PReD-Bench/PRed-Bench huggingface dataset:
Evaluation of the efficacy of paclitaxel with curcumin combination in ovarian cancer cells
Authors: Yuan-Yuan Zhu
Si-Qing Ning
Zeng Liu
Zhao-Yuan Li
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: curcumin; multidrug resistance; nanoparticles; ovarian cancer; paclitaxel.
Affiliations: Department of Nuclear Medicine, Central Hospital of Xiangyang, Xiangyang, Hubei 441021, P.R. China., No. 1 Hospital of Xiangyang, Xiangyang, Hubei 441000, P.R. China.

Abstract:  The aim of the present study was to evaluate the efficacy of paclitaxel combined with curcumin (CUR) against drug resistance in ovarian cancer cells. PLGA-phospholipid-PEG nanoparticles were prepared using the nano precipitation method. The size and morphology of the nanoparticles were determined using a transmission electron microscope and particle size analyzer. The encapsulation efficiency of nanoparticles was determined using the ultrafiltration centrifugation method. The dialysis method was used to study the release of PLGA-phospholipid-PEG nanoparticles. ADM was used to induce the A2780 cell line (human ovarian cancer cell line) to establish the model of the multidrug-resistant (MDR) cell line, and the protein activity of P-glycoprotein (P-gp) in the A2780 cell line and A2780/ADM resistant cell line was determined using western blot analysis. The results showed that, the prepared nanoparticles were uniform in size, with a size of approximately 100 nm, and round in shape. Additionally, the nanoparticles had a more gentle and slow release than the free drug release. The results of the protein trace printing experiment showed that the P-gp content of the drug-resistant cell line was significantly reduced by the CUR nanoparticles. In conclusion, PLGA-phospholipid nanoparticles containing taxol and CUR have improved solubility and stability together with a slow release effect. In addition, CUR was able to overcome the MDR of tumor cells by elevating the paclitaxel concentration in the tumor cells to improve the antitumor activity of this combination. 

Retracted: No

PubPeer comments:
  Figure 4. - The expression of P-glycoprotein (P-gp) protein in the two types of cells . ![file] Not clear on the concept of  loading control . Suggested by a colleague on social media. ,
Early impact of a fat-enriched diet on behavioral responses of male and female rats
Authors: E Papalexi
G Soulis
E Kitraki
C Kittas
Journal: Behavioral Neuroscience (2007)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: high-fat diets; stress responsiveness; neuroendocrine level; behavioral impact; moderately fat diet
Affiliations: Laboratory of Histology and Embryology, Athens University Medical School, Athens, Greece.

Abstract:  Prolonged high-fat diets have been shown to affect an organism's stress responsiveness at the neuroendocrine level. In the present study, the authors used a 7-day protocol of fat administration in adult rats of both sexes to investigate the early behavioral impact of a moderately fat (20%) diet, often used by Western societies, on rats' reaction to acute stress and novelty. Their results show that this diet can reduce the rats' active behavioral responses to subsequent stressors and influence their corticosterone secretion. Fat-fed male rats adopted a less active behavior to cope with forced swimming stress, whereas their exploratory behavior in the open field environment was rather increased compared with chow-fed males. Fat-fed female rats exhibited a less active behavioral response to both stress paradigms compared with their chow-fed counterparts. Fat diet abolished facilitation in corticosterone secretion following a subsequent stressor in both sexes. However, only in males did fat diet exaggerate corticosterone response to novelty, irrespective of the previous stress history of the rat. These data indicate that a short-term metabolic stress can modify the rats' stress coping strategy in interaction with the gender. 

Retracted: No

PubPeer comments:
 Fig 6J,  H929 cells transfected with Agomir NC + sh-NC, Agomir miR-27 + sh-NC, or Agomir miR-27 + sh-Notch1 were subcutaneously injected into nude mice . ![file] Fig 4b from [Yang et al (2021)] ,  Representatives images of transplanted tumors formed in nude mice . ![file] Two rulers have the same smudges or stains despite being used in laboratories in different institutions (different provinces, in fact). How did this happen? ![file] , 
 Retracted [30 December 2021] . ------------------------- The journal and Chief Editors retract the 11 November 2020 article cited above. Following publication, concerns were raised regarding the validity of the data in the article. The authors failed to provide the raw data or a satisfactory explanation during the investigation, which was conducted in accordance with Frontiersu2019 policies. Given the concerns, and the lack of raw data, the editors no longer have confidence in the findings presented in the article. This retraction was approved by the Chief Editors of Frontiers in Oncology and the Chief Executive Editor of Frontiers. The authors have not responded to any correspondence regarding the retraction. ,
Effects of Orange Extracts on Longevity, Healthspan, and Stress Resistance in Caenorhabditis elegans
Authors: Ling Chen
Hong Wang
Na Deng
Tong Li
Rui Hai Liu
Jing Wang
Bisheng Zheng
Journal: Molecules (2020)
Discipline: CHEMISTRY
Keywords: C. elegans; anti-aging; antioxidant properties; orange extracts.
Affiliations: Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China., Department of Food Science, Stocking Hall, Cornell University, Ithaca, NY 14853, USA., Ministry of Education Engineering Research Centre of Starch & Protein Processing, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China.

