PReD-Bench/PRed-Bench huggingface dataset:
TGF-β induces miR-182 to sustain NF-κB activation in glioma subsets
Authors: Jueheng Wu
Yun Li
Bo Hu
Mengfeng Li
Chuyong Lin
Jun Li
Liping Liu
Zhiqiang Wu
Zhe Ying
Shi-Yuan Cheng
Libing Song
Journal: Journal of Clinical Investigation (2012)
Discipline: CLINICAL MEDICINE
Keywords: NF-κB signaling; negative feedback mechanisms; miR-30e*; IκBα; miR-182
Affiliations: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Zhongshan School of Medicine, Ministry of Education, Sun Yat-sen University, Guangzhou, China.

Abstract:  The strength and duration of NF-κB signaling are tightly controlled by multiple negative feedback mechanisms. However, in cancer cells, these feedback loops are overridden through unclear mechanisms to sustain oncogenic activation of NF-κB signaling. Previously, we demonstrated that overexpression of miR-30e* directly represses IκBα expression and leads to hyperactivation of NF-κB. Here, we report that miR-182 was overexpressed in a different set of gliomas with relatively lower miR-30e* expression and that miR-182 directly suppressed cylindromatosis (CYLD), an NF-κB negative regulator. This suppression of CYLD promoted ubiquitin conjugation of NF-κB signaling pathway components and induction of an aggressive phenotype of glioma cells both in vitro and in vivo. Furthermore, we found that TGF-β induced miR-182 expression, leading to prolonged NF-κB activation. Importantly, the results of these experiments were consistent with an identified significant correlation between miR-182 levels with TGF-β hyperactivation and activated NF-κB in a cohort of human glioma specimens. These findings uncover a plausible mechanism for sustained NF-κB activation in malignant gliomas and may suggest a new target for clinical intervention in human cancer. 

Retracted: No

PubPeer comments:
 Supplemental Figure 3C and Supplemental Figure 7C. More similar than expected. ![file] , 
 Figure 7H contains two images which appear to overlap. ![file] , 
 #2 Dear Lecithocera Eumenopisuff1a For the first WB question, here is the scanned original loading control WB of u03b1-tubulin for these two panels in our article. However, we did not use the right Figure S3 WB instead of using Figure S7 WB in Figure S3 unintentionally. For the tube formation images, the image for the PDGC#1 cells was mistakenly used in PDGC1#2 cells during figure assembly. We are extremely sorry for such oversight and apologize for any inconvenience it may have caused. We will make corrigendum as soon as possible. Jun Li ![file] ,
Losartan metabolite EXP3179 activates Akt and endothelial nitric oxide synthase via vascular endothelial growth factor receptor-2 in endothelial cells: angiotensin II type 1 receptor-independent effects of EXP3179
Authors: Shey-Shing Sheu
Virendra K Sharma
Bradford C Berk
Hideyuki Yamawaki
Tetsu Watanabe
Jun Suzuki
Journal: Circulation (2005)
Discipline: CLINICAL MEDICINE
Keywords: angiotensin type 1 receptor; eNOS; Akt; phosphatidylinositol 3-kinase; losartan
Affiliations: Cardiovascular Research Institute, Department of Medicine, University of Rochester, Rochester, NY 14642, USA.

Abstract:  Background: Recent studies suggest that angiotensin type 1 receptor (AT1R) blockers have vascular protective effects beyond blood pressure lowering. Because of the importance of endothelial nitric oxide synthase (eNOS) in vascular and platelet function, we hypothesized that losartan and its metabolites would stimulate eNOS and its upstream activators Akt and phosphatidylinositol 3-kinase (PI3K). Methods and results: Losartan is metabolized into EXP3174 (AT1R-blocking metabolite) and EXP3179 (no AT1R-blocking properties). Treatment of endothelial cells (ECs) with losartan and both metabolites stimulated phosphorylation of Akt and eNOS in the absence of angiotensin II. However, the magnitude for EXP3179 was much greater than EXP3174, and the EC50 was significantly lower (-logEC50, 8.2+/-0.1 versus 5.4+/-0.2 mol/L), suggesting an AT1R-independent effect. Inhibiting PI3K or vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine phosphorylation abrogated EXP3179-induced eNOS phosphorylation. In endothelium of intact rat aorta, EXP3179 also stimulated Akt and eNOS phosphorylation. VEGFR2 activation was shown to be calcium and Src family kinase dependent by use of specific drug inhibitors and dominant negative kinase transfection. EXP3179 significantly inhibited tumor necrosis factor alpha-induced apoptosis by approximately 60% (from 30.1+/-5.8% to 12.2+/-2.0% TUNEL-positive cells), which was abolished by pretreatment with the PI3K inhibitor LY294002. Cleaved caspase-3 was suppressed by 48% with EXP3179. Conclusions: The losartan metabolite EXP3179 stimulates eNOS phosphorylation and suppresses tumor necrosis factor alpha-induced EC apoptosis by activating the VEGFR2/PI3K/Akt pathway. 

