PReD-Bench/PRed-Bench huggingface dataset:
Insulin-Like Growth Factor-1 Receptor Signaling Increases the Invasive Potential of Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer Cells via Src-Focal Adhesion Kinase and Forkhead Box Protein M1
Authors: Meghan C Buss
Elisavet Paplomata
Siobhan M Donnelly
Robert C Castellino
Latonia Taliaferro-Smith
Rita Nahta
Pravin T P Kaumaya
Eduardo Sanabria-Figueroa
Kevin C Foy
Journal: Molecular pharmacology (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HER2; trastuzumab resistance; IGF-1R; invasion; Src

Abstract:  Resistance to the human epidermal growth factor receptor (HER2)-targeted antibody trastuzumab is a major clinical concern in the treatment of HER2-positive metastatic breast cancer. Increased expression or signaling from the insulin-like growth factor-1 receptor (IGF-1R) has been reported to be associated with trastuzumab resistance. However, the specific molecular and biologic mechanisms through which IGF-1R promotes resistance or disease progression remain poorly defined. In this study, we found that the major biologic effect promoted by IGF-1R was invasion, which was mediated by both Src-focal adhesion kinase (FAK) signaling and Forkhead box protein M1 (FoxM1). Cotargeting IGF-1R and HER2 using either IGF-1R antibodies or IGF-1R short hairpin RNA in combination with trastuzumab resulted in significant but modest growth inhibition. Reduced invasion was the most significant biologic effect achieved by cotargeting IGF-1R and HER2 in trastuzumab-resistant cells. Constitutively active Src blocked the anti-invasive effect of IGF-1R/HER2 cotargeted therapy. Furthermore, knockdown of FoxM1 blocked IGF-1-mediated invasion, and dual targeting of IGF-1R and HER2 reduced expression of FoxM1. Re-expression of FoxM1 restored the invasive potential of IGF-1R knockdown cells treated with trastuzumab. Overall, our results strongly indicate that therapeutic combinations that cotarget IGF-1R and HER2 may reduce the invasive potential of cancer cells that are resistant to trastuzumab through mechanisms that depend in part on Src and FoxM1. 

Retracted: No

PubPeer comments:
 Two images in figure 7B appear to overlap. *** ![file] ,
MIF promotes perineural invasion through EMT in salivary adenoid cystic carcinoma
Authors: Min Zheng
Ya-Ling Tang
Mei Zhang
Xiang-Hua Yu
Zhu-Feng Li
Sha-Sha Wang
Xin Pang
Jia-Shun Wu
Jing-Biao Wu
Ya-Jie Tang
Xiao Yang
Hao-Fan Wang
Xin-Hua Liang
Li Li
Journal: Molecular Carcinogenesis (2019)
Discipline: CLINICAL MEDICINE
Keywords: Epithelial-to-mesenchymal transition (EMT); Macrophage migration inhibitory factor (MIF); Perineural invasion (PNI); Salivary adenoid cystic carcinoma (SACC); Schwann-like cell differentiation.
Affiliations: State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China., Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China., Department of Stomatology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, Zhejiang, China.

Abstract:  Macrophage migration inhibitory factor (MIF) is a prominent orchestrator during the onset and progression of cancer. Recently, MIF was detected in salivary adenoid cystic carcinoma (SACC). However, its functional effect in perineural invasion (PNI) of SACC remained unknown. To illuminate the effect of MIF in genesis of PNI in SACC, we examined the expression of MIF, epithelial-to-mesenchymal transition (EMT)-related markers, and Schwann cell markers by immunohistochemical analysis in 158 cases of SACC samples. Meanwhile, the correlation between MIF and PNI of SACC species was analyzed. Our data indicated that MIF expression was associated with PNI of SACC significantly. In vitro, the silence and overexpression experiments of MIF were performed in SACC cell lines. The ability of migration, invasion and PNI could be inhibited significantly by siRNA-mediated MIF silence, and the occurrence of EMT and Schwann-like cell differentiation was also inhibited by MIF silence in SACC-LM cells. Overexpression of MIF in SACC-83 cells using expressive plasmid showed the opposite effects. Our findings identified that an association between PNI and MIF expression existed. MIF may promote PNI of SACC by participating in cytoskeletal reorganization and pseudo foot formation induced by EMT and the Schwann-like cell differentiation of SACC cells. 

Retracted: No

PubPeer comments:
 Figure 4A appears to have an overlap ![file] , 
 An additional similar overlap in Figure 6B ![file] ,
Diffuse midline glioma with an H3 K27M mutation: A comparison integrating the clinical, radiological, molecular features between adult and pediatric patients
Authors: Mingxiao Li
Yong Cui
Yifei Lei
Song Lin
Xiaohui Ren
Kaiyuan Yang
Haihui Jiang
Journal: Neuro-Oncology (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: H3 K27M; adult; characteristic; diffuse midline glioma; pediatric.
Affiliations: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China., National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China., Qingdao University, Qingdao, China.

