PReD-Bench/PRed-Bench huggingface dataset:
Spironolactone inhibits apoptosis in rat mesangial cells under hyperglycaemic conditions via the Wnt signalling pathway
Authors: Hongwei Yu
Jiuli Ding
Hongjiang He
Dan Cao
Jie Tang
Dan Zhu
Lirong Hao
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Mesangial cells; apoptosis; mineralocorticoid receptor; spironolactone; diabetic nephropathy
Affiliations: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Heilongjiang 150001, China.

Abstract:  Mesangial cells (MCs) play a crucial role in maintaining structure and function of glomerular tufts, providing structural support for capillary loops and modulating glomerular filtration by their contractility. MCs apoptosis occurs in experimental diabetic nephropathy, and this correlates with worsening albuminuria. Accumulating evidence suggests that mineralocorticoid receptor (MR) blockade effectively reduces proteinuria in diabetic nephropathy; however, it is rarely known whether spironolactone (SPI), a nonspecific MR antagonist, inhibits apoptosis in MCs under hyperglycaemic conditions. The objectives of this study are to determine the relationship between SPI and apoptosis, and investigate the cell signalling pathway by which SPI inhibits apoptosis. Rat MCs were treated with 30 mM D-glucose and 10(-8), 10(-7) or 10(-6) M aldosterone (ALD) for 24 h. In some experiments, MCs were pretreated with 10(-7) M SPI or 10 mM LiCl for 1 h. Apoptosis was evaluated by cell nucleus staining and flow cytometric analyses, and caspase-3 activity was assayed. Gene and protein expression were quantified using quantitative real-time PCR and Western blotting, respectively. SPI directly inhibited high glucose and ALD-induced MCs apoptosis in a caspase-dependent manner. Importantly, SPI inhibited MCs apoptosis via the Wnt signalling pathway. SPI promoted activation of the Wnt signalling pathway in MCs, leading to upregulation of Wnt4 and Wnt5a mRNA expression, decreased GSK-3Œ≤ protein expression and increased Œ≤-catenin protein expression. As a conclusion, this study suggests that SPI may inhibit apoptosis in MCs during hyperglycaemic conditions via the Wnt signalling pathway. Blockade of the ALD system may represent a novel therapeutic strategy to prevent MCs injury under hyperglycaemic conditions. 

Retracted: No

PubPeer comments:
 Figure 1A and 2A. * Several panels appear to overlap with each other. Figure 1C and 2C. * Several unexpected similarities between quadrants Reported to the journal in October 2015 (minus the cyan boxes, which I just added), with a friendly reminder in 2017, but no response as of today.  ,
The Orphan Receptor Tyrosine Kinase ROR2 Facilitates MSCs to Repair Lung Injury in ARDS Animal Model
Authors: Qi-Hong Chen
Song Chen
Ai-Ran Liu
Jing-Yuan Xu
Hai-Bo Qiu
Hong-Li He
Shi-Xia Cai
Feng-Mei Guo
Ling Liu
Yi Yang
Chun Pan
Ying-Zi Huang
Journal: Cell Transplantation (2016)
Discipline: CLINICAL MEDICINE
Keywords: mesenchymal stem cells; acute respiratory distress syndrome; Wnt5a signaling; receptor tyrosine kinase-like orphan receptor 2; differentiation
Affiliations: Department of Critical Care Medicine, Nanjing Zhong-da Hospital, School of Medicine, Southeast University, Nanjing, China, Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China

Abstract:  There are some limitations to the therapeutic effects of mesenchymal stem cells (MSCs) on acute respiratory distress syndrome (ARDS) due to their low engraftment and differentiation rates in lungs. We found previously that noncanonical Wnt5a signaling promoted the differentiation of mouse MSCs (mMSCs) into type II alveolar epithelial cells (AT II cells), conferred resistance to oxidative stress, and promoted migration of MSCs in vitro. As receptor tyrosine kinase-like orphan receptor 2 (ROR2) is an essential receptor for Wnt5a, it was reasonable to deduce that ROR2 might be one of the key molecules for the therapeutic effect of MSCs in ARDS. The mMSCs that stably overexpressed ROR2 or the green fluorescent protein (GFP) control were transplanted intratracheally into the ARDS mice [induced by intratracheal injection of lipopolysaccharide (LPS)]. The results showed that ROR2-overexpressing mMSCs led to more significant effects than the GFP controls, including the retention of the mMSCs in the lung, differentiation into AT II cells, improvement of alveolar epithelial permeability, improvement of acute LPS-induced pulmonary inflammation, and, finally, reduction of the pathological impairment of the lung tissue. In conclusion, MSCs that overexpress ROR2 could further improve MSC-mediated protection against epithelial impairment in ARDS. 

