PReD-Bench/PRed-Bench huggingface dataset:
Aging-associated metabolic disorder induces Nox2 activation and oxidative damage of endothelial function
Authors: Sarah Cahill-Smith
Li Geng
Gavin Brooks
Junjie Du
Lampson M Fan
Jian-Mei Li
Journal: Free Radical Biology and Medicine (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Aging; Endothelial dysfunction; Knockout mice; Metabolic disorder; NADPH oxidase
Affiliations: Division of Cardiovascular Medicine, University of Oxford, UK., Faculty of Health and Medical Sciences, University of Surrey, UK., Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, UK., Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, UK. Electronic address: .

Abstract:  Oxidative stress attributable to the activation of a Nox2-containing NADPH oxidase is involved in the development of vascular diseases and in aging. However, the mechanism of Nox2 activation in normal aging remains unclear. In this study, we used age-matched wild-type (WT) and Nox2 knockout (KO) mice at 3-4 months (young); 11-12 months (middle-aged) and 21-22 months (aging) to investigate age-related metabolic disorders, Nox2 activation and endothelial dysfunction. Compared to young mice, middle-aged and aging WT mice had significant hyperglycaemia, hyperinsulinaemia, increased systemic oxidative stress and higher blood pressure. Endothelium-dependent vessel relaxation to acetylcholine was significantly impaired in WT aging aortas, and this was accompanied by increased Nox2 and ICAM-1 expressions, MAPK activation and decreased insulin receptor expression and signaling. However, these aging-associated disorders were significantly reduced or absent in Nox2KO aging mice. The effect of metabolic disorder on Nox2 activation and endothelial dysfunction was further confirmed using high-fat diet-induced obesity and insulin resistance in middle-aged WT mice treated with apocynin (a Nox2 inhibitor). In vitro experiments showed that in response to high glucose plus high insulin challenge, WT coronary microvascular endothelial cells increased significantly the levels of Nox2 expression, activation of stress signaling pathways and the cells were senescent, e.g. increased p53 and β-galactosidase activity. However, these changes were absent in Nox2KO cells. In conclusion, Nox2 activation in response to aging-associated hyperglycaemia and hyperinsulinaemia plays a key role in the oxidative damage of vascular function. Inhibition or knockout of Nox2 preserves endothelial function and improves global metabolism in old age. 

Retracted: No

PubPeer comments:
 Figure 7C: * Red and yellow boxes highlight portions of panels that are similar to panels in Figure 6D of another paper by the same research group, i.e. Lei Teng et al., Arterioscler Thromb Vasc Biol. 2012;32:1488-1496, DOI: 10.1161 ATVBAHA.112.247775 - https: pubpeer.com publications E235242EE392C88DFC8110145E5016 ![file] Pointed out to me by a reader. ,
A fluorescence-microscopic and cytofluorometric system for monitoring the turnover of the autophagic substrate p62/SQSTM1
Authors: Shensi Shen
Oliver Kepp
Amena BenYounès
Didier Métivier
Ilio Vitale
Nicolas Tajeddine
Shoaib Ahmad Malik
Guido Kroemer
Maria Chiara Maiuri
Maximilien Tailler
Journal: Autophagy (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Autophagic flux; p62; HaloTag; protein synthesis; degradation
Affiliations: INSERM, Institut Gustave Roussy, Villejuif, France.

Abstract:  Autophagic flux can be measured by determining the declining abundance of autophagic substrates such as sequestosome 1 (SQSTM1, better known as p62), which is sequestered in autophagosomes upon its direct interaction with LC3. However, the total amount of p62 results from two opposed processes, namely its synthesis (which can be modulated by some cellular stressors including autophagy inducers) and its degradation. To avoid this problem, we generated a stable cell line expressing a chimeric protein composed by p62 and the HaloTag (®) protein, which serves as a receptor for fluorescent HaloTag (®) ligands. Upon labeling with HaloTag (®) ligands (which form covalent, near-to-undissociable bonds with the Halotag (®) receptor) and washing, the resulting fluorescent labeling is not influenced by de novo protein synthesis, therefore allowing for the specific monitoring of the fusion protein decline without any interference by protein synthesis. We demonstrate that a HaloTag (®) -p62 fusion protein stably expressed in suitable cell lines can be used to monitor autophagy by flow cytometry and automated fluorescence microscopy. We surmise that this system could be adapted to high-throughput applications. 

Retracted: No

PubPeer comments:
 Fig. 2E: More similar than expected, could authors check it please? ![file] ,
Inhibition of the proteasomal function in chondrocytes down-regulates growth plate chondrogenesis and longitudinal bone growth
Authors: Shufang Wu
Francesco De Luca
Journal: Endocrinology (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: proteasome; osteoblast differentiation; bone formation; growth plate; chondrocyte proliferation
Affiliations: Section of Endocrinology and Diabetes, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134, USA.

Abstract:  The proteasome is a large multiprotein complex that processes intracellular proteins functioning as cell cycle regulators and transcription factors. It has been shown that the chymotryptic component of the proteasome is an important regulator of osteoblast differentiation and bone formation, with inhibitors of the proteasome increasing osteoblast differentiation and bone formation. Yet, little is known about the effects of the proteasomal activity in the growth plate. In the present study, we cultured rat metatarsal bones in the presence of proteasome inhibitor I (PSI), a known inhibitor of the chymotrypsin-like activity of the 20S proteasome. PSI suppressed growth plate chondrocyte proliferation and hypertrophy/differentiation, and induced chondrocyte apoptosis. All these cellular effects led to reduced metatarsal linear growth. In cultured chondrocytes, PSI increased the expression of beta-catenin (a negative regulator of chondrogenesis) and reduced the DNA binding of nuclear factor kappaB, a transcription factor that stimulates growth plate chondrogenesis. In conclusion, our findings suggest that the proteasomal activity facilitates growth plate chondrogenesis and, in turn, longitudinal bone growth. 

