PReD-Bench/PRed-Bench huggingface dataset:
Prognostic value of microRNA-223/epithelial cell transforming sequence 2 signaling in patients with osteosarcoma
Authors: Kai Ning
Lei Wang
Zhe Ji
Rui Guo
Zongsheng Yin
Haoshaqiang Zhang
Journal: Human Pathology (2014)
Discipline: CLINICAL MEDICINE
Keywords: Clinicopathological features; Disease-free survival; Epithelial cell transforming sequence 2; MicroRNA-223; Osteosarcoma
Affiliations: Department of Orthopedics Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230000, China. Electronic address: ., Department of Orthopedics Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230000, China., Department of Orthopedics Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China.

Abstract:  MicroRNA-223 (miR-223) has been demonstrated to be implicated in cell proliferation and cell cycle progression of osteosarcoma cell lines by regulating its target gene epithelial cell transforming sequence 2 (ECT2). However, the clinical significance of the deregulation of the miR-223/Ect2 axis in human osteosarcoma has not been fully elucidated. To address this problem, we firstly showed that the expression levels of miR-223 and Ect2 messenger RNA were, respectively, down-regulated and up-regulated in osteosarcoma tissues compared with those in noncancerous bone tissues significantly (both P &lt; .001), according to the results of quantitative real-time reverse transcription-polymerase chain reaction. Notably, miR-223 down-regulation was negatively correlated with Ect2 messenger RNA up-regulation in osteosarcoma tissues (r = -0.68, P = .01). Then, the combined low miR-223 expression and high Ect2 expression (miR-223-low/Ect2-high) was significantly associated with high tumor grade (P = .01), poor response to chemotherapy (P = .01), positive metastasis (P &lt; .001), and recurrence (P &lt; .001) of osteosarcomas. Moreover, patients with miR-223-low/Ect2-high expression had the shortest overall survival (P &lt; .001) and disease-free survival (P &lt; .001) compared with patients in the other 3 groups (miR-223-low/Ect2-low, miR-223-high/Ect2-high, and miR-223-high/Ect2-low). Furthermore, the multivariate analysis identified miR-223/Ect2 expression and the status of metastasis as independent prognostic factors for overall survival and disease-free survival. In conclusion, our data offer convincing evidence that the deregulation of miR-223 and its target gene ECT2 may be associated with the aggressive tumor progression of human osteosarcoma. Of note, the combined miR-223 down-regulation and Ect2 up-regulation may be a possible marker of poor prognosis in this malignancy. 

Retracted: No

PubPeer comments:
 Fig. 1 Representative histologic image for osteosarcoma tissue sample.  I hope that Fig 1 is not representative of **anything**. ,
Two distinct interleukin-3-mediated signal pathways, Ras-NFIL3 (E4BP4) and Bcl-xL, regulate the survival of murine pro-B lymphocytes
Authors: T Inukai
A T Look
A Miyajima
T Shinjyo
K Ozawa
T Inaba
T Kinoshita
R Kuribara
T Yoshihara
Journal: Molecular and cellular biology (1999)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hematopoietic cells; cytokine-initiated signals; NFIL3; Bcl-xL; Ras signal transduction pathways
Affiliations: Departments of Molecular Biology, Jichi Medical School, Tochigi 329-0498, Japan., Institute of Molecular and Cellular Bioscience, the University of Tokyo, Tokyo 174, 3 Japan, and, Departments of Molecular Biology 1 and, Department of Experimental Oncology, St. Jude Children‚Äôs Research Hospital, Memphis, Tennessee 381054, Hematology, 2 Jichi Medical School, Tochigi 329-0498, and

Abstract:  Hematopoietic cells require cytokine-initiated signals for survival as well as proliferation. The pathways that transduce these signals, ensuring timely regulation of cell fate genes, remain largely undefined. The NFIL3 (E4BP4) transcription factor, Bcl-xL, and constitutively active mutants of components in Ras signal transduction pathways have been identified as key regulation proteins affecting murine interleukin-3 (IL-3)-dependent cell survival. Here we show that expression of NFIL3 is regulated by oncogenic Ras mutants through both the Raf-mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. NFIL3 inhibits apoptosis without affecting Bcl-xL expression. By contrast, Bcl-xL levels are regulated through the membrane proximal portion in the cytoplasmic domain of the receptor (betac chain), which is shared by IL-3 and granulocyte-macrophage colony-stimulating factor. Activation of either pathway alone is insufficient to ensure cell survival, indicating that multiple independent signal transduction pathways mediate the survival of developing B-lymphoid cells. 

Retracted: No

PubPeer comments:
 Figures 9A and 3A. Much more similar than you would expect. https: imgur.com bpkGUZU ,
The influence of stress factors on the reactivation of latent herpes simplex virus type 1 in infected mice
Authors: Ping Li
Peng Xie
Wen Huang
Mingming Xu
Gaonian Zao
Journal: Cell Biochemistry and Biophysics (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: stress factors; reactivation; latent herpes simplex virus type 1 (HSV-1); trigeminal ganglion; hyperthermia
Affiliations: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

Abstract:  This study shows that the influence of different stress factors impacts the reactivation of latent herpes simplex virus type 1 (HSV-1) specifically in the trigeminal ganglion of infected mice. Different stress factors including hyperthermia, hypothermia, fatigue, and immunosuppression were exerted on mice infected with HSV-1. These viral antigens were then detected in the trigeminal ganglion region of infected mice under the influence of each stress factor, with hyperthermia having the most influence on reactivation. Interestingly, an increase in IL-6 was also detected in mice subjected to hyperthermia. These studies therefore suggest that stress can induce the reactivation of latent HSV-1, possibly through the induction of IL-6, in the trigeminal ganglion region of infected mice. This reveals a new insight on the pathogenesis of relapse infection of HSV-1. 