Retracted: No

PubPeer comments:
 Most of this article appears to be computer-generated with [Scigen] ![file] --- This comment was written by Guillaume Cabanac and Cyril Labbu00e9. Contact: [SeekAndBlastn-Operators@univ-grenoble-alpes.fr](mailto:SeekAndBlastn-Operators@univ-grenoble-alpes.fr). ,
InvA protein is a Nudix hydrolase required for infection by pathogenic Leptospira in cell lines and animals
Authors: Xuai Lin
Rongguang Zhang
Dexter Sun
Jie Yan
Lanjuan Li
David M Ojcius
Yan Liu
Yihui Luo
Ming Chen
Dong Wu
Jinfang Zhao
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Leptospirosis; zoonotic disease; Leptospira; invA gene; Nudix domain
Affiliations: Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital of Medical College, Hangzhou, Zhejiang 310003, China.

Abstract:  Leptospirosis caused by pathogenic species of the genus Leptospira is a re-emerging zoonotic disease, which affects a wide variety of host species and is transmitted by contaminated water. The genomes of several pathogenic Leptospira species contain a gene named invA, which contains a Nudix domain. However, the function of this gene has never been characterized. Here, we demonstrated that the invA gene was highly conserved in protein sequence and present in all tested pathogenic Leptospira species. The recombinant InvA protein of pathogenic L. interrogans strain Lai hydrolyzed several specific dinucleoside oligophosphate substrates, reflecting the enzymatic activity of Nudix in Leptospira species. Pathogenic leptospires did not express this protein in media but temporarily expressed it at early stages (within 60 min) of infection of macrophages and nephric epithelial cells. Comparing with the wild type, the invA-deficient mutant displayed much lower infectivity and a significantly reduced survival rate in macrophages and nephric epithelial cells. Moreover, the invA-deficient leptospires presented an attenuated virulence in hamsters, caused mild histopathological damage, and were transmitted in lower numbers in the urine, compared with the wild-type strain. The invA revertant, made by complementing the invA-deficient mutant with the invA gene, reacquired virulence similar to the wild type in vitro and in vivo. The LD(50) in hamsters was 1000-fold higher for the invA-deficient mutant than for the invA revertant and wild type. These results demonstrate that the InvA protein is a Nudix hydrolase, and the invA gene is essential for virulence in pathogenic Leptospira species. 

Retracted: Yes

PubPeer comments:
 Figure 3a. Much more similar than expected. https: imgur.com 8ic1wTa.jpg ,
One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell
Authors: Roger Chung
Dayong Jin
Shihui Wen
Yiqing Lu
Yue Cong
Bingyang Shi
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Gene therapies; liver cancers; delivery systems; cationic polymers; glycyrrhetinic acid
Affiliations: Institute of Pharmacy, Pharmaceutical College, Henan University, Jin Ming Avenue, Kaifeng, Henan, 475004, China., College of Life Sciences, Henan University, Jin Ming Avenue, Kaifeng, Henan, 475004, China., Advanced Cytometry Labs, ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, Sydney, NSW, 2109, Australia., Faculty of Medicine &Health Sciences, Macquarie University, Sydney, NSW, 2109, Australia.

Abstract:  Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,(1)H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25 kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy. 

Retracted: No

PubPeer comments:
 Figure 6. * Cyan box: The panel representing GA-PPI-5 with HepG2 cells looks remarkably similar to a panel in an older paper by Bingyang Shi et al, Colloids and Surfaces (2014), DOI: 10.1016 j.colsurfb.2014.04.005, where it represents HeLa cells incubated with FA-SLICS-2 N P 10. * Yellow boxes: two light-microscopy image appear to overlap. ![file] , 
 Figure S10. * Orange box: The panel representing PPI(G4) N P10 with HepG2 cells looks remarkably similar to a panel in an older paper by Bingyang Shi et al, Polymer Chemistry (2013), 10.1039 c2py20494k, where it represents HEK239 cells incubated with Lipofectamine 2000. ![file] , 
 Dear Elisabeth M Bik, We thank you for these issues which have brought our attention. We are seriously checking all the raw data related to this article and will respond as soon as possible. Sincerely Bingyang ,
Mitochondria-mediated disturbance of fatty acid metabolism in proximal tubule epithelial cells leads to renal interstitial fibrosis
Authors: Q He
Y-W Li
X-X Jiang
W Shen
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Mitochondria; fatty acid metabolism; proximal tubule epithelial cells; renal interstitial fibrosis; withdrawal
Affiliations: Department of Nephrology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China. .

Abstract:  The article "Mitochondria-mediated disturbance of fatty acid metabolism in proximal tubule epithelial cells leads to renal interstitial fibrosis" by W. Shen, X.-X. Jiang, Y.-W. Li, Q. He, published in Eur Rev Med Pharmacol Sci 2018; 22 (3): 810-819 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,
Orai-1 and Orai-2 regulate oral cancer cell migration and colonisation by suppressing Akt/mTOR/NF-κB signalling
Authors: Anuj Kumar Singh
Kishore Banik
Amrita Devi Khwairakpam
Devivasha Bordoloi
Piruthivi Sukumar
Nand Kishor Roy
Ganesan Padmavathi
Ajaikumar B Kunnumakkara
Journal: Life Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Calcium; Orai; Oral cancer; SOCE; STIM.
Affiliations: Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India., Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India. Electronic address: ., Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK. Electronic address: .

