PReD-Bench/PRed-Bench huggingface dataset:
MiR-454 promotes the progression of human non-small cell lung cancer and directly targets PTEN
Authors: Song Zhao
Dong-Lei Liu
Yang Yang
Chun-Yang Zhang
Deng-Yan Zhu
Yu Qi
Xiang-Nan Li
Kai Wu
Jia Zhao
Journal: Biomedicine & Pharmacotherapy (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Apoptosis; MiR-454; Non-small cell lung cancer; PTEN; Prognosis
Affiliations: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China., Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China. Electronic address: .

Abstract:  Purpose: MicroRNA-454 has been proven dysregulated in some human malignancies and correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to explore the effects of miR-454 in NSCLC tumorigenesis and development. Methods: Using quantitative RT-PCR, we detected miR-454 expression in NSCLC cell lines and primary tumor tissues. The association of miR-454 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-454 on the biological behavior of NSCLC cells were investigated. At last, the potential regulatory function of miR-454 on PTEN expression was confirmed. Results: miR-454 was found to be up-regulated in NSCLC tissues and cell lines. High miR-454 expression was closely correlated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis corroborated that miR-454 overexpression was an independent unfavourable prognostic factor for patients with NSCLC. Down-regulation of miR-454 could significantly reduce NSCLC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while up-regulation of miR-454 showed opposite effects. Further, PTEN was confirmed as a direct target of miR-454 by using Luciferase Reporter Assay. Conclusions: These findings indicate that miR-454 may act as an oncogene in NSCLC and would serve as a potential therapy target for this disease. 

Retracted: No

PubPeer comments:
 Fig 3C: ![file] Fig 3 D E.  (D, E) Down-regulation of miR-454 impeded the invasion migration of A549 cells, while up-regulation of miR454 promoted cell invasion migration ability in H1299 cells . Rearranged for convenience. ![file] The repeated portions in the marked panel speak for themselves. Other panels are familiar from (e.g.) Fig 2 of [Hou et al (2015)] and other papers linked there. ![] ---------------------------------------- A broader context is available from [a Chinese science-integrity enthusiast] , blogging in 2016 and citing work by the now-vanished site PlagiarismWatch, to reconstruct a network of multiple mutually-plagiarised papers, not including this one. All presumably the work of a papermill. Some of this series of retractions was [covered by RetractionWatch] . ![] ![file] ![file] ,
Acute Effects of the New Method Sarcoplasma Stimulating Training Versus Traditional Resistance Training on Total Training Volume, Lactate and Muscle Thickness
Authors: Jonato Prestes
Alex Harley Crisp
Nuno Manuel Frade de Sousa
Raphael Machado da Conceição
Luan Oenning
Thiago Barbosa Trindade
Fernando Noronha de Almeida
Charles Ricardo Lopes
Jeffrey M Willardson
Journal: Frontiers in Physiology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: muscle pump; muscle thickness; resistance exercise; training method; training volume.
Affiliations: Graduation Program on Physical Education, Catholic University of Brasilia, Brazilia, Brazil., Human Performance Research Group, Methodist University of Piracicaba, São Paulo, Brazil., Adventist Faculty of Hortolândia (UNASP), São Paulo, Brazil., Laboratory of Exercise Physiology, Faculty Estacio of Vitoria, Espírito Santo, Brazil., Department of Health and Human Performance, Montana State University Billings, Billings, MT, United States.

Abstract:  Background: Trained subjects have difficulty in achieving continued results following years of training, and the manipulation of training variables through advanced resistance training (RT) methods is widely recommended to break through plateaus. Objective: The purpose of the present study was to compare the acute effects of traditional RT (TRT) versus two types of sarcoplasma stimulating training (SST) methods on total training volume (TTV), lactate, and muscle thickness (MT). Methods: Twelve trained males (20.75 ± 2.3 years; 1.76 ± 0.14 meters; body mass = 79.41 ± 4.6 kg; RT experience = 4.1 ± 1.8 years) completed three RT protocols in a randomly sequenced order: TRT, SST contraction type (SST-CT), or SST rest interval variable (SST-RIV) with 7 days between trials in arm curl (elbow flexors) and triceps pulley extension (elbow extensors) performed on the same day. Results: The SST groups displayed greater acute biceps and triceps brachii (TB) MT versus the TRT session, with no difference in lactate levels between them. The SST-CT resulted in greater biceps and TB MT versus the SST-RIV session. The TTV was greater for the TRT session versus the SST sessions, except in the case of the elbow flexors (no difference was observed between TRT and SST-CT), and higher for the SST-CT versus the SST-RIV. Conclusion: Trained subjects may benefit from using the SST method as this method may offer a superior MT stimulus and reduced training time, even with a lower TTV. 

