PReD-Bench/PRed-Bench huggingface dataset:
KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway
Authors: A Duensing
G D Demetri
J A Fletcher
S Bauer
Journal: Oncogene (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Gastrointestinal stromal tumor (GIST); KIT inhibition; Imatinib resistance; KIT functional roles; PI3-K
Affiliations: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02155, USA. 

Abstract:  Most gastrointestinal stromal tumor (GIST) patients respond to KIT inhibition with imatinib, yet will eventually exhibit resistance. Imatinib-resistance mechanisms are heterogeneous, and little is known about KIT functional roles in imatinib-resistant GIST. Biological consequences of biochemical inhibition of KIT, phosphatidyl-inositol-3-kinase (PI3-K), PLCgamma, MAPK/ERK kinase/mitogen-activated protein kinase (MEK/MAPK), mammalian target of rapamycin (mTOR) and JAK were determined by immunoblotting for protein activation, and by cell proliferation and apoptosis assays in GIST cell lines from imatinib-sensitive GIST (GIST882), imatinib-resistant GISTs (GIST430 and GIST48) and KIT-negative GIST (GIST62). KIT activation was 3- to 6-fold higher in GIST430 and GIST48 than in GIST882, whereas total KIT expression was comparable in these three GIST lines. In addition to the higher set point for KIT activation, GIST430 and GIST48 had intrinsic imatinib resistance. After treatment with 1 muM imatinib, residual KIT activation was 6- and 2.8-fold higher in GIST430 and GIST48, respectively, compared to GIST882. In all GIST lines, cell growth arrest resulted from PI3-K inhibition, and - to a lesser extent - from MEK/MAPK and mTOR inhibition. Inhibition of JAK/STAT or PLCgamma did not affect cell proliferation. Similarly, only PI3-K inhibition resulted in substantial apoptosis in the imatinib-resistant GISTs. We conclude that GIST secondary KIT mutations can be associated with KIT hyperactivation and imatinib resistance. Targeting critical downstream signaling proteins, such as PI3-K, is a promising therapeutic strategy in imatinib-resistant GISTs. 

Retracted: No

PubPeer comments:
 Stat1 and Stat3 bands are (GIST 62) same in this blot in Figure 4. Stat1 bands are exposed slightly less than Stat3 , 
 #1 Figure 4. Much more similar than expected. ![file] ,
Encephalomyocarditis Virus 3C Protease Relieves TRAF Family Member-associated NF-κB Activator (TANK) Inhibitory Effect on TRAF6-mediated NF-κB Signaling through Cleavage of TANK
Authors: Li Yu
Huibin Yu
Yan Wang
Tao Xiong
Jiangnan Li
Guohua Deng
Li Huang
Changyao Li
Xiaojun Wang
Liang Hu
Yuanfeng Zhang
Quan Zhang
Changjiang Weng
Zhaohua Zhong
Shengnan Wang
Lijie Zhang
Xuehui Cai
Shangjin Cui
Qinfang Liu
Xueshan Xia
Journal: Journal of Biological Chemistry (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NF-kappa B (NF-KB); cell signaling; immunology; viral protease; virus.
Affiliations: From the State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001., From the State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, the College of Life Sciences, Yangtze University, Jingzhou 434100., From the State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, the Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650093, and., the Department of Microbiology, Harbin Medical University, Harbin 150081, China., the College of Life Sciences, Yangtze University, Jingzhou 434100., the Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650093, and., From the State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, .

Abstract:  TRAF family member-associated NF-κB activator (TANK) is a negative regulator of canonical NF-κB signaling in the Toll-like receptor- and B-cell receptor-mediated signaling pathways. However, functions of TANK in viral infection-mediated NF-κB activation remain unclear. Here, we reported that TANK was cleaved by encephalomyocarditis virus 3C at the 197 and 291 glutamine residues, which depends on its cysteine protease activity. In addition, encephalomyocarditis virus 3C impaired the ability of TANK to inhibit TRAF6-mediated NF-κB signaling. Interestingly, we found that several viral proteases encoded by the foot and mouth disease virus, porcine reproductive and respiratory syndrome virus, and equine arteritis virus also cleaved TANK. Our results suggest that TANK is a novel target of some viral proteases, indicating that some positive RNA viruses have evolved to utilize their major proteases to regulate NF-κB activation. 

Retracted: No

PubPeer comments:
 ![file] ,
Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines
Authors: John Crown
Martin Clynes
Alex J Eustace
Norma O&#x27;Donovan
Journal: Journal of Translational Medicine (2008)
Discipline: CLINICAL MEDICINE
Keywords: Metastatic melanoma; chemotherapy resistant; targeted therapies; dasatinib; kinase inhibitor
Affiliations: National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland. 

