PReD-Bench/PRed-Bench huggingface dataset:
Anti-cancer, pharmacokinetics and tumor localization studies of pH-, RF- and thermo-responsive nanoparticles
Authors: Muthunarayanan Muthiah
N Sanoj Rejinold
Yong Yeon Jeong
K Manzoor
In-Kyu Park
K P Chennazhi
Reju George Thomas
R Jayakumar
Journal: International Journal of Biological Macromolecules (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chitosan-graft-PNVCL; Curcumin; Gold; RF therapy; Tumor localization.
Affiliations: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India., Department of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju 501-746, South Korea., Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, South Korea., Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, South Korea. Electronic address: ., Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India. Electronic address: .

Abstract:  The curcumin-encapsulated chitosan-graft-poly(N-vinyl caprolactam) nanoparticles containing gold nanoparticles (Au-CRC-TRC-NPs) were developed by ionic cross-linking method. After "optimum RF exposure" at 40 W for 5 min, Au-CRC-TRC-NPs dissipated heat energy in the range of ∼42°C, the lower critical solution temperature (LCST) of chitosan-graft-poly(N-vinyl caprolactam), causing controlled curcumin release and apoptosis to cancer cells. Further, in vivo PK/PD studies on swiss albino mice revealed that Au-CRC-TRC-NPs could be sustained in circulation for a week with no harm to internal organs. The colon tumor localization studies revealed that Au-CRC-TRC-NPs were retained in tumor for a week. These results throw light on their feasibility as multi-responsive nanomedicine for RF-assisted cancer treatment modalities. 

Retracted: No

PubPeer comments:
 In Figure 3, two panels portraying different types of nanoparticles and different RF conditions appear to look very similar. However, one of the two shows a red signal, while that is missing in the other panel. Shown with blue boxes. ![file] , 
 The tumor sizes in some of these mouse appear to be very large (5000 mm3 or see photo). Is this in line with regular ethical guidelines? ![file] , 
 Corrigendum published [15 August 2019] . --------------------------------------- In the original manuscript, the Fig. 3A (no RF, Au-CRC TRC NPs group) had wrong scale bar. Additionally, the Fig. 3B, (live dead images of MCF-7 cells is treated with Au-CRC-TRC NPs under no RF), was inadvertently given wrong. These mistakes have been rectified and the corrected Fig. 3 is given below. ![] These changes in the figure would not affect the conclusion from the figure nor the overall conclusion of the whole manuscript. The authors would like to apologise for any inconvenience caused. ,
Modeling of linear programming and extended TOPSIS in decision making problem under the framework of picture fuzzy sets
Authors: Agha Kashif
Tabasam Rashid
M Sarwar Sindhu
Journal: PloS one (2019)
Discipline: Multidisciplinary
Keywords: Picture fuzzy sets; PFSs; unknown weights; linear programming; LP model
Affiliations: Department of Mathematics University of Management and Technology, Lahore - 54770, Pakistan.

Abstract:  Picture fuzzy sets (PFSs) are comparatively a new extension of fuzzy sets which describe the human opinions that has more answers like acceptance, rejection, neutral and desist, which cannot be correctly presented in fuzzy sets (FSs) and intuitionistic fuzzy sets (IFSs). The PFSs are categorized by three objects, the degree of belonging, the degree of neutral belonging and the degree of non- belonging such that the total of these three degrees must not be more than one. So far, there is no such work presented in the literature which deals with unknown weights of criteria based on PFSs. In the present work, we have developed a linear programming (LP) model to find the exact weights from the given constraints of weights for the criteria and construct a modified distance based on similarity measure between picture fuzzy sets. Then we have utilized this similarity measure to achieve the best option in the multiple criteria decision making (MCDM) problem. Lastly, two practical examples for the selection of alternatives are presented to compare the obtained results with the existing similarity measures. 

Retracted: No

PubPeer comments:
 This paper proposed a multi-attribute decision making method using u201c**picture fuzzy numbers**u201d. A picture fuzzy number is a triplet $$(alpha, gamma, beta)$$ such that $$alpha, gamma, beta in [0,1] quad alpha + gamma + beta le 1$$ In eq.(7) and eq.(8), the authors defined u201c**the picture fuzzy positive ideal solution**u201d and u201c**picture fuzzy negative ideal solution**u201d. However, it is clear that eq.(7) and eq.(8) are not sound. For instance, for an $J_2$ index criterion, it may happen that $$(1,0,0), quad (0,1,0) to (1,1,0)qquad text{for eq.(7)}$$ $$(0,0,1), quad (0,1,0) to (0,1,1)qquad text{for eq.(8)}$$ **The obtained results are not picture fuzzy numbers.** As a consequence, the multi-criteria decision making method based on such notions is not sound. Besides, the numerical results presented in eq.(13) are also not convincing. For the constraints in eq.(13), the only feasible solution is $(0.2, 0.1, 0.3, 0.4)$. There is no need to solve the LP model in Step 5 for this particular case. ![file] ![file] ![file] ,
LncRNA LOXL1-AS1 Promotes the Proliferation and Metastasis of Medulloblastoma by Activating the PI3K/AKT Pathway
Authors: Yingwu Liang
Weining Tang
Rui Zhang
Ran Gao
Cuicui Zhang
Journal: Analytical Cellular Pathology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Medulloblastoma; long noncoding RNA; LOXL1-AS1; cell proliferation; metastasis
Affiliations: Department of Pediatrics, Jining No. 1 People's Hospital, Shandong, China., Department of Pediatrics, Sishui People's Hospital, Shandong, China., Intensive Care Unit, Affiliated Hospital of Jining Medical University, Shandong, China.

