the PI3K/AKT pathway. The dual-luciferase reporter assay, RNA pull-down assay, and RIP determination all confirmed that there was a targeting relationship between SNHG1 and miR-140-5p, and there was no difference between KNS-81 and KALS-1 cells transfected with SNHG1+mimics and si-SNHG1+inhibitor and those in the si-NC group with unrelated sequences in terms of cell malignant progression. Conclusion: SNHG1/miR-140-5p axis and its regulation on PI3K/AKT pathway might be a novel therapeutic direction to curb the malignant progression of glioma. 

Retracted: Yes

PubPeer comments:
 Figure 2D and 4E: * Three panels appear to show areas of overlap, although they represent different cell lines and treatments. Found by ImageTwin.io  , 
 #1 Reply: Thank you very much for your attention to our article. We feel so sorry and so ashamed about the mistakenly use of images in Figure. 2D and 4E. The study covered many experiments, and many images were used. When organizing the data, the author who is responsible for data analysis and graph drawing does not have a comprehensive communication with the author who is responsible for data management. We have provided a suitably revised version of Figure 2 and 4 and have carefully checked all the other data to ensure that they are correctly presented. We will try our best to avoid such mistake in future, and sincerely hope that our action could get your understanding.  ,
p14ARF promotes RB accumulation through inhibition of its Tip60-dependent acetylation
Authors: E Col
S Gazzeri
B Eymin
P Claverie
C Leduc
E Brambilla
S Khochbin
Journal: Oncogene (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p14ARF; tumour suppressor; p53-dependent; p53-independent; cell growth control
Affiliations: INSERM U578, Groupe de Recherche sur le Cancer du Poumon, Universit√© Joseph Fourier, Facult√© de Medecine, Institut Albert Bonniot, La Tronche Cedex, France.

Abstract:  p14ARF is a tumour suppressor which plays a critical role in p53-dependent or -independent cell growth control. Several studies have recently provided evidence that p14ARF can also interfere either directly or indirectly with some components of the RB signalling pathway to mediate its antiproliferative activity. The aim of this study was to explore the existence of direct relationships between p14ARF and RB proteins. We show that p14ARF promotes the accumulation of a hypoacetylated RB protein, when it is upregulated in a model of stable-inducible clones or physiologically induced following cell exposure to cytotoxic agents. Looking for the mechanisms involved in this process, we demonstrate that the histone acetyl transferase Tip60 directly interacts with RB and stimulates its degradation by the proteasome through acetylation of its C-terminus. Furthermore, and consistent with p14ARF-induced RB accumulation, we provide evidence that p14ARF prevents Tip60-mediated RB acetylation, therefore precluding its proteasomal degradation. Overall, our results identify a novel mechanism by which p14ARF controls the RB pathway to trigger its antiproliferative function. 

Retracted: No

PubPeer comments:
 Figure 6. Some bands appear to look similar to each other, as marked with arrows of the same color.  In addition, the Western blots in this paper show resemblance to those in other papers from different research groups. Compare to : * Figure 3 from XM Sun et al (2019): https: pubpeer.com publications 9319E643F702A1E9267F76FBDF0866 * Figure 3 from Y Long et al (2019): https: pubpeer.com publications 94DBAB3CDCF9D7C00792762576D297 * Figure 4 from HD Lou et al (2019): https: pubpeer.com publications D1194F22B8521E1BBF96F17D378181 * Figure 5 from XD Pan et al (2019): https: pubpeer.com publications A8530707339CB1A5287E7FFBD46CFE  or to:  Both taken from compositions by Hoya Camphorifolia. ,
Reduced expression of proteolipid protein 2 increases ER stress‚Äêinduced apoptosis and autophagy in glioblastoma
Authors: Anjing Chen
Qichao Qi
Mingzhi Han
Yulin Zhang
Anbin Chen
Yang Kong
Rolf Bjerkvig
Jiwei Wang
Qing Zhang
Yaotian Hu
Wenjing Zhou
Wenjie Li
Bin Huang
Frits Thorsen
Jian Wang
Di Zhang
Zichao Feng
Xingang Li
Journal: Journal of Cellular and Molecular Medicine (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ER stress; apoptosis; autophagy; glioblastoma; proteolipid protein 2.
Affiliations: Department of Neurosurgery, Qilu Hospital of Shandong University, Shandong Key Laboratory of Brain Functional Remodeling and Brain Science Research Institute, Shandong University, Shandong, China., Department of Biomedicine, University of Bergen, Bergen, Norway., Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg., The Molecular Imaging Center, Department of Biomedicine, University of Bergen, Bergen, Norway.