Retracted: No

PubPeer comments:
 Figure 6B. Much more similar than expected. ![file] ,
Effect of the histone deacetylase inhibitor LBH589 against epidermal growth factor receptor–dependent human lung cancer cells
Authors: Peter Atadja
Arthur Edwards
Kapil Bhalla
Jiannong Li
Eric B Haura
Journal: Molecular Cancer Therapeutics (2007)
Discipline: CLINICAL MEDICINE
Keywords: EGFR; STAT3; Akt; Hsp90; HDACi
Affiliations: Thoracic Oncology and Experimental Therapeutics Programs, H. Lee Moffitt Cancer Center and Research Institute, MRC3 East, Room 3056, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA.

Abstract:  Activating mutations in the epidermal growth factor receptor (EGFR) selectively activate signal transducers and activators of transcription (STAT) and Akt survival signaling pathways important in lung cancer cell growth and survival. Many kinases, such as EGFR, rely on heat shock protein 90 (Hsp90) chaperone function for conformational maturation and proper function. Histone deacetylase inhibitors (HDACi) have been suggested to regulate signaling protein interactions via modulation of protein chaperone function through Hsp90. For these reasons, we evaluated the effect of a HDACi in lung cancer cells with defined EGFR status. Cell lines with defined EGFR status and sensitivity to EGFR tyrosine kinase inhibitors were exposed to the HDACi LBH589, and the effects on cell survival, proliferation, and downstream signaling were evaluated. LBH589 resulted in increased acetylation of Hsp90 and reduced association of Hsp90 with EGFR, Akt, and STAT3. LBH589 selectively depleted proteins important in signaling cascades in cell lines harboring EGFR kinase mutations, such as EGFR, STAT3, and Akt, and these cells underwent apoptosis following exposure to LBH589. In addition, we found depletion of STAT3-dependent survival proteins, including Bcl-xL, Mcl-1, and Bcl-2. Conversely, LBH589 had little effect on apoptosis in cells not dependent on EGFR for survival, no changes were identified in the expression of EGFR or other survival proteins, and the predominant effect was cell cycle arrest rather than apoptosis. A 10-fold increase in LBH589 was necessary to observe durable depletion of EGFR and Akt in cells not harboring EGFR mutation. Treatment of cells with erlotinib and LBH589 resulted in synergistic effects on lung cancer cells dependent on EGFR for growth and/or survival. Based on these results, LBH589 can acetylate Hsp90, deplete EGFR and other key survival signaling proteins, and trigger apoptosis only in lung cancer cells harboring EGFR mutations. Therefore, EGFR mutation status may be predictive of outcome with LBH589 and possibly other HDACi. 

Retracted: No

PubPeer comments:
 ![file] , 
 Seems to be a clear duplication. Can the authors respond? *** ![file] ,
The protective role of verbenalin in rat model of focal cerebral ischemia reperfusion
Authors: Jingyi Qiao
Ming Bai
Ruiqi Li
Mingsan Miao
Lihua Cao
Journal: Saudi Journal of Biological Sciences (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Apoptosis; Focal cerebral ischemia-reperfusion; Verbenalin.
Affiliations: Department of Pharmacology, Henan University of TCM, Zhengzhou 450046, China.

Abstract:  To investigate the protective mechanism of verbenalin on cerebral ischemia-reperfusion injury. Middle cerebral artery occlusion in the left hemisphere was induced in rats by filament insertion, and rat model of focal cerebral ischemia-reperfusion was established. The high, medium and low dose of verbenalin groups were injected in the tail vein of corresponding drugs 10 min before reperfusion, and submitted for 22 h of reperfusion after the operation. Mortality rate was then calculated, and neurological deficits of rats were scored. The serum of rats was got to determine the S-100β protein level, and the brain tissue was removed to determine the levels of Bax, Bcl-2, Caspase-3 and ATPase. TTC staining was performed on the brain tissue to calculate the percentage of cerebral infarct size. Changes in brain tissue morphology were observed. Rat model of focal cerebral ischemia-reperfusion was successfully replicated. In groups that have taken different doses of verbenalin, the mortality rate, neurological deficit score and the percentage of cerebral infarction size were significantly reduced, and the levels of Bax, Caspase-3, S-100β level of the serum in the brain tissue were also significantly reduced. Increases in the levels of Bcl-2 and ATPase in brain tissue and improvement of pathological damage of hippocampus and cortex were observed. Verbenalin can inhibit the expression of apoptosis genes, promote the expression of anti-apoptosis genes, improve brain microcirculation and energy metabolism, hence reducing cerebral ischemia-reperfusion injury. 