Abstract:  Background: Diffuse midline glioma (DMG), H3 K27M mutant, occurs in both adult and pediatric populations. The characteristics of the 2 DMG groups were systematically explored in this study. Methods: H3 K27M-mutant DMG was diagnosed in 116 patients at Beijing Tiantan Hospital from May 2016 to December 2018 who were included in our study. Patients were classified into an adult group (n = 57; 49.1%) and a pediatric group (n = 59; 50.9%). Clinical, radiological, and molecular features were compared between the groups. Univariate and multivariate analyses were performed to identify prognostic factors. Results: Compared with the adult group, pediatric patients had a younger age (8.9 ± 4.1 y vs 35.1 ± 11.8 y, P &lt; 0.001), a lower preoperative Karnofsky performance scale score (62.9 ± 15.5 vs 72.1 ± 16.5, P = 0.004), a lower rate of total resection (5.7% vs 26.8%, P = 0.009), a larger tumor size (4.4 ± 0.9 vs 3.9 ± 1.5 cm, P = 0.045), a higher Ki-67 index (63.0% vs 37.8%, P = 0.047), and higher rates of postoperative cranial nerve palsy (61.0% vs 36.8%, P = 0.009) and ataxia (45.8% vs 26.3%, P = 0.029). Adult DMG was located predominantly in the thalamus, while the predilection site for pediatric DMG was brainstem (P &lt; 0.001). Kaplan-Meier plot showed that the median survival of adult and pediatric DMG was 16.0 (9.7-22.3) months and 10.0 (8.3-11.7) months, respectively, which imparted a significant difference (P = 0.008). Age at diagnosis, radiotherapy, and motor deficit were confirmed as independent prognostic factors according to the multivariate analysis (P &lt; 0.05). Conclusion: Compared with adult patients, children with H3 K27M-mutant DMG confer distinct clinical, radiological, and molecular characteristics and have a dismal prognosis. Radiotherapy is an independent factor associated with prolonged survival. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: academic.oup.com neuro-oncology advance-article doi 10.1093 neuonc noaa012 5756150 Neuro-Oncology is retracting this article at the request of the authors. The journal understands that permission to analyze and publish part of the data had not been granted. All authors agree with this retraction, and apologize for any inconvenience caused. ,
Phospholipase D elevates the level of MDM2 and suppresses DNA damage-induced increases in p53
Authors: Troy Joseph
Jill Bargonetti
David A Foster
Rafal M Pielak
Tarek Abbas
Li Hui
Journal: Molecular and Cellular Biology (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Phospholipase D; apoptosis; DNA damage; p53; MDM2
Affiliations: Department of Biological Sciences, Hunter College of the City University of New York, 695 Park Ave., New York, NY 10021, USA., Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10021

Abstract:  Phospholipase D (PLD) has been reported to generate survival signals that prevent apoptosis induced by serum withdrawal. We have now found that elevated expression of PLD also suppresses DNA damage-induced apoptosis. Since DNA damage-induced apoptosis is often mediated by p53, we examined the effect of elevated PLD expression on the regulation of p53 stabilization. We report here that PLD suppresses DNA damage-induced increases in p53 stabilization in cells where PLD has been shown to provide a survival signal. Elevated expression of PLD also led to increased expression of the p53 E3 ubiquitin ligase MDM2 and increased turnover of p53. PLD1-stimulated increases in MDM2 expression and suppression of p53 activation were blocked by inhibition of mTOR and the mitogen-activated protein kinase pathway. Although PLD did not activate the phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway activate the basal levels of PI3K activity were partially required for PLD1-induced increases in MDM2. These data provide evidence that survival signals generated by PLD involve suppression of the p53 response pathway. 

Retracted: No

PubPeer comments:
 Figure 8B and 8D. Much more similar than expected. ![file] ,
Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition
Authors: Peter C Keng
Xiaodong Yang
Ying Tsai
Yuhchyau Chen
MingJing Shen
Li Yang
Soo Ok Lee
Li Jun Xu
Journal: Scientific reports (2017)
Discipline: Multidisciplinary
Keywords: PD-1; PD-L1; NK cells; cisplatin-resistant cells; cytotoxicity
Affiliations: Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA., Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA. .

Abstract:  Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell's function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors. In contrast, we observed that the expression of PD-1 in NK cells was induced after co-culture with cisplatin-resistant cells. We also observed increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity when neutralizing antibody of PD-1 or PD-L1 was added. Further, we found that the NK group 2, member D (NKG2D) ligand levels were lower in A549CisR and H157CisR cells than in parental cells. Meanwhile, we discovered that the MEK/Erk signaling pathway played a significant role in this regulation, and the addition of a MEK/Erk pathway inhibitor significantly enhanced the PD-L1 Ab effect in enhancing NK cell cytotoxicity to cisplatin-resistant cells. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have two images which overlap, with differing dimensions, representing different treatments. *** ![file] , 
 Seems to be a similar issue with Figure 4. *** ![file] , 
 Seems to be a similar issue with Figure 7, with different brightness or contrast. *** ![file] ,
Interfacial Phenomenon and Nanostructural Enhancements in Palladium Loaded Lanthanum Hydroxide Nanorods for Heterogeneous Catalytic Applications
Authors: Ammar Bin Yousaf
Muhammad Imran
Muhammad Farooq
Peter Kasak
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: Hydrogenation; cross-coupling reactions; noble metal catalysts; Lanthanum hydroxide; Pd NPs
Affiliations: Center for Advanced Materials, Qatar University, Doha, 2713, Qatar. ., Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, P.R. China. ., Department of Chemistry, University of Management and Technology, Lahore, 54000, Pakistan.