Abstract:  Background: Metastatic melanoma is a highly chemotherapy resistant tumour. The use of newer targeted therapies alone and in combination with chemotherapy may offer new hope of improving response to treatment. Dasatinib, a multi-target kinase inhibitor, is currently approved for the treatment of chronic myeloid leukaemia and has shown promising results in preclinical studies in a number of solid tumours. Methods: We examined the effects of dasatinib on proliferation, chemo-sensitivity, cell cycle arrest, apoptosis, migration and invasion in human melanoma cell lines. Expression and activation of Src kinase, FAK and EphA2 were also examined in the melanoma cells. Results: Dasatinib inhibited growth of three of the five melanoma cell lines. Comparison with sorafenib showed that in these three cell lines dasatinib inhibited growth at lower concentrations than sorafenib. Dasatinib in combination with the chemotherapy drug temozolomide showed greater efficacy than either drug alone. Dasatinib induced cell cycle arrest and apoptosis and significantly inhibited cell migration and invasion of melanoma cells. Dasatinib inhibition of proliferation was associated with reduced phosphorylation of Src kinase, while decreased phosphorylation of FAK was implicated in dasatinib-mediated inhibition of migration and invasion in melanoma cells. Conclusion: Dasatinib has both anti-proliferative and anti-invasive effects in melanoma cells and combined with chemotherapy may have clinical benefit in the treatment of malignant melanoma. 

Retracted: No

PubPeer comments:
 Undisclosed splicing in Fig.5A ![file] , 
 Plenty of undisclosed splicing in Fig.5B; lower panel is contrast enhanced. ![file] ,
Canine parvovirus induces G1/S cell cycle arrest that involves EGFR Tyr1086 phosphorylation
Authors: Xiaofeng Dai
Xuanhao Zhang
Yujie Miao
Peiyu Han
Jianying Zhang
Journal: Virulence (2020)
Discipline: IMMUNOLOGY
Keywords: Canine parvovirus; EGFR; cell cycle arrest; virotherapy.
Affiliations: Wuxi School of Medicine, Jiangnan University, Wuxi, China, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, School of Biotechnology, Jiangnan University, Wuxi, China, Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China, Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA

Abstract:  Canine parvovirus (CPV) has been used in cancer control as a drug delivery vehicle or anti-tumor reagent due to its multiple natural advantages. However, potential host cell cycle arrest induced by virus infection may impose a big challenge to CPV associated cancer control as it could prevent host cancer cells from undergoing cell lysis and foster them regain viability once the virotherapy was ceased. To explore CPV-induced cell cycle arrest and the underlying mechanism toward improved virotherapeutic design, we focus on epidermal growth factor receptor (EGFR), a cellular receptor interacting with TfR that mediates CPV-host interactions, and alterations on its tyrosine phosphorylation sites in response to CPV infection. We found that CPV could trigger host G1/S cell cycle arrest via the EGFR (Y1086)/p27 and EGFR (Y1068)/STAT3/cyclin D1 axes, and EGFR inhibitor could not reverse this process. Our results contribute to our understandings on the mechanism of CPV-induced host cellular response and can be used in the onco-therapeutic design utilizing CPV by preventing host cancer cells from entering cell cycle arrest. 

Retracted: No

PubPeer comments:
 Figure 1D CRFK column. The 12h and 24h images share more than 50% of them ![file] , 
 Thank you for pointing out this similarity in Figure 1D. These should be observations under microscope after CRFK cells were infected with CDV for 12 h and 24 h. First, I am sincerely sorry for having not identified this similarity during the draft preparation and revision stages, and even not being aware of this problem until I saw this u2018problematic paperu2019 notification just now. I apologize in the name of all authors for this accidental mistake. I immediately contacted the student who conducted the experiments and graduated from our lab last year. He realized that he had mistakenly put a wrong image in this figure. We will go to the raw data materials to find the original results and make this correction to the journal as early as possible. Luckily, the mistake occurs for images taken at 12 and 24 h, and cell morphology at 48 h showed significant changes as compared with images taken at the initial time points, which does not affect our conclusion that cell shape changes from spheric to spindle-like after being infected by CPV. Thanks again for helping us identifying this problem, and we will be more prudent in the future to avoid any potential mistakes or errors during manuscript preparation, revision and proofreading. ,
MicroRNA-101 inhibits the proliferation and invasion of bladder cancer cells via targeting c-FOS
Authors: Xinyi Liu
Lei Chen
Xinhua Yang
Zhijun Han
Jinge Liu
Wenjin Liu
Zhiping Wu
Yulong Zhang
Yongqi Long
Journal: Molecular Medicine Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miR-101; bladder cancer; proliferation; invasion
Affiliations: Department of Urinary Surgery, Central Hospital of Zhuzhou, Zhuzhou, Hunan 412000, P.R. China., Department of Urinary Surgery, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.