Retracted: No

PubPeer comments:
 Figure 2: One of the panels is contained within a panel that is supposed to show a different experimental group. I ve added the red rectangles to show where I mean (there is a rotation). Would the authors please comment? ![file] , 
 Figure 3 also contains an overlap. This one has a stretch as well as a rotate. I ve annotated the panels below. Would the authors please comment? ![file] , 
 Dear Mycosphaerella arachidis, We thank you for pointing out this issue. We also noticed the mistake a few weeks ago. There was an unexpected error on paste, but didn t catch it in time. We have contacted the journal editorial office, and submited the correct H E picture and erratum request. Thank you again for your reminder on this research work. Best Wishes All authors ,
Negative regulation of STAT3 protein-mediated cellular respiration by SIRT1 protein
Authors: Vilhelm A Bohr
Rafael de Cabo
Alejandro Martin-Montalvo
Rajib K Paul
Sean M Armour
Yaping Zong
Morten Scheibye-Knudsen
Basil P Hubbard
David A Sinclair
Hua-Jun He
Michel Bernier
Shaoming Song
Lili Wang
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: STAT3; SIRT1; mitochondria; oxidative phosphorylation; gene knock-out
Affiliations: Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. 

Abstract:  In mammals, the transcriptional activity of signal transducer and activator of transcription 3 (STAT3) is regulated by the deacetylase SIRT1. However, whether the newly described nongenomic actions of STAT3 toward mitochondrial oxidative phosphorylation are dependent on SIRT1 is unclear. In this study, Sirt1 gene knock-out murine embryonic fibroblast (MEF) cells were used to delineate the role of SIRT1 in the regulation of STAT3 mitochondrial function. Here, we show that STAT3 mRNA and protein levels and the accumulation of serine-phosphorylated STAT3 in mitochondria were increased significantly in Sirt1-KO cells as compared with wild-type MEFs. Various mitochondrial bioenergetic parameters, such as the oxygen consumption rate in cell cultures, enzyme activities of the electron transport chain complexes in isolated mitochondria, and production of ATP and lactate, indicated that Sirt1-KO cells exhibited higher mitochondrial respiration as compared with wild-type MEFs. Two independent approaches, including ectopic expression of SIRT1 and siRNA-mediated knockdown of STAT3, led to reduction in intracellular ATP levels and increased lactate production in Sirt1-KO cells that were approaching those of wild-type controls. Comparison of profiles of phospho-antibody array data indicated that the deletion of SirT1 was accompanied by constitutive activation of the pro-inflammatory NF-κB pathway, which is key for STAT3 induction and increased cellular respiration in Sirt1-KO cells. Thus, SIRT1 appears to be a functional regulator of NF-κB-dependent STAT3 expression that induces mitochondrial biogenesis. These results have implications for understanding the interplay between STAT3 and SIRT1 in pro-inflammatory conditions. 

Retracted: No

PubPeer comments:
 The same band seems to have been used in Figure 1C and Figure 6D for different conditions. Do the authors still have access to the original data? *** ![file] ,
[RETRACTED ARTICLE] Risk factors for early-onset ventilator-associated pneumonia in aneurysmal subarachnoid hemorrhage patients
Authors: T T Liu
Q Q Chen
J B Cui
S J Li
Journal: Brazilian Journal of Medical and Biological Research (2018)
Discipline: CLINICAL MEDICINE
Keywords: Ventilator-acquired pneumonia; Aneurysmal subarachnoid hemorrhage; Risk factors; Mechanical ventilation; Male gender
Affiliations: Weifang People's Hospital,  China

Abstract:  This study aimed to investigate the risk factors related to ventilator-acquired pneumonia (VAP) in aneurysmal subarachnoid hemorrhage (SAH) patients. From January 2011 to December 2015, a single-center retrospective study including 200 SAH patients requiring mechanical ventilation (MV) ≥48 h was performed. The clinical data of these patients were collected and analyzed. The age range of the patients were 41-63 and 72 (36%) were male. The Glasgow coma scale score range was 5-15 and the Simplified Acute Physiology Score II range was 31-52. One hundred and forty-eight (74%) patients had a World Federation of Neurosurgeons (WNFS) score ≥III. Aneurysm was secured with an endovascular coiling procedure in 168 (84%) patients and 94 (47%) patients presented VAP. Male gender (OR=2.25, 95%CI=1.15-4.45), use of mannitol (OR=3.02, 95%CI=1.53-5.94) and enteral feeding above 20 kcal·kg-1·day-1 (OR=2.90, 95%CI=1.26-6.67) after day 7 were independent factors for VAP. Patients with early-onset VAP had a longer duration of sedation (P=0.03), MV (P=0.001) and ICU length of stay (P=0.003) and a worse Glasgow Outcome Scale score (P&lt;0.001), but did not have a higher death rate. 

Retracted: Yes

PubPeer comments:
 Retraction for: Braz J Med Biol Res | doi: http: 10.1590 1414-431X20176830 | PMID: 29791584 The Brazilian Journal of Medical and Biological Research was contacted by one specialist questioning the validity of this study. The Editors decided to retract the article: u201cRisk factors for early-onset ventilator-associated pneumonia in aneurysmal subarachnoid hemorrhage patientsu201d that was published in volume 51 no. 7 (2018) (Epub May 17, 2018) in the Brazilian Journal of Medical and Biological Research http: dx.doi.org 10.1590 1414-431X20176830 PMID: 29791584 | PMCID: PMC5972009 The authors agreed that this article should be retracted. All authors will be prohibited to publish in the Brazilian Journal of Medical and Biological Research in the future. ,
The effect of down-regulation of CCL5 on lipopolysaccharide-induced WI-38 fibroblast injury: a potential role for infantile pneumonia
Authors: Shan Cong
Anbang Han
Dong Bai
Journal: Iranian journal of basic medical sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: CCL5; Infantile pneumonia; JNK pathway; Lipopolysaccharide (LPS); NF-κB pathway
Affiliations: Department of Pediatrics, Jining No. 1 People's Hospital, Jining 272011, Shandong, China.