Retracted: No

PubPeer comments:
 Figure 1A appears to have some images which overlap (green and red boxes). ***  ,
Over-expression of miR-100 is responsible for the low-expression of ATM in the human glioma cell line: M059J
Authors: Dan Yan
Yin-Yuan Mo
Ya Wang
Wooi Loon Ng
Xiangming Zhang
Journal: DNA repair (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: M059J cells; M059K cells; radiosensitive; DNA-PKcs; ATM
Affiliations: Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.

Abstract:  M059J and M059K cells were isolated from different portions of the same human malignant glioma. M059J cells are more radiosensitive than M059K cells due to the absence of DNA-PKcs and low-expression of ATM. The mechanism concerning the absence of DNA-PKcs in M059J is due to the frameshift mutation in PRKDC (DNA-PKcs gene); however, the reason for the low-expression of ATM in M059J cells remains unclear. We showed here that the main reason for the lower ATM level in M059J cells was not related to the transcriptional regulation or protein degradation but was related to post-transcriptional regulation. Based on database information, we found that the 3'-untranslational region (UTR) of ATM contains a miR-100 binding site. By using an RNase protection assay and qRT-PCR, we identified that miR-100 is highly-expressed in M059J cells. We further demonstrated that miR-100 bound to the 3'-UTR of ATM. Knocking down miR-100 promotes ATM expression in M059J cells. Up-regulating miR-100 in M059K cells and other cancer cells reduces ATM expression and sensitizes these cells to ionizing radiation. These results indicate that ATM is a target of miR-100, elucidating that the low-expression of ATM in M059J cells is mainly due to the high expression of miR-100. These results also suggest that miR-100 could be a useful tool to target ATM and sensitize tumor cells to ionizing radiation. 

Retracted: No

PubPeer comments:
 Figure 3A. Much more similar than you would expect. https: imgur.com MwQ0jo2 , 
 https: retractionwatch.com 2021 09 16 former-emory-division-director-committed-misconduct-says-federal-watchdog ,
Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis
Authors: Marek Los
Sudharsana Rao Ande
Subbareddy Maddika
Emilia Wiechec
Lise Lotte Hansen
Sebastian Wesselborg
Journal: Journal of Cell Science (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CDK2; Akt; cell cycle progression; apoptosis; phosphorylation
Affiliations: Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, R3E 0V9, Canada., Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, R3E 0V9, Canada, Department of Human Genetics, University of Aarhus, DK-8000 C Aarhus, Denmark, Department of Experimental and Clinical Radiobiology, Oncology Center, Maria Sklodowka-Curie Memorial Institute, Wybrzeze Armii Krajowej 15, PL-44100 Gliwice, Poland, Department of Internal Medicine I, University of TuÃàbingen, TuÃàbingen, Germany, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, R3E 0V9, Canada

Abstract:  Here, we show that CDK2, an S-phase cyclin-dependent kinase, is a novel target for Akt during cell cycle progression and apoptosis. Akt phosphorylates CDK2 at threonine 39 residue both in vitro and in vivo. Although CDK2 threonine 39 phosphorylation mediated by Akt enhances cyclin-A binding, it is dispensable for its basal binding and the kinase activity. In addition, for the first time, we report a transient nucleo-cytoplasmic shuttling of Akt during specific stages of the cell cycle, in particular during the late S and G2 phases. The Akt that is re-localized to the nucleus phosphorylates CDK2 and causes the temporary cytoplasmic localization of the CDK2-cyclin-A complex. The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Thus, the constitutive activation of the Akt/CDK2 pathway and changed subcellular localization promotes apoptosis. By contrast, the transient, physiological Akt/CDK2 activation is necessary for cell cycle progression. 

Retracted: No

PubPeer comments:
 Much more similar than expected!  , 
 Much more similar than expected  ,
The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling
Authors: Elena Katsyuba
Norman Moullan
Young-Suk Jo
Laurent Mouchiroud
Leonard Guarente
Kristina Schoonjans
Riekelt H Houtkooper
Dongryeol Ryu
Carles Cant√≥
Mohan Viswanathan
Johan Auwerx
Adrienne Mottis
Journal: Cell (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: NAD(+); metabolic homeostasis; sirtuin deacylases; aging; lifespan
Affiliations: Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique F√©d√©rale de Lausanne, 1015 Lausanne, Switzerland.

Abstract:  NAD(+) is an important cofactor regulating metabolic homeostasis and a rate-limiting substrate for sirtuin deacylases. We show that NAD(+) levels are reduced in aged mice and Caenorhabditis elegans and that decreasing NAD(+) levels results in a further reduction in worm lifespan. Conversely, genetic or pharmacological restoration of NAD(+) prevents age-associated metabolic decline and promotes longevity in worms. These effects are dependent upon the protein deacetylase sir-2.1 and involve the induction of mitonuclear protein imbalance as well as activation of stress signaling via the mitochondrial unfolded protein response (UPR(mt)) and the nuclear translocation and activation of FOXO transcription factor DAF-16. Our data suggest that augmenting mitochondrial stress signaling through the modulation of NAD(+) levels may be a target to improve mitochondrial function and prevent or treat age-associated decline. 