Abstract:  Despite remarkable progress in understanding and treating oral cancer (OC), it still remains one of the life-threatening diseases and predominant cancers in the world. Therefore, deciphering the molecular mechanisms of this disease would help us to develop highly efficacious therapies. Multiple lines of evidence suggest that calcium and its dysregulation play significant role in the development of various cancers. As an adaptation of survival mechanism, upon depletion of ER calcium stores, store-operated calcium entry (SOCE) has been induced via SOCE channels (SOCC) in various mammalian cells. SOCC are regulated by Orai-1, Orai-2 and Orai-3 located on plasma membrane and two calcium-sensing ER membrane proteins known as stromal interaction molecules (STIM-1 and STIM-2). Hence, the present study was aimed at analysing the role of Orai-1 and Orai-2 in oral cancer and the underlying mechanism. Our results suggest that both Orai-1 and Orai-2 proteins were overexpressed in oral cancer tissues and cell lines (SAS) compared to normal epithelial tissues and cell lines respectively. In addition, silencing of Orai-1 and Orai-2 via chemical SOCE inhibitors and siRNAs inhibited calcium uptake and suppressed oral cancer cell proliferation, colony formation and migration. Furthermore, silencing of Orai-1 and Orai-2 inhibited Akt/mTOR/NF-κB pathway in oral cancer cells. Interestingly, tobacco carcinogen NNN and synthetic carcinogen 4-NQO, enhanced the expression of Orai-1 and Orai-2 in SAS cells. Therefore, we conclude that Orai-1 and Orai-2 have significant role in oral cancer and can be further explored to develop novel therapies for the treatment of this disease. 

Retracted: No

PubPeer comments:
 In this very interesting study, dogs are used to detect Covid-19. However, dogs appear to be also able to catch Covid-19: https: www.msn.com en-us news us dogs-can-get-covid-19-from-humans-vet-says ar-BB13oo72 https: www.cdc.gov coronavirus 2019-ncov daily-life-coping animals.html Do the authors have a way to offer protection to Covid-19-sniffing dogs without affecting their ability to detect the virus? , 
 In this study the Virus was inactivated. We are currently working on a device which would be safe for the dogs and circumvent the need to inactivate the virus ,
MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling
Authors: Jae-Sung Yi
Hua Zhu
Nga Nguyen
Malith Karunasiri
Young-Mi Ham
Hana Cho
Seung Hee Lee
Kyong Soo Park
Jae-Seon Lee
Jun Sub Park
Jianjie Ma
Peihui Lin
Pu Duann
Shi-Young Park
Cheol Soo Choi
Yoon Ki Kim
Chang-Seok Lee
Jin Hong
Hyun Kyu Song
Young-Gyu Ko
Na-Rae Lee
Inho Choi
Tao Tan
Woo Jin Park
Haksub Shin
Hyun Lee
Byung-Cheon Jeong
Bong-Woo Kim
Journal: Nature Communications (2013)
Discipline: Multidisciplinary
Keywords: MG53; skeletal myogenesis; insulin receptor substrate 1; ubiquitin E3 ligase; UBE2H
Affiliations: Department of Life Sciences, Korea University, Seoul 136-701, Korea.

Abstract:  Mitsugumin 53 (MG53) negatively regulates skeletal myogenesis by targeting insulin receptor substrate 1 (IRS-1). Here, we show that MG53 is an ubiquitin E3 ligase that induces IRS-1 ubiquitination with the help of an E2-conjugating enzyme, UBE2H. Molecular manipulations that disrupt the E3-ligase function of MG53 abolish IRS-1 ubiquitination and enhance skeletal myogenesis. Skeletal muscles derived from the MG53-/- mice show an elevated IRS-1 level with enhanced insulin signalling, which protects the MG53-/- mice from developing insulin resistance when challenged with a high-fat/high-sucrose diet. Muscle samples derived from human diabetic patients and mice with insulin resistance show normal expression of MG53, indicating that altered MG53 expression does not serve as a causative factor for the development of metabolic disorders. Thus, therapeutic interventions that target the interaction between MG53 and IRS-1 may be a novel approach for the treatment of metabolic diseases that are associated with insulin resistance. 

Retracted: No

PubPeer comments:
 Readers should become aware of a recent preprint entitled  MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle that calls into question part of the conclusions of Yi et al., study https: www.biorxiv.org content 10.1101 2020.12.24.424288v1 From the Discussion:  Our results failed to confirm the role of MG53 as a critical regulator of insulin signaling pathway in vitro and of glucose homeostasis in vivo in contrast to earlier reports [7,8]. While we cannot exclude the possibility that different reagents may lead to different results, our data raise significant doubts about the involvement of MG53 in the regulation of insulin signaling. ,
A Combination of Tamarindus indica seeds and Curcuma longa Rhizome Extracts Improves Knee Joint Function and Alleviates Pain in Non-Arthritic Adults Following Physical Activity
Authors: Leon J Schurgers
Victor R Prisk
Yendluri Sita Ramanjaneyulu
Posani Srinivas Rao
Journal: International journal of medical sciences (2019)
Discipline: CLINICAL MEDICINE
Keywords: Knee joint pain; Musculoskeletal function; NXT15906F6; Six-minute walk test.
Affiliations: Sravani Hospital; Guntur-522001 Andhra Pradesh, India., Prisk Orthopaedics and Wellness, PC Monroeville, PA., Department of Biochemistry, Maastricht University, Maastricht, The Netherlands.