Retracted: No

PubPeer comments:
 Figures 1 and 2 appear to be the same except for a portion of the middle lane. ***  *** Original  *** False color  ,
RETRACTED: Synthetic triterpenoids, CDDO-Imidazolide and CDDO-Ethyl amide, induce chondrogenesis
Authors: D Medici
A I Son
M B Sporn
S Paul
N Shah
A H Reddi
T Yoon
H J Lee
N Suh
Journal: Osteoarthritis and Cartilage (2012)
Discipline: CLINICAL MEDICINE
Keywords: chondrogenesis; triterpenoids; cartilage tissue engineering; regeneration; CDDO-Imidazolide
Affiliations: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States., Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States; Department of Food Science and Technology, Chung-Ang University, Anseong 456-756, South Korea., Department of Orthopaedic Surgery, University of California at Davis School of Medicine, Sacramento, CA 95817, United States., Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States., Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, United States. Electronic address: .

Abstract:  Novel methods for inducing chondrogenesis are critical for cartilage tissue engineering and regeneration. Here we show that the synthetic oleanane triterpenoids, CDDO-Imidazolide (CDDO-Im) and CDDO-Ethyl amide (CDDO-EA), at concentrations as low as 200 nM, induce chondrogenesis in organ cultures of newborn mouse calvaria. The cartilage phenotype was measured histologically with metachromatic toluidine blue staining for proteoglycans and by immunohistochemical staining for type II collagen. Furthermore, real-time polymerase chain reaction (PCR) analysis using mRNA from calvaria after 7-day treatment with CDDO-Im and CDDO-EA showed up-regulation of the chondrocyte markers SOX9 and type II collagen (alpha1). In addition, TGF-Œ≤; BMPs 2 and 4; Smads 3, 4, 6, and 7; and TIMPs-1 and -2 were increased. In contrast, MMP-9 was strongly down-regulated. Treatment of human bone marrow-derived mesenchymal stem cells with CDDO-Im and CDDO-EA (100 nM) induced expression of SOX9, collagen IIŒ±1, and aggrecan, as well as BMP-2 and phospho-Smad5, confirming that the above triterpenoids induce chondrogenic differentiation. This is the first report of the use of these drugs for induction of chondrogenesis. 

Retracted: Yes

PubPeer comments:
 The separability indicator in Table 5 is not defined in the context. The names like u201cSongjingu201d, u201cSecret roadu201d, and u201cMisunderstandingu201d are confusing for textile defects.  , 
 Thank you very much for your comments. There are some problems with the definition of these defects. I ll contact the editor to withdraw the manuscript. Thank youuff01 , 
 Retracted according to the retraction note (DOI: 10.3233 JIFS-219267) on the webpage https: content.iospress.com articles journal-of-intelligent-and-fuzzy-systems ifs219267 ,
Intestinal, Systemic, and Oral Gluten-related Alterations in Patients With Nonceliac Gluten Sensitivity
Authors: Marco Di Tola
Carmelo Rizzo
Silvia Lonardi
Giuseppe Donato
Claudia Isonne
Gabriele Rumi
Antonio Picarelli
Caterina Urciuoli
Antonio Tiberti
Marianna Salemme
Vincenzo Villanacci
Barbara Porowska
Marta Puzzono
Raffaele Borghini
Mariacatia Marino
Journal: Journal of clinical gastroenterology (0)
Discipline: CLINICAL MEDICINE
Keywords: Nonceliac gluten sensitivity; NCGS; gluten-related disorders; antigliadin antibody; HLA typing
Affiliations: Departments of *Internal Medicine and Medical Specialties ‚Ä†General and Special Surgery "Paride Stefanini" ¬∂Clinical Medicine, Sapienza University ‚Ä°Allergy Unit, Complesso Integrato Columbus ‚à•AINuC, Rome ¬ßDepartment of Pathology, Spedali Civili, Brescia, Italy.

Abstract:  Background: Nonceliac gluten sensitivity (NCGS) is an emergent condition, the framework of which is yet unclear, whereas the diagnosis is suggested only by gluten-dependent symptoms after excluding wheat allergy and celiac disease (CD). Our goal was to highlight intestinal, systemic, and oral alterations to clarify the NCGS pathogenesis and identify new diagnostic tools. Study: A total of 60 NCGS patients, 20 untreated CD, 20 treated CD, and 20 healthy volunteers were recruited. The differential diagnosis among gluten-related disorders was performed by serological, allergy, and histologic tools. NCGS patients were also subjected to antigliadin antibody (AGA) detection and HLA typing. All participants underwent an oral mucosa patch test for gluten (GOMPT), whereas an oral provocation test (OPT) for gluten was performed in 26 NCGS patients. Results: About 6/60 (10%) NCGS patients showed IgG AGA-positive results, whereas 45/60 (75%) patients carried HLA-DQ2 and/or HLA-DQ8 genes. GOMPT showed positive results in 45/60 (75%) NCGS patients, 3/20 (15%) untreated CD patients, 5/20 (25%) treated CD patients, and in no healthy volunteers. No significant difference was found between the severity of symptoms reported by NCGS patients subjected to OPT with gluten-containing croissants and those who underwent OPT with gluten-free croissants. Conclusions: GOMPT seems to be a specific tool for NCGS diagnosis, although further investigations are needed to overcome limits due to the small population studied and to contextualize GOMPT false-positive results. 