Abstract:  MicroRNAs (miRs) have important roles in the parthenogenesis of malignancies. While it has been suggested that deregulation of miR‑101 is involved in bladder cancer, the underlying mechanisms have remained largely elusive. The present study aimed to investigate the roles of miR‑101 in the regulation of bladder cancer cell proliferation and invasion. Reverse‑transcription quantitative polymerase chain reaction analysis revealed that the expression of miR‑101 was significantly reduced in the HT‑1376, BIU87, T24 and 5637 several human bladder cancer cell lines compared to that in the SV‑HUC‑1 normal bladder epithelial cell line. Furthermore, a Targetscan search and a luciferase assay were used to identify c‑FOS as a novel target of miR‑101, and western blot analysis indicated that the protein expression of c‑FOS was shown to be negatively regulated by miR‑101 in bladder cancer T24 cells; however, c‑FOS mRNA expression was not affected. In addition, plasmid‑mediated overexpression of miR‑101 and small hairpin RNA‑mediated inhibition of c‑FOS significantly inhibited the proliferation and invasive capacity of T24 cells, as indicated by an MTT and a Transwell assay, respectively. However, plasmid‑mediated overexpression of c‑FOS reversed the inhibitory effects of miR‑101 overexpression on T24‑cell proliferation and invasion. In conclusion, the present study demonstrated that miR‑101 inhibits the proliferation and invasion of bladder cancer cells, at least partly via targeting c‑FOS, suggesting that miR-101/c‑FOS signaling may represent a potential therapeutic target for bladder cancer. 

Retracted: Yes

PubPeer comments:
 This article has a 2006 Erratum about the legend of Table 4, found here: https: breast-cancer-research.biomedcentral.com articles 10.1186 bcr1409 Could the authors please also check the Pat 9 row in Figure 2? Red boxes highlight two panels that looked more similar than expected. Reported to the journal in July 2015, with several reminders. ![file] ,
ABC50 promotes translation initiation in mammalian cells
Authors: Luis Izquierdo
Eric Jan
Xuemin Wang
Mairi J Hunter
Christopher G Proud
Yun W Lam
Sonia Paytubi
Harinder S Hundal
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ABC50; ATP-binding cassette protein; eIF2; translation initiation; ribosomes

Abstract:  ABC50 is an ATP-binding cassette (ABC) protein, which, unlike most ABC proteins, does not possess membrane-spanning domains. ABC50 interacts with eukaryotic initiation factor 2 (eIF2), which plays a key role in translation initiation and its control. ABC50 binds to ribosomes, and this interaction requires both the N-terminal domain and at least one ABC domain. Knockdown of ABC50 by RNA interference impaired translation of both cap-dependent and -independent reporters, consistent with a positive role for ABC50 in the function of eIF2, which is required for both types of translation initiation. Mutation of the Walker box A or B motifs in both ABC regions of ABC50 yielded a mutant protein that exerted a dominant-interfering phenotype with respect to protein synthesis and translation initiation. Importantly, although dominant-interfering mutants of ABC50 impaired cap-dependent translation, translation driven by certain internal ribosome entry segments was not inhibited. ABC50 is located in the cytoplasm and nucleoplasm but not in the nucleolus. Thus, ABC50 is not likely to be directly involved in early ribosomal biogenesis, unlike some other ABC proteins. Taken together, the present data show that ABC50 plays a key role in translation initiation and has functions that are distinct from those of other non-membrane ABC proteins. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar and different than expected. ![file] ,
Polyunsaturated Fatty Acid Diet and Upregulation of Lipoxin A4 Reduce the Inflammatory Response of Preeclampsia
Authors: Qian Zhang
Chang Shu
Huidong Zhao
Minghui Ou
Journal: Journal of Proteome Research (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: inflammation; lipoxin A4; polyunsaturated fatty acid; preeclampsia.
Affiliations: Department of Vascular Surgery, Qingdao Municipal Hospital, Qingdao 266000, China, Department of Obstetrics, Qingdao Municipal Hospital, Qingdao 266000, China, Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Jilin University, No.71 Xinmin Street, Changchun, Jilin Province 130021, China

Abstract:  The aim of this study was to investigate the effects and mechanisms of polyunsaturated fatty acids (PUFAs) and lipoxin A4 (LXA4) on preeclampsia (PE). The LXA4 level was significantly reduced in PE rats. The PUFA diet upregulated the expressions of lipoxygenase 12 (LOX12) and lipoxygenase 15 (LOX15) and downregulated those of cyclooxygenase-2, tumor necrosis factor-α (TNF-α), and endoglin. Lipopolysaccharides could inhibit cell growth and cause inflammatory response, while the presence of PUFAs inhibited the inflammatory response and promoted the expressions of LOX12, LOX15, and LXA4. Nordihydroguaiaretic acid (NDGA) regulated LXA4 expression and inflammation levels by affecting LOX. Inhibition of lipoxygenase 5 activity by NDGA upregulated the expressions of LOX12 and LOX15, while LXA4 reversed LXA4, nitric oxide downregulation, and TNF-α upregulation by NDGA. A decrease in LXA4 levels played an important role in the development and progression of PE. 