Abstract:  Proteolipid protein 2 (PLP2) is an integral ion channel membrane protein of the endoplasmic reticulum. The protein has been shown to be highly expressed in many cancer types, but its importance in glioma progression is poorly understood. Using publicly available datasets (Rembrandt, TCGA and CGGA), we found that the expression of PLP2 was significantly higher in high-grade gliomas than in low-grade gliomas. We confirmed these results at the protein level through IHC staining of high-grade (n = 56) and low-grade glioma biopsies (n = 16). Kaplan-Meier analysis demonstrated that increased PLP2 expression was associated with poorer patient survival. In functional experiments, siRNA and shRNA PLP2 knockdown induced ER stress and increased apoptosis and autophagy in U87 and U251 glioma cell lines. Inhibition of autophagy with chloroquine augmented apoptotic cell death in U87- and U251-siPLP2 cells. Finally, intracranial xenografts derived from U87- and U251-shPLP2 cells revealed that loss of PLP2 reduced glioma growth in vivo. Our results therefore indicate that increased PLP2 expression promotes GBM growth and that PLP2 represents a potential future therapeutic target. 

Retracted: No

PubPeer comments:
 Figure 5A and 5B the flow cytometry plots of siNC and CQ share many identical dots. I only marked a couple of them in 5A  ,
Effect of taxol on the expression of ovarian cancer-associated gene
Authors: Y U Xiao
Zeng Liu
Siqing Ning
Yuanyuan Zhu
Zhao Yuan Li
Gang Hu
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: FoxM1; RT-polymerase chain reaction; interrelation; ovarian cancer; western blotting.
Affiliations: Department of Nuclear Medicine, Central Hospital of Xiangyang, Xiangyang, Hubei 441021, P.R. China., State Drug Clinical Trial Agency, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Science, Chengdu, Sichuan 610072, P.R. China., Department of Nuclear Medicine, Xiangyang No. 1 People's Hospital, Xiangyang, Hubei 441000, P.R. China., Department of Breast Surgery, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Science, Chengdu, Sichuan 610072, P.R. China.

Abstract:  The incidence of ovarian cancer in women has been on the increase in recent years. The aim of the present study was to examine the effects of taxol on the expression of ovarian cancer-associated gene forkhead box transcription factor M1 (FoxM1) and its therapeutic effects for ovarian cancer. The expression of FoxM1 gene was examined in patients with or without ovarian cancer. RNA and protein levels of FoxM1 gene of ovarian cancer patients were detected at different time periods (1, 3, 6, 8, 12 and 24 months) after treatment with taxol. The results showed that the mRNA level of FoxM1 gene in patients with ovarian cancer was significantly higher than that in normal women (P&lt;0.05). With time and progression of the disease, the expression of FoxM1 gene significantly increased in the patients not being administered taxol, whereas the expression of FoxM1 in the patients administered taxol was significantly lower comparatively (P&lt;0.05). In conclusion, an asssociation was identified between the FoxM1 gene and ovarian cancer. The FoxM1 gene therefore promotes the generation and deterioration of ovarian cancer, whereas taxol reduces it. These findings provide a certain theoretical basis for the later treatment of ovarian cancer disease. 

Retracted: No

PubPeer comments:
 Figure 1 may have some repeated bands in the GAPDH band. Marked in red. The GAPDH band in the S1 lane also appears similar. Could the authors please post the uncropped original image? Although not necessarily a concern, I also note that neither non institutional email address provided for the corresponding authors seem to include portions of their respective names. *** Inverse  *** Original  ,
Multisensory Perception: Magnetic Disruption of¬†Attention in Human Parietal Lobe
Authors: Luigi Tam√®
Nicholas P Holmes
Journal: Current Biology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: sounds; touches; parietal lobe; human brain; multisensory perception
Affiliations: School of Psychology, University of Nottingham, Nottingham, NG7 2RD, UK. Electronic address: ., Department of Psychology, Birkbeck, University of London, London, WC1E 7HX, UK.

Abstract:  Paying attention to sounds and touches at the same time is demanding. New research shows how the parietal lobe of the human brain mediates multisensory perception of stimulus frequency and intensity. 

Retracted: No

PubPeer comments:
 This paper was criticised as part of a self-reflection posted on Twitter on 2nd-3rd April, 2021 (twitter TheHandLab status 1377760796130869248) Criticism: The writing was Too English . Working in Israel I was impressed by their academic freedom rigour. Sometimes this caused fights, but was overall positive. My commentary here is actually a harsh criticism of the paper. Can you tell? Criticisms of others work should be clear and easy to understand, especially for non-Native English readers. I m not sure the journal would have allowed it, though! ,
The silencing of LncRNA-H19 decreases chemoresistance of human glioma cells to temozolomide by suppressing epithelial-mesenchymal transition via the Wnt/&beta;-Catenin pathway
Authors: Gang Zhang
Yonghan Chen
Yaohui Tian
Linwei Jia
Journal: OncoTargets and Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: EMT; LncRNA-H19; Wnt/Œ≤-Catenin; chemoresistance; glioma
Affiliations: Department of Neurosurgery, CangZhou Central Hospital, Hebei, China.