Abstract:  Medulloblastoma is the most common malignant brain tumor of childhood, with great potential to metastasize. However, the mechanisms of how medulloblastoma develops and progresses remain to be elucidated. The present study assessed the role of long noncoding RNA LOXL1-AS1 (lncRNA LOXL1-AS1) in the cell proliferation and metastasis in human medulloblastoma. It was initially found that LOXL1-AS1 was significantly overexpressed in clinical medulloblastoma tissues compared with the adjacent noncancerous tissues. LOXL1-AS1 was also highly expressed in medulloblastoma at advanced stages and differentially expressed in a series of medulloblastoma cell lines. Knockdown of LOXL1-AS1 using shRNAs significantly inhibited cell viability and colony formation capacities in D283 and D341 cells. Moreover, the cell proportion in the S phase was significantly increased, while the cell proportion in the G2/M phase was decreased after knockdown of LOXL1-AS1 in D283 cells and D341 cells. Cell cycle arrest led to eventual cell apoptosis by LOXL1-AS1 knockdown. Moreover, in a xenograft model of human medulloblastoma, knockdown of LOXL1-AS1 significantly inhibited tumor growth and promoted tumor cell apoptosis. In addition, knockdown of LOXL1-AS1 inhibited cell migration and reversed epithelial-to-mesenchymal transition (EMT). Western blot analysis further revealed that knockdown of LOXL1-AS1 decreased the phosphorylated levels of PI3K and AKT without affecting their total protein levels. These results suggest that LncRNA LOXL1-AS1 promoted the proliferation and metastasis of medulloblastoma by activating the PI3K-AKT pathway, providing evidence that knockdown of LncRNA LOXL1-AS1 might be a potential therapeutic strategy against medulloblastoma. 

Retracted: No

PubPeer comments:
 Figure 4A. * The D283 shRNA1 and D283 shRNA2 panels appear to look more similar than expected. * The D341 shRNA1 and D341 shRNA2 panels appear to look more similar than expected. Panels of the same color highlight particular areas that look similar, although I did not highlight all of them. ![file] , 
 Figure 6, center panels. * Red boxes: the D341 shRNA1 and D341 shRNA2 panels appear to show an overlap. ![file] ,
The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV-2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID-19 infections
Authors: Konstantin G Kousoulas
Achyut Dahal
Rafiq Nabi
Seetharama D Jois
Vladimir Chouljenko
Farhana Musarrat
Tamara Chouljenko
Journal: Journal of Medical Virology (2020)
Discipline: MICROBIOLOGY
Keywords: SARS coronavirus; antiviral agents; cell fusion; cellular effect; coronavirus
Affiliations: Division of Biotechnology and Molecular Medicine, Louisiana State University, Baton Rouge, Louisiana., Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana., School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, Louisiana., Louisiana State University Agricultural Center, Agricultural Biotechnology Laboratory, Baton Rouge, Louisiana.

Abstract:  Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is the causative agent of the coronavirus disease-2019 (COVID-19) pandemic. Coronaviruses enter cells via fusion of the viral envelope with the plasma membrane and/or via fusion of the viral envelope with endosomal membranes after virion endocytosis. The spike (S) glycoprotein is a major determinant of virus infectivity. Herein, we show that the transient expression of the SARS CoV-2 S glycoprotein in Vero cells caused extensive cell fusion (formation of syncytia) in comparison to limited cell fusion caused by the SARS S glycoprotein. Both S glycoproteins were detected intracellularly and on transfected Vero cell surfaces. These results are in agreement with published pathology observations of extensive syncytia formation in lung tissues of patients with COVID-19. These results suggest that SARS CoV-2 is able to spread from cell-to-cell much more efficiently than SARS effectively avoiding extracellular neutralizing antibodies. A systematic screening of several drugs including cardiac glycosides and kinase inhibitors and inhibitors of human immunodeficiency virus (HIV) entry revealed that only the FDA-approved HIV protease inhibitor, nelfinavir mesylate (Viracept) drastically inhibited S-n- and S-o-mediated cell fusion with complete inhibition at a 10-μM concentration. In-silico docking experiments suggested the possibility that nelfinavir may bind inside the S trimer structure, proximal to the S2 amino terminus directly inhibiting S-n- and S-o-mediated membrane fusion. Also, it is possible that nelfinavir may act to inhibit S proteolytic processing within cells. These results warrant further investigations of the potential of nelfinavir mesylate to inhibit virus spread at early times after SARS CoV-2 symptoms appear. 