Abstract:  Background: Knee joint pain is the most common reason for physical disability which associates with age. TamaFlexTM (NXT15906F6) is a synergistic anti-inflammatory formulation which contains ethanol/aqueous extracts of Tamarindus indica seeds and ethanol extract of Curcuma longa rhizome. Methods: In a 90-day randomized, double-blind, placebo-controlled study, we evaluated efficacy of NXT15906F6 in relieving pain and improving joint function in non-arthritic adults. Ninety non-arthritic subjects who experienced knee pain and joint discomfort following a six-minute walk test (SMWT) and Stair climb test (SCT) participated in the present trial. Subjects received either 250 mg (n=30) or 400 mg (n=30) of NXT15906F6 or matched placebo (PL: n=30) daily for 90 days. Improvement from baseline six-minute walk distance (SMWD) in NXT15906F6 groups, compared with placebo (PL) was the primary outcome of the study. Results: At post-intervention, subjects in NXT15906F6-250 (p&lt;0.001) and NXT15906F6-400 (p&lt;0.0001) groups showed substantial improvements in mean changes of SMWD from baseline compared to placebo. The 250 mg and 400 mg NXT15906F6 groups also improved average walking speed from baseline by 0.08±0.07 m/s (p=0.0010) and 0.11±0.08 m/s (p&lt;0.0001), respectively. The NXT15906F6 groups experienced significant improvement in SMWT performances as early as 14 days. NXT15906F6-supplemented participants showed a consistent benefit of pain relief and improved musculoskeletal functions, compared to placebo. Conclusion: NXT15906F6 provided substantial relief from knee pain after physical activity and improved joint function in non-arthritic adults. Study participants did not show any major adverse events, and they tolerated well this novel herbal formulation. 

Retracted: No

PubPeer comments:
 This study was performed in India and funded by NXT (producer of the formulation tested). The participants were randomized into three groups, but the baseline characteristics for height and BMI are surprisingly similar (Table 2). It is also surprising that the p-values are not higher for these measurments. In addition, the last two digits for the values presented in Table 5 (NXT 250 treated) are repeated surprisingly many times. ![file] ,
An ATM-independent S-phase checkpoint response involves CHK1 pathway
Authors: Jun Guan
G Iliakis
George Iliakis
Xiang Wang
Baocheng Hu
Ya Wang
Xiang-Yang Zhou
Journal: Cancer research (2002)
Discipline: CLINICAL MEDICINE
Keywords: genotoxic stress; DNA replication; S-phase checkpoint; ATM-dependent pathway; ATM-independent pathway
Affiliations: Department of Radiation Oncology, Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Abstract:  After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar than you would expect. https: imgur.com AlD8xQX ,
Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression
Authors: Ying-Hua Yang
Hua Zhou
Patrizia Proia
John R Basile
Nada O Binmadi
Journal: Angiogenesis (2012)
Discipline: CLINICAL MEDICINE
Keywords: Semaphorins; Plexins; angiogenesis; tumor; VEGF
Affiliations: Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650 West Baltimore Street, 7-North, Baltimore, MD 21201, USA.

Abstract:  The semaphorins and plexins comprise a family of cysteine-rich proteins implicated in control of nerve growth and development and regulation of the immune response. Our group and others have found that Semaphorin 4D (SEMA4D) and its receptor, Plexin-B1, play an important role in tumor-induced angiogenesis, with some neoplasms producing SEMA4D in a manner analogous to vascular endothelial growth factor (VEGF) in order to attract Plexin-B1-expressing endothelial cells into the tumor for the purpose of promoting growth and vascularity. While anti-VEGF strategies have been the focus of most angiogenesis inhibition research, such treatment can lead to upregulation of pro-angiogenic factors that can compensate for the loss of VEGF, eventually leading to failure of therapy. Here, we demonstrate that SEMA4D cooperates with VEGF to promote angiogenesis in malignancies and can perform the same function in a setting of VEGF blockade. We also show the potential value of inhibiting SEMA4D/Plexin-B1 signaling as a complementary mechanism to anti-VEGF treatment, particularly in VEGF inhibitor-resistant tumors, suggesting that this may represent a novel treatment for some cancers. 

Retracted: Yes

PubPeer comments:
 This paper addresses the u201c**display systems quality of excavator instrumentation**u201d. However, the preference list contains no papers related to u201dexcavator instrumentationu201d. Actually, the reference list of this paper contains 57 items in total among which 27 are authored by G.W. Wei and his co-authors. ![file] ![file] , 
 As the title suggest, the paper is about u201c**evaluating the display systems quality of excavator instrumentation**u201d. However, the second and the last paragraphs of Section 1 address u201c**reliability of electrical engineering automation**u201d, which are not related to the topic of this paper. These paragraphs actually come from another paper (the same journal and same volume). Xianglin Meng. Model for **reliability evaluation of electrical engineering automation** with 2-tuple linguistic information. Journal of Intelligent Fuzzy Systems 37 (2019) 1827u20131834. DOI:10.3233 JIFS-179245 See https: pubpeer.com publications 6BDDEDFB8D3F648D7D3667ACE092B5 Actually, **these two papers are almost identical**. For example, the abstract and keywords are almost identical. ![file] ![file] ![file] ,
Metabolic signaling of insulin secretion by pancreatic β-cell and its derangement in type 2 diabetes
Authors: Y. Gong
C.-Y. Zou
J. Liang
Journal: European review for medical and pharmacological sciences (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Metabolic signaling; insulin secretion; pancreatic β-cell; type 2 diabetes; derangement