Abstract:  Objectives: Aberrant expression of CCL5 has been found in several kinds of inflammatory diseases, and the roles of CCL5 in these diseases have also been reported. However, the role of CCL5 in infantile pneumonia is still unclear. Thus, the function and acting mechanism of CCL5 in the in vitro model of infantile pneumonia were researched in this study. Materials and methods: Human fetal lung fibroblast WI-38 cells were subjected with lipopolysaccharide (LPS) to mimic an in vitro model of pneumonia. CCL5 was silenced by transfection with CCL5-targeted siRNA, and then cell viability, apoptosis, and the expressions of apoptosis-associated factors were respectively assessed by CCK-8 assay, flow cytometry and Western blot. Besides, expressions of CCL5 and pro-inflammatory factors were analyzed by qRT-PCR and Western blot. The secretions of pro-inflammatory factors were measured by ELISA. Finally, the expressions of main factors in JNK and NF-κB pathways were detected. Results: LPS treatment suppressed cell viability, promoted cell apoptosis, and enhanced the secretion of IL-6, MCP-1, and TNF-α. Overexpression of CCL5 was found in LPS-treated cells. CCL5 silence protected WI-38 cells from LPS-induced inflammatory damage, with increasing cell viability, inhibiting cell apoptosis, and reducing the production of pro-inflammatory cytokines. Besides, CCL5 silence inhibited LPS-induced activations of JNK and NF-κB pathways. Conclusion: Down-regulation of CCL5 could protect WI-38 cells from LPS-induced inflammatory damage via inactivating JNK and NF-κB pathways. 

Retracted: No

PubPeer comments:
 Western blots share similar background. ![file] , 
 #1 This paper conforms to a style identified by [Dr Elisabeth Bik] and [Dr Jana Christopher] , among others. ,
Genome sequence of the potato pathogenic fungus Alternaria solani HWC-168 reveals clues for its conidiation and virulence
Authors: Zhi-Hui Yang
Lisong Ma
Jia-Yu He
Parham Haddadi
Dai Zhang
Jie-Hua Zhu
Journal: BMC Microbiology (2018)
Discipline: MICROBIOLOGY
Keywords: Alternaria solani; Conidiation; Genome sequence; Secretome; Virulence.
Affiliations: Center of Plant Disease and Plant Pests of Hebei Province, College of Plant Protection, Hebei Agricultural University, Baoding, 071001, China., Saskatoon Research and Development Centre, Agriculture and Agri-Food Canada, Saskatoon, SK, S7N0X2, Canada., Center of Plant Disease and Plant Pests of Hebei Province, College of Plant Protection, Hebei Agricultural University, Baoding, 071001, China. .

Abstract:  Background: Alternaria solani is a known air-born deuteromycete fungus with a polycyclic life cycle and is the causal agent of early blight that causes significant yield losses of potato worldwide. However, the molecular mechanisms underlying the conidiation and pathogenicity remain largely unknown. Results: We produced a high-quality genome assembly of A. solani HWC-168 that was isolated from a major potato-producing region of Northern China, which facilitated a comprehensive gene annotation, the accurate prediction of genes encoding secreted proteins and identification of conidiation-related genes. The assembled genome of A. solani HWC-168 has a genome size 32.8 Mb and encodes 10,358 predicted genes that are highly similar with related Alternaria species including Alternaria arborescens and Alternaria brassicicola. We identified conidiation-related genes in the genome of A. solani HWC-168 by searching for sporulation-related homologues identified from Aspergillus nidulans. A total of 975 secreted protein-encoding genes, which might act as virulence factors, were identified in the genome of A. solani HWC-168. The predicted secretome of A. solani HWC-168 possesses 261 carbohydrate-active enzymes (CAZy), 119 proteins containing RxLx[EDQ] motif and 27 secreted proteins unique to A. solani. Conclusions: Our findings will facilitate the identification of conidiation- and virulence-related genes in the genome of A. solani. This will permit new insights into understanding the molecular mechanisms underlying the A. solani-potato pathosystem and will add value to the global fungal genome database. 

Retracted: No

PubPeer comments:
 The axis scales used in Figure 1 are different for all 3 genomes, which is misleading. After resizing the plots for matching x and y scales, a color overlay of the 3 data sets does not support any significant difference in distribution of intergenic distances, as opposed to the statement made in the article. ![file] , 
 Original Figure 1 ![file] ,
Monepantel induces autophagy in human ovarian cancer cells through disruption of the mTOR/p70S6K signalling pathway
Authors: Lucien Rufener
Farnaz Bahrami
Mohammad H Pourgholami
Ahmed H Mekkawy
David L Morris
Journal: American journal of cancer research (2014)
Discipline: CLINICAL MEDICINE
Keywords: Monepantel; PARP; apoptosis; autophagy; mTOR
Affiliations: Cancer Research Laboratory, Department of Surgery, University of New South Wales, St George Hospital Sydney, New South Wales, 2217, Australia., Cancer Research Laboratory, Department of Surgery, St George Hospital Sydney, New South Wales, 2217, Australia., Novartis Centre de Recherche Santé Animale CH-1566 St Aubin (FR), Switzerland.