Retracted: No

PubPeer comments:
  , 
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PKCa Agonists Enhance the Protective Effect of Hyaluronic Acid on Nitric Oxide-Induced Apoptosis of Articular Chondrocytes in Vitro
Authors: Bo Qiu
Jian-Lin Zhou
Hao Peng
Qiong-Jie Hu
Shi-Qing Liu
Jiang-Hua Ming
Hong-Song Fang
Journal: Iranian journal of basic medical sciences (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Apoptosis; Nitric Oxide; PKC-Œ±; PMA.
Affiliations: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China., Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China.

Abstract:  Objective(s): Protein kinase C (PKCŒ±) is involved in modulating articular chondrocytes apoptosis induced by nitric oxide (NO). Hyaluronic acid (HA) inhibits nitric oxide-induced apoptosis of articular chondrocytes by protecting PKCŒ±, but the mechanism remains unclear. The present study was performed to investigate the effects and mechanisms of PKCŒ± regulate protective effect of hyaluronic acid. Materials and Methods The ratio of apoptotic cell and cell viability was surveyed by PCNA and MTT assay. The expression of caspase-3 was determined by real-time PCR and western blot. Results: It was showed that HA was able to reduce the nuclei fragment and PCNA expression, and NO-induced articular apoptosis blocked by HA, pretreated chondrocytes with PMA, HA significantly inhibits the activation of caspase-3 induced by NO, but pretrement with CHR, HA significantly incresed the expression of caspase-3. Conclusion: The results may be showed that PKCa regulate the expresion of caspase-3, which contribute to the apoptosis of chondrocytes induced by NO. PKC Œ± agonists enhance the protective effect of hyaluronic acid on nitric oxide-induced articular chondrocytes apoptosis. 

Retracted: No

PubPeer comments:
 The following site indicates that a paper by the same authors, with a similar title ( Reference rot, a digital preservation issue beyond file formats ), has been withdrawn: https: scholarworks.umass.edu acrl_nec_conf 2017 posters 4 Could the authors offer some insight into this withdrawal. , 
 #1 We have not withdrawn anything - But it appears the ACRL website that hosts the file may have some sort of directory or indexing problem. The poster presented at ACRL has also been deposited in Figshare. Please see this link: https: figshare.com articles poster Reference_Rot_a_digital_preservation_issue_beyond_file_formats 5271880 ,
In¬†Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming
Authors: Pradeep Reddy
Isabel Guillen
Estrella Nu√±ez Delicado
Alejandro Ocampo
Jose Luis Roman
Toshikazu Araoka
Pedro Guillen
Paloma Martinez-Redondo
Tomoaki Hishida
Aida Platero-Luengo
Fumiyuki Hatanaka
Jinna Xu
David Donoso
Juan Carlos Izpisua Belmonte
Concepcion Rodriguez Esteban
Josep M Campistol
Eric Vazquez-Ferrer
Masakazu Kurita
Mo Li
Gabriel Nu√±ez
Ergin Beyret
David Lam
Journal: Cell (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: aging; cellular reprogramming; epigenetics; lifespan.
Affiliations: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Universidad Cat√≥lica San Antonio de Murcia (UCAM) Campus de los Jer√≥nimos, 30107 Guadalupe, Murcia, Spain., Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Universidad Cat√≥lica San Antonio de Murcia (UCAM) Campus de los Jer√≥nimos, 30107 Guadalupe, Murcia, Spain., Hospital Clinic, University of Barcelona, IDIBAPS, 08036 Barcelona, Spain., Fundaci√≥n Dr. Pedro Guill√©n, Cl√≠nica Cemtro, 28035 Madrid, Spain., Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: .

Abstract:  Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice. The amelioration of age-associated phenotypes by epigenetic remodeling during cellular reprogramming highlights the role of epigenetic dysregulation as a driver of mammalian aging. Establishing in vivo platforms to modulate age-associated epigenetic marks may provide further insights into the biology of aging. 

Retracted: No

PubPeer comments:
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 #2 This is absolutely wrong. Lysosomal beta-galactosidase enzymatic activity is widely used as a marker of cellular senescence but not the expression levels measured by IHC. And as commented also on another post, the authors used an antibody against bacterial beta-galactosidase that do not cross react with the mouse enzyme. , 
 There is controversy over where the notion that iPS  reprogramming factors can be used to induce rejuvenation without de-differentiation was first put forward and tested (see comments in https: pubpeer.com publications E006ECA3F03CA48839B631F5682C7A. It is this hypothesis that is tested in this work and other recent papers. ,
PD-L1 Distribution and Perspective for Cancer Immunotherapy‚ÄîBlockade, Knockdown, or Inhibition
Authors: Weiyu Chen
Zhi Ping Xu
Wenyi Gu
Yilun Wu
Journal: Frontiers in Immunology (2019)
Discipline: IMMUNOLOGY
Keywords: PD-1/PD-L1 immune checkpoint; PD-L1 regulation; cancer immunotherapy; cellular PD-L1 distribution; combination therapy
Affiliations: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD, Australia.