Abstract:  The article "Metabolic signaling of insulin secretion by pancreatic β-cell and its derangement in type 2 diabetes" by C.-Y. Zou, Y. Gong, J. Liang, published in Eur Rev Med Pharmacol Sci 2014; 18 (15): 2215-2227 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,
Glial β-oxidation regulates Drosophila energy metabolism
Authors: Paul P Van Veldhoven
Joachim G Schulz
Leen Van Huffel
Jarl Bastianen
Sven Vilain
Antonio Laranjeira
Carlos G Dotti
Annette Gärtner
Journal: Scientific Reports (2015)
Discipline: Multidisciplinary
Keywords: brain; fatty acids; energy production; Drosophila; CPT2
Affiliations: VIB Center for the Biology of Disease, Leuven and Center for Human Genetics, KU Leuven, Leuven, Belgium., Laboratory of Lipid Biochemistry, KU Leuven, Herestraat 49, 3000 Leuven, Belgium., 1] VIB Center for the Biology of Disease, Leuven and Center for Human Genetics, KU Leuven, Leuven, Belgium [2] Centro Biología Molecular "Severo Ochoa" CSIC-UAM, Madrid, Spain.

Abstract:  The brain's impotence to utilize long-chain fatty acids as fuel, one of the dogmas in neuroscience, is surprising, since the nervous system is the tissue most energy consuming and most vulnerable to a lack of energy. Challenging this view, we here show in vivo that loss of the Drosophila carnitine palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial β-oxidation of long-chain fatty acids as substrates for energy production, results in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to restore triacylglyceride homeostasis, and we suggest that this is mediated by the release of ketone bodies from the rescued glial cells. These results demonstrate that the adult brain is able to catabolize fatty acids for cellular energy production. 

Retracted: No

PubPeer comments:
 expression in cortex glia (NP2222-Gal4; p = 0.004 and Nrv2-Gal4; p = 0.0009) or astrocyte-like glia Is there experimental evidence that this is indeed a specific driver for the glia? As I see from different papers, people typically use it as a glial driver but sometimes also as general nervous or as a neuronal driver. So far I didn t find a definitive data on whether it is exclusively expressed in the glia or not. PS: One of the transcriptomics studies confirms that Nrv2 itself is indeed expressed mostly in glia ([Henry et al, 2012] ). , 
 https: www.nature.com articles s41598-020-70053-7 The Editors are issuing an Editorial Expression of Concern for this Article. The Editors have been recently made aware by the Authors that neither the CPT2 fly stocks generated in this study nor DNA constructs with maps have been stored, and are therefore not available for request by readers wishing to repeat this work. Joachim G. Schulz, Antonio Laranjeira, Leen Van Huffel, Annette Gu00e4rtner, Jarl Bastianen, Paul P. Van Veldhoven Carlos G. Dotti agree with the Editorial Expression of Concern. Sven Vilain could not be reached. ,
Pattern Recognition Receptor Signaling in Human Dendritic Cells is Enhanced by ICOS Ligand and Modulated by the Crohn’s Disease ICOSLG Risk Allele
Authors: Clara Abraham
Judy H Cho
Matija Hedl
Amit Lahiri
Kaida Ning
Journal: Immunity (2014)
Discipline: IMMUNOLOGY
Keywords: Inflammatory bowel disease; dysregulated intestinal immune homeostasis; cytokine secretion; pattern-recognition receptor; monocyte-derived dendritic cells
Affiliations: Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT 06510, USA., Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT 06510, USA. Electronic address: .

Abstract:  Inflammatory bowel disease (IBD) is characterized by dysregulated intestinal immune homeostasis and cytokine secretion. Multiple loci are associated with IBD, but a functional explanation is missing for most. Here we found that pattern-recognition receptor (PRR)-induced cytokine secretion was diminished in human monocyte-derived dendritic cells (MDDC) from rs7282490 ICOSLG GG risk carriers. Homotypic interactions between the costimulatory molecule ICOS and the ICOS ligand on MDDCs amplified nucleotide-binding oligomerization domain 2 (NOD2)-initiated cytokine secretion. This amplification required arginine residues in the ICOSL cytoplasmic tail that recruited the adaptor protein RACK1 and the kinases PKC and JNK leading to PKC, MAPK, and NF-κB activation. MDDC from rs7282490 GG risk-carriers had reduced ICOSL expression and PRR-initiated signaling and this loss-of-function ICOSLG risk allele associated with an ileal Crohn's disease phenotype, similar to polymorphisms in NOD2. Taken together, ICOSL amplifies PRR-initiated outcomes, which might contribute to immune homeostasis. 