Abstract:  We have recently shown that the novel anthelmintic drug monepantel (MPL) inhibits growth, proliferation and colony formation, arrests the cell cycle and induces cleavage of PARP-1 in ovarian cancer cell lines. Here we report on the mechanism behind the anticancer properties of MPL. The cytotoxic effect of MPL on ovarian cancer cells (OVCAR-3 and A2780) was investigated employing a panel of tests used for the detection of apoptosis and autophagy. Apoptosis and autophagy were defined by caspase activity, DNA-laddering, Annexin-V and acridine orange (AO) staining. Autophagy markers such as LC3B, SQSTM1/p62 and mammalian target of rapamycin (mTOR) pathway related proteins were assessed by western blotting and ELISA techniques. MPL did not activate caspases 3 or 8, nor did it alter the percentage of Annexin V positive stained cells. Failure to cause DNA laddering and the inability of z-VAD-fmk to block the MPL antiproliferative effects led to the ruling out of apoptosis as the mechanism behind MPL-induced cell death. On the other hand, accumulation of acidic vacuoles with distinct chromatin morphology and an increase in punctuate localization of green fluorescent protein-LC3B, and MPL-induced changes in the expression of SQSTM1/p62 were all indicative of MPL-induced autophagy. Consistent with this, we found inhibition of mTOR phosphorylation leading to suppression of the mTOR/p70S6K signalling pathway. Our findings provide the first evidence to show that MPL triggers autophagy through the deactivation of mTOR/p70S6K signalling pathway. 

Retracted: No

PubPeer comments:
 Have a close look at Figure 1E of this paper. You will see that the OVCAR-3 0uM MPL lane is a copy of the A2780 25uM MPL lane and it has been cropped and pasted into the figure over the top of the OVCAR-3 0uM MPL lane. Also, and may not be technically wrong as much  unusual but the images of the OVCAR untreated control cells in figures 2A, 4B and 5B are the same and the OVCAR 10um MPL images are also reused in Figure 4B and 5B. Are the experiments represented in these images from independent experiments? If they were then these controls are being used inappropriately. ,
MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling
Authors: Roman L Bogorad
Andrew A Li
Vamsi K Mootha
Nathan Taneja
Laura Strittmatter
Hany S Girgis
Molly Plovanich
Jonathan Oshea
Yasemin Sancak
Jack De Groot
Victor Koteliansky
Kimberli J Kamer
Lauren Speciner
Satya Kuchimanchi
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Mitochondrial calcium uptake; uniporter; MICU1; MCU; gene duplication
Affiliations: Departments of Molecular Biology and Medicine, Massachusetts General Hospital, and Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.

Abstract:  Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel. 

Retracted: No

PubPeer comments:
 Fig 2D ATP5B and SDHB have unexpected similarities including in background (circled) ![file] ,
Clinical Significance, Cellular Function, and Potential Molecular Pathways of CCT7 in Endometrial Cancer
Authors: Hui Li
Liwen Wang
Hui Yang
Wei Zhou
Nianchun Shan
Journal: Frontiers in Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: CCT7; FIGO stage; endometrial cancer; myometrial invasion; overall survival.
Affiliations: Department of Gynecology and Obstetrics, Xiangya Hospital, Central South University, Changsha, China., Xiangya School of Medicine, Central South University, Changsha, China., Department of Reproductive, Xiangya Hospital, Central South University, Changsha, China.

Abstract:  Objective: Endometrial cancer (EC) is a common gynecologic malignancy; myometrial invasion (MI) is a typical approach of EC spreads and an important index to assess tumor metastasis and outcome in EC patients. CCT7 is a member of the TCP1 chaperone family, involved in cytoskeletal protein folding and unfolding. In this study, the role of CCT7 in EC development was investigated. Methods: Clinical data for 87 EC cases and expression of CCT7 were analyzed. CCT7 was knocked out using siRNA-CCT7 in Ishikawa and RL95-2 cells, and their function about proliferation, apoptosis, and invasion was further tested. Bioinformatics methods were used to predict the potential pathways of CCT7 in EC development. Results: The rates of CCT7-positive cells in EC and adjacent normal endometrium tissues had a significant difference (67.8 vs. 51.4%, p = 0.035), and the expression rate increased from low to high pathological stage (39.7% in the I/II stage, 71.4% in the III/IV stage, p = 0.029). A similar change was found in protein level. CCT7 expression differed significantly between the deep MI group (&gt;1/2) and the superficial MI group (≤1/2) (p = 0.039). However, there were no differences with respect to age, pathological type, and histological grade. CCT7 suppression induced a function loss in both Ishikawa and RL95-2 cells. Bioinformatics analysis demonstrated that EC patients with lower-level CCT7 expression had better overall survival (p = 0.0081). Gene ontology enrichment indicated that "RNA binding," "Mitochondrion," "Translation," and "Spliceosome" were most significantly enriched potential pathways. Five hub genes, PSMA5, PSMD14, SNRPB, SNRPG, and TXNL4A, were all significantly upregulated in EC and had a positive correlation with CCT7. Conclusions: CCT7 may be involved in EC development by excessively activating tumor cell function to promote MI or distant/nodal metastasis, which may contribute to the prognosis of EC patients. 