Retracted: No

PubPeer comments:
 How does a training method can be connoted as sarcoplasma stimulating, while sarcoplasmic hypertrophy was not measured? There is only muscle thickness analysis. ,
Haemophilus influenzae Porin Contributes to Signaling of the Inflammatory Cascade in Rat Brain
Authors: M D&#x27;Isanto
C Di Filippo
F Gorga
M Vitiello
M Galdiero
A Longanella
A Tortora
M D&#x27;Amico
Journal: Infection and Immunity (2001)
Discipline: IMMUNOLOGY
Keywords: Haemophilus influenzae type b; porin; bacterial meningitis; interleukin-1alpha; tumor necrosis factor alpha
Affiliations: Dipartimento di Patologia e Sanità Animale, Facoltà di Veterinaria, Università degli Studi di Napoli Federico I, 80137 Naples., Istituto di Farmacologia e Tossicologia2and, Istituto di Microbiologia,3Facoltà di Medicina e Chirurgia, Seconda Universitàdegli Studi di Napoli, 80138 Naples, Italy

Abstract:  In the present study we observed that the Haemophilus influenzae type b (Hib) porin, among the different surface bacterial components, is involved in the pathophysiology of bacterial meningitis. This study demonstrates that inoculation of Hib porin into the fourth cerebral ventricle causes the simultaneous expression of interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha (TNF-alpha), and macrophage inflammatory protein 2 (MIP-2) at 6 h after inoculation. At 24 h, the expression of MIP-2 decreases while the expression of IL-1alpha and TNF-alpha increases. The mRNA expression of IL-1alpha, TNF-alpha, and MIP-2 is correlated with injury to the blood-brain barrier as demonstrated by the appearance of serum proteins and leukocytes in cerebrospinal fluid and by the increase in brain water content. 

Retracted: No

PubPeer comments:
 Figure 2A: 6h expression profiles. * Orange boxes: Most of the marker lanes appear to look more similar than expected. * Pink, yellow, cyan boxes: Some PCR bands look unexpectedly similar ![file] Figure 3A, showing expression after 24h, appears to have similar concerns. Not marked, but left blank as an exercise for the reader. Of note, the b-actin panel looks quite similar to that in Figure 2A. ![file] ,
Progression of esophageal dysplasia to cancer
Authors: Marianna Salemme
Marco Matejcic
Vincenzo Villanacci
Paul E Swanson
Henry D Appelman
Robert H Riddell
M Iqbal Parker
Journal: Annals of the New York Academy of Sciences (2014)
Discipline: Multidisciplinary
Keywords: Barrett's esophagus; OESO; esophageal adenocarcinoma; lectin; p52
Affiliations: Department of Pathology, University of Michigan, Ann Arbor, Michigan., International Centre for Genetic Engineering and Biotechnology; Cape Town Component; Observatory; Cape Town South Africa, Department of Pathology; Mount Sinai Hospital; Toronto Ontario Canada, Department of Pathology; Spedali Civili of Brescia; Brescia Italy, Anatomic Pathology; University of Washington Medical Center; Seattle Washington

Abstract:  The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the evolution of low-grade squamous and glandular dysplasia to invasive carcinoma; the mutational spectra of Barrett's esophagus and adenocarcinoma; the risk of p53-immunoreactive glandular dysplasia compared to non-immunoreactive mucosa for progression to cancer; the role of lectins in progression to adenocarcinoma; and the role of racemase immunoreactivity in the prediction of risk of adenocarcinoma. 

Retracted: No

PubPeer comments:
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 ,
Mineralocorticoid receptor antagonist‐mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF‐H 2 S‐Nrf2 signaling
Authors: Xia She
Lina Zhang
Chaochao Gu
Li Chen
Li Chong
Rui Shi
Rui Li
Journal: Fundamental & clinical pharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Alzheimer's disease; Hippocampus; Morris water maze; beta-amyloid; frontal cortex.
Affiliations: Department of Neurology, Shaanxi Provincial People's Hospital, 256 Friendship West Road, Beilin District, Xi'an, Shaanxi, 710068, China., Department of Ophthalmology, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an City, Shaanxi Province, 710068, China., Nuclear Magnetic Resonance Room, Shaanxi Provincial People's Hospital, 256 Friendship West Road, Beilin District, Xi'an, Shaanxi, 710068, China.

Abstract:  The present study explored the role and mechanisms of mineralocorticoid receptor antagonists in β-amyloid (Aβ)-induced cognitive impairment. A single intracerebroventricular injection of Aβ1-42 was given to mice, and after 14 days of injection, memory was evaluated using the Morris water maze test. Spironolactone (25 and 50 mg/kg) and eplerenone (50 and 100 mg/kg) were administered for two days before and for 14 days after Aβ injection. Mineralocorticoid receptor blockers attenuated Aβ-induced cognitive impairment assessed in terms of decrease in day 4 escape latency time (ELT) in comparison to day 1 ELT (suggesting an increase in learning) along with an increase in time spent in target quadrant on day 5 (suggesting the retrieval of learned things). These drugs also increased the expression of BDNF, H2 S, Nrf2, reduced glutathione, and decreased β-amyloid and TNF-α in the frontal cortex and hippocampus. Co-administration of ANA-12, BDNF receptor antagonist (0.25 and 0.5 mg/kg) abolished cognitive improving functions of mineralocorticoid receptor blockers, attenuated H2 S, Nrf2, reduced glutathione, and decreased β-amyloid and TNF-α. It is concluded that spironolactone and eplerenone attenuate cognitive decline of Alzheimer's type, possibly through upregulation of BDNF levels in the frontal cortex and hippocampus, which may increase H2 S, decrease Aβ, activate Nrf2-dependent antioxidant system, and decrease neuroinflammation. 