Retracted: No

PubPeer comments:
 Concern about Figure 3. Boxes of the same color show areas that are similar, as found by ImageTwin. ![file] , 
 The Western blots all show a uniform and blank background, and bear resemblance to those found in paper mill article sets. In addition, the left and bottom ends of the panels appear to show remnants of other labels. Could the authors show the full uncropped films or blot scans please? ![file] ,
Nimodipine attenuates the parkinsonian neurotoxin, MPTP-induced changes in the calcium binding proteins, calpain and calbindin
Authors: Kochupurackal P Mohanakumar
Poonam Verma
Anu Raju
Alpana Singh
Journal: Journal of Chemical Neuroanatomy (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Apoptosis; Calcium regulatory proteins; Caspase 3 activity; Dopaminergic neuroprotection.

Abstract:  We have recently demonstrated neuroprotective abilities of nimodipine, an L-type voltage dependent calcium channel (VDCC) blocker in cellular and animal models of Parkinson's disease (PD). To understand the calcium regulatory mechanisms in the disease pathogenesis, the present study examined calcium regulatory proteins calbindin and calpain mRNA and protein levels employing quantitative PCR and western blot in 1-methyl-4-phenyl pyridinium ion (MPP+)-treated SH-SY5Y cell lines and in the striatum of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). mRNA and protein levels of calbindin were lower, while that of calpain were higher in MPP+-treated SH-SY5Y cells and MPTP-treated mouse striatum as compared to their respective controls. Nimodipine pretreatment significantly attenuated these effects in the parkinsonian neurotoxin-treated SH-SY5Y cell line and in the mouse striatum. The activities of the apoptotic mediator, caspase-3 and calpain were increased in the neurotoxin-treated groups as compared to their respective controls, which was ameliorated by nimodipine pretreatment. These results suggest that parkinsonian neurotoxin-mediated dopaminergic neuronal death might involve defects in calcium regulatory proteins that control intracellular calcium homeostasis, and these could be corrected by inhibiting L-type VDCC activity. These findings support the notion that hypertensive patients who are on long-term intake of dihydropyridine have reduced risk for PD. 

Retracted: No

PubPeer comments:
 Both panels in Fig.1F were assembled with different WB images. ![file] ,
Infection with Leishmania amazonensis upregulates purinergic receptor expression and induces host-cell susceptibility to UTP-mediated apoptosis
Authors: Bartira Rossi-Bergmann
Robson Coutinho-Silva
Suzana Passos Chaves
Mariana M Chaves
Claudiana Lameu
David M Ojcius
Suzana Corte-Real
Henning Ulrich
Vanessa Ribeiro Figliuolo
Camila Marques-da-Silva
José Roberto Meyer-Fernandes
Journal: Cellular Microbiology (2011)
Discipline: MICROBIOLOGY
Keywords: Nucleotides; purinergic receptors; leishmanial infection; macrophages; UTP
Affiliations: Laboratory of Immunophysiology, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro RJ, 21941-902, Brazil.

Abstract:  Nucleotides are released into the extracellular milieu from infected cells and cells at inflammatory sites. The extracellular nucleotides bind to specific purinergic (P2) receptors and thereby induce a variety of cellular responses including anti-parasitic effects. Here we investigated whether extracellular nucleotides affect leishmanial infection in macrophages, and found that UTP reduces strongly the parasite load in peritoneal macrophages. Ultrastructural analysis of infected cells revealed that UTP induced morphological damage in the intracellular parasites. Uridine nucleotides also induced dose-dependent apoptosis of macrophages and production of ROI and RNI only in infected macrophages. The intracellular calcium measurements of infected cells showed that the response to UTP, but not UDP, increased the sensitivity and amplitude of cytosolic Ca(2+) changes. Infection of macrophages with Leishmania upregulated the expression of P2Y(2) and P2Y(4) receptor mRNA. The data suggest indirectly that Leishmania amazonensis infection induces modulation and heteromerization of P2Y receptors on macrophages. Thus UTP modulates the host response against L. amazonensis infection. UTP and UTP homologues should therefore be considered as novel components of therapeutic strategies against cutaneous leishmaniasis. 