Retracted: No

PubPeer comments:
 Please see https: pubpeer.com publications FBBD614EBC3F23CA02361A9C8C99E1 ,
Adaptor protein-3 in dendritic cells facilitates phagosomal toll-like receptor signaling and antigen presentation to CD4(+) T cells
Authors: Miwa Sasai
Hao Shen
Michael S Marks
Susan H Guttentag
Akiko Iwasaki
Terri M Laufer
Adriana R Mantegazza
Jamel El-Benna
Journal: Immunity (2012)
Discipline: IMMUNOLOGY
Keywords: MHC-II antigen presentation; phagosome; Toll-like receptor signaling; dendritic cells; adaptor protein-3
Affiliations: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract:  Effective major histocompatibility complex-II (MHC-II) antigen presentation from phagocytosed particles requires phagosome-intrinsic Toll-like receptor (TLR) signaling, but the molecular mechanisms underlying TLR delivery to phagosomes and how signaling regulates antigen presentation are incompletely understood. We show a requirement in dendritic cells (DCs) for adaptor protein-3 (AP-3) in efficient TLR recruitment to phagosomes and MHC-II presentation of antigens internalized by phagocytosis but not receptor-mediated endocytosis. DCs from AP-3-deficient pearl mice elicited impaired CD4(+) T cell activation and Th1 effector cell function to particulate antigen in vitro and to recombinant Listeria monocytogenes infection in vivo. Whereas phagolysosome maturation and peptide:MHC-II complex assembly proceeded normally in pearl DCs, peptide:MHC-II export to the cell surface was impeded. This correlated with reduced TLR4 recruitment and proinflammatory signaling from phagosomes by particulate TLR ligands. We propose that AP-3-dependent TLR delivery from endosomes to phagosomes and subsequent signaling mobilize peptide:MHC-II export from intracellular stores. 

Retracted: No

PubPeer comments:
 Supplemental Fig. 3B u2013 more similar than expected. ![file] Fig. 6C D u2013 More similar than expected. Could authors check please? ![file] ,
The effects of estrogen administration on bone mineral density in adolescents with anorexia nervosa
Authors: J Argente
M T Muñoz
J A García-Centenera
F Hervás
G Morandé
J Pozo
Journal: European journal of endocrinology (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: osteopenia; anorexia nervosa; bone mineral density; estrogen administration; women
Affiliations: Department of Pediatrics, Division of Pediatric Endocrinology, Universidad Autonoma, Hospital Universitario Niño Jésus, Avda Menéndez Pelayo, 65, 28009 Madrid, Spain.

Abstract:  Objective: Profound osteopenia is a serious complication of anorexia nervosa (AN). The aim of this work was to study the effect of prolonged AN on lumbar spine bone mineral density (BMD) and to determine whether oral estrogen administration prevents bone loss in women with this disorder. Subjects and methods: Thirty-eight amenorrheic women with AN (mean age: 17.3 years) were treated with estrogen (50 microg of ethinyl estradiol) and gestagen (0.5 mg of norgestrel) during 1 year. Clinical variations, biochemical indices and BMD were studied at three different time points, including after a period of amenorrhea of at least 12 months (n=38), after the administration of estrogens for 1 year (n=22), and after a 1-year follow-up period (n=12). Results: Initial mean BMD was significantly lower than normal (-2.1+/-0.8 s.d.) and less than -2.5 s.d. below normal in 38% of the women with AN. The estrogen-treated group had no significant change in BMD even after the follow-up period and partial recovery of weight. Estradiol and total IGF-I levels were significantly lower throughout the study. All subjects had normal thyroxine (T(4)) and TSH levels and calcium metabolism. However, total tri-iodothyronine (T(3)) was decreased in all anorexic subjects in the first and second study points and were within normal limits after the follow-up period. Conclusions: (1) Estrogen replacement alone cannot prevent progressive osteopenia in young women with AN. (2) Other factors, such as the loss of weight, the duration of the amenorrhea and the low levels of total insulin-like growth factor-I (IGF-I) could contribute to the loss of bone mass in women with this disorder. 

Retracted: No

PubPeer comments:
 This paper heavily **plagiarizes** the following manuscript, published in 1995: Klibanski A, Biller BM, Schoenfeld DA, Herzog DB, Saxe VC. *The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa.* J Clin Endocrinol Metab. 1995;80(3):898-904. doi:10.1210 jcem.80.3.7883849 ,
Regulation of protein synthesis by inducible wild-type p53 in human lung carcinoma cells
Authors: Constantina Constantinou
Vivienne Tilleray
Michael J Clemens
Journal: FEBS Letters (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: tumour suppressor protein p53; protein synthesis; mutant form; doxycycline-inducible lung carcinoma cell line; wild-type p53
Affiliations: Translational Control Group, Centre for Molecular and Metabolic Signalling, Division of Basic Medical Sciences, St. George's, University of London, Cranmer Terrace, London SW17 0RE, UK.

Abstract:  Activation of an over-expressed mutant form of the tumour suppressor protein p53 has been shown to inhibit protein synthesis. To determine whether this effect is due only to high level expression or the mutant nature of the protein, we have used a doxycycline-inducible lung carcinoma cell line capable of expressing wild-type p53. We now show that levels of wild-type p53 similar to those expressed endogenously also inhibit protein synthesis. The mechanism involves dephosphorylation and accumulation of the translational inhibitor 4E-BP1, and increased association of 4E-BP1 with initiation factor eIF4E. The inhibition of translation is not a consequence of p53-mediated apoptosis. 