Abstract:  Introduction: Temozolomide (TMZ) is commonly used for glioma chemotherapy. However, TMZ resistance limits the therapeutic effect of TMZ in glioma treatment. LncRNA-H19 acts as an oncogenic LncRNA in some types of cancers and has been reported to be up-regulated in glioma. Materials and methods: In our present study, we established TMZ-resistant glioma cells (U-251TMZ and M059JTMZ) to explore the effect of H19 on the chemoresistance of glioma cells. Results: We observed that the expression of H19 was significantly increased in U-251TMZ and M059JTMZ cells. Knockdown of H19 expression using specific shRNA in U-251TMZ and M059JTMZ led to decreased half maximal inhibitory concentration (IC50) values for TMZ and increased cell apoptosis rates, indicating that the silencing of H19 decreased chemoresistance of glioma cells to TMZ. In addition, silencing of H19 suppressed epithelial-mesenchymal transition (EMT) by increasing the expression of epithelial marker E-cadherin and decreasing the expression of mesenchymal marker Vimentin and ZEB1. Moreover, inducing EMT by TGF-Œ≤1 treatment led to increased IC50 values for TMZ and decreased cell apoptosis rates compared with TMZ+H19 shRNA group, suggesting that the induction of EMT counteracted the inhibitory effect of H19 shRNA on chemoresistance of glioma cells to TMZ. Furthermore, the reduced expression of H19 down-regulated the expression of Œ≤-Catenin and its downstream targets c-myc and Survivin in TMZ-treated glioma cells. Activation of Wnt/Œ≤-Catenin pathway by Licl treatment promoted EMT and enhanced chemoresistance to TMZ compared with TMZ+H19 shRNA group. Conclusion: Taken together, our data suggest that H19 decreased chemoresistance of glioma cells to TMZ by suppressing EMT via the inhibition of Wnt/Œ≤-Catenin pathway. Our study might represent a novel therapeutic target for TMZ-resistant glioma. 

Retracted: Yes

PubPeer comments:
 In Figure 4 E,F, a western blot is more similar than you would expect. No significant similarity was found for any of the 5 primers listed in Table 1. Search was only performed for the Forward primers, and filtered for Homo Sapiens.  , 
 The primers in Table 1 have been used in another Cell Cycle publication. Please see: https: pubpeer.com publications CA951238F4AC70A418AA19FFCCEABC#1 ,
Characterization of an alternative splice variant of LKB1
Authors: Natalie J Hiscock
David Carling
Fiona C Denison
Angela Woods
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: LKB1; AMP-activated protein kinase; alternative splicing; downstream kinases; LKB1L
Affiliations: Cellular Stress Group, Medical Research Council Clinical Sciences Centre, DuCane Road, London W12 0NN, United Kingdom.

Abstract:  LKB1 is an upstream activating kinase for the AMP-activated protein kinase (AMPK) and at least 12 other AMPK-related kinases. LKB1 therefore acts as a master kinase regulating the activity of a wide range of downstream kinases, which themselves have diverse physiological roles. Here we identify a second form of LKB1 generated by alternative splicing of the LKB1 gene. The two LKB1 proteins have different C-terminal sequences generating a 50-kDa form (termed LKB1L) and a 48-kDa form (LKB1S). LKB1L is widely expressed in mouse tissues, whereas LKB1S has a restricted tissue distribution with predominant expression in the testis. LKB1S, like LKB1L, forms a complex with MO25 and STRAD, and phosphorylates and activates AMPK both in vitro and in intact cells. A phosphorylation site (serine 431 in mouse) and a farnesylation site (cysteine 433 in mouse) within LKB1L are not conserved in LKB1S raising the possibility that these sites might be involved in differential regulation and/or localization of the two forms of LKB1. However, we show that phosphorylation of serine 431 has no effect on LKB1L activity and that both LKB1L and LKB1S have similar patterns of subcellular localization. These results indicate that the physiological significance of the different forms of LKB1 is not related directly to differences in the C-terminal sequences but may be due to their differential patterns of tissue distribution. 

Retracted: No

PubPeer comments:
  Much more similarity than expected between the immunoblots in Figure 1A and 3C. Could the authors check? ,
Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes
Authors: Micah G Gammon
Casey B Phillips
Paul A Cobine
Stanley A Moore
Xinyu Zhu
Katherine M Buckley
Aren Boulet
Laura E Oldfather
Scot C Leary
Journal: eLife (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: S. cerevisiae; biochemistry; chemical biology; copper; evolution
Affiliations: Department of Biological Sciences, Auburn University, Auburn, United States., Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, Canada.

Abstract:  The mitochondrial carrier family protein SLC25A3 transports both copper and phosphate in mammals, yet in Saccharomyces cerevisiae the transport of these substrates is partitioned across two paralogs: PIC2 and MIR1. To understand the ancestral state of copper and phosphate transport in mitochondria, we explored the evolutionary relationships of PIC2 and MIR1 orthologs across the eukaryotic tree of life. Phylogenetic analyses revealed that PIC2-like and MIR1-like orthologs are present in all major eukaryotic supergroups, indicating an ancient gene duplication created these paralogs. To link this phylogenetic signal to protein function, we used structural modeling and site-directed mutagenesis to identify residues involved in copper and phosphate transport. Based on these analyses, we generated an L175A variant of mouse SLC25A3 that retains the ability to transport copper but not phosphate. This work highlights the utility of using an evolutionary framework to uncover amino acids involved in substrate recognition by mitochondrial carrier family proteins. 