Abstract:  Cancer immunotherapy involves blocking the interactions between the PD-1/PD-L1 immune checkpoints with antibodies. This has shown unprecedented positive outcomes in clinics. Particularly, the PD-L1 antibody therapy has shown the efficiency in blocking membrane PD-L1 and efficacy in treating some advanced carcinoma. However, this therapy has limited effects on many solid tumors, suspecting to be relevant to PD-L1 located in other cellular compartments, where they play additional roles and are associated with poor prognosis. In this review, we highlight the advances of 3 current strategies on PD-1/PD-L1 based immunotherapy, summarize cellular distribution of PD-L1, and review the versatile functions of intracellular PD-L1. The intracellular distribution and function of PD-L1 may indicate why not all antibody blockade is able to fully stop PD-L1 biological functions and effectively inhibit tumor growth. In this regard, gene silencing may have advantages over antibody blockade on suppression of PD-L1 sources and functions. Apart from cancer cells, PD-L1 silencing on host immune cells such as APC and DC can also enhance T cell immunity, leading to tumor clearance. Moreover, the molecular regulation of PD-L1 expression in cells is being elucidated, which helps identify potential therapeutic molecules to target PD-L1 production and improve clinical outcomes. Based on our understandings of PD-L1 distribution, regulation, and function, we prospect that the more effective PD-L1-based cancer immunotherapy will be combination therapies. 

Retracted: No

PubPeer comments:
 This review published in August 2019 presents all the data about the different PD-L1 isoforms distributions. I do not think this review is impartial. For example, the authors claim that there is a nuclear PD-L1 isoform, but in January 2019 another group published a paper claiming that the nuclear PD-L1 detection by IHC is an artefact: https: link.springer.com article 10.1007%2Fs13402-018-00419-7. The authors should have cited and reported this information. Table 2 shows that cytoplasmic PD-L1 has been detected by Western Blot (WB) with ref 23 and 28, but ref 23 has no WB at all; ref 28 has WB but is membrane PD-L1, not cytoplasmic (as indicated in the figure 4C legend). Table 2 indicated also nuclear PD-L1 ref 24 and 25, again, by WB. But ref 24 has no WB; about ref 25, the WB demonstrate that cell fractionation did not work because GAPDH is detected everywhere (membrane, cytoplasm and nuclei). Honestly, I stopped to read the paper here. ,
Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study
Authors: Vikramjit Khangoora
Racquel Rivera
Michael H Hooper
John Catravas
Paul E Marik
Journal: Chest (2017)
Discipline: CLINICAL MEDICINE
Keywords: corticosteroid; hydrocortisone; septic shock; thiamine; vitamin C.
Affiliations: Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA. Electronic address: ., Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA., Department of Pharmacy, Sentara Norfolk General Hospital, Norfolk, VA., School of Medical Diagnostic & Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, VA; Department of Medicine and Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA.

Abstract:  Background: The global burden of sepsis is estimated as 15 to 19 million cases annually, with a mortality rate approaching 60% in low-income countries. Methods: In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone, and thiamine during a 7-month period (treatment group) with a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome. Results: There were 47 patients in both treatment and control groups, with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared with 40.4% (19 of 47) in the control group (P &lt; .001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI, 0.04-0.48; P = .002). The Sepsis-Related Organ Failure Assessment score decreased in all patients in the treatment group, with none developing progressive organ failure. All patients in the treatment group were weaned off vasopressors, a mean of 18.3 ¬± 9.8 h after starting treatment with the vitamin C protocol. The mean duration of vasopressor use was 54.9 ¬± 28.4 h in the control group (P &lt; .001). Conclusions: Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine, are effective in preventing progressive organ dysfunction, including acute kidney injury, and in reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings. 

Retracted: No

PubPeer comments:
 A trenchant letter to the editor regarding statistically improbable results: https: kylesheldrick.blogspot.com 2022 03 evidence-of-fabricated-data-in-vitamin.html , 
 See this blog post: https: kylesheldrick.blogspot.com 2022 03 evidence-of-fabricated-data-in-vitamin.html Also: https: twitter.com nickmmark status 1506402015936581635 ,
Motor deficit in a Drosophila model of mucolipidosis type IV due to defective clearance of apoptotic cells
Authors: Kartik Venkatachalam
Craig Montell
A Ashleigh Long
Kendal Broadie
Daria Nikolaeva
Rebecca Elsaesser
Journal: Cell (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Transient Receptor Potential; TRPML1; mucolipin 1; MLIV; neurodegenerative disorder
Affiliations: Departments of Biological Chemistry and Neuroscience, Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract:  Disruption of the Transient Receptor Potential (TRP) mucolipin 1 (TRPML1) channel results in the neurodegenerative disorder mucolipidosis type IV (MLIV), a lysosomal storage disease with severe motor impairments. The mechanisms underlying MLIV are poorly understood and there is no treatment. Here, we report a Drosophila MLIV model, which recapitulates the key disease features, including abnormal intracellular accumulation of macromolecules, motor defects, and neurodegeneration. The basis for the buildup of macromolecules was defective autophagy, which resulted in oxidative stress and impaired synaptic transmission. Late-apoptotic cells accumulated in trpml mutant brains, suggesting diminished cell clearance. The accumulation of late-apoptotic cells and motor deficits were suppressed by expression of trpml(+) in neurons, glia, or hematopoietic cells. We conclude that the neurodegeneration and motor defects result primarily from decreased clearance of apoptotic cells. Since hematopoietic cells in humans are involved in clearance of apoptotic cells, our results raise the possibility that bone marrow transplantation may limit the progression of MLIV. 