Retracted: No

PubPeer comments:
 It is not clear why the authors selected the QS World University Ranking [1] system to base the selection of their study subjects, who they then classified as being  top economists , equating this, perhaps erroneously, with being  members of economics departments of world top universities . Why did the authors, who applied two indexes, PPI and PPB, not simply use citation metrics within established indexes, to establish who the  top economists were? Some of the literature related to this university ranking system suggests data integrity problems. [1] https: en.wikipedia.org wiki QS_World_University_Rankings ,
In vivo functional dissection of human inner kinetochore protein CENP-C
Authors: William C Earnshaw
Giovanni Perini
Stefania Trazzi
Giuliano Della Valle
Valeria Politi
Daniel Diolaiti
Roberto Bernardoni
Journal: Journal of Structural Biology (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CENP-C; kinetochore; centromeres; recruitment; domains

Abstract:  CENP-C is a fundamental component of the inner kinetochore plate and contributes to the formation of functional centromeres in eukaryotic organisms. Recruitment of CENP-C to kinetochore requires other centromere proteins, particularly CENP-A, CENP-H, and CENP-I. However, how CENP-C is correctly localized at the kinetochore is not clearly determined, mainly due to the functional variety of its domains, which hints at a complex recruitment mechanism. Here, by both immunofluorescent labeling and chromatin/immunoprecipitation we could show that human CENP-C contains two distinct domains, one in the central region, between amino acids 426 and 537, and the second one in the carboxyl terminal region, between amino acids 638 and 943, which are both capable of localizing at centromeres and binding alpha-satellite DNA. The presence of two domains that iterate the same function despite being significantly different in their amino acid sequence and structure suggests that CENP-C may target the centromere by establishing multiple contacts with both the DNA and protein constituents of the kinetochore. 

Retracted: No

PubPeer comments:
 The same image was published twice, however spliced differently: in J Struct Biol and J Cell Sci ![file] ,
Self-assembling anticaries mucosal vaccine containing ferritin cage nanostructure and glucan-binding region of S. mutans glucosyltransferase effectively prevents caries formation in rodents
Authors: Tian-Feng Wang
Ming-Wen Fan
Yu-Hong Li
Qian-Lin Ye
Xi-Xi Cao
Xuan Hu
Journal: Human vaccines & immunotherapeutics (2017)
Discipline: IMMUNOLOGY
Keywords: adjuvants; dendritic cells; dental caries; mucosal immunity; nanoparticle
Affiliations: a The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM) , School & Hospital of Stomatology, Wuhan University , Wuhan , China., b Department of Endodontics , School and Hospital of Stomatology, Wuhan University , Wuhan , China., c Department of Oral Radiology , Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam , Amsterdam , The Netherlands.

Abstract:  Anticaries protein vaccines that induce a mucosal immune response are not effective. Therefore, development of effective and convenient anticaries vaccines is a priority of dental research. Here we generated self-assembling nanoparticles by linking the glucan-binding region of Streptococcus mutans glucosyltransferase (GLU) to the N-terminal domain of ferritin to determine whether these novel nanoparticles enhanced the immunogenicity of an anticaries protein vaccine against GLU in rodents. We constructed the expression plasmid pET28a-GLU-FTH and purified the proteins from bacteria using size-exclusion chromatography. BALB/c mice were used to evaluate the ability of GLU-ferritin (GLU-FTH) nanoparticles to induce GLU-specific mucosal and systemic responses. The protective efficiency of GLU-FTH nanoparticles was compared with that of GLU alone or a mixture of GLU and poly(I:C) after administering an intranasal infusion to Wistar rats. The phagocytosis and maturation of dendritic cells (DCs) exposed in vitro to the nanoparticles were assessed using flow cytometry. The GLU-FTH nanoparticle vaccine elicited significantly higher levels of GLU-specific antibodies compared with GLU or a mixture of GLU and poly(I:C). Immunization with GLU-FTH achieved lower caries scores compared with those of the other vaccines. Administration of GLU-FTH nanoparticles enhanced phagocytosis by DCs and their maturation. Thus, self-assembling GLU-FTH is a highly effective anticaries mucosal vaccine that enhanced antibody production and inhibited S. mutans infection in rodents. 

Retracted: Yes

PubPeer comments:
 Figure 1C: Both panels also appear in a different study (Hu, 2019), under a different premise: Wei Hu, Hang Yang, Jungping Yu, Hongping Wei (2019) A Novel Double Core-Shell Bionanoparticle Formed by Ferritin and Baculoviral Polyhedrin, Journal of Nanoscience and Nanotechnology, https: doi.org 10.1166 jnn.2019.17130 ![file] ![file] ,
Mutational analysis of the p50 subunit of NF-kappa B and inhibition of NF-kappa B activity by trans-dominant p50 mutants
Authors: K Brown
U Siebenlist
V Bours
A S Fauci
W Timmer
P Bressler
Journal: Journal of virology (1993)
Discipline: MICROBIOLOGY
Keywords: NF-kappa B; DNA binding; protein dimerization; Rel homology region; homodimers
Affiliations: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.