Retracted: No

PubPeer comments:
 ![file] ![file] ,
MicroRNA-106b regulates the tumor suppressor RUNX3 in laryngeal carcinoma cells
Authors: Kai Wang
Wei Gao
Fuhui Huang
Ying Xu
Shuxin Wen
Binquan Wang
Chunming Zhang
Journal: FEBS Letters (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Invasion; Laryngeal carcinoma; Proliferation; RUNX3; miR-106b.
Affiliations: Department of Otolaryngology, Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.

Abstract:  Our study focuses on a set of laryngeal tumors that show reduced RUNX3 expression in the absence of transcriptional silencing of tumor suppressor gene RUNX3 by aberrant methylation of CpG islands. We report that the loss of expression of RUNX3 correlates with up-regulation of miR-106b in human laryngeal carcinoma tissue. The downregulation of RUNX3 is mediated by miR-106b through binding of its 3'UTR. Moreover, miR-106b can promote the proliferation and invasion of laryngeal carcinoma cells by directly targeting RUNX3, and RUXN3 knockdown can abolish this phenotype. These results shed a new insight into the mechanism of miRNA regulation in laryngeal carcinoma. 

Retracted: No

PubPeer comments:
 Figure6 ![file] Figure3D and Figure4D ![file] , 
 #1 How does one even get a standard deviation (error bar) out of a single T sample? , 
 Comment1uff1a Thank you very much for pointing out this error. We checked the data. During the preparation of figures submitted in the original manuscript, we inadvertently provided an incorrect image for Figure 6, Figure 3D and 4D. In the figure 6A: For WB, the expression of RUNX3 in patient 1-7 is correct, 8-14 group was wrong image by mistake. For transwell assay, figure 3D is correct, figure 4D group was wrong image by mistake. We will check the original pictures and upload it. The correction did not affect the overall conclusions and we will make the corrigendum. We apologize for this mistake due to our carelessness. Ying Xu Best regards Comment 2uff1a Thank you very much for this question. Indeed, three experiments were carried out on the WB of each sample, and three gray values were obtained with a standard deviation. Thanks for your question. Ying Xu Best regards , 
 Fig 2D: There appears to be a duplicated band. ![file] , 
 #4 ![file] ,
Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry
Authors: K Sreekumaran Nair
Christiane D Wrann
Bruce M Spiegelman
John Szpyt
Steven P Gygi
Matthew M Robinson
Kaitlyn K Gerber
Mark P Jedrychowski
Joao A Paulo
Journal: Cell Metabolism (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Exercise; Health benefits; Metabolism; Cardiovascular health; Cognition
Affiliations: Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA., Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue Boston, MA 02115., Division of Endocrinology, 200 First Street SW, Joseph 5-193, Mayo Clinic, Rochester, MN 55905.

Abstract:  Exercise provides many health benefits, including improved metabolism, cardiovascular health, and cognition. We have shown previously that FNDC5, a type I transmembrane protein, and its circulating form, irisin, convey some of these benefits in mice. However, recent reports questioned the existence of circulating human irisin both because human FNDC5 has a non-canonical ATA translation start and because of claims that many human irisin antibodies used in commercial ELISA kits lack required specificity. In this paper we have identified and quantitated human irisin in plasma using mass spectrometry with control peptides enriched with heavy stable isotopes as internal standards. This precise state-of-the-art method shows that human irisin is mainly translated from its non-canonical start codon and circulates at ∼ 3.6 ng/ml in sedentary individuals; this level is increased to ∼ 4.3 ng/ml in individuals undergoing aerobic interval training. These data unequivocally demonstrate that human irisin exists, circulates, and is regulated by exercise. 

Retracted: No

PubPeer comments:
 Published today in Molecular Metabolism (Albrecht et al., 2020; https: www.sciencedirect.com science article pii S2212877820300247; DOI: 10.1016 j.molmet.2020.01.016)  We initially did not find FNDC5 irisin signatures in two human serum samples obtained after different exercise forms. However, repeated preparations of one of these samples led to a positive result with 0.09ng irisin mL serum and 0.15 ng mL in a repeated measurement. This value is 25u201340-fold lower than the levels reported by Jedrychowski et al.[7] for sedentary individuals (3.62 ng mL). and  We did not observe a specific irisin band in the size range between 10 and 15 kDa in human serum after both deglycosylation procedures and incubation with the same antibody as used by Jedrychowski et al. [7], and with other antibodies. Our results contradict the data of the latter group reporting bands at 25 kDa before and at 12 kDa after deglycosylation of human serum. ,
The Effects of Folate Supplementation on Carotid Intima-Media Thickness and Metabolic Status in Patients with Metabolic Syndrome
Authors: Hamid Reza Talari
Zatollah Asemi
Omid Reza Tamtaji
Manijeh Darooghegi Mofrad
Alireza Farrokhian
Fariba Raygan
Motahereh Rafiee
Fereshteh Bahmani
Yaser Hamidian
Fatemeh Karamali
Journal: Annals of Nutrition and Metabolism (2016)
Discipline: CLINICAL MEDICINE
Keywords: folate supplementation; carotid intima-media thickness; metabolic syndrome; type 2 diabetes mellitus; coronary heart disease
Affiliations: Department of Radiology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