Retracted: No

PubPeer comments:
 In numerous figure panels, the authors compare multiple groups using a one-way ANOVA test. However, despite clearly having carried out post hoc comparisons, I can find no mention of the specific method used nor whether it included a correction for multiple comparisons. Such corrections are certainly necessary, because the authors themselves highlight multiple comparisons. This problem arises in Fig. 1BCEF, Fig. 6BC, Fig. 7BCEF. The authors seem not to respect the prerequisite of equal variances for their ANOVA tests. This appears to be troublesome in Fig. 1BE, Fig. 7DEF. On several occasions the authors deploy a two-factor design but do not analyse it as such. In particular, they do not test the significance of the interaction term. This applies to Fig. 1EF, Fig. 7DEF. It is not easy to examine the consequences of these possible errors, because the data for these figures don t seem to have been shared, notwithstanding eLife s strict data-access policy and the following  Data availability statement:  All data generated or analyzed during this study are included in the manuscript, supplementary file, and available on GenBank. ,
Lactobacillus maintains healthy gut mucosa by producing L-Ornithine
Authors: Huan Yun
Rongcun Yang
Houbao Qi
Jin Zhong
Yingquan Liu
Tong Zhang
Jianmei Wei
Dashuai Zhu
Yugang Huang
Xiaomin Su
Yongzhe Che
Zhiqian Zhang
Jiang Zhou
Yuanyuan Li
Yuan Zhang
Hui Yan
Yunhuan Gao
Journal: Communications Biology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bacterial host response; Mucosal immunology.
Affiliations: 1State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071 Tianjin, China., 2Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, 300071 Tianjin, China., 3Department of Immunology, School of Medicine, Nankai University, 300071 Tianjin, China., 4State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China., 5School of Life Science, University of Chinese Academy of Sciences, 100039 Beijing, China.

Abstract:  Gut mucosal layers are crucial in maintaining the gut barrier function. Gut microbiota regulate homeostasis of gut mucosal layer via gut immune cells such as RORŒ≥t (+) IL-22(+) ILC3 cells, which can influence the proliferation of mucosal cells and the production of mucin. However, it is unclear how gut microbiota execute this regulation. Here we show that lactobacilli promote gut mucosal formation by producing L-Ornithine from arginine. L-Ornithine increases the level of aryl hydrocarbon receptor ligand L-kynurenine produced from tryptophan metabolism in gut epithelial cells, which in turn increases RORŒ≥t (+)IL-22(+) ILC3 cells. Human REG3A transgenic mice show an increased proportion of L-Ornithine producing lactobacilli in the gut contents, suggesting that gut epithelial REG3A favors the expansion of L-Ornithine producing lactobacilli. Our study implicates the importance of a crosstalk between arginine metabolism in Lactobacilli and tryptophan metabolism in gut epithelial cells in maintaining gut barrier. 

Retracted: No

PubPeer comments:
 image duplication  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. ,
Disuccinyl betulin triggers metacaspase-dependent endonuclease G-mediated cell death in unicellular protozoan parasite Leishmania donovani
Authors: Parasuraman Jaisankar
Hemanta K Majumder
Souvik Sengupta
Tulika Mukherjee
Sibabrata Mukhopadhyay
Somenath Roy Chowdhury
Sayan Chowdhury
Journal: Antimicrobial Agents and Chemotherapy (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Leishmania; apoptosis-like cell death; oxidative stress; reactive oxygen species; mitochondrial membrane potential
Affiliations: Molecular Parasitology Laboratory, Indian Institute of Chemical Biology, Kolkata, India.

Abstract:  The unicellular organism Leishmania undergoes apoptosis-like cell death in response to external stress or exposure to antileishmanial agents. Here, we showed that 3-O,28-O-disuccinyl betulin (DiSB), a potent topoisomerase type IB inhibitor, induced parasitic cell death by generating oxidative stress. The characteristic feature of the death process resembled the programmed cell death (PCD) seen in higher eukaryotes. In the current study, the generation of reactive oxygen species (ROS), followed by the depolarization of mitochondrial membrane potential (ŒîŒ®m), caused a loss in ATP production in Leishmania parasites. This further gave positive feedback to produce a large amount of ROS, which in turn caused oxidative DNA lesions and genomic DNA fragmentation. The treatment of promastigotes with DiSB induced high expression levels of metacaspase protein that led to cell death in this unicellular organism. The PCD was insensitive to benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), suggesting that the death process was not associated with the activation of caspases. DiSB treatment translocated Leishmania donovani endonuclease G (LdEndoG) from mitochondria to the nucleus, which was responsible for the DNA degradation process. Conditional antisense knockdown of L. donovani metacaspase (LdMC), as well as EndoG, -subverted death of the parasite and rescued cell cycle arrest in G1 phase. The present study on the effector molecules associated with the PCD pathway of the parasite should help to manifest the mechanisms of PCD and also might be exploited in antileishmanial chemotherapy. 