Retracted: No

PubPeer comments:
 ---RETRACTED--- Quote Frontiers:  The journal retracts the 28th August 2020 article cited above. Following publication, concerns were raised regarding the integrity of Figures 1 and 3. An investigation was conducted in accordance with Frontiers guidelines and the authors failed to provide a satisfactory explanation. This retraction was approved by the Chief Editors of Frontiers in Oncology and the Editor-in-Chief of Frontiers. The authors agree to this retraction. ---- The publication contained Western Blot and FACS plot irregularities: ![file] ![file] ,
Cholesterol Homeostatic Regulator SCAP-SREBP2 Integrates NLRP3 Inflammasome Activation and Cholesterol Biosynthetic Signaling in Macrophages
Authors: Linrong Lu
Li Zhang
Wenxin Li
Yingliang Wu
Chuansheng Guo
Di Wang
Xue Zhang
Xingchen Guo
Sheng Chen
Ting Xu
Weiwei Yu
Zhexu Chi
Bao-Liang Song
Zhen Wang
Qianyun Liu
Danlu Jiang
Journal: Immunity (2018)
Discipline: IMMUNOLOGY
Keywords: NLRP3 inflammasome; SCAP; SREBP2; cholesterol biosynthetic signaling; inflammation

Abstract:  Cholesterol metabolism has been linked to immune functions, but the mechanisms by which cholesterol biosynthetic signaling orchestrates inflammasome activation remain unclear. Here, we have shown that NLRP3 inflammasome activation is integrated with the maturation of cholesterol master transcription factor SREBP2. Importantly, SCAP-SREBP2 complex endoplasmic reticulum-to-Golgi translocation was required for optimal activation of the NLRP3 inflammasome both in vitro and in vivo. Enforced cholesterol biosynthetic signaling by sterol depletion or statins promoted NLPR3 inflammasome activation. However, this regulation did not predominantly depend on changes in cholesterol homeostasis controlled by the transcriptional activity of SREBP2, but relied on the escort activity of SCAP. Mechanistically, NLRP3 associated with SCAP-SREBP2 to form a ternary complex which translocated to the Golgi apparatus adjacent to a mitochondrial cluster for optimal inflammasome assembly. Our study reveals that, in addition to controlling cholesterol biosynthesis, SCAP-SREBP2 also serves as a signaling hub integrating cholesterol metabolism with inflammation in macrophages. 

Retracted: No

PubPeer comments:
  Figure 1. Effect of miRNA-520a-3p on cell proliferation and apoptosis of NCI-H1975 cell. ... B, Apoptosis rates were determined by flow cytometry I would have expected more difference between the Control and Inhibitor results. ![file] ,
Multivalent presentation of MPL by porous silicon microparticles favors T helper 1 polarization enhancing the anti-tumor efficacy of doxorubicin nanoliposomes
Authors: David J Savage
Jianhua Gu
Claire H Hearnden
Marie Yang
Kenji Yokoi
Laura Williams
Xuewu Liu
Ismail M Meraz
Ed C Lavelle
Jessica R Rhudy
Rita E Serda
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Porous silicon; microparticles; pathogen-associated molecular patterns; dendritic cells; MPL-adsorbed
Affiliations: Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America., Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland., Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; Advanced Materials and BioEngineering Research (AMBER), Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College, Dublin, Ireland., Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America; The University of Texas School of Medicine, Houston, Texas, United States of America., Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.

Abstract:  Porous silicon (pSi) microparticles, in diverse sizes and shapes, can be functionalized to present pathogen-associated molecular patterns that activate dendritic cells. Intraperitoneal injection of MPL-adsorbed pSi microparticles, in contrast to free MPL, resulted in the induction of local inflammation, reflected in the recruitment of neutrophils, eosinophils and proinflammatory monocytes, and the depletion of resident macrophages and mast cells at the injection site. Injection of microparticle-bound MPL resulted in enhanced secretion of the T helper 1 associated cytokines IFN-γ and TNF-α by peritoneal exudate and lymph node cells in response to secondary stimuli while decreasing the anti-inflammatory cytokine IL-10. MPL-pSi microparticles independently exhibited anti-tumor effects and enhanced tumor suppression by low dose doxorubicin nanoliposomes. Intravascular injection of the MPL-bound microparticles increased serum IL-1β levels, which was blocked by the IL-1 receptor antagonist Anakinra. The microparticles also potentiated tumor infiltration by dendritic cells, cytotoxic T lymphocytes, and F4/80+ macrophages, however, a specific reduction was observed in CD204+ macrophages. 

Retracted: No

PubPeer comments:
 Figure 5H. * Red panels: Two panels appear to look the same. Reported to the journal in October 2015, but no action taken as of today. ![file] ,
Krüppel-like factor 4 acts as a potential therapeutic target of Sijunzi decoction for treatment of colorectal cancer
Authors: Y Jie
X Yang
W Chen
W He
Journal: Cancer Gene Therapy (2017)
Discipline: CLINICAL MEDICINE
Keywords: Sijunzi decoction; colorectal cancer; therapeutic target; microarray analysis; mRNA targets
Affiliations: Radiotherapy Center, Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, China., Department of Oncology No. 2, Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, China., Department of Anorectal, Urumqi City Hospital of Traditional Chinese Medicine, Urumqi, China., Department of Anorectal, Hospital (TCM) Affiliated to Southwest Medical University, Luzhou, China.