Abstract:  The NF-kappa B family of DNA-binding proteins regulates the expression of many cellular and viral genes. Each of these proteins has an N-terminal region that is homologous to the c-Rel proto-oncogene product, and this Rel homology region defines both DNA binding and protein dimerization properties of the individual proteins. Most of the NF-kappa B family members have been shown to associate with themselves or with each other to form homodimers or heterodimers, and previous studies have shown that dimerization of NF-kappa B factors is necessary to provide a functional DNA binding domain. We have used site-directed mutagenesis to identify regions in the Rel homology domain of the p50/NF-kappa B protein that are important for DNA binding and protein dimerization. Our studies have identified mutations of p50 that interfere with DNA binding only and those that interfere with protein dimerization. Mutations of p50 which disrupt only DNA binding were still able to associate with other members of the NF-kappa B protein family. We demonstrate that such heterodimeric complexes inhibit transcriptional activation mediated in trans through a cis-acting kappa B motif; therefore, we have identified trans-dominant negative mutants of p50. 

Retracted: No

PubPeer comments:
 unlikely time course ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Attenuation of the Innate Immune Response against Viral Infection Due to ZNF598-Promoted Binding of FAT10 to RIG-I
Authors: Guanming Wang
Takahisa Kouwaki
Hiroyuki Oshiumi
Masaaki Okamoto
Journal: Cell Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FAT10; RIG-I; ZNF598; innate immunity; interferon
Affiliations: Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan., Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. Electronic address: .

Abstract:  Excessive innate immune response is harmful to the host, and aberrant activation of the cytoplasmic viral RNA sensors RIG-I and MDA5 leads to autoimmune disorders. ZNF598 is an E3 ubiquitin ligase involved in the ribosome quality control pathway. It is also involved in the suppression of interferon (IFN)-stimulated gene (ISG) expression; however, its underlying mechanism is unclear. In this study, we show that ZNF598 is a negative regulator of the RIG-I-mediated signaling pathway, and endogenous ZNF598 protein binds to RIG-I. ZNF598 ubiquitin ligase activity is dispensable for the suppression of RIG-I signaling. Instead, ZNF598 delivers a ubiquitin-like protein FAT10 to the RIG-I protein, resulting in the inhibition of RIG-I polyubiquitination, which is required for triggering downstream signaling to produce type I IFN. Moreover, ZNF598-mediated suppression is abrogated by FAT10 knockout. Our data elucidate the mechanism by which ZNF598 inhibits RIG-I-mediated innate immune response. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. ,
Antitumor and antiangiogenic activities of curcumin in cervical cancer xenografts in nude mice
Authors: Pornphrom Yoysungnoen-Chintana
Suthiluk Patumraj
Parvapan Bhattarakosol
Journal: BioMed Research International (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: curcumin; tumor progression; angiogenesis; cervical cancer; nude mice
Affiliations: Division of Physiology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Rangsit Campus, Klong Luang, Pathum Thani 12120, Thailand., Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand., Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Abstract:  To evaluate the effects of curcumin (CUR) on tumor progression and angiogenesis in cervical cancer- (CaSki-) implanted nude mice and on the angiogenic biomarkers: vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and epidermal growth factor receptor (EGFR). CaSki cells were subcutaneously injected in nude mice to establish subcutaneous tumors. One month after injection, mice were orally administered vehicle or 500, 1,000, and 1,500 mg/kg of CUR daily × 30 consecutive days. Tumor volume was measured every 3-4 days. At the end of the study, tumor microvasculature was observed under confocal microscope, and immunohistochemical analyses were performed to detect CD31, VEGF, COX-2, and EGFR. CUR at the doses of 1,000 and 1,500 mg/kg showed significant tumor growth retardation (21.03% and 35.57%) versus CaSki + vehicle group. The microvascular density (MVD) in CaSki + vehicle group was significantly increased versus Control + vehicle group and significantly reduced by CUR (1,000 and 1,500 mg/kg). VEGF, COX-2, and EGFR expressions were upregulated in CaSki + vehicle group and attenuated significantly by CUR (1,000 and 1,500 mg/kg). In conclusion, high dose CUR inhibited tumor growth and angiogenesis in CaSki-implanted mice probably mediated by the downregulation of VEGF, COX-2 and EGFR. CUR may have a role in treating human cervical cancer and should be explored further. 

Retracted: No

PubPeer comments:
 partial image duplication contradicts labels ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
lncRNA SNHG16 Exerts Oncogenic Functions in Promoting Proliferation of Glioma Through Suppressing p21
Authors: Hong Liu
Hai-Peng Xi
Guang-Wei Wang
Zheng-Bin Ding
Xiang-Yang Zhou
Journal: Pathology & Oncology Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: Glioma; Long non-coding RNA; SNHG16; p21.
Affiliations: Department of Neurosurgery, The First Affiliated Hospital of University of South China, No.69, Chuanshan Road, Shigu District, Hengyang, 421001, Hunan Province, People's Republic of China., Department of Neurosurgery, The First Affiliated Hospital of University of South China, No.69, Chuanshan Road, Shigu District, Hengyang, 421001, Hunan Province, People's Republic of China. .