Abstract:  Hydrogenation and cross-coupling reactions are of great importance for industrial applications and noble metal based catalysts are filling the void since the last few decades. However, the high cost of noble metals and poor recycling performance provides an opportunity for chemists to look for alternate options. Herein, we present the use of Lanthanum hydroxide as support for loading ultra-low amount of Pd for hydrogenation and cross-coupling reactions. Lanthanum hydroxide having controlled morphologies comprises exposed crystallographic facets which interact with small sized Pd NPs and shows versatile and effective catalytic performance. The reduction of 4-NP over Pd/La(OH)3 was achieved within very short time (45s) with a rate constant of 60 × 10-3 s-1. The hydrogenation of styrene was also accomplished within 1 hour with much high TOF value (3260 h-1). Moreover, the Suzuki cross-couplings of iodobenzene and phenyl boronic acid into biphenyl completed within 35 min with a TOF value of 389 h-1. The strong interfacial electronic communication regulates electron density of catalytic sites and lowers energy for adsorption of reactant and subsequently conversion into products. Moreover, abundant hydroxyl groups on the surface of La(OH)3, large surface area, mono-dispersity and ultra-small size of Pd NPs also favors the efficient conversion of reactants. 

Retracted: No

PubPeer comments:
 Fig.2 Two copies of the same XRD pattern for different materials. ![file] ,
Musca domestica larva lectin induces apoptosis in BEL-7402 cells through a mitochondria-mediated reactive oxygen species way
Authors: Chengjian Xu
Qi Zhao
Xiaohong Cao
Bin Zeng
Chunling Wang
Le Yan
Journal: Biological & pharmaceutical bulletin (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lectin; Musca domestica larva; BEL-7402 cells; apoptosis; Hoechst 33258 staining
Affiliations: Key Laboratory of Food Safety and Sanitation, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China. 

Abstract:  A lectin from Musca domestica larva was purified by affinity chromatography on a glactose-Sepharose 4B column. Musca domestica larva lectin (MLL) inhibited the growth of BEL-7402 cells in a time and concentration-dependent way. The results of Hoechst 33258 staining indicated that MLL induce BEL-7402 cells apoptosis based on the typical apoptotic morphological changes. Subsequently, we found that MLL treatment abrogated glutathione antioxidant system and induced mitochondria to generate reactive oxygen species (ROS) accumulation, resulting in reduction of mitochondrial transmembrane potential. The induction of cell apoptosis was caused by the upregulation of Bax, the downregulation of Bcl-2, the cytochrome c release and the activation of the caspases pathways. 

Retracted: No

PubPeer comments:
 Figure 3. Some cells appear to be visible in both panels A (untreated normal cells) and B (apoptotic cells), or multiple times within the same panel. Boxes of the same color show cells that look unexpectedly similar. ![file] , 
 Figure 4. Some cells appear to be visible multiple times within the same panel. Boxes of the same color show cells that look unexpectedly similar. ![file] , 
 #2 Sorry, mostly duplicate post from #1. You may also wish to carefully review Figures 3A and 3B, crudely marked up here with enhanced contrast. There appear to be common internal features. *** ![file] ,
Puerarin reduces apoptosis in rat hippocampal neurons cultured in high glucose medium by modulating the p38 mitogen activated protein kinase and c-Jun N-terminal kinase signaling pathways
Authors: Hong Zhang
Jingbo Wang
Yuqin Liu
Guoqing Tian
Xiaohan Xu
Journal: Journal of Traditional Chinese Medicine (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: neuroprotective; puerarin; hippocampal neurons; high glucose; p38 MAPK

Abstract:  Objective: To investigate the neuroprotective etfect of puerarin on rat hippocampal neurons cultured in high glucose medium, and to examine the role of the p38 mitogen activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) signaling pathways in this effect. Methods: Primary cultures of hippocampal neurons were prepared from newborn Sprague Dawley rats. Neuron-specific enolase immunocytochemistry was used to identify neurons. The neurons were cultured with normal medium (control group) or with high-glucose medium (high-glucose group), and puerarin (puerarin group), a p38 MAPK inhibitor (SB239063; p38 MAPK inhibitor group) or a JNK inhibitor (SP600125; JNK inhibitor group) were added. After 72 h of treatment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was performed to detect apoptosis, and western blotting was used to assess protein levels of p-p38, p38, p-JNK and JNK. Results: In the high-glucose group, the neuronal apoptosis rate and the p-p38/p38 and p-JNK/JNK ratios were higher than in the control group. The p38 MAPK and JNK inhibitors prevented this increase in the apoptosis rate. The apoptosis rates in the puerarin group, the p38 MAPK inhibitor group and the JNK inhibitor group were significantly decreased compared with the high-glucose group. Moreover, protein levels of p-p38 and p-JNK were significantly reduced, and the p-p38/p38 and p-JNK/JNK ratios were decreased in the puerarin group compared with the high-glucose group. In addition, compared with the high-glucose group, p-p38 levels and the p-p38/p38 ratio were reduced in the p38 MAPK inhibitor group, and p-JNK levels and the p-JNK/JNK ratio were decreased in the JNK inhibitor group. Conclusion: Puerarin attenuates neuronal apoptosis induced by high glucose by reducing the phosphorylation of p38 and JNK. 