Abstract:  Sijunzi decoction (SJZD) is a traditional Chinese medicine prescription for the prevention and treatment of colorectal cancer. Our study is aimed to identify the potential therapeutic target of SJZD. Microarray analysis was performed on the patients with colorectal cancer under treatment of SJZD. The mRNA targets of SJZD were predicted by BATMAN-TCM database and were further identified by integrated analysis of expression data from TCGA. The correlation of gene expression and clinical characteristics was analyzed. Microarray analysis indicated that Krüppel-like factor 4 (KLF4) was significantly upregulated after intervention of SJZD. BATMAN-TCM prediction showed that KLF4 was an mRNA target of SJZD and it was downregulated in colorectal cancer by integrated analysis of expression data from TCGA. KLF4 may act as an administered indicator to assess whether adjuvant postoperative pharmaceutical therapy is needed for patients with colorectal cancer. Low KLF4 expression was significantly correlated with reductions of overall survival and recurrence rate. Our results suggested that KLF4 may be the potential therapeutic target of SJZD for the treatment of colorectal cancer. 

Retracted: No

PubPeer comments:
 There is no scientific proof that traditional Chinese Medicine has any health benefits, and in the discussion in this article they state that  absence of scientific basis for the effectiveness of TCMs against cancer hindered the globalization of TCMs . In this study they studied three patients without any control. Like all other TCM studies, it is not providing any new knowledge, only speculations. I am surprised that the Nature journal Cancer Gene Therapy let this study pass the peer-reviewing. I am also wondering why the number 3 is so frequent in Table 1. ,
Plasmodium yoelii 17XL infection modified maturation and function of dendritic cells by skewing Tregs and amplificating Th17
Authors: Shuang-Chun Liu
Guang Chen
Fang-Fang Wang
Ji-Wei Du
De-Hui Liu
Yun-Ting Du
Hui-Ming Zhang
Qing Nie
Journal: BMC Infectious Diseases (2020)
Discipline: IMMUNOLOGY
Keywords: Dendritic cells; Malaria infection; Plasmodium yoelii 17XL; Th17; Tregs.
Affiliations: Department of Basic Medical Sciences, Taizhou University Hospital, Taizhou University, No 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China. ., Nursing Department, Xiang'An Hospital, Xiamen University, No 2000, Xian'an East Road, Xiang'an District, Xiamen, 361005, China., Weifang Centers for Disease Control and Prevention, No 4801 Huixian Road, Gaoxin District, Shandong Province, Weifang, 261061, China., Department of Laboratory Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No 44, Xiaoheyan Road, Dadong District, Shenyang, 110042, China., Municipal Hospital Affiliated to Medical School of Taizhou University, No 381, Zhongshan East Road, Jiaojiang District, Taizhou, 318000, China., College of Basic Medical Sciences, Jiamusi University, No 148 Xuefu Street, Jiamusi, 154007, China.

Abstract:  Background: Emerging data has suggested that Tregs, Th17, Th1 and Th2 are correlated with early immune mechanisms by controlling Plasmodium infection. Plasmodium infection appeared to impair the antigen presentation and maturation of DCs, leading to attenuation of specific cellular immune response ultimately. Hence, in this study, we aim to evaluate the relevance between DCs and Tregs/Th17 populations in the process and outcomes of infection with Plasmodium yoelii 17XL (P.y17XL). Methods: DCs detection/analysis dynamically was performed by Tregs depletion or Th17 neutralization in P.y17XL infected BALB/c mice via flow cytometry. Then the levels of cytokines production were detected using enzyme-linked mmunosorbent assay (ELISA). Results: Our results indicated that Tregs depletion or Th17 neutralization in BALB/c mice infected with P.y17XL significantly up-regulated the percentages of mDC and pDC, increased the expressions of major histocompatibility complex (MHC) class II, CD80, CD86 on DCs and the levels of IL-10/IL-12 secreted by DCs, indicating that abnormal amplification of Tregs or Th17 may damage the maturation and function of DCs during the early stage of malaria infection. Interestingly, we also found that the abnormal amplification of Th17, as well as Tregs, could inhibit the maturation of DCs. Conclusions: Tregs skewing or Th17 amplification during the early stage of malaria infection may inhibit the maturation and function of DCs by modifying the subsets of DCs, expressions of surface molecules on DCs and secretion mode of cytokines. 

Retracted: No

PubPeer comments:
 The Treg staining in Figure 1 looks like the permeabilization did not work entirely. Did you try to stain with the Foxp3 Transcription Factor Fixation Permeabilization kit? This one works really nice and you should have a better clearer staining for the Tregs. ,
Metaviral SPAdes: assembly of viruses from metagenomic data
Authors: Mikhail Raiko
Alla Lapidus
Pavel A Pevzner
Dmitry Antipov
Journal: Bioinformatics (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: viruses; metagenomic sequencing; MetaviralSPAdes; viral genomes; computational challenge
Affiliations: Institute of Translational Biomedicine, Center of Algorithmic Biotechnology, Institute for Translational Biomedicine, St. Petersburg State University, St. Petersburg 199004, Russia., Department of Computer Science and Engineering, University of California, San Diego, CA 92093-0404, USA.