Abstract:  Orange, with various bioactive phytochemicals, exerts various beneficial health effects, including anti-cancer, antioxidant, and anti-inflammatory properties. However, its anti-aging effects remain unclear. In this study, the Caenorhabditis elegans (C. elegans) model was used to evaluate the effects of orange extracts on lifespan and stress resistance. The results indicated that orange extracts dose-dependently increased the mean lifespan of C. elegans by 10.5%, 18.0%, and 26.2% at the concentrations of 100, 200, and 400 mg/mL, respectively. Meanwhile, orange extracts promoted the healthspan by improving motility, and decreasing the accumulation of age pigment and intracellular reactive oxygen species (ROS) levels without damaging fertility. The survival rates of orange extract-fed worms were obviously higher than those of untreated worms against thermal and ultraviolet-B (UV-B) stress. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly enhanced while malondialdehyde (MDA) contents were diminished. Further investigation revealed that worms supplemented with orange extracts resulted in upregulated levels of genes, including daf-16, sod-3, gst-4, sek-1, and skn-1, and the downregulation of age-1 expression. These findings revealed that orange extracts have potential anti-aging effects through extending the lifespan, enhancing stress resistance, and promoting the healthspan. 

Retracted: No

PubPeer comments:
 There are serveral issues where numbers are repeated in Table 2 which is odd. ![file] , 
 Thanks for your comments. We checked for the raw data, as follows: (1) Table 2: ![file] (2) Table 3: ![file] Thus, data were as shown in the paper. ,
Regulation of hepatic insulin-like growth factor-binding protein-1 gene expression by insulin: central role for mammalian target of rapamycin independent of forkhead box O proteins
Authors: Barry I Posner
Victor Dumas
Catherine Mounier
Journal: Endocrinology (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: IGF-binding protein-1; insulin; PI3 kinase; Akt; Foxo1
Affiliations: Polypeptide Hormone Laboratory, Faculty of Medicine, McGill University, Montréal, Quebéc, Canada.

Abstract:  The expression of IGF-binding protein-1 (IGFBP-1) is induced in rat liver by dexamethasone and glucagon and is completely inhibited by 100 nM insulin. Various studies have implicated phosphatidylinositol 3-kinase, protein kinase B (Akt), phosphorylation of the transcription factors forkhead in rhabdomyosarcoma 1 (Foxo1)/Foxo3, and the mammalian target of rapamycin (mTOR) in insulin's effect. In this study we examined insulin regulation of IGFBP-1 in both subconfluent and confluent hepatocytes. In subconfluent hepatocytes, insulin inhibition of IGFBP-1 mRNA levels was blocked by inhibiting PI3 kinase activation, and there was a corresponding inhibition of Foxo1/Foxo3 phosphorylation. In these same cells, inhibition of the insulin effect by rapamycin occurred in the presence of insulin-induced Foxo1/Foxo3 phosphorylation. In confluent hepatocytes, insulin could not activate the phosphatidylinositol 3-kinase (PI3 kinase)-Akt-Foxo1/Foxo3 pathway, but still inhibited IGFBP-1 gene expression in an mTOR-dependent manner. In subconfluent hepatocytes, the serine/threonine phosphatase inhibitor okadaic acid (100 nM) partially inhibited IGFBP-1 gene expression by 40%, but did not produce phosphorylation of either Akt or Foxo proteins. In contrast, 1 nm insulin inhibited the IGFBP-1 mRNA level by 40% and correspondingly activated Akt and Foxo1/Foxo3 phosphorylation to a level comparable to that observed with 100 nM insulin. These results suggest a potential role for a serine/threonine phosphatase(s) in the regulation of IGFBP-1 gene transcription, which is not downstream of mTOR and is independent of Akt. In conclusion, we have found that in rat liver, insulin inhibition of IGFBP-1 mRNA levels can occur in the absence of the phosphorylation of Foxo1/Foxo3, whereas activation of the mTOR pathway is both necessary and sufficient. 

Retracted: No

PubPeer comments:
 Figure 6 seems to present a splicing. Also left and right panels are more similar than expected ![file] ,
MicroRNA‐99b suppresses human cervical cancer cell activity by inhibiting the PI3K/AKT/mTOR signaling pathway
Authors: Yue Wang
Yi-Ying Wang
Yong-Jie Li
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PI3K/AKT/mTOR; cell invasion; cell migration; cervical cancer; microRNA-99b
Affiliations: Department of Obstetrics and GynecologyHenan Provincial People's Hospital, People's Hospital of Zhengzhou UniversityZhengzhou China

Abstract:  Cervical cancer is common cancer among women with high morbidity. MicroRNAs (miRs) are involved in the progression and development of cervical cancer. This study aimed to explore the effect of miR-99b-5p (miR-99b) on invasion and migration in cervical cancer through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. The microarray-based analysis was used to screen out differentially expressed miRNAs. Expression of miR-99b, PI3K, AKT, mTOR, and ribosomal protein S6 kinase (p70S6K) was determined in both cervical cancer tissues and paracancerous tissues. Next, alteration of miR-99b expression in cervical cancer was conducted to evaluate levels of PI3K, AKT, mTOR, p70S6K matrix metallopeptidase 2, epithelial cell adhesion molecule, and intercellular adhesion molecule 1, as well as the effect of miR-99b on cell proliferation, invasion, migration, cell cycle distribution, and apoptosis. The results demonstrated that miR-99b expression was decreased and levels of PI3K, AKT, mTOR, and p70S6K were elevated in cervical cancer tissues. More important, overexpressed miR-99b repressed the PI3K/AKT/mTOR signaling pathway, inhibited cell proliferation, invasion, and migration, blocked cell cycle entry, and promoted apoptosis in cervical cancer. These results indicate that miR-99b attenuates the migration and invasion of human cervical cancer cells through downregulation of the PI3K/AKT/mTOR signaling pathway, which provides a therapeutic approach for cervical cancer treatment. 