Retracted: No

PubPeer comments:
 Fig 2C.  wound-healing assay were conducted to determine cell ... migration. Nontransfected U2OS cells were used as the control group .  Lilac, blue-grey and magenta rectangles mark panels that also appear in Fig 7, LOVO half, of [Tian et al (2015)] . Other manifestations are linked in that thread.  ,
Preparation of endostatin-loaded chitosan nanoparticles and evaluation of the antitumor effect of such nanoparticles on the Lewis lung cancer model
Authors: Ling-Lin Yang
Yue Hu
Fang Xie
Sheng Lin
Jing-Bo Wu
Qing-Lian Wen
Rui-Lin Ding
Wen-Feng He
Juan Fan
Yu He
Shao-Zhi Fu
Journal: Drug Delivery (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Endostatin; chitosan; drug carrier; lung cancer; nanoparticles.
Affiliations: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, P.R. China

Abstract:  The purpose of this study was to prepare ES-loaded chitosan nanoparticles (ES-NPs) and evaluate the antitumor effect of these particles on the Lewis lung cancer model. ES-NPs were prepared by a simple ionic cross-linking method. The characterization of the ES-NPs, including size distribution, zeta potential, loading efficiency and encapsulation efficiency (EE), was performed. An in vitro release test was also used to determine the release behavior of the ES-NPs. Cell viability and cell migration were assayed to detect the in vitro antiangiogenic effect of ES-NPs. In order to clarify the antitumor effect of ES-NPs in vivo, the Lewis lung cancer model was used. ES-NPs were successfully synthesized and shown to have a suitable size distribution and high EE. The nanoparticles were spherical and homogeneous in shape and exhibited an ideal releasing profile in vitro. Moreover, ES-NPs significantly inhibited the proliferation and migration of human umbilical vascular endothelial cells (HUVECs). The in vivo antiangiogenic activity was evaluated by ELISA and immunohistochemistry analyses, which revealed that ES-NPs had a stronger antiangiogenic effect for reinforced anticancer activity. Indeed, even the treatment cycle in which ES-NPs were injected every seven days, showed stronger antitumor effect than the free ES injected for 14 consecutive days. Our study confirmed that the CS nanoparticle is a feasible carrier for endostatin to be used in the treatment of lung cancer. 

Retracted: No

PubPeer comments:
 Figure 5 appears to have some image overlap, after rotation. ***  ,
The impact of contraceptive access on high school graduation
Authors: Jane A Menken
Katie R Genadek
Sara Yeatman
Stefanie Mollborn
Amanda J Stevenson
Journal: Science Advances (2021)
Discipline: Multidisciplinary
Keywords: contraceptive methods; educational attainment; family planning programs; Colorado policy change; high school graduation
Affiliations: Department of Sociology, University of Colorado Boulder, Boulder, CO 80309, USA., Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO 80309, USA., U.S. Census Bureau, Suitland-Silver Hill, MD 20746, USA., Department of Health and Behavioral Sciences, University of Colorado Denver, Denver, CO 80217, USA.

Abstract:  Does access to the full range of contraceptive methods increase young women's educational attainment? Family planning programs are often justified by claims that it does, but contemporary evidence is unexpectedly weak. We use a natural experiment afforded by a 2009 Colorado policy change to assess the impact of expanded access to contraception on women's high school graduation. Linking survey and Census data, we follow a population-representative U.S. sample, including large subsamples of young women living in Colorado in 2010 and in comparison states. Using a difference-in-differences design, we find expansion of access to contraception was associated with a statistically significant 1.66 percentage-point increase in high school graduation. This increase in graduation represents a 14% decrease in the baseline percentage not graduating high school before the policy change. Results are robust to a variety of sensitivity tests. Our findings indicate that improving access to contraception increases young women's human capital formation. 

Retracted: No

PubPeer comments:
  At the request of the author, the Editor and Publisher of Cancer Management and Research wish to retract the published paper. Following a review of their study the authors were unable to repeat the results described in the published paper for subsequent experiments. As a result, the authors can no longer confirm that overexpression of miR-489-3p was able to suppress luciferase activity by transfection with an miR-489 expression plasmid. The authors also found an error in Figure 6. The image used for Figure 6A Panel 22Rv1 miR-489-3p had been duplicated with the image used for Figure 6C 22Rv1 miR-489-3p+DLX1. In the interests of scientific integrity, the authors have determined it best to retract the published article. The Editor has determined the findings of the paper are no longer valid and has agreed with the authors request to retract the article. The author wished to apologise for this error. *** Showing figure overlap (not duplication).  ,
Sulforaphane improves voiding function via the preserving mitochondrial function in diabetic rats
Authors: Tsung-Hung Chueh
Tzu-Ching Chang
Cheng-Hsun Chung
Chia-Fa Lin
Shue-Dong Chung
Chiang-Ting Chien
Journal: Journal of the Formosan Medical Association (2020)
Discipline: CLINICAL MEDICINE
Keywords: Diabetic bladder; Mitochondria; NF-E2-related nuclear factor erythroid-2; Voiding function.
Affiliations: School of Life Science, National Taiwan Normal University, Taipei, 11677, Taiwan., Department of Urology, Far-East Memory Hospital, New Taipei City, 220, Taiwan., School of Life Science, National Taiwan Normal University, Taipei, 11677, Taiwan. Electronic address: .