Abstract:  Motivation: Although the set of currently known viruses has been steadily expanding, only a tiny fraction of the Earth's virome has been sequenced so far. Shotgun metagenomic sequencing provides an opportunity to reveal novel viruses but faces the computational challenge of identifying viral genomes that are often difficult to detect in metagenomic assemblies. Results: We describe a MetaviralSPAdes tool for identifying viral genomes in metagenomic assembly graphs that is based on analyzing variations in the coverage depth between viruses and bacterial chromosomes. We benchmarked MetaviralSPAdes on diverse metagenomic datasets, verified our predictions using a set of virus-specific Hidden Markov Models and demonstrated that it improves on the state-of-the-art viral identification pipelines. Availability and implementation: Metaviral SPAdes includes ViralAssembly, ViralVerify and ViralComplete modules that are available as standalone packages: https://github.com/ablab/spades/tree/metaviral_publication, https://github.com/ablab/viralVerify/ and https://github.com/ablab/viralComplete/. Contact: d.antipov@spbu.ru. Supplementary information: Supplementary data are available at Bioinformatics online. 

Retracted: No

PubPeer comments:
 Hi, Thank your for putting together this publication and open-source code. It isn t a huge problem (and I don t have access to the main article). However, I noticed that **Supplemental Figure S2** has comments in what I believe is Russian. I think this is like not turning off  Track Changes or not deleting comments after the manuscript revision process. I am not sure if this can be corrected without a formal correction, but I thought that I should mention something. Thank You, Charles ,
Targeted deletion of the CD59 gene causes spontaneous intravascular hemolysis and hemoglobinuria
Authors: B P Morgan
S M Hanna
M J Walport
M Botto
D S Holt
A E Bygrave
Journal: Blood (2001)
Discipline: CLINICAL MEDICINE
Keywords: glycolipid-anchored glycoprotein; CD59; complement; hemolysis; thrombosis
Affiliations: Complement Biology Group, Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, United Kingdom., From the Complement Biology Group, Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, United Kingdom; and the Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Campus, London, United Kingdom.

Abstract:  The glycolipid-anchored glycoprotein CD59 inhibits assembly of the lytic membrane attack complex of complement by incorporation into the forming complex. Absence of CD59 and other glycolipid-anchored molecules on circulating cells in the human hemolytic disorder paroxysmal nocturnal hemoglobinuria is associated with intravascular hemolysis and thrombosis. To examine the role of CD59 in protecting host tissues in health and disease, CD59-deficient (CD59(-/-)) mice were produced by gene targeting in embryonic stem cells. Absence of CD59 was confirmed by staining cells and tissues with specific antibody. Despite the complete absence of CD59, mice were healthy and fertile. Erythrocytes in vitro displayed increased susceptibility to complement and were positive in an acidified serum lysis test. Despite this, CD59(-/-) mice were not anemic but had elevated reticulocyte counts, indicating accelerated erythrocyte turnover. Fresh plasma and urine from CD59(-/-) mice contained increased amounts of hemoglobin when compared with littermate controls, providing further evidence for spontaneous intravascular hemolysis. Intravascular hemolysis was increased following administration of cobra venom factor to trigger complement activation. CD59(-/-) mice will provide a tool for characterizing the importance of CD59 in protection of self tissues from membrane attack complex damage in health and during diseases in which complement is activated. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,
PPARgamma controls cell proliferation and apoptosis in an RB-dependent manner
Authors: Lluis Fajas
Stéphanie Miard
Raphael Reiter
Johan Auwerx
Anne-Marie Lefebvre
Viviane Egler
Journal: Oncogene (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: nuclear receptor; PPARgamma; cell proliferation; apoptosis; molecular mechanisms
Affiliations: Institut de Génétique et de Biologie Moléculaire et Cellulaire/CNRS/INSERM/ULP, 67404 Illkirch, France.

Abstract:  The nuclear receptor PPARgamma is implicated in the control of cell proliferation and apoptosis. However, the molecular mechanisms by which it controls these processes remain largely elusive. We show here that PPARgamma activation in the presence of the retinoblastoma protein (RB) results in the arrest of cells at the G1 phase of the cell cycle, whereas in the absence of RB, cells accumulate in G2/M, endoreduplicate, and undergo apoptosis. Through the use of HDAC inhibitors and coimmunoprecipitations, we furthermore demonstrate that the effects of RB on PPARgamma-mediated control of the cell cycle and apoptosis depend on the recruitment of histone deacetylase 3 (HDAC3) to PPARgamma. In combination, these data hence demonstrate that the effects of PPARgamma on cell proliferation and apoptosis are dependent on the presence of an RB-HDAC3 complex. 

Retracted: No

PubPeer comments:
 Figure 2 and figure 4 appear to have some image overlaps ![file] ![file] , 
 Dear Dendrodoa ,u00a0 During the preparation of figures, in order to make the size of the picture consistent and symmetrical. We inserted the first row of images, and then copied the first line into the second line, and then replaced the matched image. This ensured consistent image size and symmetrical distribution. Errors occurred in the process due to image wrongly selected. The same picture were put in migration and invasion for Anti-NC group in Figure 2B; There were similar mistakes for miR-942+BARX2 group and Anti-942+siBARX2 group in Figure 4C. We contacted the editor of the magazine five months ago, hoping to correct the error . We will update the erratum results on this website as soon as possible. Thanks again for your careful reading. , 
 Retracted [7 March 2022] . -------------------------- The above article, published online on 24 June 2019 in Wiley Online Library , has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on public allegations, and after the authors asked to correct the article. Several flaws and inconsistencies between results presented and experimental methods described were found, and so the editors consider the conclusions of this article to be invalid. ,