Retracted: Yes

PubPeer comments:
 Images in Figure 5A appear to overlap. *** ![file] ![file] , 
 I admit I am confused by Figure 9. *** ![file] ,
Combining cues to judge distance and direction in an immersive virtual reality environment
Authors: Andrew Glennerster
Peter Scarfe
Journal: Journal of vision (2021)
Discipline: CLINICAL MEDICINE
Keywords: visual direction; cue combination rules; virtual reality; head-mounted display; proprioceptive information
Affiliations: University of Reading, Earley Gate, Reading, UK., .

Abstract:  When we move, the visual direction of objects in the environment can change substantially. Compared with our understanding of depth perception, the problem the visual system faces in computing this change is relatively poorly understood. Here, we tested the extent to which participants' judgments of visual direction could be predicted by standard cue combination rules. Participants were tested in virtual reality using a head-mounted display. In a simulated room, they judged the position of an object at one location, before walking to another location in the room and judging, in a second interval, whether an object was at the expected visual direction of the first. By manipulating the scale of the room across intervals, which was subjectively invisible to observers, we put two classes of cue into conflict, one that depends only on visual information and one that uses proprioceptive information to scale any reconstruction of the scene. We find that the sensitivity to changes in one class of cue while keeping the other constant provides a good prediction of performance when both cues vary, consistent with the standard cue combination framework. Nevertheless, by comparing judgments of visual direction with those of distance, we show that judgments of visual direction and distance are mutually inconsistent. We discuss why there is no need for any contradiction between these two conclusions. 

Retracted: No

PubPeer comments:
 A conversation with the second author about this paper s depth distance cue modelling, plus discussion of the broader context of modelling in vision. https: psyarxiv.com nmrqv ,
MicroRNA-449a Is Downregulated in Cervical Cancer and Inhibits Proliferation, Migration, and Invasion
Authors: Lianyun Wang
Wen Ye
Ying Hua
Yu Zhao
Wendong Xiong
Weidong Zhao
Journal: Oncology Research and Treatment (2019)
Discipline: CLINICAL MEDICINE
Keywords: Cervical cancer; Invasion; MicroRNA-449a; Migration; Prognosis
Affiliations: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China, .

Abstract:  Introduction: Cervical cancer is one of the most common malignant tumors among women in the world. MicroRNA-449a (miR-449a) has been identified as a tumor suppressor gene in various cancers. Our present study aimed to explore the biological role of miR-449a in cervical cancer. Methods: The expression of miR-449a in cervical cancer tissues and cell lines was detected using real-time quantitative PCR. Kaplan-Meier survival analysis and a Cox regression assay were used to identify the prognostic significance of miR-449a in cervical cancer. A CCK-8 assay and a Transwell assay were performed to determine the impact of miR-449a on the proliferation, migration, and invasion of cervical cancer cells. Results: The expression of miR-449a was decreased in both cervical cancer tissues and cell lines. The decreased expression of miR-449a was significantly associated with lymph node metastasis, differentiation, and FIGO stage, as well as with poor survival. In vitro, transfection of miR-449a mimic into cervical cancer cells inhibited cell proliferation, migration, and invasion. Conclusion: All of the results revealed that miR-449a functions as a suppressor gene and inhibits cell proliferation, migration, and invasion in cervical cancer. In addition, it may serve as a prognostic biomarker for cervical cancer. 

Retracted: No

PubPeer comments:
 Figure 4A. * Red boxes: two panels appear to show an overlap. ![file] ,
Cross-talk between oxysterols and glucocorticoids: differential regulation of secreted phopholipase A2 and impact on oligodendrocyte death
Authors: Christian Slomianny
Charbel Massaad
Sophie Bernard
Patrice X Petit
Amalia Trousson
Michael Schumacher
Joelle Makoukji
Journal: PLoS ONE (2009)
Discipline: Multidisciplinary
Keywords: Oxysterols; Glucocorticoids; Oligodendrocytes; Apoptosis; Inflammation
Affiliations: UMR788, Inserm and University Paris-Sud 11, IFR 93, Le Kremlin-Bicêtre, France.