Retracted: No

PubPeer comments:
 Figure S1 shows that protein PARylation increases in the liver of mice during aging. This result could not be reproduced by a more recent paper, showing that the opposite u201cConsistent with a decrease in PARP1 protein expression, levels of PARylated proteins declined in the liver of aged mice (u2026)These findings indicate that the decline in PARylation was potentially a consequence of a decrease in either NAD+ or PARP1 levels, and do not support a causal role for PARP1 in the age-related NAD+ declineu201d Reference: Cell Metab. 2016 Jun 14; 23(6): 1127u20131139. doi: 10.1016 j.cmet.2016.05.006 ,
Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling
Authors: Qi Zhao
Yan Zhou
Shao-Qiang Xia
Shi-Qing Liu
Shi-Hao Wu
Bin He
Ling Yu
Hong-Jun Mei
Journal: APOPTOSIS (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Chondrocyte apoptosis; Berberine; Osteoarthritis; Sodium nitroprusside; Anti-inflammatory
Affiliations: Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan, 430060, People's Republic of China.

Abstract:  Chondrocyte apoptosis is an important mechanism involved in osteoarthritis (OA). Berberine (BBR), a plant alkaloid derived from Chinese medicine, is characterized by multiple pharmacological effects, such as anti-inflammatory and anti-apoptotic activities. This study aimed to evaluate the chondroprotective effect and underlying mechanisms of BBR on sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis and surgically-induced rat OA model. The in vitro results revealed that BBR suppressed SNP-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, down-regulated expressions of inducible nitric oxide synthase (iNOS) and caspase-3, and up-regulated Bcl-2/Bax ratio and Type II collagen (Col II) at protein levels, which were accompanied by increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK). Furthermore, the anti-apoptotic effect of BBR was blocked by AMPK inhibitor Compound C (CC) and adenosine-9-Œ≤-D-arabino-furanoside (Ara A), and enhanced by p38 MAPK inhibitor SB203580. In vivo experiment suggested that BBR ameliorated cartilage degeneration and exhibited an anti-apoptotic effect on articular cartilage in a rat OA model, as demonstrated by histological analyses, TUNEL assay and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. These findings suggest that BBR suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via activating AMPK signaling and suppressing p38 MAPK activity. 

Retracted: No

PubPeer comments:
 https: cosmocoffee.info viewtopic.php?f=2 t=3263 p=8950 sid=b54746c8486443e45cf0018447acf98c#p8950 ,
Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats
Authors: K Shagirtha
S Milton Prabu
M Muthumani
Journal: European review for medical and pharmacological sciences (2011)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cadmium; Melatonin; Neuroprotective efficacy; Acetylcholinesterase; Oxidative stress
Affiliations: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, India.

Abstract:  Background: Cadmium is a potent neurotoxic heavy metal, which induces oxidative stress and membrane disturbances in brain. Melatonin is an effective antioxidant and free radical scavenger against oxidative stress. The present study was designed to investigate the neuroprotective efficacy of melatonin in protecting the Cd induced changes in the activity of acetylcholinesterase (AChE), levels of lipid peroxidation, protein carbonyls, non-enzymatic antioxidant, enzymatic antioxidant status, membrane bound ATPases and histopathology in the brain of rats. Materials and methods: Twenty four male albino rats were used. Cadmium induced oxidative neurotoxicity was induced by oral administration of Cd for four weeks. Melatonin was pretreated along with Cd for four weeks to assess its neuroprotective activity against Cd intoxication. Rats treated with vehicles alone were used as controls. Results: Rats intoxicated with cadmium (5 mg/kg/day) for 4 weeks significantly (p &lt; 0.05) reduced the AChE levels in the plasma and brain, elevated the levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides and protein carbonyls along with the significant (p &lt; 0.05) decrease in the levels of non-enzymatic antioxidants (GSH, TSH and vitamins C and E), enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and membrane bound ATPases in the brain tissue. Administration of melatonin (10 mg/kg/day) for 4 weeks in cadmium intoxicated rats significantly (p &lt; 0.05) diminished the levels of oxidative stress markers, lipid peroxidation and protein carbonyls in brain and significantly (p &lt; 0.05) elevated the levels of nonenzymatic and enzymatic antioxidants, brain and the activities of AChE, enzymatic antioxidants and ATPases in brain. The histopathological studies in the brain of rats also supported that melatonin markedly reduced the Cd induced pathological changes and preserved the normal histological architecture of the brain tissue. Conclusions: The results of the present study suggest that melatonin may be beneficial in combating the cadmium induced oxidative neurotoxicity in the brain of rats. 