Abstract:  Glioma is a malignant brain tumor that accounts for 30% of all brain tumors and 80% of malignant brain tumors. This poor clinical outcome makes the study of molecular mechanisms in glioma as an urgent subject. However, the certain mechanism remains unclear. Long non-coding RNAs (lncRNAs) plays a key role in glioma development and progression. In the present study, we aimed to explore the potential mechanisms of lncRNA SNHG16 in glioma. The levels of lncRNA SNHG16 were qualified in both glioma tissues and cell lines using qRT-PCR assay. The ability of cell proliferation was tested via CCK-8 and colony formation assays. Transfections were performed to knockdown SNHG16 and its target gene p21. The cell cycles and cell apoptosis were evaluated using flow cytometry, and the expression of SNHG16, p21 and apoptosis biomarkers were qualified with qRT-PCR and western blot assays. The expression of SNHG16 were up-regulated in both glioma tissues and cell lines. Knockdown of SNHG16 was associated with poor proliferation, decreased monoclonal formation rates, but increased apoptosis rates, which also caused the high expression of p21. Moreover, p21 could mediate cell proliferation and monoclonal formation, promote cell apoptosis in glioma, which was negatively correlated with lncRNA SNHG16. The molecule mechanism experiments revealed that SNHG16 could not only inhibit the expression of p21 but also suppressed the level of caspase 3 and 9, while promoted cyclinD1 and cyclinB1 expression. lncRNA SNHG16 could promote the cell proliferation and inhibit the apoptosis of glioma through suppressing p21, indicating that lncRNA SNHG16 might be quite vital for the diagnosis and progression of glioma and could even be a novel therapeutic target for glioma. 

Retracted: No

PubPeer comments:
 In Figure 4B, a flow cytometry dot plot has been duplicated and presented as something else. ![file] ,
Does tool use extend peripersonal space? A review and re-analysis
Authors: Nicholas P Holmes
Journal: Experimental Brain Research (2012)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: tools; extensions; body; neural representation; multisensory space
Affiliations: Department of Psychology, School of Psychology and Clinical Language Sciences, University of Reading, Earley Gate, Reading, RG6 6BE, UK. 

Abstract:  The fascinating idea that tools become extensions of our body appears in artistic, literary, philosophical, and scientific works alike. In the last 15 years, this idea has been reframed into several related hypotheses, one of which states that tool use extends the neural representation of the multisensory space immediately surrounding the hands (variously termed peripersonal space, peri-hand space, peri-cutaneous space, action space, or near space). This and related hypotheses have been tested extensively in the cognitive neurosciences, with evidence from molecular, neurophysiological, neuroimaging, neuropsychological, and behavioural fields. Here, I briefly review the evidence for and against the hypothesis that tool use extends a neural representation of the space surrounding the hand, concentrating on neurophysiological, neuropsychological, and behavioural evidence. I then provide a re-analysis of data from six published and one unpublished experiments using the crossmodal congruency task to test this hypothesis. While the re-analysis broadly confirms the previously reported finding that tool use does not literally extend peripersonal space, the overall effect sizes are small and statistical power is low. I conclude by questioning whether the crossmodal congruency task can indeed be used to test the hypothesis that tool use modifies peripersonal space. 

Retracted: No

PubPeer comments:
 This paper was criticised as part of a self-reflection posted on Twitter on 2nd-3rd April, 2021 (twitter TheHandLab status 1377760796130869248) Criticism: This is where my self-criticism really begins. As I wrote in this paper, re-analysis of my own work 70471-4, https: doi.org 10.1007 s00221-007-1060-7), showed that, overall, the effect size we studied was too small to be worth any further study using this particular approach. ,
Antiangiogenic effects of ganetespib in colorectal cancer mediated through inhibition of HIF-1α and STAT-3
Authors: Wungki Park
Iman El-Hariry
Jing Wen
Hemchandra Mahaseth
Latonia Taliaferro-Smith
Bassel F El-Rayes
Alton B Farris
Ganji Purnachandra Nagaraju
Patrick S Sullivan
Field Willingham
Roberto Diaz
Jerome Landry
David A Proia
Journal: Angiogenesis (2013)
Discipline: CLINICAL MEDICINE
Keywords: Hypoxia-inducible factors; STAT-3; angiogenesis; HSP90; ganetespib
Affiliations: Department of Hematology and Medical Oncology, Emory University, 1365 Clifton RD NE, Office 2080, Atlanta, GA, 30322, USA.