Abstract:  Background: Oxysterols are oxidized forms of cholesterol. They have been shown to be implicated in cholesterol turnover, inflammation and in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis. Glial cells are targets of oxysterols: they inhibit astrocyte proliferation after brain injury, and we have previously shown that 25-hydroxycholesterol (25OH) provokes oligodendrocyte apoptosis and stimulates the expression of sPLA2 type IIA (sPLA2-IIA), which has a protective effect. Methodology/principal findings: As glucocorticoids are well-known for their anti-inflammatory effects, our aim was to understand their direct effects on oxysterol-induced responses in oligodendrocytes (sPLA2-IIA stimulation and apoptosis). We demonstrate that the synthetic glucocorticoid dexamethasone (Dex) abolishes the stimulation of sPLA2-IIA by 25-hydroxycholesterol (25-OH). This inhibition is mediated by the glucocorticoid receptor (GR), which decreases the expression of the oxysterol receptor Pregnane X Receptor (PXR) and interferes with oxysterol signaling by recruiting a common limiting coactivator PGC1alpha. Consistent with the finding that sPLA2-IIA can partially protect oligodendrocytes against oxysterol-triggered apoptosis, we demonstrate here that the inhibition of sPLA2-IIA by Dex accelerates the apoptotic phenomenon, leading to a shift towards necrosis. We have shown by atomic force microscopy and electron microscopy that 25-OH and Dex alters oligodendrocyte shape and disorganizes the cytoplasm. Conclusions/significance: Our results provide a new understanding of the cross-talk between oxysterol and glucocorticoid signaling pathways and their respective roles in apoptosis and oligodendrocyte functions. 

Retracted: No

PubPeer comments:
 Figure 6B. Much more similar than you would expect. https: imgur.com cv1JTpD , 
 We contacted the external collaborator who was responsible for the flow cytometry experiments. We asked this co-author to provide us with the raw data. ,
Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations
Authors: Emilia Rejmak
Carmen Sandi
Michael A van der Kooij
Martina Fantin
Celine Fournier
Katarzyna Kalita
Jocelyn Grosse
Krishnendu Ganguly
Olivia Zanoletti
Leszek Kaczmarek
Journal: Nature Communications (2014)
Discipline: Multidisciplinary
Keywords: Chronic stress; psychopathologies; cognitive dysfunction; social behaviours; cell adhesion molecules
Affiliations: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne 1015, Switzerland., Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street 02-093 Warsaw, Poland.

Abstract:  Chronic stress is a risk factor for the development of psychopathologies characterized by cognitive dysfunction and deregulated social behaviours. Emerging evidence suggests a role for cell adhesion molecules, including nectin-3, in the mechanisms that underlie the behavioural effects of stress. We tested the hypothesis that proteolytic processing of nectins by matrix metalloproteinases (MMPs), an enzyme family that degrades numerous substrates, including cell adhesion molecules, is involved in hippocampal effects induced by chronic restraint stress. A reduction in nectin-3 in the perisynaptic CA1, but not in the CA3, compartment is observed following chronic stress and is implicated in the effects of stress in social exploration, social recognition and a CA1-dependent cognitive task. Increased MMP-9-related gelatinase activity, involving N-methyl-D-aspartate receptor, is specifically found in the CA1 and involved in nectin-3 cleavage and chronic stress-induced social and cognitive alterations. Thus, MMP-9 proteolytic processing emerges as an important mediator of stress effects in brain function and behaviour. 

Retracted: No

PubPeer comments:
 ![file] , 
 Figure 1d enhanced contrast ![file] ,
LncRNA SNHG7 promotes the proliferation and inhibits apoptosis of renal cell cancer cells by downregulating CDKN1A
Authors: B Jiang
B Wu
J-S Dong
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; SNHG7; RCC; tumor progression; cell proliferation
Affiliations: Department of Urology Surgery, Lianshui County People's Hospital, Huaian, China. .

Abstract:  Objective: Recent studies have revealed that long non-coding RNAs (lncRNAs) have a crucial role in tumor progression. Renal cell cancer (RCC) is a common type of fatal gynecological cancer worldwide. This study aims to identify the role of lncRNA Small nucleolar RNA host gene 7 (SNHG7) in the progression of RCC. Patients and methods: Expression of lncRNA SNHG7 in both RCC cells and 50 pairs of tissue samples was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, the function of SNHG7 was identified by performing cell apoptosis assay, colony formation assay and proliferation assay in vitro. The underlying mechanism assays including RT-qPCR and Western blot assay were conducted. Results: SNHG7 expression was remarkably upregulated in tumor tissues when compared with adjacent tissues. Moreover, RCC cell proliferation was inhibited and cell apoptosis was promoted after knockdown of SNHG7 in vitro. Moreover, after knockdown of SNHG7, CDKN1A was upregulated at mRNA and protein level in vitro. Furthermore, the expression of CDKN1A in tumor tissues was negatively correlated to the expression of SNHG7. Conclusions: These results above suggest that SNHG7 could promote cell proliferation and inhibit cell apoptosis in RCC through downregulating CDKN1A, which may offer a new therapeutic intervention for RCC patients. 