Retracted: No

PubPeer comments:
 Concern about Figure 2. Lane 2 (DNA from control rat brain) looks remarkably similar to lane 5 (assumed to be DNA from Melatonin-treated rat brain). Shown with yellow boxes.  ,
Epidemiological aspects of heart diseases
Authors: Ziqi Tao
Jing Zhao
Aimin Shi
Peng Wei
Journal: Experimental and Therapeutic Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: cardiovascular diseases; coronary heart disease; rheumatic heart disease.
Affiliations: School of Public Health of Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China., Department of Science and Education, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, P.R. China., Department of Cardiology, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, P.R. China., Department of Science and Education Division, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, P.R. China.

Abstract:  Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Coronary heart disease (CHD) is the main cause of mortality in heart patients following stroke, rheumatic heart disease and myocardial infarctions. Approximately 80% of individuals succumb to CVDs, due to poor living conditions in low and middle income families and malnutrition. Infectious diseases, human immunodeficiency, tuberculosis, malaria, high blood pressure or hypertension, obesity and overweight, and nutritional disorders including smoking, excessive alcohol consumption, high salt and sugar intake, as well as other factors are responsible for CVDs and CHDs in young as well as elderly individuals. The focus of the present review are recent epidemiological aspects of CVD and CHD as well as the usefulness of a Mediterranean diet for heart patients and the prevention of heart diseases. 

Retracted: No

PubPeer comments:
 This review seems to owe an unacknowledged debt to [ Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health ] , Chapter 2 of  Institute of Medicine (US) Committee on Preventing the Global Epidemic of Cardiovascular Disease: Meeting the Challenges in Developing Countries (2010). Here I will outsource the comparison to SimTexter, https: people.f4.htw-berlin.de ~weberwu simtexter app.html     , 
 Adding to the impression that the present paper is a Readers Digest summary of the 2010 chapter, it is difficult to find a reference that is not also present in the 2010 reference section (though the latter is much longer, and in alphabetical order rather than order of appearance).  For a state-of-the-literature Review published in 2016, one might reasonably expect more citations of research subsequent to 2010. ,
Blood vessel imaging using radiofrequency-induced second harmonic acoustic response
Authors: Yuanhui Huang
George Sergiadis
Vasilis Ntziachristos
Stephan Kellnberger
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: contrast mechanism; blood vessels; radiofrequency-induced second harmonic acoustic (RISHA) signals; blood conductivity; imaging system
Affiliations: Helmholtz Zentrum M√ºnchen, Institute for Biological and Medical Imaging (IBMI), Neuherberg, D-85764, Germany., Technische Universit√§t M√ºnchen, Chair for Biological Imaging, M√ºnchen, D-81675, Germany., Helmholtz Zentrum M√ºnchen, Institute for Biological and Medical Imaging (IBMI), Neuherberg, D-85764, Germany. ., Technische Universit√§t M√ºnchen, Chair for Biological Imaging, M√ºnchen, D-81675, Germany. ., Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, 02114, USA. ., Aristotle University of Thessaloniki, School of Electrical and Computer Engineering, Thessaloniki, 54124, Greece., Chinese Academy of Sciences, Suzhou Institute of Biomedical Engineering and Technology, Suzhou, 215163, China.

Abstract:  We introduce a contrast mechanism for visualizing blood vessels based on radiofrequency-induced second harmonic acoustic (RISHA) signals sensing blood conductivity. We develop a novel imaging system using commonly available inexpensive components, and demonstrate in vivo RISHA visualization of blood vessels based on low-power quasi-continuous radiofrequency excitation of tissue at frequencies of a few MHz. We show how the novel approach also implicitly enables radiofrequency-induced passive ultrasound imaging and can be readily applied to non-invasive imaging of blood vessels ex vivo and in vivo. We discuss the implications of non-invasive conductivity measurements in the context of biomedical applications. 

Retracted: No

PubPeer comments:
 I was very interested in this impressive work showing that the second harmonic of RF induced ultrasound can be used to image blood vessels. I would like to add an earlier reference to the body of work surrounding this hybrid imaging technique. We published a description of electromagnetic acoustic imaging (EMAI) in IEEE in 2013 in which we described the theory and experimental results for using both the first and second harmonic of RF-induced US, and cited the potential to image blood filled spaces owing to the large conductivity gradients encountered at the boundaries. DOI http: dx.doi.org 10.1109 TUFFC.2013.2372. I look forward to seeing publications of further work in this area. ,
Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer
Authors: Nobuhiro Takeshita
Yoshihito Kotera
Atsushi Aruga
Masakazu Yamamoto
Ryuji Okuyama
Norimasa Matsushita
Takehiro Ohta
Kazuyoshi Takeda
Journal: Journal of translational medicine (2014)
Discipline: CLINICAL MEDICINE
Keywords: Biliary tract cancer; Peptide vaccination; Cancer-testis antigens; Immune response; Anti-tumor effect
Affiliations: Department of Gastroenterological Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. .