Abstract:  Background: This study was carried out to evaluate the effects of folate supplementation on carotid intima-media thickness (CIMT) and metabolic status among patients with metabolic syndrome (MetS). Methods: This randomized, double-blind, placebo-controlled trial was conducted among 60 patients with type 2 diabetes mellitus and coronary heart disease. They were all overweight in the age range 40-85 years. Participants were randomly divided into 2 groups: group A (n = 30) received 5 mg folate supplements and group B (n = 30) received placebo for 12 weeks. Results: Folate supplementation resulted in a significant reduction in maximum levels of left CIMT (-0.05 ± 0.13 vs. +0.02 ± 0.11 mm, p = 0.01) compared with the placebo. Changes in fasting plasma glucose (-2.2 ± 37.5 vs. +30.2 ± 65.8 mg/dl, p = 0.02), serum insulin concentration (-2.0 ± 10.7 vs. +3.0 ± 7.6 µIU/ml, p = 0.04) and homeostasis of assessment-estimated insulin resistance (-0.6 ± 2.3 vs. +0.9 ± 2.3, p = 0.01) in supplemented patients were significantly different from those of patients in the placebo group. Changes in serum triglycerides (p = 0.04), high-density lipoprotein-cholesterol (p = 0.001), high sensitivity C-reactive protein (p = 0.01) and plasma nitric oxide concentrations (p &lt; 0.001) were significantly different between the supplemented patients and placebo group. Conclusions: Overall, 5 mg/day folate supplementation for 12 weeks among patients with MetS had beneficial effects on CIMT and the metabolic status. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A80 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
Downregulation of LINC00115 inhibits the proliferation and invasion of lung cancer cells in vitro and in vitro
Authors: Qiongzhu Yu
Zhixiang Zhuang
Xiaomin Lu
Lili Shao
Xiaodong Zhang
Journal: Annals of Translational Medicine (2021)
Discipline: CLINICAL MEDICINE
Keywords: LINC00115; invasion; lung cancer cells; proliferation.
Affiliations: Department of Medical Oncology, Tumor Hospital Affiliated to Nantong University, Nantong, China., Department of Pathology, The Affiliated Changshu Hospital of Xuzhou Medical University, Suzhou, China., Department of Medical Oncology, The Affiliated Haian Hospital of Nantong University, Nantong, China., Department of Medical Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Abstract:  Background: Lung cancer is a common malignant tumor in clinical practice. Its morbidity and mortality rank first among malignant tumors. However, the pathogenesis of lung cancer has not been fully clarified. This study found that LINC00115 is highly expressed in lung cancer tissues, but the role and molecular mechanisms of LINC00115 in the occurrence and progression of lung cancer are still unclear. Methods: Fluorescence quantitative PCR was used to detect the expression of LINC00115 in lung cancer tissues and para-carcinoma tissues. Cell counting kit-8 (CCK-8), clone formation, and Transwell assays were used to detect the effects of LINC00115 knockdown on the proliferation, clone formation, invasion, and migration of lung cancer cells. Western blot was used to detect the effects of LINC00115 knockdown on the expression of epithelial-mesenchymal transition (EMT)-related molecules. Finally, a xenograft model in nude mice was used to detect the effect of LINC00115 knockdown on the proliferation of lung cancer cells in vivo. Results: Compared with para-carcinoma tissue, LINC00115 was highly expressed in lung cancer tissue. Cell function experiments showed that knockdown of LINC00115 could significantly inhibit the proliferation, invasion, and migration of lung cancer cells. Western blot results showed that knockdown of LINC00115 could significantly inhibit the expression of the EMT-related proteins N-cadherin, vimentin, and fibronectin, and promoted the expression of E-cadherin. In vivo experiments in nude mice showed that knockdown of LINC00115 could significantly inhibit the proliferation of lung cancer tissues in vivo. Conclusions: LINC00115 is highly expressed in lung cancer tissues, and knockdown of LINC00115 can significantly inhibit the proliferation and invasion of lung cancer, which provides a theoretical basis for the design of targeted molecules for the subsequent treatment of lung cancer. 

Retracted: No

PubPeer comments:
 Two sets of images in Figure 4B appear to overlap. The intensity and aspect ratios seem different in the regions marked in red. This issue is sometimes seen in papers that have been outsourced. *** ![file] ,
Retracted: Intestinal fatty acid‐binding protein mediates atherosclerotic progress through increasing intestinal inflammation and permeability
Authors: Fan Wang
Jiajun Wang
Yan Fang
Yongshun Wang
Lulu Zhang
Journal: Journal of Cellular and Molecular Medicine (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: atherosclerosis; inflammation; intestinal fatty acid-binding protein; intestinal permeability.
Affiliations: Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China., The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, China.