Retracted: Yes

PubPeer comments:
 ![file] Figure 7 apoptosis assay by flowcytometry. The images marked with same color are duplicated and manipulated by changing the gating. ,
Peptidomimetic inhibitors of APC–Asef interaction block colorectal cancer migration
Authors: Xinyi Liu
Y Eugene Chinn
Yanlong Zhao
Jian Li
Qiufen Zhang
Xiuyan Yang
Kun Song
Shaoyong Lu
Jian Zhang
Rong Deng
Yu Chen
Guoqiang Chen
Jialin Shang
Geng Wu
Haiming Jiang
Jianxiu Yu
Journal: Nature Chemical Biology (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: adenomatous polyposis coli (APC); Asef; cell migration; colorectal cancer; peptidomimetics
Affiliations: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai, China., Department of Biochemistry and Molecular Cell Biology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao-Tong University School of Medicine, Shanghai, China., Medicinal Bioinformatics Center, Shanghai Jiao-Tong University School of Medicine, Shanghai, China., State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, China., Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai, China., State Key Laboratory of Microbial Metabolism, Shanghai Jiao-Tong University, Shanghai, China., Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Abstract:  The binding of adenomatous polyposis coli (APC) to its receptor Asef relieves the negative intramolecular regulation of Asef and leads to aberrant cell migration in human colorectal cancer. Because of its crucial role in metastatic dissemination, the interaction between APC and Asef is an attractive target for anti-colorectal-cancer therapy. We rationally designed a series of peptidomimetics that act as potent inhibitors of the APC interface. Crystal structures and biochemical and cellular assays showed that the peptidomimetics in the APC pocket inhibited the migration of colorectal cells by disrupting APC-Asef interaction. By using the peptidomimetic inhibitor as a chemical probe, we found that CDC42 was the downstream GTPase involved in APC-stimulated Asef activation in colorectal cancer cells. Our work demonstrates the feasibility of exploiting APC-Asef interaction to regulate the migration of colorectal cancer cells, and provides what to our knowledge is the first class of protein-protein interaction inhibitors available for the development of cancer therapeutics targeting APC-Asef signaling. 

Retracted: No

PubPeer comments:
 In the supplementary information there is a puzzling figure. The two WB are very similar except for a different contrast and the beta-actin line. In the paper I couldn t find an explanation for this, could authors explain it? ![file] ,
microRNA-126 targeting PIK3R2 promotes rheumatoid arthritis synovial fibro-blasts proliferation and resistance to apoptosis by regulating PI3K/AKT pathway
Authors: Xiao-Li Zhou
Dong-Bao Zhao
Lian-Mei Ji
Jie Gao
Rui-Na Kong
Ling-Ling He
Journal: Experimental and Molecular Pathology (2016)
Discipline: CLINICAL MEDICINE
Keywords: Apoptosis; PI3K/AKT signaling pathway; PIK3R2; Proliferation; Rheumatoid arthritis
Affiliations: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China., Department of Pathology, Changzhou Second People's Hospital, Changzhou 213003, PR China., Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China. Electronic address: .

Abstract:  Objective: The purpose of our study was to elucidate the impact of microRNA-126 (miR-126) targeting PIK3R2 gene on cell proliferation and apoptosis of rheumatoid arthritis synovial fibro-blasts (RASFs) by regulating PI3K/AKT signal pathway. Methods: The synovial tissue samples of this study were from 55 RA patients undergoing joint replacement and 27 healthy people undergoing joint repair due to trauma. The target genes of miR-126 were collected by the TargetScan and PIK3R2 as the direct target gene of miR-126 was confirmed by dual-luciferase reporter assay system. Our experiment had five groups including the blank control, miR-126 mimic, miR-126 mimic control, miR-126 inhibitor and miR-126 inhibitor control groups. Additionally, real-time quantitative polymerase chain reaction (RT-qPCR), Western-Blot, cell counting kit (CCK-8) and flow cytometry were carried out in this study. Results: Compared with healthy individuals, the RA patients had increased miR-126, but decreased PIK3R2 mRNA expressions in the synovial tissues. Pearson correlation analysis indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression (all P&lt;0.05). When compared with the blank group respectively, the miR-126 mimic group had raising cell proportions in S and G2/M phases with reduced rate of cell apoptosis, while the miR-126 inhibitor group had raising cell proportions in G0/G1 and G2/M phases with increased rate of cell apoptosis (all P&lt;0.05). Besides, compared with the blank control group, the miR-126 mimic group had declined expression of PIK3R2 protein with ascended expression of PI3K and p-AKT (all P&lt;0.05), while the miR-126 inhibitor group had increased expression of PIK3R2 protein with decreased expression of PI3K and p-AKT (all P&lt;0.05). Conclusion: Our study demonstrated that down-regulation of miR-126 may indirectly inhibit PI3K/AKT signaling pathway to disrupt the imbalance between growth and death of RASFs by targeting PIK3R2, which may be clinically helpful to find therapeutic strategies directed toward miR-126 function for RA patients. 

Retracted: No

PubPeer comments:
 Fig 5: ![file] Panels (a) and (b) have similarities in the lower left quadrants. (a) and (d) are very simlar in their right halves. ![file] Someone used (e) for target practice. ![file] ,
Accelerative effect of a selective cyclooxygenase-2 inhibitor on Fas-mediated apoptosis in human neutrophils
Authors: Masaru Ohashi
Masao Nagumo
Masayasu Iwase
Gen Kondo
Hitoshi Watanabe
Makiko Uchida
Sayaka Takaoka
Journal: International Immunopharmacology (2006)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Inflammatory stimuli; cytokines; cyclooxygenase-2 (COX-2); selective COX-2 inhibitors; tumor cell growth
Affiliations: Department of Oral and Maxillofacial Surgery, Showa University School of Dentistry, 2-1-1, Kitasenzoku, Ota-ku, Tokyo, 145-8515, Japan. 