Abstract:  Background: The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and only a few standard treatments are available for this condition. We performed a phase I trial to investigate the safety, immune response and anti-tumor effect of vaccination with three peptides derived from cancer-testis antigens. Methods: This study was conducted as a phase I trial. Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. Three HLA-A*2402 restricted epitope peptides-cell division cycle associated 1 (CDCA1), cadherin 3 (CDH3) and kinesin family member 20A (KIF20A)-were administered subcutaneously, and the adverse events and immune response were assessed. The clinical effects observed were the tumor response, progression-free survival (PFS) and overall survival (OS). Results: The three-peptide vaccination was well-tolerated up to a dose of 3 mg per peptide (9 mg total). No grade 3 or 4 adverse events were observed after vaccination. Peptide-specific T cell immune responses were observed in all patients and stable disease was observed in 5 of 9 patients. The median PFS and OS were 3.4 and 9.7 months. The Grade 2 injection site reaction and continuous vaccination after PD judgment appeared to be prognostic of OS. Conclusions: Multiple-peptide vaccination was well tolerated and induced peptide-specific T-cell responses. Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003229). 

Retracted: No

PubPeer comments:
 more similar than expected  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. ,
Studies on the relationship between P13K/AKT signal pathway-mediated MMP-9 gene and lung cancer
Authors: J-F Liu
H Zheng
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: P13K/AKT signal pathway; matrix metalloproteinase-9 (MMP-9) gene; lung cancer; gene expression; fluorescence quantitative PCR
Affiliations: Department of Ultrasonography, Hebei Chest Hospital, Shijiazhuang, Hebei, China. .

Abstract:  Objective: The present study has been planned to explore the relationship between P13K/AKT signal pathway-mediated matrix metalloproteinase-9 (MMP-9) gene and lung cancer. Patients and methods: The adjacent lesion tissues were removed from 68 cases of patients with lung cancer admitted to our hospital from February 2013 to February 2015. They were selected as observation group, and the pulmonary adjacent normal section specimens from 18 cases were taken as control group. The differences in expression quantities of P13K, AKT and MMP-9 genes in adjacent lesion tissues and adjacent normal tissues were detected by fluorescence quantitative PCR technology, enzyme-linked immunosorbent assay (ELISA), Western-blotting technology and immunohistochemical technique and SP staining technology. Results: The mRNA expression quantities of P13K, AKT and MMP-9 genes in adjacent lesion tissues increased significantly in comparison to adjacent normal tissues, and the differences were statistically significant (p&lt;0.05). The results of Spearman correlation detection showed that the expression quantity of MMP-9 in adjacent lesion tissues had a significantly positive correlation with that of P13K and AKT (r=0.232, p&lt;0.05). Conclusions: MMP-9 gene could promote the generation of lung cancer through P13K/AKT signal pathway, which provides certain theoretical and experimental basis for subsequent diagnosis and treatment of lung cancer. 

Retracted: No

PubPeer comments:
 There is no statement about IRB approval or informed consent. This is of grave concern.  , 
 Figure 2, as pointed out by a reader. * The bands are all presented  ransom note style, with little reference to their sizes or exposures.  ,
The Hong Kong Principles for assessing researchers: Fostering research integrity
Authors: Lex Bouter
Paul Glasziou
Ulrich Dirnagl
Nicole Foeger
David Moher
Virginia Barbour
Sabine Kleinert
Mai Har Sham
Anne-Marie Coriat
Journal: PLoS Biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: trustworthy research; robust; rigorous; transparent; assessment
Affiliations: Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada., School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada., Department of Epidemiology and Biostatistics, Amsterdam University Medical Centers, location VUmc, Amsterdam, the Netherlands., Department of Philosophy, Faculty of Humanities, Vrije Universiteit, Amsterdam, the Netherlands., The Lancet, London Wall Office, London, United Kingdom., Institute for Evidence-Based Healthcare, Bond University, Gold Coast, Queensland, Australia., School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Queensland University of Technology (QUT), Brisbane, Australia., Wellcome Trust, London, United Kingdom., Austrian Agency for Research Integrity, Vienna, Austria., Berlin Institute of Health, QUEST Center for Transforming Biomedical Research, Berlin, Germany.

Abstract:  For knowledge to benefit research and society, it must be trustworthy. Trustworthy research is robust, rigorous, and transparent at all stages of design, execution, and reporting. Assessment of researchers still rarely includes considerations related to trustworthiness, rigor, and transparency. We have developed the Hong Kong Principles (HKPs) as part of the 6th World Conference on Research Integrity with a specific focus on the need to drive research improvement through ensuring that researchers are explicitly recognized and rewarded for behaviors that strengthen research integrity. We present five principles: responsible research practices; transparent reporting; open science (open research); valuing a diversity of types of research; and recognizing all contributions to research and scholarly activity. For each principle, we provide a rationale for its inclusion and provide examples where these principles are already being adopted. 