Abstract:  Hypoxia-inducible factors (HIFs) and STAT-3 play essential roles in angiogenesis. HIF-1α and STAT-3 are clients of the heat shock protein 90 (HSP90). We hypothesized that ganetespib, a potent HSP90 inhibitor, would disrupt angiogenesis in colorectal cancer (CRC) through inhibition of HIF-1α and STAT-3. CRC cell lines (HCT116 and HT29) were used in all the experiments. Egg CAM and HUVEC assays revealed decreased angiogenesis in ganetespib treated cell lines. Ganetespib inhibited matrigel plug vascularization and tumor growth of xenografts. Significant inhibition of PDGFA, FGF2, Ang-1, Ang-2, TGFβ1, VEGF, HIF-1α and STAT-3 expression was observed in both cell lines treated ganetespib. HIF-1α overexpression resulted in the increase VEGF and STAT-3 expression and this was inhibited by ganetespib. HIF-1α knockdown inhibited VEGF and STAT-3 expression. STAT-3 knockdown inhibited VEGF but not HIF-1α expression. HSP90, STAT-3 and VEGF expression was significantly higher in CRC compared to adjacent normal tissue. Significant downregulation of PDGFA, FGF2, Ang-1, Ang-2, TGFβ1, VEGF, STAT-3 and HIF-1α mRNA was observed in the post ganetespib treatment tumor samples from patients with rectal cancer. These results collectively suggest that inhibition of HSP90 is a promising antiangiogenic strategy in CRC. HSP90 angiogenic effects are mediated through HIF-1α and STAT-3. 

Retracted: No

PubPeer comments:
 Figure 6b. Much more similar than you would expect. https: imgur.com xx0ntzL , 
 The 2013 erratum mentions  Angiogenesis. 2013 Oct;16(4):919. Ganji, Purnachandra Nagaraju [corrected to Nagaraju, Ganji Purnachandra]. It does not mention figure 6b. ,
Encapsulated plant extract (Gelsemium sempervirens) poly (lactide-co-glycolide) nanoparticles enhance cellular uptake and increase bioactivity in vitro
Authors: Saili Paul
Soumya Sundar Bhattacharyya
Anisur Rahman Khuda-Bukhsh
Journal: Experimental Biology and Medicine (2010)
Discipline: CLINICAL MEDICINE
Keywords: Gelsemium sempervirens; EEGS; nanoparticle encapsulation; PLGA; bioactivity
Affiliations: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235, West Bengal, India

Abstract:  Ethanolic extract of Gelsemium sempervirens (family: Loganiaceae), henceforth to be called EEGS, is used in various traditional systems of medicine. In homeopathy, EEGS is known as mother tincture of G. sempervirens, which is generally used to treat pain and respiratory ailments. We demonstrated earlier anticancer activity of crude EEGS by in vitro studies on human HeLa cells. To test the hypothesis if nanoparticle-encapsulated extract (now onwards to be called NEEGS) could enhance cellular uptake and thereby improve bioactivity, we formulated nanoparticle encapsulation based on poly (lactide-co-glycolide) (PLGA) and confirmed encapsulation by scanning electron microscopy (SEM) and atomic force microscopy. EEGS was encapsulated with 81.6% efficiency in PLGA biodegradable nanoparticle formulation and F68 (polyoxyethylene-polyoxypropylene) was used as a stabilizer. Dynamic laser light scattering and SEM indicated a particle diameter of 122.6 nm. The zeta potential of the drug-loaded nanoparticles was -14.8 mV. NEEGS was characterized for their biological activities in a skin cancer cell line A375 in vitro. NEEGS exhibited relatively rapid (30 min) and more efficient cellular uptake than their un-encapsulated counterpart (45 min). Analysis of data of apoptosis study using Annexin V-FITC, terminal transferase dUTP nick end labeling assay and DNA ladder revealed that encapsulated EEGS was more potent than their un-encapsulated counterpart in inducing apoptosis of A375 cells. Reverse transcriptase-polymerase chain reaction data of survivin, cyclin-D1, caspase-3, PCNA and p53 also corroborated well to suggest greater potentials of NEEGS as anticancer agents. 