Retracted: No

PubPeer comments:
 Figure 2. Sharp vertical transitions appear to be visible between several lanes in several panels, giving these Western blots a ransom-note like appearance, and making it hard to judge if bands are of the same molecular weight and exposed the same time. Could the authors please provide the original blots, if these are still available? Image contrast adjusted to bring out more details. ![file] ,
DNA-binding specificity and trans-activating potential of the leukemia-associated E2A-hepatic leukemia factor fusion protein
Authors: R A Ashmun
A E Sinclair
T Funabiki
T Inaba
L H Shapiro
B G Jones
A T Look
Journal: Molecular and Cellular Biology (1994)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hybrid transcription factors; gene fusions; chromosomal translocations; leukemogenesis; E2A-HLF fusion gene

Abstract:  Hybrid transcription factors, resulting from gene fusions in the wake of chromosomal translocations, have been implicated in leukemogenesis, but their precise contributions to oncogenic conversion remain unclear. The E2A-HLF fusion gene, formed by a t(17;19)(q22;p13) in childhood pro-B-cell acute lymphoid leukemia, encodes a hybrid protein that contains the trans-activation domain of E2A (E12/E47) linked to the bZIP DNA-binding and dimerization domain of hepatic leukemia factor (HLF). Here we report that both HLF and E2A-HLF bind to a 10-bp consensus sequence, 5'-GTTACGTAAT-3', with a core dyad-symmetric motif characteristic of the bZIP scissors-grip model of DNA binding. A probe containing this sequence bound chimeric E2A-HLF proteins in nuclear extracts of a leukemic cell line (UOC-B1) containing the t(17;19), as demonstrated by complexes supershifted with antibodies specific for amino-terminal epitopes of E2A or carboxyl-terminal eptiopes of HLF. E2A-HLF functioned as a potent trans activator of reporter gene expression from a plasmid that contained the consensus DNA-binding sequence. Interestingly, wild-type HLF was restricted in its capacity to act as a trans activator, functioning in human fetal kidney cells but not HepG2 hepatocarcinoma cells or NIH 3T3 mouse fibroblasts. The ability of the E2A-HLF hybrid protein to bind DNA in a sequence-specific manner and trans activate the expression of artificial reporter genes suggests that it could subvert transcriptional programs that normally control the growth, differentiation, and survival of lymphoid progenitor cells. 

Retracted: No

PubPeer comments:
 Figure 5B. https: imgur.com lmPGjMa ,
Cardiac Regeneration by Statin‐Polymer Nanoparticle‐Loaded Adipose‐Derived Stem Cell Therapy in Myocardial Infarction
Authors: Yasuhiko Tabata
Masaaki Ii
Misaki Masuda
Masaaki Hoshiga
Ryo Yokoyama
Nobukazu Ishizaka
Michio Asahi
Journal: Stem Cells Translational Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Adipose stem cells; Cardiac; Stem cell transplantation; Tissue regeneration.
Affiliations: Department of Cardiology, Faculty of Medicine, Osaka Medical College, Osaka, Japan., Division of Research Animal Laboratory and Translational Medicine, Research and Development Center, Osaka Medical College, Osaka, Japan., Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan., Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.

Abstract:  Clinical trials with autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHDs) are ongoing. However, little is known about combinational therapeutic effect of AdSCs and statin poly(lactic-co-glycolic) acid (PLGA) nanoparticles on the ischemic myocardium. We investigated the hypothesis that statins, which have pleiotropic effects, augment the therapeutic potential of AdSCs and that AdSCs also act as drug delivery tools. Simvastatin-conjugated nanoparticles (SimNPs) significantly promoted migration activity without changing proliferation activity and upregulated growth factor gene expression in vitro. A small number of intravenously administered SimNP-loaded AdSCs (10,000 cells per mouse) improved cardiac function following myocardial infarction, inducing endogenous cardiac regeneration in the infarcted myocardium. The de novo regenerated myocardium was thought to be derived from epicardial cells, which were positive for Wilms' tumor protein 1 expression. These findings were attributed to the sustained, local simvastatin release from the recruited SimNP-loaded AdSCs in the infarcted myocardium rather than to the direct contribution of recruited AdSCs to tissue regeneration. SimNP-loaded AdSCs may lead to a novel somatic stem cell therapy for IHDs. Stem Cells Translational Medicine 2019;8:1055-1067. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have a repeated image. Although both are control images, it isnu2019t clear to me that the repetition is intentional. *** ![file] *** Full figure ![file] , 
 ![file] ![file] ,
Optimising selective excitation pulses to maximise saturation transfer difference NMR spectroscopy
Authors: Richard A Williamson
Mark J Howard
Nathan B Ley
Michelle L Rowe
Journal: RSC advances (0)
Discipline: CHEMISTRY
Keywords: STD NMR; Gaussian pulse; amplification factors; ligand; wheat-germ agglutinin
Affiliations: School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.