Retracted: No

PubPeer comments:
 Authors might want to consider other aspects of post-publication in a future version. For example, there is no mention to how corrections retractions might impact a researcher s score on Research Integrity. Another suggestion, as previously proposed by Sophien Kamoun and Cyril Zipfel, is to consider which researchers are responsive or not to criticism after the publication , 
 #1 Thanks for this feedback. dm ,
Chronic isolation stress predisposes the frontal cortex but not the hippocampus to the potentially detrimental release of cytochrome c from mitochondria and the activation of caspase-3
Authors: D Filipoviƒá
D Inta
J Zlatkoviƒá
I Bjelobaba
P Gass
M Stojiljkovic
Journal: Journal of Neuroscience Research (2011)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Mitochondria; p53; apoptosis; cytochrome c; caspase-3
Affiliations: Laboratory of Molecular Biology and Endocrinology, Institute of Nuclear Sciences Vinƒça, University of Belgrade, Belgrade, Serbia. 

Abstract:  Mitochondria are central integrators and transducers of proapoptotic signals for neuronal apoptosis. The tumor suppressor protein p53 can trigger apoptosis independently of its transcriptional activity, through subcellular translocation of cytochrome c and caspase activation. To define better the proapoptotic role of p53 under various stress conditions, we investigated the protein levels of p53 and cytochrome c in mitochondrial and cytosolic fractions, as well as caspase-3 activation and apoptosis, in the prefrontal cortex and hippocampus of male Wistar rats subjected to acute, chronic, or combined stressors. Mitochondrial p53 can suppress the antioxidant enzyme MnSOD, so its activity was also determined. In the prefrontal cortex, but not in hippocampus, increased protein levels of p53 were found in mitochondria, leading to cytochrome c release into cytoplasm, activation of caspase-3, and apoptotic cell death following combined stressors. Decreased mitochondrial MnSOD activity following combined stressors in both brain structures indicated a state of oxidative stress. This suggests that chronic isolation stress compromises mitochondrial MnSOD activity in both the prefrontal cortex and the hippocampus but likely results in mitochondrial-triggered proapoptotic signaling mediated by a transcription-independent p53 mechanism only in the prefrontal cortex. Thus, our data demonstrate a tissue-specific (prefrontal cortex vs. hippocampus) response to applied stressors. 

Retracted: No

PubPeer comments:
 Identified by another reader. ***  ,
The position of cysteine relative to the transmembrane domain is critical for palmitoylation of H1, the major subunit of the human asialoglycoprotein receptor
Authors: Jasper H N Yik
Paul H Weigel
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ASGP-R; hepatic; receptor; glycoproteins; lysosomes
Affiliations: Department of Biochemistry & Molecular Biology and the Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA.

Abstract:  The mammalian hepatic asialoglycoprotein receptor (ASGP-R) is an endocytic recycling receptor that mediates the internalization of desialylated glycoproteins and their delivery to lysosomes where they are degraded. The human ASGP-R is a hetero-oligomeric complex composed of two subunits designated H1 and H2. Both subunits are palmitoylated at the cytoplasmic Cys residues near their transmembrane domains (TMD). The cytoplasmic Cys(36) in H1 is located at a position that is five amino acids from the transmembrane junction. Because the sequences of subunits in all mammalian ASGP-R species are highly conserved especially at the region near the palmitoylated Cys, we sought to identify a recognition signal for the palmitoylation of H1. Various types of H1 mutants were created by site-directed or deletion mutagenesis including alteration of the amino acids surrounding Cys(36), replacing portions of the TMD with that of a different protein and partial deletion of the cytoplasmic domain as well as transposing the palmitoylated Cys to positions further away from the TMD. Mutant H1 cDNAs were transiently expressed in COS-7 cells, and the H1 proteins were analyzed after metabolic labeling with [(3)H]palmitate. The results indicate that neither the native amino acid sequence surrounding Cys(36) nor the majority of the cytoplasmic domain sequence is critical for palmitoylation. Palmitoylation was also not dependent on the native TMD of H1. In contrast, the attachment of palmitate was abolished if the Cys residue was transposed to a position that was 30 amino acids away from the transmembrane border. We conclude that the spacing of a Cys residue relative to the TMD in the primary protein sequence of H1 is the major determinant for successful palmitoylation. 