Retracted: No

PubPeer comments:
 Figure 5C. Splice Total 4E-BP1 panel, no splice eIF4E panel ![file] ,
Retracted: Single Nucleotide Polymorphisms in the PTPN1 Gene Are Associated with Susceptibility to Esophageal Squamous Cell Carcinoma: A Case–Control Study in Inner Mongolia, China
Authors: Le-Le Wang
Sheng-Jie Yin
Lei Wang
Hong-Bo Ji
Xiao-Ying Wang
Di Shang
Li-Li Sun
Journal: Genetic Testing and Molecular Biomarkers (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Inner Mongolia; PTPN1; case–control study; esophageal squamous cell carcinoma; single nucleotide polymorphism
Affiliations: Department of Medical Oncology in Section One, Chifeng Municipal Hospital , Chifeng, China .

Abstract:  Objective: This case-control study investigated the association of single nucleotide polymorphisms in the PTPN1 gene with susceptibility to esophageal squamous cell carcinoma (ESCC) in Inner Mongolia, China. Methods: A total of 302 patients living in Inner Mongolia China who were pathologically diagnosed with ESCC between April 2012 and 2016 were selected for the ESCC group; 373 healthy individuals were selected for the control group. The rs2904268 C&gt;G, rs2230605 A&gt;G, and rs16995309 C&gt;T polymorphisms in the PTPN1 gene were detected by bidirectional polymerase chain reaction amplification of specific alleles. The haplotype frequencies were analyzed by SHEsis software. Binary logistic regression analysis was conducted to analyze risk factors associated with ESCC. Results: Statistical differences between the ESCC and control groups were observed for history of smoking, drinking, and poor eating habits (all p &lt; 0.05). Both the rs2904268 C&gt;G CG and GG genotype frequencies were markedly higher in the ESCC group relative to the control group (both p &lt; 0.05). However, the genotype frequencies of rs2230605 A&gt;G and rs16995309 C&gt;T were similar between the ESCC and control groups (all p &gt; 0.05). Compared with the control group, the ESCC group had notably elevated frequencies of the GGC and GAT haplotypes and significantly reduced frequencies of CGC and GGT haplotypes (all p &lt; 0.05). A history of smoking, drinking, poor eating habits, the rs2904268 C&gt;G CG+GG genotypes, and the GAT haplotype were all identified as risk factors for ESCC (all p &lt; 0.05). Conclusion: These results indicated that the PTPN1 gene polymorphism rs2904268 is associated with susceptibility to ESCC in Inner Mongolia. 

Retracted: Yes

PubPeer comments:
 Figure 7. right set of panels. Splicing in BRCA1 and tubulin panels, but not in 53BP1, or SRC3 panels. ![file] ,
miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells
Authors: Lei Hou
Xing-Rong Song
Yu-Mei Xiong
Jun-Xiang Huang
Wen-Hua Zhang
Hang Tian
Yong-Ying Pan
Journal: American journal of translational research (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: E2F5; Ovarian cancer; invasion; migration; proliferation.
Affiliations: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University Guangzhou 510623, China., Department of Anesthesiology, Shanxi Cancer Hospital Taiyuan 030013, China., Department of Pediatric Emergency, Guangzhou Women and Children's Medical Center, Guangzhou Medical University Guangzhou 510623, China.

Abstract:  Accumulating evidence showed that microRNA-132 (miR-132) are involved in development and progression of several types of cancers, however, the function and underlying molecular mechanism of miR-132 in ovarian cancer remains unclear. In this study we investigated the biological roles and molecular mechanism of miR-132 in ovarian cancer. Here, we found that that the expression levels of miR-132 were dramatically decreased in ovarian cancer cell lines and clinical ovarian cancer tissue samples. Then, we found that introduction of miR-132 significantly suppressed the proliferation, colony formation, migration and invasion of ovarian cancer cells. Mechanism investigation revealed that miR-132 inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3'UTR. Moreover, the expression level of E2F5 was significantly increased in ovarian cancer tissues than in the adjacent normal tissues, and its expression was inversely correlated with miR-132 expression in clinical ovarian cancer tissues. Additionally, silencing E2F5 was able to inhibit the proliferation, colony formation, migration and invasion of ovarian cancer cells, parallel to the effect of miR-132 overexpression on the ovarian cancer cells. Meanwhile, overexpression of E2F5 reversed the inhibition effect mediated by miR-132 overexpression. These results indicate that miR-132 suppresses the cell proliferation, invasion, migration in ovarian cancer cells by targeting E2F5. 

Retracted: Yes

PubPeer comments:
 Question regarding Figure 5: Why do the curves in Figure 5b,c and d show these unusual bends. I presume that the circles define a measuring point. Why then is some part of the curve at a higher level (current efficiency) than the highest measuring point? ![file] ,
p38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis
Authors: Gabriella De Vita
Aneta Swat
Ana Cuadrado
Nuria Ajenjo
Ignacio Dolado
Angel R Nebreda
Journal: Cancer Cell (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p38alpha; stress-activated protein kinase; oncogenic H-Ras; malignant transformation; oncogenes
Affiliations: CNIO (Spanish National Cancer Center), Melchor Fernández Almagro 3, 28029 Madrid, Spain.