Abstract:  Background: Hyperglycemia evoked oxidative stress contributing to diabetes (DM)-induced voiding dysfunction. We explored whether antioxidant sulforaphane,a NF-E2-related nuclear factor erythroid-2 (Nrf-2) activator, may ameliorate DM-induced bladder dysfunction. Methods: DM was induced by streptozotocin and sulforaphanewas administered before DM induction.Bladder reactive oxygen species (ROS) were determined by an ultrasensitive chemiluminescence analyzer. Mitochondrial function index mitochondrial Bax and cytosolic cytochrome c, antioxidant defense Nrf-2/HO-1, endoplasmic reticulum stress marker ATF-6/CHOP, and caspase 3/PARP were evaluated by Western blot. Results: DM increased Keap1 and reduced Nrf-2 expression, associated with increase of bladder ROS, mitochondrial Bax translocation, cytosolic cytochrome c release, ATF-6/CHOP, caspase-3/PARP in bladders which resulted in voiding dysfunction by increased intercontraction intervals and micturition duration. However, sulforaphanesignificantly increased nuclear Nrf-2/HO-1axis expression, decreased bladder ROS amount, mitochondrial Bax translocation, cytochrome c release, ATF-6/CHOP and caspase 3/PARP/apoptosis, thereby improved the voiding function by the shortened intercontraction intervals and micturition duration. Conclusion: We suggest that sulforaphanevia activating Nrf-2/HO-1 signaling preserved mitochondrial function and suppressed DM-induced ROS, endoplasmic reticulum stress, apoptosis and voiding dysfunction. 

Retracted: No

PubPeer comments:
 Plagiarism in figure 5 H. This figure (TUNEL of Con) was published in previous research (Sulforaphane Improves Ischemia-Induced Detrusor Overactivity by Downregulating the Enhancement of Associated Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Rat Bladder).  ,
Chamomile: an anti-inflammatory agent inhibits inducible nitric oxide synthase expression by blocking RelA/p65 activity
Authors: Natarajan Bhaskaran
Janmejai K Srivastava
Sanjay Gupta
Sanjeev Shukla
Journal: International journal of molecular medicine (2010)
Discipline: CLINICAL MEDICINE
Keywords: Chamomile; inflammation; nitric oxide; iNOS; RAW 264.7 macrophages
Affiliations: Department of Urology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.

Abstract:  Chamomile has long been used in traditional medicine for the treatment of inflammation-related disorders. In this study we investigated the inhibitory effects of chamomile on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression, and explored its potential anti-inflammatory mechanisms using RAW 264.7 macrophages. Chamomile treatment inhibited LPS-induced NO production and significantly blocked IL-1Œ≤, IL-6 and TNFŒ±-induced NO levels in RAW 264.7 macrophages. Chamomile caused reduction in LPS-induced iNOS mRNA and protein expression. In RAW 264.7 macrophages, LPS-induced DNA binding activity of RelA/p65 was significantly inhibited by chamomile, an effect that was mediated through the inhibition of IKKŒ≤, the upstream kinase regulating NF-Œ∫B/Rel activity, and degradation of inhibitory factor-Œ∫B. These results demonstrate that chamomile inhibits NO production and iNOS gene expression by inhibiting RelA/p65 activation and supports the utilization of chamomile as an effective anti-inflammatory agent. 

Retracted: No

PubPeer comments:
 Some, but not all, of the bands in Figure 5A appear to show signs of splicing when contrast is enhanced. Could the authors explain? ***  , 
 Comment Some, but not all, of the bands in Figure 5A appear to show signs of splicing when contrast is enhanced. Could the authors explain? Response In the original, Lane 3, 5 u00b5g ml chamomile was replaced with lane 7, L-NMMA to match the panel.  , 
 Then what about other proteins? Lane 3 of other proteins didn t show signs of splicing. Please explain and provide original blots. ,
<p>Establishment and validation of an AJCC stage- and histologic grade-based nomogram for pancreatic neuroendocrine tumors after surgical resection</p>
Authors: Hongkai Zhuang
Zi Yin
Dezhi Li
Ye Lin
Xin Lu
Zhixiang Jian
Yanxia Wu
Chuanzhao Zhang
Baohua Hou
Journal: Cancer Management and Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: AJCC stage; P-NET; grading; nomogram; overall survival.