Retracted: No

PubPeer comments:
 In Figure 5, there is undeclared splicing of two WB lanes in the middle of membrane.  ,
Scutellarin protects cardiomyocyte ischemia‚Äìreperfusion injury by reducing apoptosis and oxidative stress
Authors: Zhijie Xu
Jingui Yu
Huanliang Wang
Jianbo Wu
Feng Qi
Zhou Wang
Zhigang Wang
Journal: Life Sciences (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Apoptosis; Cardiomyocyte; Ischemia; JAK2; Scutellarin.
Affiliations: Department of Anesthesiology, Qilu Hospital of Shandong University, No. 107 West of Wenhua Road, Jinan, 250012 Shandong, China., Department of Anesthesiology, Qilu Hospital of Shandong University, No. 107 West of Wenhua Road, Jinan, 250012 Shandong, China. Electronic address: .

Abstract:  Aims: Ischemic heart disease is a leading cause of death and disability worldwide. Despite recent advances, there is no effective therapy for preventing myocardial ischemia-reperfusion (I/R) injury. In this study, we aimed to examine the therapeutic effect of scutellarin, a flavone isolated from the traditional Chinese medicine Scutellaria barbata and Erigeron breviscapus, on cardiomyocyte I/R injury. Main methods: Neonatal rat cardiomyoblast cells H9C2 were used to study the role of scutellarin in cardiomyocyte injury. I/R injury was induced by 2h of hypoxia plus glucose and serum deprivation, followed by 6-hour recovery. Cardiomyocyte damage was evaluated by the release of pro-inflammatory cytokines and creatine kinase (CK), apoptosis, and cell proliferation. Oxidative responses were assessed by reactive oxygen species (ROS) production, MDA generation, SOD expression, and mitochondrial membrane potential detection. Activation of JAK2/STAT3 signaling and expression of pro- or anti-survival molecules were detected by Western blot. Key findings: I/R injury increased the release of CK as well as pro-inflammatory cytokines TNFŒ±, IL-1Œ≤, IL-6, and IL-8 from cardiomyocytes. ROS, MDA, and apoptosis were enhanced in cardiomyocytes underwent I/R injury, while cell proliferation, mitochondrial membrane potential, SOD expression were reduced. Scutellarin treatment dose-dependently suppressed I/R injury-induced pro-inflammatory cytokine and CK release, oxidative response, loss of mitochondrial membrane potential, and enhanced cell proliferation and anti-oxidant SOD expression. Further analysis suggests scutellarin promotes JAK/STAT3 activation and expression of pro-survival proteins Bcl2, VEGF, MMP2, and MMP9. Pro-apoptotic molecules Bax and caspase-3 were suppressed by scutellarin. Significance: We identified a previously unrecognized pathway by which scutellarin protects myocardial I/R injury. Scutellarin modulates I/R injury-induced oxidative stress and apoptosis probably by enhancing JAK2/STAT3 pro-survival signaling. 

Retracted: No

PubPeer comments:
 Fig 3A.  Apoptosis upon I R injury and scutellarin treatment: H9C2 myocytes were cultured under normal condition (MOCK), or serum deprivation + hypoxia conditions followed by 6 h recovery in normal culture condition (ischemia) with indicated treatments. Apoptosis was evaluated by annexin-V and PI staining . Unexpected region of identical cells, shared between two scatterplots. LIght blue rectangle.  ,
Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer
Authors: Xiaoli Li
Yafei Chen
Yu Wang
Zhixin Wang
Jie Zheng
Yuhong Xia
Huaikun Ming
Rui Zhang
Journal: Biochemical and biophysical research communications (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Diagnostic marker; Exosomes; MALAT-1; Migration; Non-small cell lung cancer
Affiliations: Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China. Electronic address: ., Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China., Thoracic Surgery Department 1, The Central Hospital of Xinxiang City, Xinxiang, China.

Abstract:  Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC. 

Retracted: No

PubPeer comments:
 Figuress 2D and 3C. * Red boxes: The T47D Ctrl Migration panel in Figure 2D appears to show an overlap with the MCF-7 shCtrl Invasion panel in Figure 3C.  ,
lazaro encodes a lipid phosphate phosphohydrolase that regulates phosphatidylinositol turnover during Drosophila phototransduction
Authors: Elaine Macdonald
Plamen Georgiev
Michael Wakelam
Hanneke Okkenhaug
Trevor Pettitt
Padinjat Raghu
Isaac Garcia-Murillas
Deepti Trivedi
Bassam Hassan
Journal: Neuron (2006)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Drosophila; phototransduction; phosphatidylinositol; phospholipase Cbeta; diacylglycerol kinase
Affiliations: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, United Kingdom.

Abstract:  An essential step in Drosophila phototransduction is the hydrolysis of phosphatidylinositol 4,5 bisphosphate PI(4,5)P2 by phospholipase Cbeta (PLCbeta) to generate a second messenger that opens the light-activated channels TRP and TRPL. Although the identity of this messenger remains unknown, recent evidence has implicated diacylglycerol kinase (DGK), encoded by rdgA, as a key enzyme that regulates its levels, mediating both amplification and response termination. In this study, we demonstrate that lazaro (laza) encodes a lipid phosphate phosphohydrolase (LPP) that functions during phototransduction. We demonstrate that the synergistic activity of laza and rdgA regulates response termination during phototransduction. Analysis of retinal phospholipids revealed a reduction in phosphatidic acid (PA) levels and an associated reduction in phosphatidylinositol (PI) levels. Together our results demonstrate the contribution of PI depletion to the rdgA phenotype and provide evidence that depletion of PI and its metabolites might be a key signal for TRP channel activation in vivo. 