Abstract:  p38alpha is a stress-activated protein kinase that negatively regulates malignant transformation induced by oncogenic H-Ras, although the mechanisms involved are not fully understood. Here, we show that p38alpha is not a general inhibitor of oncogenic signaling, but that it specifically modulates transformation induced by oncogenes that produce reactive oxygen species (ROS). This inhibitory effect is due to the ROS-induced activation of p38alpha early in the process of transformation, which induces apoptosis and prevents the accumulation of ROS and their carcinogenic effects. Accordingly, highly tumorigenic cancer cell lines have developed a mechanism to uncouple p38alpha activation from ROS production. Our results indicate that oxidative stress sensing plays a key role in the inhibition of tumor initiation by p38alpha. 

Retracted: No

PubPeer comments:
 Figures 2C and 6C much more similar after horizontal flip than expected, even though the experiments are different. ![file] ,
mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation
Authors: Augustine M K Choi
Mi-Ae Park
Shu Hisata
Gina M DeNicola
Stefan W Ryter
Jong-Seok Moon
Kiichi Nakahira
Journal: Cell reports (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mTORC1; glycolysis; NLRP3 inflammasome; HK1; immune cells
Affiliations: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY 10065, USA., Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA., Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: .

Abstract:  The mammalian target of rapamycin complex 1 (mTORC1) regulates activation of immune cells and cellular energy metabolism. Although glycolysis has been linked to immune functions, the mechanisms by which glycolysis regulates NLRP3 inflammasome activation remain unclear. Here, we demonstrate that mTORC1-induced glycolysis provides an essential mechanism for NLRP3 inflammasome activation. Moreover, we demonstrate that hexokinase 1 (HK1)-dependent glycolysis, under the regulation of mTORC1, represents a critical metabolic pathway for NLRP3 inflammasome activation. Downregulation of glycolysis by inhibition of Raptor/mTORC1 or HK1 suppressed both pro-IL-1β maturation and caspase-1 activation in macrophages in response to LPS and ATP. These results suggest that upregulation of HK1-dependent glycolysis by mTORC1 regulates NLRP3 inflammasome activation. 

Retracted: No

PubPeer comments:
null, 
 Providing image of 5B. Could the authors post the uncropped scan? ![file] ,
Downregulated lncRNA CRNDE contributes to the enhancement of nerve repair after traumatic brain injury in rats
Authors: Qiuxia Li
Yanyi Chen
Min Yi
Dongsheng Wang
Xia Xu
Xingping Dai
Journal: Cell Cycle (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Long non-coding RNA CRNDE; Traumatic brain injury; nerve repair.
Affiliations: Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University , Changsha , PR China.

Abstract:  Objective: Long non-coding RNAs (lncRNAs) have recently been demonstrated to be involved in craniocerebral disease, but their expression in traumatic brain injury (TBI) is still unearthed. Therefore, we aimed to elucidate the effect of lncRNA CRNDE on TBI. Methods: Firstly, CRNDE expression was determined in serum of TBI patients and healthy controls. The TBI rat model was established based on Feeney's freefall impact method. The modeled rats were injected with siRNA against CRNDE, and the rats' neurobehavioral function were measured. Besides, expression of inflammatory factors, size, shape and number of hippocampal neurons, neuron apoptosis, Beclin I, LC3-I, LC3-II, glial fibrillary acidic protein (GFAP), BrdU, nerve growth factor (NGF), nestin, and neuronal nuclei (NeuN) expression were detected through different methods. Results: In TBI, CRNDE was found to be upregulated. Downregulated CRNDE improved neurobehavioral function, repressed expression of neuroinflammatory factors, elevated number of Nissl bodies, as well as restricted neuronal apoptosis and autophagy in TBI rats. Besides, downregulated CRNDE also promoted expression of GFAP, BrdU, NGF, nestin, and NeuN, thus induced the differentiation of neurons and the directional growth and regeneration of nerve fibers. Conclusion: Altogether, we found that silencing of CRNDE might be able to promote the nerve repair after TBI in rats. 

Retracted: Yes

PubPeer comments:
 Figure 5.  Transwell assay showing invasion of miR-NC and miR-322 mimics transfected MCF7 breast cancer cells. ![file] Orange green boxes for comparison with *[left]* Figs 4 and 5 from [Wu et al (2020)] . *[right]* Figure 4A from [Wang Wen (2020)] .  miR-335 reduces breast cancer cell migration and invasion. A: Transwell assay for analysis of migration and invasion of Hs578T cancer cells transfected with miR-NC, miR-335 mimics or miR-335 inhibitor showing miR335 overexpression inhibits cell **migration** and invasion . Rotated through 90 deg for convenience of comparison. ![] ,
A conserved region of nonstructural protein 1 from alphacoronaviruses inhibits host gene expression and is critical for viral virulence
Authors: Liurong Fang
Gang Wang
Fang Li
Zhen F Fu
Shaobo Xiao
Jiale Shi
Zhou Shen
Guiqing Peng
Yiling Yang
Journal: Journal of Biological Chemistry (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: coronavirus; crystal structure; host gene expression; immune evasion; nonstructural protein 1 (nsp1)
Affiliations: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China., Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China., Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota 55108., Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602., State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China ., College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Abstract:  Coronaviruses are enveloped, single-stranded RNA viruses that are distributed worldwide. They include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and the human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), many of which seriously endanger human health and well-being. Only alphacoronaviruses and betacoronaviruses harbor nonstructural protein 1 (nsp1), which performs multiple functions in inhibiting antiviral host responses. The role of the C terminus of betacoronavirus nsp1 in virulence has been characterized, but the location of the alphacoronavirus nsp1 region that is important for virulence remains unclear. Here, using TGEV nsp1 as a model to explore the function of this protein in alphacoronaviruses, we demonstrate that alphacoronavirus nsp1 inhibits host gene expression. Solving the crystal structure of full-length TGEV at 1.85-Å resolution and conducting several biochemical analyses, we observed that a specific motif (amino acids 91-95) of alphacoronavirus nsp1 is a conserved region that inhibits host protein synthesis. Using a reverse-genetics system based on CRISPR/Cas9 technology to construct a recombinant TGEV in which this specific nsp1 motif was altered, we found that this mutation does not affect virus replication in cell culture but significantly reduces TGEV pathogenicity in pigs. Taken together, our findings suggest that alphacoronavirus nsp1 is an essential virulence determinant, providing a potential paradigm for the development of a new attenuated vaccine based on modified nsp1. 