Retracted: No

PubPeer comments:
 the 100 and 200 ug NEEGS panels of figure 7a contain some duplicated elements original ![file] ![file] with some of duplicated elements marked. Note that the duplicated elements are shifted between the 2 panels, ie the duplicated cells in the 100 ug panel are offset to the N and NE of the yellow lines (the geometric arrangement of the yellow lines isidentical between the 2 panels). this can not possibly be a simple duplication of images as groups of duplicated cells are shifted and there are different cells along with the duplicated groups of cells. , 
 There appears to be a similar issue in the adjacent panels of Figure 7a. There are a number of similarly unaddressed concerns: https: pubpeer.com search?q=Khuda-Bukhsh *** ![file] ,
Role of mitochondrial Bax, caspases, and MAPKs for ceramide-induced apoptosis in renal proximal tubular cells
Authors: Norishi Ueda
Hideyuki Iwayama
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: crosstalk; mitochondrial Bax; caspases; mitogen-activated protein kinases (MAPKs); epidermal growth factor (EGF)
Affiliations: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Abstract:  It remains elusive whether crosstalk exists among mitochondrial Bax, caspases, and mitogen-activated protein kinases (MAPKs), and whether epidermal growth factor (EGF), which may activate MAPKs, affects ceramide-induced apoptosis through the crosstalk in renal proximal tubular cells (RPTCs). Effect of ceramide on expression of mitochondrial Bax and phosphorylated (p)-ERK, p38MAPK and JNK, that of MAPKs inhibition, and of EGF in the presence or absence of MAPKs inhibition on ceramide-induced apoptosis were examined in HK-2 cells. Apoptosis and expression of mitochondrial Bax and p-MAPKs were measured by Hoechst 33258 staining and Western blotting. C2-ceramide, but not dihydroC2-ceramide, inactive C2-ceramide, induced apoptosis at 24 h. C2-ceramide enhanced the mitochondrial Bax expression at 1 h, which was peaked at 3-6 h and decreased at 24 h, but remained increased, compared to control. An inhibitor of caspases, zVAD-fmk, ameliorated ceramide-induced apoptosis, suggesting a role of caspases for ceramide-induced apoptosis. C2-ceramide enhanced the expression of p-ERK and p-p38MAPK, but not p-JNK, at 1 h, which was increased till 24 h. An inhibitor of ERK, PD98059, or of p38MAPK, SB202190, failed to affect C2-ceramide-induced apoptosis. EGF, which enhanced the expression of p-ERK and p-p38MAPK but not p-JNK, ameliorated C2-ceramide-induced apoptosis without affecting mitochondrial Bax. Inhibition of ERK or p38MAPK failed to abolish the protective effect of EGF on C2-ceramide-induced apoptosis. Mitochondrial Bax and caspases, but not MAPKs, play a role for ceramide-induced apoptosis in RPTCs. EGF ameliorates ceramide-induced apoptosis in Bax- and MAPKs-independent pathways. The mechanism of ceramide-induced apoptosis and anti-apoptotic effect of EGF deserves further investigations. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: The ERK panel in Figure 4A looks similar to the p38MAPK panel in Figure 4B. * The Actin panels also look similar but those represent the same protein and experiments, so that is not a concern. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. I would love to hear from the authors if the journal ever contacted them in the past five years. ![file] ,
Vitamin D and COVID-19: evidence and recommendations for supplementation
Authors: Rose Kenny
Martin Hewison
Sreedhar Subramanian
Jonathan Rhodes
Julian Hopkin
Richard Quinton
David Thickett
George Griffin
Journal: Royal Society Open Science (2020)
Discipline: Multidisciplinary
Keywords: COVID-19; immunology; vitamin D.
Affiliations: Infectious Diseases and Medicine, St George's University of London, London, UK., Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK., Medical School, Swansea University, Swansea, West Glamorgan, UK., Medical Gerontology, Trinity College Dublin School of Medicine, Dublin, Ireland., Endocrinology, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK., Institute of Translational Medicine, University of Liverpool, Liverpool, UK., Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK., Institute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK.

Abstract:  Vitamin D is a hormone that acts on many genes expressed by immune cells. Evidence linking vitamin D deficiency with COVID-19 severity is circumstantial but considerable-links with ethnicity, obesity, institutionalization; latitude and ultraviolet exposure; increased lung damage in experimental models; associations with COVID-19 severity in hospitalized patients. Vitamin D deficiency is common but readily preventable by supplementation that is very safe and cheap. A target blood level of at least 50 nmol l-1, as indicated by the US National Academy of Medicine and by the European Food Safety Authority, is supported by evidence. This would require supplementation with 800 IU/day (not 400 IU/day as currently recommended in UK) to bring most people up to target. Randomized placebo-controlled trials of vitamin D in the community are unlikely to complete until spring 2021-although we note the positive results from Spain of a randomized trial of 25-hydroxyvitamin D3 (25(OH)D3 or calcifediol) in hospitalized patients. We urge UK and other governments to recommend vitamin D supplementation at 800-1000 IU/day for all, making it clear that this is to help optimize immune health and not solely for bone and muscle health. This should be mandated for prescription in care homes, prisons and other institutions where people are likely to have been indoors for much of the summer. Adults likely to be deficient should consider taking a higher dose, e.g. 4000 IU/day for the first four weeks before reducing to 800 IU-1000 IU/day. People admitted to the hospital with COVID-19 should have their vitamin D status checked and/or supplemented and consideration should be given to testing high-dose calcifediol in the RECOVERY trial. We feel this should be pursued with great urgency. Vitamin D levels in the UK will be falling from October onwards as we head into winter. There seems nothing to lose and potentially much to gain. 

Retracted: No

PubPeer comments:
 https: twitter.com sTeamTraen status 1355108067902369793 , 
 https: twitter.com sTeamTraen status 1355176410890035200 ,
Target inhibition on GSK-3β by miR-9 to modulate proliferation and apoptosis of bladder cancer cells
Authors: S-B Wang
Z-Q Lin
D Zhang
Z-C Dong
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Glycogen synthase kinase-3β; miR-9; Wnt/β-catenin signaling pathway; bladder cancer; proliferation
Affiliations: Department of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Gansu Province for Urological Diseases, Lanzhou University Second Hospital, Lanzhou, Gansu, China. .