Abstract:  A simple method is presented that optimizes the STD NMR Gaussian pulse to deliver significant increases in STD amplification factors with minimal perturbation of the ligand. This approach is practically demonstrated using the wheat-germ agglutinin/N-acetyl-D-glucosamine protein-ligand system. 

Retracted: No

PubPeer comments:
 ![file] The peak marked with an arrow in Fig 1a looks more clumsily drawn on than youu2019d normally expect an NMR peak to be. Note the circular nick at the base, and the way the peak seems to go in, out and then in again. , 
 #1 The peak is odd. However, so is the noise; this is particularly visible in the small peaks to the left. The lines really don t seem to have a uniform thickness and the noise sticks out sharply in very odd directions. I wonder whether it s not an issue with line settings in Illustrator (or other graphics program used to assemble the figure). Settings such as  cap (rounded, mitre, etc) or maybe the lines got accidentally filled. , 
 I can confirm itu2019s definitely real but understand your comments. The resolution from Adobe Illustrator for publication can create some weird effects in the PNG files. Anyone want to see the original spectrum can contact me...Iu2019m now at The University of Leeds . ,
Influence of acyl chain length on transfection mediated by acylated PEI nanoparticles
Authors: Pradeep Kumar
Surendra Nimesh
Ramesh Chandra
Anita Aggarwal
Yogendra Singh
K C Gupta
Journal: International Journal of Pharmaceutics (2007)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Polyethylenimine; nanoparticles; acylation; gene delivery; transfection
Affiliations: Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.

Abstract:  Polyethylenimine (750 kDa) has been derivatized to influence the proton sponge mechanism and hydrophobic-hydrophilic balance. The polymer was acylated using acid anhydrides of varying carbon chain length, followed by cross-linking with PEG-bis-P to form compact nanoparticles. The chemical linkages in the particles were characterized by FTIR and NMR spectroscopy. The hydrodynamic diameter of nanoparticles was found to be in the range of 83.5-124 nm. AFM imaging of native and DNA-loaded nanoparticles revealed highly compact and spherical shape. The positive surface charge on particles decreased with the increase in percentage of acylation and also on complexing with DNA. The buffering capacity of PEI was reduced considerably on preparing acylated nanoparticles. The nanoparticles formed stable complexes with DNA and higher weight ratios were required for formation of electro-neutral complexes. Further, these nanoparticles were investigated for their gene delivery efficacy on COS-1 cells. It was found that acylated PEI nanoparticles were 5-12-fold more efficient transfecting agents as compared to native PEI (750 kDa) and commercially available transfecting agent lipofectin. The MTT colorimetric assay revealed of considerable reduction in toxicity of acylated PEI nanoparticles as compared PEI. Of all the systems prepared, nanoparticles with 30% acylation using propionic anhydride were found to be the most efficient in in vitro transfection. 

Retracted: No

PubPeer comments:
 Fig. 5: (+40.0%) Brightness. Panels seem to overlap. Could authors check please? ![file] , 
 Thank you for bringing this to our notice. Indeed, another frame of the same photo has been inadvertently pasted in the next panel. We sincerely apologize for the mistake that was overlooked while preparing the manuscript. We have updated the figure as attached. Since this is a control that shows that ire-1 is required for transcription of the hsp-4::gfp transgene, a fact that is already well-established in the field, it does not change any interpretation of the data. Also, we had already provided quantification of the fluorescence data on the right-hand side, from two independent experiments, using 15-20 worms each. We will contact the journal for publishing an Erratum.![file] ,
Gold nanoparticles for sustained antileukemia drug release: development, optimization and evaluation by quality-by-design approach
Authors: Mansi Upadhyay
Sandeep Kumar Reddy Adena
Harsh Vardhan
Brahmeshwar Mishra
Journal: Nanomedicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: chronic myeloid leukemia; cytotoxicity study; dasatinib; full factorial design; gold nanoparticles
Affiliations: Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, India.

Abstract:  Aim: To design, develop, optimize and evaluate sustained-release dasatinib-loaded gold nanoparticles (DSB-GNPs) to treat chronic myeloid leukemia (CML) by using quality by design. Materials &amp; methods: In this study, we performed risk assessment, optimization, in vitro characterizations, stability study, drug release studies, cytotoxicity study and in vivo pharmacokinetic evaluation. Results: DSB-GNPs of desired size, entrapment, smooth, spherical, stable and sustained drug release for 48 h were achieved. DSB-GNPs exhibited significantly more percentage growth inhibition and enhanced systemic bioavailability compared with pure DSB. Conclusion: The in vitro and in vivo evaluation exhibited that the DSB-GNPs have a potential cytotoxic effect, systemic bioavailability and sustained release making them a promising system of DSB delivery in the treatment of chronic myeloid leukemia. 