Retracted: No

PubPeer comments:
 Fig 2R, Fig 4E and Fig 7A (Trpml1) are the same. , 
 The images in question are representative of annexinV staining in trpml[1] brains. In each panel, we clearly indicate that the image is from trpml[1] brains. Importantly, in none of the panels is the genotype indicated as being anything but trpml[1] alone. The study involved different strategies to rescue the trpml[1] mutant phenotype. In 2R, we first described the mutant phenotype of increased annexinV labeling. The purpose of showing this image again with the rescues (in 4E and 7A) was to provide a visual yardstick for the reader to appreciate the qualitative features of the rescue in comparison to the trpml[1] mutants. Quantification of the rescues are shown appropriately in Figs. 4 and 7. ,
Antitumor activity of selective MEK1/2 inhibitor AZD6244 in combination with PI3K/mTOR inhibitor BEZ235 in gefitinib-resistant NSCLC xenograft models
Authors: Yiqing Qu
Yunhong Yin
Dedong Ma
Xiuxiu Wu
Hao Li
Yan Yang
Journal: Journal of Experimental & Clinical Cancer Research (2014)
Discipline: CLINICAL MEDICINE
Keywords: EGFR-TKI; gefitinib; resistance; AZD6244; MEK1/2 inhibitor
Affiliations: Department of Respiratory medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China. .

Abstract:  Purpose: Although the EGF receptor tyrosine kinase inhibitors (EGFR-TKI) gefitinib have shown dramatic effects against EGFR mutant lung cancer, patients become resistant by various mechanisms, including gatekeeper EGFR-T790M mutation, MET amplification, and KRAS mutation, thereafter relapsing. AZD6244 is a potent, selective, and orally available MEK1/2 inhibitor. In this study, we evaluated the therapeutic efficacy of AZD6244 alone or with BEZ235, an orally available potent inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR), in gefitinib-resistant non-small cell lung carcinoma (NSCLC) models. Experimental design: NCI-H1975 with EGFR-T790M mutation, NCI-H1993 with MET amplification and NCI-H460 with KRAS/PIK3CA mutation human NSCLC cells were subcutaneous injected into the athymic nude mice respectively. Mice were randomly assigned to treatment with AZD6244, BEZ235, AZD6244 plus BEZ235, or control for 3 weeks, then all mice were sacrificed and tumor tissues were subjected to western blot analyses and immunohistochemical staining. Results: AZD6244 could inhibit the tumor growth of NCI-H1993, but slightly inhibit the tumor growth of NCI-1975 and NCI-H460. Combining AZD6244 with BEZ235 markedly enhanced their antitumor effects and without any marked adverse events. Western blot analysis and immunohistochemical staining revealed that AZD6244 alone reduced ERK1/2 phosphorylation, angiogenesis, and tumor cell proliferation. Moreover, MEK1/2 inhibition resulted in decreased AKT phosphorylation in NCI-H1993 tumor model. BEZ235 also inhibited AKT phosphorylation as well as their downstream molecules in all three tumor models. The antiangiogenic effects were substantially enhanced when the agents were combined, which may due to the reduced expression of matrix metallopeptidase-9 in tumor tissues (MMP-9). Conclusions: In this study, we evaluated therapy directed against MEK and PI3K/mTOR in distinct gefitinib-resistant NSCLC xenograft models. Combining AZD6244 with BEZ235 enhanced their antitumor and antiangiogenic effects. We concluded that the combination of a selective MEK inhibitor and a PI3K/mTOR inhibitor was effective in suppressing the growth of gefitinib-resistant tumors caused by EGFR T790M mutation, MET amplification, and KRAS/PIK3CA mutation. This new therapeutic strategy may be a practical approach in the treatment of these patients. 

Retracted: No

PubPeer comments:
 Overlap of images was detected in Fig. 6A  ,
Activation of the retinoblastoma tumor suppressor mediates cell cycle inhibition and cell death in specific cervical cancer cell lines
Authors: Wesley A Braden
Erik S Knudsen
Susanne I Wells
Ryan J Bourgo
Journal: Molecular Carcinogenesis (2009)
Discipline: CLINICAL MEDICINE
Keywords: HPV; E6; E7; oncoproteins; cervical cancer
Affiliations: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Abstract:  High-risk human papilloma virus (HPV) encodes two oncoproteins, E6 and E7, which are vital to viral replication and contribute to the development of cervical cancer. HPV16 E7 can target over 20 cellular proteins, but is best known for inactivating the retinoblastoma (RB) tumor suppressor. RB functions by restraining cells from entering S-phase of the cell cycle, thus preventing aberrant proliferation. While it is well established that HPV16 E7 facilitates the degradation of the RB protein, the ability of the RB pathway to overcome E7 action is less well understood. In this study the RB-pathway was activated via the overexpression of the p16ink4a tumor suppressor or ectopic expression of an active allele of RB (PSM-RB). While p16ink4a had no influence on cell cycle progression, PSM-RB expression was sufficient to induce a cell cycle arrest in both SiHa and HeLa cells, HPV positive cervical cancer cell lines. Strikingly, this arrest led to the downregulation of E2F target gene expression, which was antagonized via enhanced HPV-E7 expression. Since downmodulation of E7 function is associated with chronic growth arrest and senescence, the effect of PSM-RB on proliferation and survival was evaluated. Surprisingly, sustained PSM-RB expression impeded the proliferation of SiHa cells, resulting in both cell cycle inhibition and cell death. From these studies we conclude that active RB expression can sensitize specific cervical cancer cells to cell cycle inhibition and cell death. Thus, targeted therapies involving activation of RB function may be effective in inducing cell death in cervical cancer. 