Abstract:  Inflammatory stimuli, such as cytokines, can induce cyclooxygenase-2 (COX-2) expression in neutrophils. Selective, anti-inflammatory COX-2 inhibitors have been developed for patients with acute inflammatory diseases. Recent work has shown that selective COX-2 inhibitors interfere with tumor cell growth. The purpose of this study was to examine the capability of selective COX-2 inhibitors on Fas-mediated apoptosis in cytokine-stimulated neutrophils. Tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced prostaglandin E2 (PGE2) release through the induction of COX-2 in neutrophils. This effect was not seen with either interleukin (IL)-1beta or IL-8. TNF-alpha-and GM-CSF-induced PGE2 release was blocked by the addition of the selective COX-2 inhibitor, N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide (NS-398; 1 microM). GM-CSF, IL-1beta and IL-8 suppressed Fas-mediated apoptosis in neutrophils; however, this effect was not seen with TNF-alpha. The anti-apoptotic effect of cytokines on Fas-mediated neutrophil apoptosis was attenuated by the addition of NS-398 (100 microM). These results suggest that NS-398 operates via two distinct mechanisms for regulating apoptosis and COX-2 activation in neutrophils. This distinction is indicated by the difference in concentration of NS-398 required for acceleration of Fas-mediated neutrophil apoptosis, and the inhibition of PGE2 synthesis. Moreover, NS-398 suppressed the anti-apoptotic activity of IL-8 and IL-1beta, but did not induce COX-2; therefore, the pro-apoptotic mechanism of the selective COX-2 inhibitor may be unrelated to COX-2 activity. Thus, a selective COX-2 inhibitor may contribute to the reduction of acute inflammation through the enhancement of neutrophil apoptosis. 

Retracted: No

PubPeer comments:
 Figure 1: undisclosed splice (arrow), but not in control. Figure 2: much more similar than expected (blue boxes). ![file] , 
 Dear Dr. Aneurus Inconstans Thank you for the appropriate comments. I quit university 11 years ago and haven t been doing any research since then. My colleagues Dr. Kondo, Dr. Takaoka and Dr. Uchida also retired from college more than 10 years ago. I have tried to visit the academia to verify and confirm the data against your comment. However, because of COVID-19, the government is requesting restrictions on movement and actions. I would be grateful if you could give me some time. , 
 #1 There may be additional issues in these two figures (cyan). *** False color ![file] ,
New experimental correlation for the thermal conductivity of ethylene glycol containing Al2O3–Cu hybrid nanoparticles
Authors: Parsian, Amir
Akbari, Mohammad
Journal: Journal of Thermal Analysis and Calorimetry (2018)
Discipline: CHEMISTRY
Keywords: thermal conductivity; Al2O3-Cu/EG nanofluid; nanoparticles; dispersion; volume concentration

Abstract: In the present study, the thermal conductivity of the Al2O3–Cu/EG has been experimentally investigated. For this purpose, a mixture of Al2O3 and Cu nanoparticles with a ratio of 50:50 was dispersed in ethylene glycol at different concentrations (0.125, 0.25, 0.5, 1.0, 1.5 and 2.0) and temperatures (25–50&nbsp;°C). The two-step method is used for dispersing nanoparticles in the base fluid. Results show that the thermal conductivity of nanofluid is more than the base fluid, and it depends on volume concentration and temperature. Experimental results have been compared with some of the most famous models, and it has been found that these models are unable to predict the thermal conductivity of investigated nanofluid. Finally, based on the experimental data, a correlation is presented as a function of the temperature and volume fraction of nanoparticles.

Retracted: No

PubPeer comments:
 Same **Springer** journal, same image is duplicated after 3 years of publication of the previous one for **AL2O3**! One time with **WATER**, next time with **ETHYLENE GLYCOL!** **Omid Mahian** (SENIOR ASSOCIATE EDITOR) and **Somchai Wongwises** (ASSOCIATE EDITOR) in the ***Journal of Thermal Analysis and Calorimetry*** of Springer; both of them are the co-authors of the paper below published in the same journal in **2014**! Please see the link below: [Link] ![file] ,
ARK5 is associated with the invasive and metastatic potential of human breast cancer cells
Authors: Xin-Zhong Chang
Rui-Hua Dong
Jie Yu
Hai-Yin Liu
Xu-Chen Cao
Journal: Journal of Cancer Research and Clinical Oncology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Akt/ARK5 pathways; metastatic potential; human breast cancer cells; ARK5 gene; MDA-MB-231 cells
Affiliations: Tianjin Medical University, Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China. 