Retracted: No

PubPeer comments:
 Authors claim to have grown u03b3-Glycine-NLO active single crystals with the assistance of Lithium iodide and L-Proline. In the experimental it is not clear which form of glycine alpha or beta was used. Authors have taken1M of glycine and 1M of L-proline and evaporated the solution to get u03b1-form of glycine which on reaction with LiI is supposed to have given the gamma modification. The role of L-proline (which is very costly) is not clear. Authors report single crystal data in Table 1 but this is incomplete. The CCDC nos. of the CIF files of the structure determination are not given. There is mention of Supplementary material but however there is no Supplement associated with the paper. Authors are requested to clarify the above especially the single crystal structure data. ,
The tor pathway regulates gene expression by linking nutrient sensing to histone acetylation
Authors: Maria E Cardenas
John R Rohde
Journal: Molecular and cellular biology (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Tor pathway; cell growth; nutrient availability; ribosomal protein gene expression; Esa1 histone acetylase
Affiliations: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract:  The Tor pathway mediates cell growth in response to nutrient availability, in part by inducing ribosomal protein (RP) gene expression via an unknown mechanism. Expression of RP genes coincides with recruitment of the Esa1 histone acetylase to RP gene promoters. We show that inhibition of Tor with rapamycin releases Esa1 from RP gene promoters and leads to histone H4 deacetylation without affecting promoter occupancy by Rap1 and Abf1. Genetic and biochemical evidence identifies Rpd3 as the major histone deacetylase responsible for reversing histone H4 acetylation at RP gene promoters in response to Tor inhibition by rapamycin or nutrient limitation. Our results illustrate that the Tor pathway links nutrient sensing with histone acetylation to control RP gene expression and cell growth. 

Retracted: No

PubPeer comments:
 Figure 1B: Actin has 5 bands while RPL9A and RPS11B presents only 4 bands ![file] , 
 Good counting! Yes, that is the point of the figure. JRR , 
 Thanks for your response, but I think that the author didn t understand Bensingtonia Bomiensis commentary. Authors used 5 bands of actin to represent 4 time points (i.e. 0, 15, 30, 60 minutes). ,
microRNA-192-5p is involved in nerve repair in rats with peripheral nerve injury by regulating XIAP
Authors: Ying Dong
Xintao Cui
Guangwei Guan
Xing Liu
Zhenyu Zhang
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Microrna-192-5p; nerve repair; peripheral nerve injury.
Affiliations: Department of orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Abstract:  Objective: MicroRNAs (miRNAs) have been demonstrated to engage in the nerve injury, while the effect of microRNA-192-5p (miR-192-5p) on the nerve repair has not yet been well understood. This study is performed to investigate how miR-192-5p affects nerve repair in rats with peripheral nerve injury by regulating X-linked inhibitor of apoptosis protein (XIAP).Methods: The rat model of left sciatic nerve injury was established, and the expression of miR-192-5p was then detected. A series of experiments were conducted to investigate the role of miR-192-5p on nerve repair in rats with peripheral nerve injury. The expression of apoptosis-related proteins (Caspase-3, Bax and Bcl-2) and nerve repair factors (NGF, BDNF, and GAP-43) was measured. Bioinformatics analysis and dual-luciferase reporter gene assay confirmed the targeting relationship between miR-192-5p and XIAP.Results: MiR-192-5p inhibition promoted the recovery of sensory function and the recovery and regeneration in rats with sciatic nerve injury. MiR-192-5p inhibition promoted the recovery of muscle atrophy caused by nerve injury. MiR-192-5p inhibition inhibited neuronal apoptosis by affecting the expression of apoptosis-related proteins and promoted the recovery of nerve function by elevating the expression of nerve repair factors induced by peripheral nerve injury. Bioinformatics analysis and dual-luciferase reporter gene assay confirmed that XIAP was a target gene of miR-192-5p.Conclusion: This study demonstrates that miR-192-5p inhibition can up-regulate the expression of XIAP, decrease the apoptosis of nerve cells, and promote the repair and regeneration of peripheral nerve injury. 