Retracted: No

PubPeer comments:
 Figure 4A. Much more similar than expected after 180 degree rotation. https: imgur.com 5wm40gU , 
 Thank you for pointing this out. I will reach out to the journal to let them know and address as best as possible. ,
ZnO/CNT@Fe3O4 induces ROS-mediated apoptosis in chronic myeloid leukemia (CML)¬†cells: an emerging prospective for nanoparticles in leukemia¬†treatment
Authors: Davood Bashash
Zahra Fakhroueian
Amir-Mohammad Yousefi
Ava Safaroghli-Azar
Journal: Artificial Cells Nanomedicine and Biotechnology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NF-Œ∫B; Nanocomposite; apoptosis; chronic myeloid leukaemia.
Affiliations: Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran., School of Chemical Engineering, College of Engineering, Institute of Petroleum Engineering, University of Tehran, Tehran, Iran.

Abstract:  The advent of nanoparticles revolutionised the drug delivery systems in human diseases; however, their prominent role was highlighted in the cancer-based therapies, where this technology could specifically target cancer cells. Herein, we decided to combine two nanoparticles Fe3O4 and ZnO to fabricate a new anti-cancer nanocomposite. Noteworthy, hydroxylated carbon nanotube (CNT) was used to increase the water-solubility of the compound, improving its uptake by malignant cells. This study was designed to evaluate the anticancer property as well as the molecular mechanisms of ZnO/CNT@Fe3O4 nanocomposite cytotoxicity in CML-derived K562 cells. Our results outlined that ZnO/CNT@Fe3O4 decreased the proliferative capacity of K562 cells through induction of G1 arrest and induced apoptosis probably via ROS-dependent upregulation of FOXO3a and SIRT1. The results of qRT-PCR analysis also demonstrated that while ZnO/CNT@Fe3O4 significantly increased the expression of pro-apoptotic genes in K562 cells, it had no significant inhibitory effect on the expression levels of anti-apoptotic target genes of NF-Œ∫B; proposing an attenuating role of NF-Œ∫B signalling pathway in K562 cell response to ZnO/CNT@Fe3O4. Synergistic experiment showed that ZnO/CNT@Fe3O4 could enhance the cytotoxic effects of imatinib on K562 cells. Overall, it seems that pharmaceutical application of nanocomposites possesses novel promising potential for leukaemia treatment strategies. 

Retracted: No

PubPeer comments:
 I cannot see any connection between the SEM and TEM picture with regard to nanoparticle appearance.  ,
Urokinase receptor antibody can reduce tumor volume and detect the presence of occult tumor metastases in vivo
Authors: Julienne Gladu
Shafaat A Rabbani
Journal: Cancer research (2002)
Discipline: CLINICAL MEDICINE
Keywords: serine protease; urinary plasminogen activator; urokinase; uPA; uPAR
Affiliations: Departments of Medicine, Oncology, and Physiology, McGill University Health Centre, 687 Pine Avenue West, Room H4.67, Montreal, Quebec, H3A 1A1 Canada.

Abstract:  The serine protease urinary plasminogen activator or urokinase (uPA), produced in abundance by many malignancies, plays a key role in tumor cell invasion and metastasis. uPA is localized within the malignant cell milieu via its cell surface receptor [uPA receptor (uPAR)], which is expressed by tumor and tumor-associated cells. In the present study, we have used a syngeneic model of rat breast cancer to directly evaluate the role of uPAR as a diagnostic and therapeutic target in metastatic breast cancer. A polyclonal antibody against the ligand-binding NH(2)-terminal domain of rat uPAR (ruPAR) was developed. This antibody recognizes ruPAR by both immunofluorescence and Western blot analysis. Recombinant ruPAR and ruPAR IgG displaced the binding of (125)I-labeled ruPAR IgG to rat prostate cancer cells (Dunning R3227 Mat Ly Lu) and breast cancer cells (Mat B-III) overexpressing ruPAR (Mat B-III-uPAR). ruPAR IgG also blocked the invasive capacity of these tumor cells in a dose-dependent manner. Mat B-III-uPAR cells were inoculated s.c. into the mammary fat pad of syngeneic female Fischer rats. On day 10 after tumor cell inoculation, animals were injected with (125)I-labeled preimmune or ruPAR IgG and then sacrificed at timed intervals. Maximum (125)I uptake was observed in primary tumors and in tissues commonly affected by tumor metastases (liver, spleen, lungs, and lymph nodes) at 12 h. Injection of (125)I-labeled preimmune or ruPAR IgG into normal non-tumor-bearing animals resulted in minimal basal levels of uPAR expression and established the specificity of the ruPAR IgG. Similar results were obtained by Northern blot and PCR analysis of mRNA isolated from tissues of normal and tumor-bearing animals. To evaluate the effectiveness of this antibody in tumor progression, ruPAR IgG (50-100 microg/day) was injected s.c. for 7 days (day 1-7) at the site of tumor cell inoculation (mammary fat pad), and animals were sacrificed at various time points for evaluation of tumor growth and metastases. Animals receiving ruPAR IgG showed a marked decrease in tumor growth and metastases as compared with control tumor-bearing animals receiving the same dose of preimmune rabbit IgG. Histological analysis of experimental primary tumors showed marked tumor necrosis that was due to increased tumor cell apoptosis as determined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Together, these studies demonstrate the ability of anti-uPAR antibody to decrease tumor volume and detect the presence of microscopic occult tumor metastases in malignancies where uPA/uPAR play a key role in tumor progression. 