Abstract:  Purpose: To investigate the effects of Akt/ARK5 pathways on the metastatic potential of human breast cancer cells. Materials and methods: The human ARK5 gene was transfected into MDA-MB-231 cells. Effects of ARK5 on MDA-MB-231 cells were investigated in vitro. The tumorigenicity and spontaneously metastatic capability regulated by ARK5 were determined using an orthotopic xenograft tumor model. Results: ARK5 enhanced the invasive and metastatic potential of MDA-MB-231 cells under regulation by Akt. The enhancement was associated with increasing MMP-2, MMP-9, and MT1-MMP expression. The results were further demonstrated by RNA interference experiment. In an in vivo study, we also demonstrated that ARK5-transfected breast cancer cells grew faster and had more pulmonary metastases than its parental counterparts. Conclusion: ARK5 led to a more invasive phenotype and metastatic potential in human breast cancer dependent on Akt. 

Retracted: No

PubPeer comments:
 Figure 5. * Blue boxes: two panels appear to overlap ![file] ,
Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection
Authors: Lishan Su
Hongxiao Song
Naicui Zhai
Yang Yang
Junqi Niu
An Cui
Ian Nicholas Crispe
Haijun Li
Guangyi Wang
Zhongfeng Wang
Tianyang Li
Zhengkun Tu
Journal: Gut (2018)
Discipline: CLINICAL MEDICINE
Keywords: HBV; HLA-E; PD-L1; monocytes; regulatory NK cells.
Affiliations: Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China., Institute of Liver Diseases, The First Hospital, Jilin University, Changchun, China., Department of Liver and Gall Surgery, The First Hospital, Jilin University, Changchun, China., Department of Pathology, University of Washington, Seattle, Washington, USA., Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Abstract:  Background and aims: HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells. Methods: Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting. Culture and coculture of monocytes and NK cells were used to determine NK cell activation, using intracellular cytokines staining. Results: In chronic HBV infection, monocytes express higher levels of PD-L1, HLA-E, interleukin (IL)-10 and TGF-β, and NK cells express higher levels of PD-1, CD94 and IL-10, compared with healthy individuals. HBV employs hepatitis B surface antigen (HBsAg) to induce suppressive monocytes with HLA-E, PD-L1, IL-10 and TGF-β expression via the MyD88/NFκB signalling pathway. HBV-treated monocytes induce NK cells to produce IL-10, via PD-L1 and HLA-E signals. Such NK cells inhibit autologous T cell activation. Conclusions: Our findings reveal an immunosuppressive cascade, in which HBV generates suppressive monocytes, which initiate regulatory NK cells differentiation resulting in T cell inhibition. 

Retracted: No

PubPeer comments:
 Supplemental Figure 2 also appears to be showing some panels that look similar to panels in the same figure or in Figure 5A or 6A. ![file] , 
 Brought to my attention by a reader, with some additional findings by me. Figures 5A and 6A appear to show very similar panels multiple times. Boxes of the same color highlight panels that show unexpected similarities. Since these panels are low-resolution due to compression issues, would the authors be so kind as to show higher resolution images, please? ![file] ,
BCG vaccination reduces the mortality of Mycobacterium tuberculosis–infected type 2 diabetes mellitus mice
Authors: Padmaja Paidipally
Ramakrishna Vankayalapati
Buka Samten
Madeline Kay McAllister
Rajesh Kumar Radhakrishnan
Sachin Mulik
Ramya Sivangala Thandi
Deepak Tripathi
Journal: JCI Insight (2020)
Discipline: CLINICAL MEDICINE
Keywords: Bacterial vaccines; Diabetes; Immunology; Infectious disease; Tuberculosis.

Abstract:  Diabetes is a significant risk factor for the development of active tuberculosis. In this study, we used a mouse model of type 2 diabetes mellitus (T2DM) to determine the effect of prior Bacillus Calmette-Guérin (BCG) vaccination on immune responses to Mycobacterium tuberculosis (Mtb) infection. We found that, at 6-7 months after Mtb infection, 90% of the Mtb-infected T2DM mice died, whereas only 50% of BCG-vaccinated T2DM-Mtb-infected mice died. Moreover, 40% of the PBS-treated uninfected T2DM mice and 30% of the uninfected BCG-vaccinated T2DM mice died, whereas all uninfected and infected nondiabetic mice survived. BCG vaccination was less effective in reducing the lung bacterial burden of Mtb-infected T2DM mice compared with Mtb-infected nondiabetic mice. BCG vaccination significantly reduced lung inflammation in Mtb-infected T2DM mice compared with that of unvaccinated T2DM mice infected with Mtb. Furthermore, reduced mortality of BCG-vaccinated Mtb-infected T2DM mice is associated with expansion of IL-13-producing CXCR3+ Tregs in the lungs of Mtb-infected T2DM mice. Recombinant IL-13 and Tregs from BCG-vaccinated Mtb-infected T2DM mice converted proinflammatory M1 macrophages to antiinflammatory M2 macrophages. Our findings suggest a potentially novel role for BCG in preventing excess inflammation and mortality in T2DM mice infected with Mtb. 