Retracted: No

PubPeer comments:
 The connection is strong. Wuhan coronavirus CRISPR. The intention of this [paper is good] - but CRISPR would integrate in the virus, as it did here for [HBV] in this 2014 paper. We need to start accepting what data tells us. [Ignoring] it for the hype does not help. ,
Neuroprotective effect of naringenin is mediated through suppression of NF-κB signaling pathway in experimental stroke
Authors: M M Khan
F Islam
M M Safhi
S S Raza
M Ashafaq
A Ahmad
A P Wagner
Journal: Neuroscience (2013)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Oxidative stress; Inflammation; Cerebral ischemia; NF-κB signaling pathway; Flavonoids
Affiliations: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (Fund for the Improvement of Science and Technology Sponsored by DST and Special Assistance Programme Sponsored by UGC), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.

Abstract:  Oxidative stress and inflammation play an integral role in the pathogenesis of cerebral ischemia that leads to a cascade of events culminating in the death of neurons and their supporting structures. The signaling pathways that link these events are not fully understood. Recent studies have demonstrated a close link between the nuclear factor-κB (NF-κB) signaling pathway and cerebral ischemia/reperfusion (I/R)-induced inflammation. Flavonoids have been suggested to exert human health benefits by anti-oxidant and anti-inflammatory mechanisms. In this study we undertook a pharmacological approach to investigate the ability of naringenin, a potent flavonoid, to prevent oxidative stress and NF-κB-mediated inflammatory brain damage in the rat model of focal cerebral I/R injury. To test this hypothesis, male Wistar rats were pretreated with naringenin once daily for 21 days and then subjected to 1h of middle cerebral artery occlusion followed by 23 h of reperfusion. Naringenin treatment successfully upregulates the antioxidant status, decreases the infarct size and lowers the levels of myeloperoxidase, nitric oxide and cytokines, besides functional recovery returned close to the baseline. Moreover, immunohistochemical and Western blot analyses clearly demonstrated that naringenin treatment limits glial activation and downregulates the NF-κB expression level and their target genes. These results show, prophylactic treatment with naringenin improved functional outcomes and abrogated the ischemic brain injury by suppressing NF-κB-mediated neuroinflammation. The present study suggests that naringenin may be used as a potential neuroprotectant in patients at high risk of ischemic stroke. 

Retracted: No

PubPeer comments:
 Fig 1  (B) H E staining shows the neuronal alterations in the ipsilateral brain after 1-h MCAO 23-h reperfusion. Normal morphologic features of neurons are present in sham. MCAO group animals show neuronal loss and presence of numerous vacuolated spaces. Administration of naringenin at a dose of 50 mg kg clearly ameliorates ischemia-induced neuronal damage in the MCAO group . Could the authors comment on the overlap between Nar-25 and Nar-50 slides, after a 90-deg rotation? ![file] ,
Kai-Xin-San, a traditional Chinese medicine formulation, exerts antidepressive and neuroprotective effects by promoting pCREB upstream pathways
Authors: Bing-Ying Yu
Xian-Zhe Dong
Ping Liu
Dong-Xiao Wang
Yuan Hu
Journal: Experimental and Therapeutic Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: Kai-Xin-San; antidepressant effect; brain-derived neurotrophic factor; extracellular signal-regulated kinase signal pathway; traditional Chinese medicinal formula.

Abstract:  Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for the treatment of emotion-related disease. However, the underlying mechanism remains largely unknown. The present study aimed to examine whether phospho-cAMP response element-binding protein (pCREB) and upstream components, such as extracellular signal-regulated kinase (ERK), phospho-ERK (pERK), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β) and pGSK3β are associated with the antidepressive effect of KXS. In total, 24 male Wistar rats were randomly divided into three groups, including control (n=8, no treatment), induced with chronic unpredictable mild stress (CMS) (n=8), and CMS rats treated with KXS at dosage of 370 mg/kg/day orally. Primary hippocampal neuronal cultures were prepared from Wistar rats for cell survival and proliferation assays. In KXS rats, increased protein expression levels of pCREB, BDNF and tyrosine receptor kinase B (TrkB) were observed in the hippocampus and prefrontal cortex, compared with the CMS model group. Furthermore, increased expression levels of ERK, pERK, PI3K, Akt, and GSK3β were also detected in the hippocampus and prefrontal cortex of KXS-treated rats compared with CMS model rats and in primary hippocampal neuronal cells treated with KXS. These results suggest that pCREB and upstream components, including TrkB/ERK/CREB and TrkB/PI3 K/CREB, may contribute to the antidepressive effect induced by KXS. Further studies are required to confirm these findings. 