Retracted: No

PubPeer comments:
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The nature effect in motion: visual exposure to environmental scenes impacts cognitive load and human gait kinematics
Authors: T C Handy
U Leonards
D Burtan
K Joyce
J F Burn
S Ho
Journal: Royal Society Open Science (2021)
Discipline: Multidisciplinary
Keywords: cognitive load; environment; gait; image statistics; visual discomfort.
Affiliations: School of Psychological Science, University of Bristol, Bristol, UK., Queen's School of Engineering, University of Bristol, Bristol, UK., Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract:  Prolonged exposure to urban environments requires higher cognitive processing resources than exposure to nature environments, even if only visual cues are available. Here, we explored the moment-to-moment impact of environment type on visual cognitive processing load, measuring gait kinematics and reaction times. In Experiment 1, participants (n = 20) walked toward nature and urban images projected in front of them, one image per walk, and rated each image for visual discomfort. Gait speed and step length decreased for exposure to urban as compared with nature scenes in line with gait changes observed during verbal cognitive load tasks. We teased apart factors that might contribute to cognitive load: image statistics and visual discomfort. Gait changes correlated with subjective ratings of visual discomfort and their interaction with the environment but not with low-level image statistics. In Experiment 2, participants (n = 45) performed a classic shape discrimination task with the same environmental scenes serving as task-irrelevant distractors. Shape discrimination was slower when urban scenes were presented, suggesting that it is harder to disengage attention from urban than from nature scenes. This provides converging evidence that increased cognitive demands posed by exposure to urban scenes can be measured with gait kinematics and reaction times even for short exposure times. 

Retracted: No

PubPeer comments:
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 #8 Another 4 years. Could the authors please correct figure 6A2? , 
 #1 Joanna thanks for catching this and to you reviewers for seeing this. I wouldn t have noticed it ,
Quantum dot imaging for embryonic stem cells
Authors: Sanjiv S Gambhir
Jiang Hong Rao
Yan Zhang
Zongjin Li
Feng Cao
Manishkumar R Patel
Shuan Lin
Xiaoyan Xie
Oliver Gheysens
Joseph C Wu
Yao-Hung Yang
Journal: BMC Biotechnology (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Semiconductor quantum dots; cellular imaging; in vivo; mouse embryonic stem cells; Qtracker
Affiliations: Molecular Imaging Program at Stanford (MIPS) and Bio-X Program, Department of Radiology, Stanford University, Stanford, CA 94305, USA. 

Abstract:  Background: Semiconductor quantum dots (QDs) hold increasing potential for cellular imaging both in vitro and in vivo. In this report, we aimed to evaluate in vivo multiplex imaging of mouse embryonic stem (ES) cells labeled with Qtracker delivered quantum dots (QDs). Results: Murine embryonic stem (ES) cells were labeled with six different QDs using Qtracker. ES cell viability, proliferation, and differentiation were not adversely affected by QDs compared with non-labeled control cells (P = NS). Afterward, labeled ES cells were injected subcutaneously onto the backs of athymic nude mice. These labeled ES cells could be imaged with good contrast with one single excitation wavelength. With the same excitation wavelength, the signal intensity, defined as (total signal-background)/exposure time in millisecond was 11 +/- 2 for cells labeled with QD 525, 12 +/- 9 for QD 565, 176 +/- 81 for QD 605, 176 +/- 136 for QD 655, 167 +/- 104 for QD 705, and 1,713 +/- 482 for QD 800. Finally, we have shown that QD 800 offers greater fluorescent intensity than the other QDs tested. Conclusion: In summary, this is the first demonstration of in vivo multiplex imaging of mouse ES cells labeled QDs. Upon further improvements, QDs will have a greater potential for tracking stem cells within deep tissues. These results provide a promising tool for imaging stem cell therapy non-invasively in vivo. 