Abstract:  Atherosclerosis is one of leading phenotypes of cardiovascular diseases, featured with increased vascular intima-media thickness (IMT) and unstable plaques. The interaction between gastrointestinal system and cardiovascular homeostasis is emerging as a hot topic. Therefore, the present study aimed to explore the role of an intestinal protein, intestinal fatty acid-binding protein (I-FABP/FABP2) in the atherosclerotic progress. In western diet-fed ApoE-/- mice, FABP2 was highly expressed in intestine. Silence of intestinal Fabp2 attenuated western diet-induced atherosclerotic phenotypes, including decreasing toxic lipid accumulation, vascular fibrosis and inflammatory response. Mechanistically, intestinal Fabp2 knockdown improved intestinal permeability through increasing the expression of tight junction proteins. Meanwhile, intestinal Fabp2 knockdown mice exhibited down-regulation of intestinal inflammation in western diet-fed ApoE-/- mice. In clinical patients, the circulating level of FABP2 was obviously increased in patients with cardiovascular disease and positively correlated with the value of carotid intima-media thickness, total cholesterol and triglyceride. In conclusion, FABP2-induced intestinal permeability could address a potential role of gastrointestinal system in the development of atherosclerosis, and targeting on intestinal FABP2 might provide a therapeutic approach to protect against atherosclerosis. 

Retracted: Yes

PubPeer comments:
 Retracted [10 January 2022] . ------------------------- The above article, published online on 27 March 2020 on Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement among the journal s Editor-in-Chief, Stefan N. Constantinescu, the authors, the Foundation for Cellular and Molecular Medicine, and John Wiley Sons Ltd. The retraction has been agreed following concerns raised about similarities between Figure 2E in the above article and Figure 2Cu2013E in another published article.1 Upon further analysis of the images, it was determined that the images in Figure 2E in the above article had been taken without attribution from Figure 2Cu2013E1 and manipulated (resized, cropped and inverted). As a result, the journal has concerns about the results and conclusions drawn and will retract the article. - [1] Kwok KHM, Cheng KKY, Hoo RLC, Ye D, Aimin XU, Lam KSL. Adipose-specific inactivation of JNK alleviates atherosclerosis in apoE-deficient mice. Clin Sci (Lond). 2016; 130(22): 2087- 2100. 10.1042 CS20160465 ,
EHD4 and CDH23 are interacting partners in cochlear hair cells
Authors: Jing Zheng
Mayumi Naramura
Mary Ann Cheatham
Peter Dallos
Hamid Band
Khurram Naik
Soma Sengupta
Manju George
Jonathan Chou
Katharine K Miller
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cadherin 23; CDH23; EHD4; hair cells; inner ear
Affiliations: Department of Communication Sciences and Disorders, Hugh Knowles Center, Northwestern University, Evanston, Illinois 60208, USA.

Abstract:  Cadherin 23 (CDH23), a transmembrane protein localized near the tips of hair cell stereocilia in the mammalian inner ear, is important for delivering mechanical signals to the mechano-electric transducer channels. To identify CDH23-interacting proteins, a membrane-based yeast two-hybrid screen of an outer hair cell (OHC) cDNA library was performed. EHD4, a member of the C-terminal EH domain containing a protein family involved in endocytic recycling, was identified as a potential interactor. To confirm the interaction, we first demonstrated the EHD4 mRNA expression in hair cells using in situ hybridization. Next, we showed that EHD4 co-localizes and co-immunoprecipitates with CDH23 in mammalian cells. Interestingly, the co-immunoprecipitation was found to be calcium-sensitive. To investigate the role of EHD4 in hearing, compound action potentials were measured in EHD4 knock-out (KO) mice. Although EHD4 KO mice have normal hearing sensitivity, analysis of mouse cochlear lysates revealed a 2-fold increase in EHD1, but no increase in EHD2 or EHD3, in EHD4 KO cochleae compared with wild type, suggesting that a compensatory increase in EHD1 levels may account for the absence of a hearing defect in EHD4 KO mice. Taken together, these data indicate that EHD4 is a novel CDH23-interacting protein that could regulate CDH23 trafficking/localization in a calcium-sensitive manner. 

Retracted: No

PubPeer comments:
 ![file] ,
JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy
Authors: Sophie Pattingre
Sangita Sinha
Yongjie Wei
Michael Bassik
Beth Levine
Journal: Molecular Cell (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Starvation; autophagy; Bcl-2; Beclin 1; phosphorylation
Affiliations: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract:  Starvation induces autophagy to preserve cellular homeostasis in virtually all eukaryotic organisms. However, the mechanisms by which starvation induces autophagy are not completely understood. In mammalian cells, the antiapoptotic protein, Bcl-2, binds to Beclin 1 during nonstarvation conditions and inhibits its autophagy function. Here we show that starvation induces phosphorylation of cellular Bcl-2 at residues T69, S70, and S87 of the nonstructured loop; Bcl-2 dissociation from Beclin 1; and autophagy activation. In contrast, viral Bcl-2, which lacks the phosphorylation site-containing nonstructured loop, fails to dissociate from Beclin 1 during starvation. Furthermore, the stress-activated signaling molecule, c-Jun N-terminal protein kinase 1 (JNK1), but not JNK2, mediates starvation-induced Bcl-2 phosphorylation, Bcl-2 dissociation from Beclin 1, and autophagy activation. Together, our findings demonstrate that JNK1-mediated multisite phosphorylation of Bcl-2 stimulates starvation-induced autophagy by disrupting the Bcl-2/Beclin 1 complex. These findings define a mechanism that cells use to regulate autophagic activity in response to nutrient status. 

Retracted: No

PubPeer comments:
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 Some + or - starvation lanes have been swapped, and many lanes no longer line up with the corresponding loading control ![image] ,