Abstract:  Background: Development of an accurate model to predict prognosis for patients with pancreatic neuroendocrine tumors (P-NETs) after surgical resection is urgently needed. Methods: In the present study, we conducted Cox proportional hazards regression to identify critical prognostic factors for P-NETs by analyzing data from 2174 patients in the Surveillance, Epidemiology, and End Results (SEER) database. Based on the results of multivariate analysis, a novel nomogram was established. Finally, the novel nomogram for P-NETs was validated in a cohort of 81 patients from a Chinese institute. Results: In the multivariate analysis, age, tumor location, American Joint Committee on Cancer (AJCC) stage, histologic grade, lymph node ratio (LNR) and tumor size were independent risk factors for overall survival (OS) in P-NET patients who underwent radical resection. A nomogram consisting of age, sex, AJCC stage and histologic grade was found to have a concordance index (C-index) of 0.79 for OS in the SEER database, which was significantly higher than the C-index based on the AJCC stage, European Neuroendocrine Tumor Society (ENETS) stage or histologic grade alone. In the validation cohort, the C-index based on the nomogram reached 0.78 for OS. We also defined high-risk (total points &gt;13.5 based on the nomogram) and low-risk populations (total points &lt;13.5 based on the nomogram) in the validation cohort. We found that the actual 5-year recurrence rate in the high-risk group was significantly higher than that in the low-risk group (80.8% vs 23.4%, P&lt;0.001). Kaplan-Meier analysis showed that the 5-year recurrence-free survival (RFS) in the low-risk group was significantly higher than that in the high-risk group (P&lt;0.001). Conclusion: An AJCC stage- and histologic grade-based model was found to be extremely efficient in predicting survival for patients with P-NETs after surgical resection and deserves further evaluation for future clinical applications. 

Retracted: No

PubPeer comments:
 Figure 1, The authors have constructed a prognostic nomogram for P-NET patients, However, sex as a variable axis should not be included in this nomogram, as only variables those are independent prognostic factors could be included.  Based on the authors own ananlysis in Table 3, no significant difference was observed for the  sex parameter in the multivariate analysis. Thus,  sex as a variable axis in the prognostic nomogram was inappropriate.  , 
 This is Chuanzhao Zhang, fist author, and I would like to response as follow: (PS: I tried to signed log in but failed, I have contacted contact@pubpeer.com but have no response yet) Please see paragraph 3, results section in our paper. u201cSex was also included as a baseline parameteru201d Thank you.  ,
miR‚Ä?18 contributes to drug resistance in multiple myeloma via targeting LRRC28
Authors: Feiqi Zhu
Weiling Cao
Danbo Liu
Lingyun Zhou
Jiao Chen
Fang Du
Haifei Chen
Journal: Journal of Cellular Biochemistry (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LRRC28; bortezomib resistance; miR-218; multiple myeloma.
Affiliations: Department of Hematology, Shenzhen Luohu People's Hospital The Third Affiliated Hospital of Shenzhen University  Shenzhen Guangdong China, Department of Pharmacy, Shenzhen Luohu People's Hospital The Third Affiliated Hospital of Shenzhen University  Shenzhen Guangdong China, Cognitive Impairment Ward of Neurology Department, Shenzhen Luohu People's Hospital The Third Affiliated Hospital of Shenzhen University  Shenzhen Guangdong China

Abstract:  Multiple myeloma (MM) is a malignant neoplasm featured by obvious drug resistance and poor prognosis. MicroRNAs (miRNAs) are a class of small noncoding RNAs with crucial roles in many biological processes including cancer initiation and progression. The current study aims to investigate the pathogenic role and molecular mechanism of miRNAs in MM drug resistance. In the present study, The expression profile of miRNAs in MM samples was analyzed by microarray and real-time polymerase chain reaction. Protein expressions were detected by Western blot analysis. Cell apoptosis was detected by the Annexin V staining assay. The interaction between miRNA and the targeting mRNA was assessed using Dual luciferase reporter assay. Herein, we show that expression profile of miRNAs is deregulated in MM. miR-218, one of the most aberrational miRNAs in MM, is significantly decreased in MM cells compared to peripheral blood mononuclear cell (PBMC). Genetic manipulation reveals miR-218 control the response of MM cells to anticancer drug bortezomib (BTZ). Overexpression of miR-218 causes a significant aberrant genes expression including leucine rich repeat containing 28 (LRRC28). Mechanistic study shows that miR-218 control the drug response through mediating the expression of LRRC28 in MM cells. Overexpression of LRRC28 significantly reserves miR-218-mediated cell response to BTZ. Taken together, miR-218 is decreased in MM that contributes to BTZ resistance via targeting LRRC28, which might be used as a novel therapeutic target for multiple myeloma. 