Retracted: No

PubPeer comments:
 image duplication, repositioned and rotated right  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. ,
Effect of Selenium Supplementation on Glycemic Control and Lipid Profiles in Patients with Diabetic Nephropathy
Authors: Mahsa Kia
Ahmad Esmaillzadeh
Alireza Soleimani
Zatollah Asemi
Fereshteh Bahmani
Journal: Biological Trace Element Research (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Diabetic nephropathy; Metabolic status; Selenium; Supplementation.
Affiliations: Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran., Department of Internal Medicine, Kashan University of Medical Sciences, Kashan, Iran., Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran. ., Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract:  To our knowledge, data on the effects of selenium supplementation on glycemic control and lipid concentrations in patients with diabetic nephropathy (DN) are scarce. The current study was done to determine the effects of selenium supplementation on glycemic control and lipid concentrations in patients with DN. This was a randomized double-blind placebo-controlled clinical trial in which 60 patients with DN were randomly allocated into two groups to receive either 200 Œºg of selenium supplements (n = 30) or placebo (n = 30) daily for 12 weeks. Blood sampling was performed for the quantification of glycemic indicators and lipid profiles at the onset of the study and after 12 weeks of intervention. Selenium supplementation for 12 weeks resulted in a significant decrease in serum insulin levels (P = 0.01), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), homeostasis model of assessment-estimated B cell function (HOMA-B) (P = 0.009) and a significant rise in plasma glutathione peroxidase (GPx) (P = 0.001) compared with the placebo. Taking selenium supplements had no significant effects on fasting plasma glucose (FPG), quantitative insulin sensitivity check index (QUICKI) and lipid profiles compared with the placebo. Overall, our study demonstrated that selenium supplementation for 12 weeks among patients with DN had beneficial effects on plasma GPx, serum insulin levels, HOMA-IR, and HOMA-B, while it did not affect FPG, QUICKI, and lipid profiles. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A52 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
Crystal structures of the histo-aspartic protease (HAP) from Plasmodium falciparum
Authors: Yoshiaki Kiso
Huogen Xiao
Prasenjit Bhaumik
Alexander Wlodawer
Charity L Parr
Alla Gustchina
Rickey Y Yada
Journal: Journal of Molecular Biology (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: recombinant histo-aspartic protease; Plasmodium falciparum; inhibitors; pepstatin A; KNI-10006
Affiliations: Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA.

Abstract:  The structures of recombinant histo-aspartic protease (HAP) from malaria-causing parasite Plasmodium falciparum as apoenzyme and in complex with two inhibitors, pepstatin A and KNI-10006, were solved at 2.5-, 3.3-, and 3.05-A resolutions, respectively. In the apoenzyme crystals, HAP forms a tight dimer not seen previously in any aspartic protease. The interactions between the monomers affect the conformation of two flexible loops, the functionally important "flap" (residues 70-83) and its structural equivalent in the C-terminal domain (residues 238-245), as well as the orientation of helix 225-235. The flap is found in an open conformation in the apoenzyme. Unexpectedly, the active site of the apoenzyme contains a zinc ion tightly bound to His32 and Asp215 from one monomer and to Glu278A from the other monomer, with the coordination of Zn resembling that seen in metalloproteases. The flap is closed in the structure of the pepstatin A complex, whereas it is open in the complex with KNI-10006. Although the binding mode of pepstatin A is significantly different from that in other pepsin-like aspartic proteases, its location in the active site makes unlikely the previously proposed hypothesis that HAP is a serine protease. The binding mode of KNI-10006 is unusual compared with the binding of other inhibitors from the KNI series to aspartic proteases. The novel features of the HAP active site could facilitate design of specific inhibitors used in the development of antimalarial drugs. 

Retracted: No

PubPeer comments:
 The electron density map for the bound ligand in the structure described in this manuscript is poor. At a contour level of 1.0, there is hardly any density in the 2Fo-Fc map. The RSCC level is around 0.7. It is clear that ligand is not bound to the protein and the conclusions are on weak ground. ,
The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation
Authors: T Panagiotis
C A Maurer
M Cadei
F Di Fabio
A Morelli
G Bassotti
G Cathomas
V Villanacci
S Fisogni
B Salerni
Journal: Gut (2006)
Discipline: CLINICAL MEDICINE
Keywords: Idiopathic slow transit constipation; motor abnormalities; colonic neuroenteric system; neuropathological abnormalities; enteric neurones
Affiliations: Clinica di Gastroenterologia ed Epatologia, Via Enrico Dal Pozzo, Padiglione W, 06100 Perugia, Italy. 

Abstract:  Background: Idiopathic slow transit constipation is one of the most severe and often intractable forms of constipation. As motor abnormalities are thought to play an important pathogenetic role, studies have been performed on the colonic neuroenteric system, which rules the motor aspects of the viscus. Aims: We hypothesised that important neuropathological abnormalities of the large bowel are present, that these are not confined to the interstitial cells of Cajal and ganglion cells, and that the previously described reduction of enteric neurones, if confirmed, might be related to an increase in programmed cell death (apoptosis). Patients and methods: Surgical specimens from 26 severely constipated patients were assessed by conventional and immunohistochemical methods. Specific staining for enteric neurones, glial cells, interstitial cells of Cajal, and fibroblast-like cells associated with the latter were used. In addition, gangliar cell apoptosis was evaluated by means of indirect and direct techniques. Data from patients were compared with those obtained in 10 controls. Results: Severely constipated patients displayed a significant decrease in enteric gangliar cells, glial cells, and interstitial cells of Cajal. Fibroblast-like cells associated with the latter did not differ significantly between patients and controls. Patients had significantly more apoptotic enteric neurones than controls. Conclusion: Severely constipated patients have important neuroenteric abnormalities, not confined to gangliar cells and interstitial cells of Cajal. The reduction of enteric neurones may in part be due to increased apoptotic phenomena. 

Retracted: No

PubPeer comments:
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