Retracted: No

PubPeer comments:
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Burn Induces Browning of the Subcutaneous White Adipose Tissue in Mice and Humans
Authors: Peter Chen
Abdikarim Abdullahi
Mile Stanojcic
David Patsouris
Peter Qi
Alexandra Parousis
Saeid Amini-Nik
Marc G Jeschke
Journal: Cell Reports (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Burn; hypermetabolism; adipose tissue; subcutaneous fat; beige fat
Affiliations: Department of Surgery, Division of Plastic Surgery, Department of Immunology, University of Toronto, Toronto, ON M5S 1A1, Canada., Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Surgery, Division of Plastic Surgery, Department of Immunology, University of Toronto, Toronto, ON M5S 1A1, Canada., Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Surgery, Division of Plastic Surgery, Department of Immunology, University of Toronto, Toronto, ON M5S 1A1, Canada. Electronic address: .

Abstract:  Burn is accompanied by long-lasting immuno-metabolic alterations referred to as hypermetabolism that are characterized by a considerable increase in resting energy expenditure and substantial whole-body catabolism. In burned patients, the length and magnitude of the hypermetabolic state is the highest of all patients and associated with profoundly increased morbidity and mortality. Unfortunately, the mechanisms involved in hypermetabolism are essentially unknown. We hypothesized that the adipose tissue plays a central role for the induction and persistence of hypermetabolism post-burn injury. Here, we show that burn induces a switch in the phenotype of the subcutaneous fat from white to beige, with associated characteristics such as increased mitochondrial mass and UCP1 expression. Our results further demonstrate the significant role of catecholamines and interleukin-6 in this process. We conclude that subcutaneous fat remodeling and browning represent an underlying mechanism that explains the elevated energy expenditure in burn-induced hypermetabolism. 

Retracted: No

PubPeer comments:
 please note:  ,
Megakaryocytic leukemia 1 (MKL1) regulates hypoxia induced pulmonary hypertension in rats
Authors: Yong Xu
Minjie Xia
Zhibin Yuan
Gang Xu
Yuqi Gao
Dewei Chen
Jian Chen
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Hypoxia induced pulmonary hypertension; MKL1; vascular remodeling; pulmonary inflammation; extracellular matrix proteins
Affiliations: Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; Key Laboratory of High Altitude Medicine, Ministry of Education, Third Military Medical University, Chongqing, China; Key Laboratory of High Altitude Medicine, PLA, Third Military Medical University, Chongqing, China., Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu, China.

Abstract:  Hypoxia induced pulmonary hypertension (HPH) represents a complex pathology that involves active vascular remodeling, loss of vascular tone, enhanced pulmonary inflammation, and increased deposition of extracellular matrix proteins. Megakaryocytic leukemia 1 (MKL1) is a transcriptional regulator known to influence cellular response to stress signals in the vasculature. We report here that in response to chronic hypobaric hypoxia, MKL1 expression was up-regulated in the lungs in rats. Short hairpin RNA (shRNA) mediated depletion of MKL1 significantly ameliorated the elevation of pulmonary arterial pressure in vivo with a marked alleviation of vascular remodeling. MKL1 silencing also restored the expression of NO, a key vasoactive molecule necessary for the maintenance of vascular tone. In addition, hypoxia induced pulmonary inflammation was dampened in the absence of MKL1 as evidenced by normalized levels of pro-inflammatory cytokines and chemokines as well as reduced infiltration of pro-inflammatory immune cells in the lungs. Of note, MKL1 knockdown attenuated fibrogenesis in the lungs as indicated by picrosirius red staining. Finally, we demonstrate that MKL1 mediated transcriptional activation of type I collagen genes in smooth muscle cells under hypoxic conditions. In conclusion, we data highlight a previously unidentified role for MKL1 in the pathogenesis of HPH and as such lay down groundwork for future investigation and drug development. 

Retracted: No

PubPeer comments:
 Could the author clarify this image duplication in another published paper?  , 
 The authors published a corrigendum for the errors in their publication. Available at https: doi.org 10.1016 j.ejpb.2021.01.019 , 
 #2 They state that  The authors regret to inform you that a technical error has creeped into our publication which inadvertently duplicated images from a common template that were published in some of our other publications. In the light of this incident, we would like to provide correct figures to our esteemed readers. the histogram data remains the same? , 
 I do agree with the observation of Deiratonotus Cristatus. For more clarity on this concern, the images were demonstrated below.  ,