Retracted: No

PubPeer comments:
 Table 1 of the study summarizes the 30 human patients. Their relative expression of miR-218 and LRRC28 are listed as they are stratified sex, age, etc. Since they are the same patients, however, the grand mean of the expression levels should be the same in all categories. It is not. For each category we find a new grand mean, as if these are all different patient cohorts.  Perhaps the authors can shed some light on what the issue here might be? ,
Cytisine, a Partial Agonist of Œ±4Œ≤2 Nicotinic Acetylcholine Receptors, Reduced Unpredictable Chronic Mild Stress-Induced Depression-Like Behaviors
Authors: Shui-Bing Liu
Ming-Gao Zhao
Dong-Sheng Wang
Jing Han
Journal: Biomolecules & Therapeutics (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Chronic stress; Cytisine; Depression; Nicotinic receptor.
Affiliations: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi‚Äôan 710032, China, Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing 210002, China

Abstract:  Cytisine (CYT), a partial agonist of Œ±4Œ≤2-nicotinic receptors, has been used for antidepressant efficacy in several tests. Nicotinic receptors have been shown to be closely associated with depression. However, little is known about the effects of CYT on the depression. In the present study, a mouse model of depression, the unpredictable chronic mild stress (UCMS), was used to evaluate the activities of CYT. UCMS caused significant depression-like behaviors, as shown by the decrease of total distances in open field test, and the prolonged duration of immobility in tail suspension test and forced swimming test. Treatment with CYT for two weeks notably relieved the depression-like behaviors in the UCMS mice. Next, proteins related to depressive disorder in the brain region of hippocampus and amygdala were analyzed to elucidate the underlying mechanisms of CYT. CYT significantly reversed the decreases of 5-HT1A, BDNF, and mTOR levels in the hippocampus and amygdala. These results imply that CYT may act as a potential anti-depressant in the animals under chronic stress. 

Retracted: No

PubPeer comments:
null, 
 This is not the work of the Gary Stacey lab ,
Gemini Amphiphile-Based Lipoplexes for Efficient Gene Delivery: Synthesis, Formulation Development, Characterization, Gene Transfection, and Biodistribution Studies
Authors: Anil K Mishra
Mukesh Kumar
Prashant R Murumkar
Puja P Hazari
Mange R Yadav
Journal: ACS Omega (2018)
Discipline: CHEMISTRY
Keywords: quaternary gemini amphiphiles; gene delivery carriers; liposomes; transfection efficiency; cell viabilities
Affiliations: Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, 390 001 Gujarat State, India., Division of Radiopharmaceuticals, Institute of Nuclear Medicine & Allied Sciences (INMAS), Lucknow Road, Timarpur, 110 054 Delhi, India.

Abstract:  Some quaternary gemini amphiphiles (GAs) were synthesized as nonviral gene delivery carriers. The critical miceller concentration values of these amphiphiles are indicative of their superior surface-active properties. All of the synthesized GAs, alone or along with lipids like cholesterol and/or dioleoylphosphatidyl ethanolamine (DOPE), were formulated as liposomes. Formulations of GAs with DOPE showed average particle diameters of 326-400 nm with positive Œ∂-potential (30.1-46.4 mV). The lipoplexes of theses formulations showed complete pDNA retention at the base at a N/P ratio higher than 1.0 in gel retardation study. The GAs were effective in condensing pDNA into a œà-phase, as indicated by circular dichroism study, and provided complete protection of the pDNA against the enzyme DNase at a N/P ratio more than 1. In vitro cell line studies showed that GA liposomal formulations caused Œ≤-gal expression and offered a higher transfection efficiency than that of liposomes prepared with the help of N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP)/DOPE and dicyclocarbodiimide (DCC)/DOPE but comparable to those of Lipofectamine 2000 in A549 and HeLa cell lines. Modulation of head group polarity significantly affected the transfection efficacy of GAs. The cell viabilities of almost all of the formulations were comparable to those of the standards (DCC/DOPE and DOTAP/DOPE liposomes). Incorporation of cholesterol [GA/DOPE/cholesterol in the ratio of 1:1:1] further improved the serum compatibility of the formulations and improved the transfection efficacy when evaluated in A549 and HeLa cell lines. Fluorescence-assisted cell sorting studies showed comparable number of transfected cells to Lipofectamine 2000 in the HeLa cell line. Intracellular trafficking studies using confocal microscopy indicated transfection of the HeLa cells with the reporter gene within 30 min of lipoplex treatment. Œ≥-Scintigraphy using 99mTc-labeled lipoplexes showed higher concentrations of the lipoplexes in vital tissues like liver, spleen, lungs, and kidneys. 

Retracted: No

PubPeer comments:
 Figure-4b. Striking resemblance of lanes marked here are unusual and exceptional ,
Invited commentary
Authors: Paul DiMuzio
Journal: Journal of Vascular Surgery (2020)
Discipline: CLINICAL MEDICINE
Keywords: Retracted article; Elsevier Policy; Editor-in-Chief; Author; Ethics infringement
Affiliations: Division of Vascular and Endovascular Surgery, Thomas Jefferson University, Philadelphia, Pa.

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and Author. This article has not been retracted for any ethics infringement but because the article on which it is commenting has been retracted. 

Retracted: Yes

PubPeer comments:
  This article has been retracted: please see Elsevier Policy on Article Withdrawal . This article has been retracted at the request of the Editor-in-Chief and Author. This article has not been retracted for any ethics infringement but because the article on which it is commenting has been retracted. Referring to: https: www.sciencedirect.com science article pii S074152141932587X ,