Abstract:  Objective: Glycogen synthase kinase-3β (GSK-3β) can negatively regulate Wnt/β-catenin signaling pathway via degrading β-catenin protein, and plays suppressing roles in various tumors. Its role in bladder cancer pathogenesis is still unclear. In bladder cancer tissues, expression of microRNA-9 (miR-9) is significantly elevated. This study investigated the effect of miR-9 in modulating GSK-3β expression, Wnt/β-catenin pathway activity, and proliferation or apoptosis of bladder cancer cells. Patients and methods: Dual luciferase reporter gene assay confirmed targeted regulation between miR-9 and GSK-3β. Bladder cancer tissues were collected to measure expression of miR-9, GSK-3β mRNA using adjacent tissues as the control. Expression of miR-9 and GSK-3β was also measured in HBEC, RT4 and TCCSUP cells. Cultured RT4 and TCCSUP cells were transfected with miR-9 inhibitor or pSicoR-GSK-3β. The expression of miR-9, GSK-3β and β-catenin was compared, followed by using flow cytometry assay for cell apoptosis and EdU staining for cell proliferation. Results: Comparing to adjacent tissues, bladder cancer tissues illustrated significantly elevated miR-9 expression and lower GSK-3β mRNA. Bioinformatics analysis revealed complementary binding sites between miR-9 and 3'-UTR of GSK-3β mRNA, indicating targeted regulation between miR-9 and GSK-3β. Comparing to HBEC cells, RT4 and TCCSUP cells had significantly elevated miR-9 expression and lower GSK-3β expression, with enhanced proliferation. Transfection of miR-9 inhibitor or pSicoR-GSK-3β significantly elevated GSK-3β expression and suppressed β-catenin expression, promoted cell apoptosis and inhibited proliferation. Conclusions: MiR-9 up-regulation plays a role in suppressing GSK-3β expression and facilitating bladder cancer pathogenesis. Inhibition of miR-9 could potentiate GSK-3β expression, suppress proliferation of bladder cancer, and facilitate apoptosis. 

Retracted: Yes

PubPeer comments:
 Apparent reuse of an image in two figures, showing two different treatments and stainings. ![file] ,
Clotrimazole nanoemulsion for malaria chemotherapy. Part II: stability assessment, in vivo pharmacodynamic evaluations and toxicological studies
Authors: Shobhona Sharma
Sulabha Pathak
Vandana Patravale
Vivek Borhade
Journal: International Journal of Pharmaceutics (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: clotrimazole; antimalarial drug; nanoemulsion; parasitemia; Plasmodium berghei
Affiliations: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, 400019, Maharashtra, India. 

Abstract:  The aim of present investigation was to evaluate the potential of clotrimazole as antimalarial drug. Due to poor aqueous solubility and high lipophilicity, it was previously formulated in a nanoemulsion based system. The intrinsic effects of nanoemulsion on improvement of antimalarial activity of clotrimazole were assessed in mice infected with Plasmodium berghei and compared to its suspension formulation. In four-day suppressive test, mice treated with 10mg/kg clotrimazole nanoemulsion showed the highest suppression of parasitemia and; parasitemia was significantly lower than that of 10mg/kg clotrimazole suspension. In onset of activity and recrudescence test, percent reduction of parasitemia was significantly higher in 10 and 15 mg/kg clotrimazole nanoemulsion groups compared to 15 mg/kg suspension group. In both murine models, survival of mice treated with nanoemulsion was significantly prolonged compared to suspension at equivalent doses. The inhibition of parasite growth by clotrimazole in the nanoemulsion was dose dependent as determined by test for linear trend. In repeated dose oral toxicity, levels of serum liver enzymes and biomarkers of hepatotoxicity did not vary significantly from control. Six-month stability testing of the clotrimazole nanoemulsion exhibited no changes in various physiochemical attributes of drug product compared to initial analysis. 

Retracted: No

PubPeer comments:
 Could authors let the reader know the content of the erratum? The erratum site does not write anything. ,
Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner
Authors: Beth Stevens
Emily K Lehrman
Richard M Ransohoff
Dorothy P Schafer
Ryuta Koyama
Ryo Yamasaki
Alan R Mardinly
Amanda G Kautzman
Michael E Greenberg
Ben A Barres
Journal: Neuron (2012)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Microglia; synaptic pruning; neural activity; complement receptor 3; C3
Affiliations: Department of Neurology, F.M. Kirby Neurobiology Center, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Abstract:  Microglia are the resident CNS immune cells and active surveyors of the extracellular environment. While past work has focused on the role of these cells during disease, recent imaging studies reveal dynamic interactions between microglia and synaptic elements in the healthy brain. Despite these intriguing observations, the precise function of microglia at remodeling synapses and the mechanisms that underlie microglia-synapse interactions remain elusive. In the current study, we demonstrate a role for microglia in activity-dependent synaptic pruning in the postnatal retinogeniculate system. We show that microglia engulf presynaptic inputs during peak retinogeniculate pruning and that engulfment is dependent upon neural activity and the microglia-specific phagocytic signaling pathway, complement receptor 3(CR3)/C3. Furthermore, disrupting microglia-specific CR3/C3 signaling resulted in sustained deficits in synaptic connectivity. These results define a role for microglia during postnatal development and identify underlying mechanisms by which microglia engulf and remodel developing synapses. 

Retracted: No

PubPeer comments:
null, 
null, 
 Points by the unregistered submission:(posted 3 yrs ago but do not see them here so will repost. -These are important points and we are happy to clarify. Figure 5C is structured illumination microscopy which is a super-resolution imaging (not confocal); therefore the resolution is 200nm. As a result, we are able to conclude engulfment. -We always refer to engulfed material as presynaptic inputs versus purely presynaptic terminals. We agree this could be engulfed axonal material as well as synaptic. We addressed this in the results in discussion, but happy we could further clarify this point. ,