Retracted: No

PubPeer comments:
 Fig 2a.  Detection of neuronal apoptosis by TUNEL staining in rats. ![file] Fig 3 is teeming with Bikbait and I hardly know where to start. Just a few duplications marked. ![] ![] ,
Antitumor effects of the silencing of programmed cell death ligand�1 in colorectal cancer via immunoregulation
Authors: Ying Huang
Yilin Chen
Xingrong Lu
Pan Chi
Gaoxiong Wang
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: PD-1; PD-L1; colorectal cancer; tumor microenvironment; immune suppression
Affiliations: Department of Colorectal Surgery, Fujian�Medical University Union Hospital, Fuzhou, Fujian�350001, P.R.�China, Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Fujian�Medical University, Quanzhou, Fujian�362000, P.R.�China

Abstract:  Activation of programmed cell death 1 (PD‑1)/PD‑ligand 1 (PD‑L1) can promote immune suppression of the tumor microenvironment. However, the effects and mechanisms of PD‑L1 silencing on colorectal cancer growth are largely unknown. In the present study, PD‑L1 expression was compared in colorectal cancer and paracancerous tissues by immunofluorescence. A stable colorectal carcinoma cell line encoding PD‑L1 short hairpin RNA (shRNA) was established. Thereafter, inoculated tumors were modeled in C57B/L6 mice. Experiments were divided into 3 groups: control group, vector group, and PD‑L1 silencing group (inoculated with the stable CT26 cell line encoding PD‑L1 shRNA). Following decapitation of the mice, tumors were weighed and apoptosis of tumor cells was detected. The number and viability of cluster of differentiation (CD)4+ and CD8+ T cells were analyzed by flow cytometry and a cell counting kit assay, respectively. Compared with paracancerous tissue, colorectal cancer tissue extensively expressed PD‑L1, RAC‑α serine/threonine‑protein kinase (AKT), and phosphatidylinositol 3‑kinase (PI3K). Lymphocyte‑activating gene 3 (LAG‑3) expression was observed at the edge of tumor tissue, but rarely observed in paracancerous tissue. A stable CT26 cell line encoding PD‑L1 shRNA was established, and lack of PD‑L1 expression was confirmed by reverse transcription‑polymerase chain reaction and western blotting. Compared with the control, the shPD‑L1 group demonstrated reduced tumor growth, a high level of apoptosis in tumor cells, a low level of PI3K and AKT expression, and an increased number of cells and greater activity of CD4+ T and CD8+ T cells. Taken together, PD‑L1 silencing promoted tumor cell apoptosis, at least in part, through the activation of CD4+ and CD8+ T cells. 

Retracted: No

PubPeer comments:
 I have never seen CT26 cells implanted in C57BL6 mice!! This is a basic immunology fact. Should I trust the more advanced immunology results described here?? ![file] , 
 There are more inconsistencies in this paper: Fig 4 A PD-L1 and LAG-3 stainings are not from the same tissue section (marked in yellow). ![file] CD-4 and CD-8 FACS analyses are strange (red circles). Gates are named different (M2 and M5) with different sizes. From my understanding they should be equal and cover a wider range. In methods CD-8 antibody is stated to be PE-conjugated, but APC staining is shown. X-axis has differnt and uncommon values. ![file] ,
GLP-1/glucagon receptor co-agonism for treatment of obesity
Authors: Sara J Brandt
Christoffer Clemmensen
Miguel A Sánchez-Garrido
Matthias H Tschöp
Timo D Müller
Richard D DiMarchi
Journal: Diabetologia (2017)
Discipline: CLINICAL MEDICINE
Keywords: Co-agonism; Dual agonism; GLP-1; Glucagon; Multi-agonist
Affiliations: Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Business Campus Garching, Parkring 13, 85748, Garching, Germany., German Center for Diabetes Research (DZD), Neuherberg, Germany., Department of Chemistry, Indiana University, 800 E Kirkwood Ave, Bloomington, IN, 47405, USA. ., Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Business Campus Garching, Parkring 13, 85748, Garching, Germany. ., German Center for Diabetes Research (DZD), Neuherberg, Germany. ., Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, Germany. .

Abstract:  Over a relatively short period, obesity and type 2 diabetes have come to represent a large medical and economic burden to global societies. The epidemic rise in the prevalence of obesity has metabolic consequences and is paralleled by an increased occurrence of other diseases, such as diabetes, cancer and cardiovascular complications. Together, obesity and type 2 diabetes constitute one of the more preventable causes of premature death and the identification of novel, safe and effective anti-obesity drugs is of utmost importance. Pharmacological attempts to treat obesity have had limited success, with notable adverse effects, rendering bariatric surgery as the only current therapy for substantially improving body weight. Novel unimolecular, multifunctional peptides have emerged as one of the most promising medicinal approaches to enhance metabolic efficacy and restore normal body weight. In this review, we will mainly focus on the discovery and translational relevance of dual agonists that pharmacologically function at the receptors for glucagon and glucagon-like peptide-1. Such peptides have advanced to clinical evaluation and inspired the pursuit of multiple related approaches to achieving polypharmacy within single molecules. 