Retracted: No

PubPeer comments:
 There appears to be some creative re-use of western blots in this paper. I am struggling to find an innocuous explanation to how this might have happened. Perhaps the authors can explain? ![file] ,
Targeting Transforming Growth Factor-Beta1 (TGF-β1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFκkB-PUMA Signaling
Authors: Fengyun Hao
Kejun Zhang
Qiang Yin
Anbing Dong
Shan Liu
Xiufang Mi
Journal: Medical Science Monitor (2016)
Discipline: CLINICAL MEDICINE
Keywords: TGF-β1; tumorigenesis; apoptosis; proliferation; colony formation
Affiliations: Department of Oncology, People's Hospital of Rizhao, Rizhao, Shandong, China (mainland)., Department of Thyroid Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)., Department of Internal Medicine, People's Hospital of Zhangqiu, Jinan, Shandong, China (mainland)., Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).

Abstract:  BACKGROUND The transforming growth factor-beta (TGF-β) signaling pathway plays a critical role in promoting tumor growth. TGF-β1was found to be overexpressed in anaplastic thyroid cancer (ATC). We therefore tested our hypothesis that targeting TGF-β1 inhibits tumorigenesis of ATC cells. MATERIAL AND METHODS Effects of TGF-β1 stimulation or TGF-β1 inhibition by small interfering RNA (TGF-β1siRNA) on proliferation, colony formation, and apoptosis in 8505C cells in vitro was detected using siRNAs and inhibitors to examine the TGF-β1 signaling pathway. A subcutaneously implanted tumor model of 8505C cells in nude mice was used to assess the effects of TGF-β1 inhibition on tumorigenesis development. RESULTS TGF-β1siRNAs decreased proliferation and colony formation, and increased apoptosis in 8505C cells in vitro and inhibited tumor growth in vivo. TGF-β1siRNA inhibited phosphorylation ERK1/2 (pERK1/2) and increased p65-dependant PUMA mRNA and protein expression. Knockdown of p65 or PUMA by siRNA reduced TGF-β1siRNA-induced apoptosis, as well as caspase-3 and PARP activation. Upregulation of p65 or PUMA expression by TGF-β1siRNA requires pERK1/2 inhibition. TGF-β1 shRNA inhibited tumor growth in vivo. CONCLUSIONS Therapies targeting the TGF-β1 pathway may be more effective to prevent primary tumor formation. The ability of this therapy to decrease tumorigenesis may be related to ERK1/2/NF-κB/PUMA signaling. 

Retracted: Yes

PubPeer comments:
 Retraction, March 4, 2022: https: www.medscimonit.com abstract full idArt 936562  The in vitro experiments of TGF-u03b21 and the results of RT-PCR could not be repeated. In order not to affect others, the authors have asked for a retraction A quick inspection of the figures reveals a potential duplication (marked with red boxes) in Figure 1: ![file] Figure 4 appears to also show a duplication, with the backgrounds of two blots being remarkably similar. ![file] , 
 #1 Dear Dr. Bik, Thank you very much for pointing out the errors; we have also found this error and it is one of the reasons we retracted the manuscript. Fig1C s actin is mis-spliced and pasted incorrectly; FigB s p65 and PUMA are the same, both are PUMA (The previous 2 band , the exposure of the strips is inconsistent), and the paste is wrong, and the PUMA is regarded as a P65. Thanks ,
Resveratrol improves neurological outcome and neuroinflammation following spinal cord injury through enhancing autophagy involving the AMPK/mTOR pathway
Authors: De-Cheng Shao
Han Li
Hai-Yun Niu
Hong-Yu Meng
Bing Xu
Guang Yang
Xiao-Dan Huang
Journal: Molecular Medicine Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: Resveratrol; neuroprotective effects; spinal cord injury; molecular mechanisms; neuroinflammation
Affiliations: Department of Orthopedics, and Key Laboratory of Orthopedic Biomechanics of Hebei Province, Orthopedic Research Institution of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.