Retracted: Yes

PubPeer comments:
 Figure 5D is same to the Figure 3F of the previously published article by same authors ![file] , 
 Figure 6A was earlier splitted as Figure 3 G and H in . ![file] , 
 Figure 7A is same as published previously as Figure 4A in https: www.tandfonline.com doi full 10.1080 03639045.2017.1402919. ![file] , 
 Figure 9A and D are same, zoom differece only. ![file] ,
Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning
Authors: Ram Yogendra
Purvi Parikh
Javier Mora
Rodrigo A Mora-Rodríguez
Amruta Pise
Edgar B Francisco
Emily Long
Jose Guevara-Coto
Bruce K Patterson
Hallison Rodrigues
Journal: Frontiers in Immunology (2021)
Discipline: IMMUNOLOGY
Keywords: CCR5; COVID-19; PASC; chemokines; cytokines.

Abstract:  Expression of CCR5 and its cognate ligands have been implicated in COVID-19 pathogenesis, consequently therapeutics directed against CCR5 are being investigated. Here, we explored the role of CCR5 and its ligands across the immunologic spectrum of COVID-19. We used a bioinformatics approach to predict and model the immunologic phases of COVID so that effective treatment strategies can be devised and monitored. We investigated 224 individuals including healthy controls and patients spanning the COVID-19 disease continuum. We assessed the plasma and isolated peripheral blood mononuclear cells (PBMCs) from 29 healthy controls, 26 Mild-Moderate COVID-19 individuals, 48 Severe COVID-19 individuals, and 121 individuals with post-acute sequelae of COVID-19 (PASC) symptoms. Immune subset profiling and a 14-plex cytokine panel were run on all patients from each group. B-cells were significantly elevated compared to healthy control individuals (P&lt;0.001) as was the CD14+, CD16+, CCR5+ monocytic subset (P&lt;0.001). CD4 and CD8 positive T-cells expressing PD-1 as well as T-regulatory cells were significantly lower than healthy controls (P&lt;0.001 and P=0.01 respectively). CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, and VEGF were all significantly elevated compared to healthy controls (all P&lt;0.001). Conversely GM-CSF and CCL4 were in significantly lower levels than healthy controls (P=0.01). Data were further analyzed and the classes were balanced using SMOTE. With a balanced working dataset, we constructed 3 random forest classifiers: a multi-class predictor, a Severe disease group binary classifier and a PASC binary classifier. Models were also analyzed for feature importance to identify relevant cytokines to generate a disease score. Multi-class models generated a score specific for the PASC patients and defined as S1 = (IFN-γ + IL-2)/CCL4-MIP-1β. Second, a score for the Severe COVID-19 patients was defined as S2 = (IL-6+sCD40L/1000 + VEGF/10 + 10*IL-10)/(IL-2 + IL-8). Severe COVID-19 patients are characterized by excessive inflammation and dysregulated T cell activation, recruitment, and counteracting activities. While PASC patients are characterized by a profile able to induce the activation of effector T cells with pro-inflammatory properties and the capacity of generating an effective immune response to eliminate the virus but without the proper recruitment signals to attract activated T cells. 

Retracted: No

PubPeer comments:
 Comments on the preprint version. https: pubpeer.com publications 8E3B611C232BC9F2FC33357B50C641#3 ,
Overexpression of RhoGDI, a novel predictor of distant metastasis, promotes cell proliferation and migration in hepatocellular carcinoma
Authors: Bin Wang
Shuzhong Cui
Liang Zhao
Xuejun Jin
Qing Liao
Hongying An
Hui Wang
Weidong Li
Journal: FEBS Letters (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hepatocellular carcinoma; Neoplasm metastasis; Rho GDP-dissociation inhibitor alpha; Signal transduction.
Affiliations: Department of Medical Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China., Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China., Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. Electronic address: .

Abstract:  RhoGDI (Rho GDP-dissociation inhibitor alpha, or RhoGDIα) was identified as a regulator of Rho GTPases, but its role in cancer remains controversial. In this study, increased expression of RhoGDI was detected in hepatocellular carcinoma (HCC) cell lines and tissues with highly metastatic potential. RhoGDI overexpression correlated with postoperative distant metastasis. Enforced expression of RhoGDI in HCC cells significantly enhanced cell proliferation and migration. Conversely, knockdown of RhoGDI caused an inhibition of the aggressive phenotypes of HCC cells. Furthermore, RhoGDI up-regulated Rho, but not Rac, and enhanced PI3K/AKT and MAPK pathway activity. Our findings suggest that RhoGDI overexpression is a predictor of distant metastasis and plays an important role in the progression of HCC. 

Retracted: No

PubPeer comments:
 Fig. 3A. More similar than expected. ![file] ,
miR-383 inhibits ovarian cancer cell proliferation, invasion and aerobic glycolysis by targeting LDHA
Authors: R L Han
P A Zhang
X Y Zhou
F P Wang
Y Li
Journal: Neoplasma (2017)
Discipline: CLINICAL MEDICINE
Keywords: LDHA; miR-383 aerobic glycolysis.; ovarian cancer.