Retracted: No

PubPeer comments:
 Fig 1 d + e numerous breaking lines (best viewed in original pdf at high res) ![file] Supp Fig 3 very similar cell arrangement in different wells ![file] ,
Hypoxia-induced energy stress regulates mRNA translation and cell growth
Authors: Timothy P Cash
Liping Liu
Craig B Thompson
Russell G Jones
Brian Keith
M Celeste Simon
Journal: Molecular Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hypoxia; HIF; mRNA translation; eIF2alpha; eEF2
Affiliations: Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.

Abstract:  Oxygen (O2) deprivation, or hypoxia, has profound effects on cell metabolism and growth. Cells can adapt to low O2 in part through activation of hypoxia-inducible factor (HIF). We report here that hypoxia inhibits mRNA translation by suppressing multiple key regulators, including eIF2alpha, eEF2, and the mammalian target of rapamycin (mTOR) effectors 4EBP1, p70S6K, and rpS6, independent of HIF. Hypoxia results in energy starvation and activation of the AMPK/TSC2/Rheb/mTOR pathway. Hypoxic AMP-activated protein kinase (AMPK) activation also leads to eEF2 inhibition. Moreover, hypoxic effects on cellular bioenergetics and mTOR inhibition increase over time. Mutation of the TSC2 tumor suppressor gene confers a growth advantage to cells by repressing hypoxic mTOR inhibition and hypoxia-induced G1 arrest. Together, eIF2alpha, eEF2, and mTOR inhibition represent important HIF-independent mechanisms of energy conservation that promote survival under low O2 conditions. 

Retracted: No

PubPeer comments:
 Figure 4B. Multiple splicings in pAKT. The total AKT: the two triplets show an unexpected similarity. But treatments are different. ![file] , 
 Figure 3B. Multiple splicing could be seen at image representing Pleckstrin phosphorylation. ![file] ,
Vitritis and Outer Retinal Abnormalities in a Patient with COVID-19
Authors: Luiz A Zago Filho
Luiz H Lima
Michel E Farah
Claudio Zett
Gustavo B Melo
Journal: Ocular Immunology and Inflammation (2020)
Discipline: CLINICAL MEDICINE
Keywords: COVID-19; Coronavirus; outer retina; vitritis.
Affiliations: Department of Ophthalmology and Otorhinolaryngology, Federal University of Paraná , Curitiba, Brazil., Retina Service, Oftalmolages Day Hospital , Lages, Brazil., Department of Ophthalmology, Federal University of São Paulo/Paulista School of Medicine , São Paulo, Brazil., Retina Service, Hospital de Olhos de Sergipe , Aracaju, Brazil., Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso , Valparaíso, Chile.

Abstract:  Purpose: To report a unique case of intraocular inflammation and outer retinal changes in a patient with coronavirus disease (COVID-19). Case report: A 57-year-old woman was seen 12 days after COVID-19 symptoms onset confirmed by positive IgM and IgG serological tests. No anterior chamber cells were seen. Color fundus photograph showed a yellowish lesion within the macular area, and fluorescein angiography revealed hyperfluorescence on the topography of the macular lesion in both eyes. Spectral-domain optical coherence tomography demonstrated hyperreflective pinpoints at the level of posterior vitreous hyaloid, corresponding to vitritis, hyperreflective lesions at the level of inner plexiform and ganglion cell layers, and disruption of the ellipsoid zone. Conclusion and importance: COVID-19 is known to affect the inner retinal layers. The current case not only supports but also adds a vitreal and an outer retinal layer involvement that might also be caused by this infectious disease. 

Retracted: Yes

PubPeer comments:
 **Retracted** on October 7, 2021: https: www.tandfonline.com doi full 10.1080 09273948.2021.1978772  *We, the Editors and Publisher of Ocular Immunology and Inflammation, have retracted the following article:* *Luiz A. Zago Filho, Luiz H. Lima, Gustavo B. Melo, Claudio Zett Michel E. Farah (2020) Vitritis and Outer Retinal Abnormalities in a Patient with COVID-19, Ocular Immunology and Inflammation, 28:8, 1298-1300, DOI: 10.1080 09273948.2020.1821898* *After publication of this case report, concerns were raised about figure 1g and 2 in the article. After investigating the issue and contacting the authors, it was determined that figures 1g and 2 show the same OCT of the patientu2019s right eye but are described in the report as two different images. In their response the authors also identified a further error in the article, that Figure 2 refers to a 2-month follow-up but this should have been stated as a 2-week follow-up in the article. Based on these findings, it was decided to retract this case report. The authors have been notified of this retraction ahead of its publication.* *We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.* *The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u2018Retractedu2019.* ,
a novel biomarker of cervical cancer development and progression
Authors: Yongqin Jia
Geli Liu
Haiyu Li
Fangzhou Song
Journal: OncoTargets and therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: bioinformatics; cell cycle; cervical cancer; small cell adhesion glycoprotein.
Affiliations: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China, ., Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China, ., Department of Infectious Disease, Chongqing Infectious Disease Medical Center, Chongqing 400030, China.