Abstract:  Resveratrol, a natural phenolic compound, provides neuroprotective effects, however, the specific mechanisms of action remain to be elucidated. The purpose of the present study was to examine the neuroprotective effect of resveratrol on spinal cord injury (SCI) and the potential molecular mechanisms of action. A rat model of SCI was induced using Allen's method, and resveratrol (100 mg/kg) was intraperitoneally injected 1 day following surgery. The recovery of neurological function was assessed using the Basso, Beattie, Bresnahan scoring system and an inclined plane test. The concentrations of pro‑ and anti‑inflammatory factors were measured using ELISA. The expression and location of autophagy markers were measured using western blot and immunofluorescence analyses. The results suggested that resveratrol administration resulted in functional improvement of locomotor activity and reduced neuroinflammation following the induction of SCI. In addition, autophagy was activated following SCI, as demonstrated by the significantly increased ratio of microtubule‑associated protein light chain 3 (LC3)‑II/LC3‑I and expression of Beclin‑1 in the injured spinal cord. Of note, the enhancement of phosphorylated (p)‑AMP‑activated protein kinase (AMPK) and the reduction of p‑mammalian target of rapamycin (mTOR) following SCI indicated that the SCI‑induced activation of autophagy was associated with the AMPK/mTOR signaling pathway. Resveratrol treatment further enhanced the activation of autophagy via the AMPK/mTOR pathway following SCI. By contrast, the autophagic inhibitor, 3‑methyladenine, partially inhibited the neuroprotective effects of resveratrol treatment. Together, these findings suggested that resveratrol promoted functional recovery and inhibited neuroinflammation through the activation of autophagy mediated by the AMPK/mTOR pathway following SCI. 

Retracted: No

PubPeer comments:
 Figure 3. * Green boxes: The top (Sham) and bottom (SCI) panels appear to show a small area of overlap. I have only marked this in the  Merge panels. ![file] ,
Nerve growth factor cooperates with p185(HER2) in activating growth of human breast carcinoma cells
Authors: L Asnaghi
M Modugno
C Ghirelli
E Tagliabue
C Melani
G Somenzi
S Ménard
F Castiglioni
Journal: Journal of Biological Chemistry (2000)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Nerve growth factor; proto-TrkA; breast cancer cells; MAPK activation; p185(HER2)
Affiliations: Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy.

Abstract:  Nerve growth factor (NGF) is known to exert a mitogenic effect on human breast cancer cells through proto-TrkA activation. Reverse transcriptase-PCR analysis of proto-TrkA expression in human breast carcinoma specimens and cell lines revealed trkA transcript in 12 of 14 human breast carcinoma specimens and in all of four cell lines tested. While cytofluorimetric and Western blot analysis indicated proto-TrkA expression in three of the four cell lines, NGF stimulated growth in only two of the three positive cell lines. Inhibition of NGF-induced MAPK activation by an antibody directed against the extracellular domain of TrkA but not by an inhibitor of TrkA phosphorylation demonstrated the requirement of NGF binding but not of proto-TrkA kinase activity for MAPK activation, suggesting the recruitment of another kinase for transmission of the mitogenic signaling. Indeed, NGF induced tyrosine phosphorylation and stimulated kinase activity of p185(HER2), a kinase receptor of the HER family. A TrkA phosphorylation inhibitor did not affect this activation. Moreover, the two receptors were coprecipitated by antibodies directed against proto-TrkA and p185(HER2). Down-modulation of p185(HER2) expression in a breast carcinoma line transfected with a construct containing an anti-p185(HER2) antibody sequence and expressing proto-TrkA impaired NGF-induced MAPK activation and proliferation. Together these data show that in cells expressing low levels of TrkA such as breast carcinoma cells, NGF must recruit other overexpressed receptors such as p185(HER2) in order to generate a biological signal that can induce breast cancer cell growth. 

Retracted: No

PubPeer comments:
 ![file] ,
Establishing a combined stimulation protocol hFSH followed by rFSH might represent a breakthrough in the IVF practice
Authors: S. Gerli
G.C. Di Renzo
Journal: European review for medical and pharmacological sciences (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: combined stimulation protocol; hFSH; rFSH; breakthrough; IVF practice

Abstract:  The article "Establishing a combined stimulation protocol hFSH followed by rFSH might represent a breakthrough in the IVF practice" by S. Gerli, G.C. Di Renzo, published in Eur Rev Med Pharmacol Sci 2013; 2013; 17 (15): 2091-2096 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,
Bcl-2–related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury
Authors: Keiichi I Nakayama
Mei Zhong
Holger Link
Zhou Zhu
Aaron B Waxman
Robert Homer
Chuan Hua He
Jack A Elias
Morgan E Rabach
Chun Geun Lee
Keiko Nakayama
Qingsheng Chen
Bing Ma
Journal: Journal of Clinical Investigation (2005)
Discipline: CLINICAL MEDICINE
Keywords: Hyperoxic acute lung injury; HALI; Bfl-1/A1; IL-11; cytoprotection
Affiliations: Department of Internal Medicine, Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8057, USA.

Abstract:  Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we characterized the expression of A1 and the oxygen susceptibility of WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O(2) caused TUNEL(+) cell death, induction and activation of intrinsic and mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were also induced as an apparent protective response. A1 was induced in hyperoxia, and in A1-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and Bcl-xl, and enhanced murine survival in 100% O(2). In A1-null mice, IL-11-induced protection, survival advantage, and Bcl-2 and Bcl-xl induction were significantly decreased. VEGF also conferred protection via an A1-dependent mechanism. In vitro hyperoxia also stimulated A1, and A1 overexpression inhibited oxidant-induced epithelial cell apoptosis and necrosis. A1 is an important regulator of oxidant-induced lung injury, apoptosis, necrosis, and Bcl-2 and Bcl-xl gene expression and a critical mediator of IL-11- and VEGF-induced cytoprotection. 

Retracted: No

PubPeer comments:
 Figures 6B and 8B. Much more similar than expected. https: imgur.com 88OrOFs ,