Abstract:  MicroRNAs (miRNAs) are differentially expressed in various cancers and act as oncogenes or tumor suppressors. MiR-383 has been characterized as a cancer suppressor in several cancers. However, the exact expression patterns of miR-383 and the precise molecular mechanisms underlying its role in ovarian cancer have not been investigated thoroughly. In this study, we found that the expression of miR-383 was significantly downregulated in ovarian cancer tissues and ovarian cancer cell lines. Ectopic expression of miR-383 remarkably suppressed the ovarian cancer cell proliferation by enhancing cell apoptosis and significantly inhibited the invasion of ovarian cancer cells, while low expression of miR-383 exhibited the opposite effect. Bioinformatics analysis suggested LDHA as a novel target of miR-383, and miR-383 suppressed the expression level of LDHA mRNA by direct binding to its 3'-untranslated region (3'UTR). Expression of miR-383 was negatively correlated with LDHA in ovarian cancer tissues. In addition, modulation of miR-383 expression could affect the aerobic glycolysis in the ovarian cancer cells. Furthermore, Silencing of LDHA counteracted the effects of miR-383 suppression, while its overexpression reversed tumor inhibitory effects of miR-383. In conclusion, our study demonstrated that miR-383 regulated LDHA expression in ovarian cancer cells, thereby stunting glycolysis, cell proliferation and invasion. 

Retracted: No

PubPeer comments:
 A micrograph has been duplicated and presented as something else in Figure 5D (OVCAR3, left vs right). ![file] ,
Estradiol inhibits vascular endothelial cells pro-inflammatory activation induced by C-reactive protein
Authors: Émilie Cossette
Isabelle Cloutier
Geneviève DonPierre
Kim Tardif
Jean-François Tanguay
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: C-reactive protein; atherosclerosis; 17β-estradiol; endothelial cells; inflammation
Affiliations: Research Center, Montreal Heart Institute, 5000 Bélanger Street, Montreal, QC H1T 1C8, Canada.

Abstract:  In addition of being an important inflammatory biomarker and a risk factor for cardiovascular disease, much evidence indicates that the C-reactive protein (CRP) contributes to the atherosclerosis development process. This plasmatic protein synthesized by hepatocytes in response to inflammation and tissue injury induces pro-inflammatory molecules' expression by endothelial cells (ECs). Previous studies showed that the 17β-estradiol (E2) has beneficial effects on vascular cells by reducing in vitro pro-inflammatory molecules expressions in EC. Therefore, we hypothesize that E2 blocks or reduces CRP-mediated inflammatory responses by modulating endogenous production of CRP in EC and/or activation mechanisms. Using human aortic ECs (HAECs), we first evaluated CRP production by vascular EC and second demonstrated its self-induction. Indeed, recombinant human CRP stimulation induces a fivefold increase of CRP expression. A 1-h pre-treatment of E2 at a physiologic dose (10(-9 )M) leads to an important decrease of CRP production suggesting a partial blockage of its amplification loop mechanism. Furthermore, in HAEC, E2 reduces the secretion of the most potent agonist of CRP induction, the IL-6, by 21 %. E2 pre-treatment also decreased the expression of pro-inflammatory molecules IL-8, VCAM-1, and ICAM-1 induced by CRP and involved in leukocytes recruitment. In addition, we demonstrated that E2 could restore vascular endothelial growth factor-mediated EC migration response impaired by CRP suggesting another pro-angiogenic property of this hormone. These findings suggest that E2 can interfere with CRP pro-inflammatory effects via activation signals using its rapid, non-genomic pathway that may provide a new mechanism to improve vascular repair. 

Retracted: No

PubPeer comments:
 Figure 5. * Orange boxes: The  NS and  E2 panels appear to look similar. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. I would love to hear from the authors if the journal ever contacted them in the past five years. This looks like an easy-to-fix error. ![file] ,
Effect of tumor necrosis factor-α on neutralization of ventricular fibrillation in rats with acute myocardial infarction
Authors: Yu Chen
Jia-Ding Xia
Yi-Mei Du
Zhe Cao
Qing Zhang
Hua Yang
Zhi-Jian Chen
Yu-Hua Liao
Journal: Mediators of Inflammation (2011)
Discipline: IMMUNOLOGY
Keywords: tumor necrosis factor-α; ventricular fibrillation; acute myocardial infarction; rats; Monophasic action potentials
Affiliations: Department of Cardiology, Wuhan Union Hospital and Institute of Cardiovascular Disease, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1277, Jianghan District, Wuhan 430022, China., Department of Cardiology, Wuhan Union Hospital and Institute of Cardiovascular Disease, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1277, Jianghan District, Wuhan 430022, China

Abstract:  The purpose of this study was to explore the effects of tumor necrosis factor-α (TNF-α) on ventricular fibrillation (VF) in rats with acute myocardial infarction (AMI). Rats were randomly classified into AMI group, sham operation group and recombinant human tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc) group. Spontaneous and induced VFs were recorded. Monophasic action potentials (MAPs) among different zones of myocardium were recorded at eight time points before and after ligation and MAP duration dispersions (MAPDds) were calculated. Then expression of TNF-α among different myocardial zones was detected. After ligation of the left anterior descending coronary artery, total TNF-α expression in AMI group began to markedly increase at 10 min, reached a climax at 20-30 min, and then gradually decreased. The time-windows of VFs and MAPDds in the border zone performed in a similar way. At the same time-point, the expression of TNF-α in the ischemia zone was greater than that in the border zone, and little in the non-ischemia zone. Although the time windows of TNF-α expression, the MAPDds in the border zone and the occurrence of VFs in the rhTNFR:Fc group were similar to those in the AMI group, they all decreased in the rhTNFR:Fc group. Our findings demonstrate that TNF-α could enlarge the MAPDds in the border zone, and promote the onset of VFs. 