Retracted: No

PubPeer comments:
 ![file] Supplementary Fig. 11.  Duplicate plot Gating strategies to determine CD4+Foxp3+CXCR3+ T-regulatory cells in the lungs. PBS control, BCG-vaccinated, T2DM or BCG-vaccinated T2DM mice were infected with ~100 CFU of aerosolized Mtb H37Rv. A. At 4 months p.i., the lungs from PBS control, BCG-vaccinated control, T2DM, BCG-vaccinated T2DM, infected control, infected T2DM, infected BCG-vaccinated control and infected BCG-vaccinated T2DM mice were isolated. Lung cells were prepared as described in the methods section. Lung cells were gated on CD4+Foxp3+CXCR3+ cells. (A-B) Representative gating strategies for CD4+Foxp3+CXCR3+ cells are shown. Experiments were performed using n=5 mice per group. , 
 ![file] Supplementary Fig. 3.  Duplicate plot , 
 Panel A is a representative gating strategies for panel B. It is a standard way to show flow cytometry data. One flow plot was selected to show representative gating strategies. ,
A Tool for Visualization and Analysis of Single-Cell RNA-Seq Data Based on Text Mining
Authors: Gennaro Gambardella
Diego di Bernardo
Journal: Frontiers in Genetics (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cell type; enrichment analysis; feature extraction; single-cell transcriptomics; term frequency–inverse document frequency.
Affiliations: University of Naples Federico II, Department of Chemical Materials and Industrial Engineering, Naples, Italy., Telethon Institute of Genetics and Medicine, Naples, Italy.

Abstract:  Gene expression in individual cells can now be measured for thousands of cells in a single experiment thanks to innovative sample-preparation and sequencing technologies. State-of-the-art computational pipelines for single-cell RNA-sequencing data, however, still employ computational methods that were developed for traditional bulk RNA-sequencing data, thus not accounting for the peculiarities of single-cell data, such as sparseness and zero-inflated counts. Here, we present a ready-to-use pipeline named gf-icf (gene frequency-inverse cell frequency) for normalization of raw counts, feature selection, and dimensionality reduction of scRNA-seq data for their visualization and subsequent analyses. Our work is based on a data transformation model named term frequency-inverse document frequency (TF-IDF), which has been extensively used in the field of text mining where extremely sparse and zero-inflated data are common. Using benchmark scRNA-seq datasets, we show that the gf-icf pipeline outperforms existing state-of-the-art methods in terms of improved visualization and ability to separate and distinguish different cell types. 

Retracted: No

PubPeer comments:
 There are several questions with the regard of this paper: 1. Would it be possible for the authors to clarify what kind of hydrogen bonding formed in Fig. 6 between Cl1 (chlorine atom) with O2 (oxygen atom)? Could it be there is another water between these atoms to mediate the interaction? 2. Could the authors show the significant value between the groups related to Fig. 19? The author concluded that EDDA-CC had the highest activity amongst the other derivatives without showing neither the standard error measurement nor the standard deviation of each treatment. Probably the author could also clarify the citation after this paragraph:  All the data were checked by 2-way ANOVA, followed by Dunnett s and Tukey s test, which revealed a significant difference in the response between the groups [40]. Does it mean the author uses another data from another group? Thank you! ,
A Prospective Observational Study of Adoptive Immunotherapy for Cancer Using Zoledronate-Activated Killer (ZAK) Cells - An Analysis for Patients with Incurable Pancreatic Cancer
Authors: Makoto Okawaki
Masahiro Yamamura
Yoshiyuki Yamaguchi
Akira Sawaki
Yousuke Katata
Journal: Anticancer research (2016)
Discipline: CLINICAL MEDICINE
Keywords: Adoptive immunotherapy (AIT); ZAK cells; pancreatic cancer; zoledronate; γδT cells.
Affiliations: Department of Clinical Oncology, Kawasaki Medical School and Hospital, Kurashiki, Okayama, Japan ., Department of Clinical Oncology, Kawasaki Medical School and Hospital, Kurashiki, Okayama, Japan.

Abstract:  Background/aim: Adoptive immunotherapy (AIT) using autologous zoledronate-activated killer (ZAK) cells has been performed for developing a novel modality of cancer treatment. In this study, data series from incurable pancreatic cancer were analyzed. Patients and methods: Patients were treated with AIT using intravenous administration of ZAK cells every 3 to 4 weeks in combination with standard chemotherapy and possible clinical benefits were examined. Results: Seventy-five patients were treated. A median overall survival (OS) time of 6.7 months was achieved for all patients and 13.1 months for those treated 5 times or more, that increased to 14.6 and 18.3 months, respectively, when the previous treatment period of chemotherapy alone was included in the analysis. The disease control rate was 58.5 %. Multivariate regression analysis showed a significant positive correlation between the survival and baseline value of lymphocyte percentage in white blood cell counts (p=0.031). Conclusion: The data suggest that AIT using ZAK cells in combination with chemotherapy is safe and feasible and may be effective in prolonging survival for patients with incurable pancreatic cancer. The lymphocyte percentage at baseline may be a good biomarker for predicting the survival benefit of ZAK cell AIT. 

Retracted: Yes

PubPeer comments:
 2021 retraction. https: ar.iiarjournals.org content 41 8 4181 The paper entitled u201cA Prospective Observational Study of Adoptive Immunotherapy for Cancer using Zoledronate-Activated Killer (ZAK) Cells - An Analysis for Patients with Incurable Pancreatic Canceru201d by Yamaguchi et al., published in Anticancer Research 36(5): 2307-2313, 2016, is retracted by the Authors. ,