Retracted: No

PubPeer comments:
 image duplication ![file] 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. ,
Lycorine Displays Potent Antitumor Efficacy in Colon Carcinoma by Targeting STAT3
Authors: Chunze Zhang
Haiyang Yu
Yuling Qiu
Lifeng Han
Xiumei Gao
Xu Pang
Yingying Shao
Tao Wang
Bo Wu
Yi Zhang
Junhong Ma
Song Wu
Rui Wang
Sangho Koo
Shuangshuang Yin
Journal: Frontiers in Pharmacology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: STAT3; apoptosis; colorectal cancers; lycorine; target.
Affiliations: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China., School of Pharmacy, Tianjin Medical University, Tianjin, China., Department of Gastrointestinal Surgery, Nankai Hospital, Tianjin, China., Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China., School of Fundamental Sciences, China Medical University, Shenyang, China., Department of Chemistry, Myongji University, Seoul, South Korea.

Abstract:  Signal transducer and activator of transcription 3 (STAT3) is an attractive therapeutic target for cancer treatment. In this study, we identify lycorine is an effective inhibitor of STAT3, leading to repression of multiple oncogenic processes in colon carcinoma. Lycorine selectively inactivates phospho-STAT3 (Tyr-705), and subsequent molecular docking uncovers that lycorine directly binds to the SH2 domain of STAT3. Consequently, we find that lycorine exhibits anti-proliferative activity and induces cell apoptosis on human colorectal cancer (CRC) in vitro. Lycorine induces the activation of the caspase-dependent mitochondrial apoptotic pathway, as indicated by activation of caspase and increase of the ratio of Bax/Bcl-2 and mitochondrial depolarization. Overexpressing STAT3 greatly blocks these effects by lycorine in CRC cells. Finally, lycorine exhibits a potential therapeutic effect in xenograft colorectal tumors by targeting STAT3 without observed toxicity. Taken together, the present study indicates that lycorine acts as a promising inhibitor of STAT3, which blocks tumorigenesis in colon carcinoma. 

Retracted: No

PubPeer comments:
 An image in Figure 6F shares unexpected similarities with an image in Figure 7 of a different paper: Journal of Cancer (2019), doi: 10.7150 jca.25163, discussed here: https: pubpeer.com publications 59A1F81047C2848FF1D80D728608FB There does not appear to be any overlap between the authors or affiliations. Given the dates that the papers were received and were published, I am not entirely certain which group had the image first... perhaps a third party was involved? *** ![file] *** FUNDING This work was supported by from National Natural Science Foundation of China (Grant Nos. 81603253 and 21711540293 to HY, Grant No. 81673703 to TW, Grant No. 81602614 to YQ, Grant No. 81501578 to BD), Natural Science Foundation of Tianjin City (Grant No. 15JCYBJC54900 to HY, Grant No. 15PTCYSY00030 to ZL), and Tianjin Health and Family Planning Commission (Grant No. 2017057 to CZ). ,
Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice
Authors: Arun Chauhan
Mohammad Azam Ansari
Amer M Alanazi
Azmat Ali Khan
Mumtaz Jabeen
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: siRNA; delivery; GalNAc; PEGylated PLGA; nanoconjugates
Affiliations: Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia. ., Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia., Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh, 202002, India., Department of Neuroimmunology, School of Health and Medicine, University of North Dakota, Grand Forks, ND, USA., Department of Epidemic Disease Research, Institutes of Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, 31441, Dammam, Saudi Arabia.

Abstract:  Short interfering RNA (siRNA) possesses special ability of silencing specific gene. To increase siRNA stability, transportation and its uptake by tumor cells, effective delivery to the appropriate target cells is a major challenge of siRNA-based therapy. In the present study, an effective, safe and biocompatible survivin siRNA encapsulated, GalNAc decorated PEGylated PLGA nanoconjugates (NCs) viz., GalNAc@PEG@siRNA-PLGA were engineered and their synergistic antitumor efficacy was evaluated for targeted delivery in HCC bearing experimental mice. GalNAc@PEG@siRNA-PLGA NCs were characterized for size, bioavailability, toxicity and biocompatibility. Their antitumor potential was evaluated considering gene silencing, apoptosis, histopathology and survival of treated mice. Exceptional accumulation of hepatocytes, reduction in survivin expression and prominent regression in tumor size confirmed the ASGPR-mediated uptake of ligand-anchored NCs and silencing of survivin gene in a targeted manner. Increased DNA fragmentation and potential modulation of caspase-3, Bax and Bcl-2 factors specified the induction of apoptosis that helped in significant inhibition of HCC progression. The potential synchronous and tumor selective delivery of versatile NCs indicated the effective payloads towards the target site, increased apoptosis in cancer cells and improved survival of treated animals. 

Retracted: No

PubPeer comments:
 In figure 5C the migration and invasion photos for si-SPRY4-IT1 are of the same cells. ![file] ,