Abstract:  Introduction: Cervical cancer, one of the most common malignant gynecological tumors, is a significant burden on the health of females worldwide. The purpose of this study was to investigate genes associated with lymph node metastasis in cervical cancer. Methods: We report on the lymph node metastasis-associated gene, small cell adhesion glycoprotein (SMAGP), as a key regulator of cervical cancer development and progression. SMAGP expression levels were investigated in 70 cervical squamous cell carcinoma samples and 10 normal cervical squamous epithelium samples. Results: Immunohistochemistry analysis revealed that SMAGP protein levels were significantly elevated in cervical cancer tissue compared with normal cervical squamous epithelium. Silencing of SMAGP induced cell cycle arrest, inhibited the cell proliferation and colony formation ability of cervical cancer cells in vitro and suppressed their tumorigenic potential in nude mice. In addition, SMAGP knockdown reduced expression of epithelial mesenchymal transition-related proteins, including vimentin, β-cadherin, MMP2, and Twist. Conclusion: Together, our findings demonstrate that SMAGP plays a critical role in cell proliferation and tumorigenesis and could be a new therapeutic target in cervical cancer. 

Retracted: No

PubPeer comments:
 Duplication of microscopy data in Figure 4A,B. ![file] , 
 #1 Thank for your question, I have checked the all datas, and I found the figure 4B in paper is different with upload, I will contact with oncotargets and therapy to correct this mistake. Here are the pictures I uploaded and kept. This is upload figure: ![file] these are figures I kept and used in my dissertation : ![file] ![file] , 
 #1 there have the right figure 4B in my proof. Because the whole file is more than 2m, I converted the proof to image and send it to you. ![file] ,
Protective anti‐prion antibodies in human immunoglobulin repertoires
Authors: Simone Hornemann
Jingjing Guo
Geraldine Horny
Marc Emmenegger
Silvia Sorce
Stefan Ewert
Assunta Senatore
Thomas Pietzonka
Nathalie George
Marco Losa
Regina Reimann
Caihong Zhu
Sylvie Fels
Adriano Aguzzi
Karl Frontzek
Andra Chincisan
Journal: EMBO Molecular Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: anti-PrP antibodies; human immunological repertoires; next-generation sequencing; phage display; prion disease.
Affiliations: Institute of Neuropathology, University of Zurich, Zurich, Switzerland., Novartis Institutes for BioMedical Research, Basel, Switzerland.

Abstract:  Prion immunotherapy may hold great potential, but antibodies against certain PrP epitopes can be neurotoxic. Here, we identified &gt; 6,000 PrP-binding antibodies in a synthetic human Fab phage display library, 49 of which we characterized in detail. Antibodies directed against the flexible tail of PrP conferred neuroprotection against infectious prions. We then mined published repertoires of circulating B cells from healthy humans and found antibodies similar to the protective phage-derived antibodies. When expressed recombinantly, these antibodies exhibited anti-PrP reactivity. Furthermore, we surveyed 48,718 samples from 37,894 hospital patients for the presence of anti-PrP IgGs and found 21 high-titer individuals. The clinical files of these individuals did not reveal any enrichment of specific pathologies, suggesting that anti-PrP autoimmunity is innocuous. The existence of anti-prion antibodies in unbiased human immunological repertoires suggests that they might clear nascent prions early in life. Combined with the reported lack of such antibodies in carriers of disease-associated PRNP mutations, this suggests a link to the low incidence of spontaneous prion diseases in human populations. 

Retracted: No

PubPeer comments:
 Normally, immune responses against autologous proteins do not occur. If they do, they often trigger autoimmune disease. Here it is shown that such responses against the prion protein can occur, albeit rarely. A number of F(ab) fragments with high affinity were identified (Fig. 2) ![file] ,
Transferrin mediated solid lipid nanoparticles containing curcumin: enhanced in vitro anticancer activity by induction of apoptosis
Authors: Jukka Mönkkönen
Risto O Juvonen
Rohit S Mulik
Anant R Paradkar
Kakasaheb R Mahadik
Journal: International Journal of Pharmaceutics (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: curcumin; solid lipid nanoparticles; transferrin; photostability; anticancer activity
Affiliations: Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth University, Erandwane, Pune 411038, India.

Abstract:  Photodegradation and low bioavailability are major hurdles for the therapeutic use of curcumin. Aim of the present study was to formulate transferrin-mediated solid lipid nanoparticles (Tf-C-SLN) to increase photostability, and enhance its anticancer activity against MCF-7 breast cancer cells. Tf-C-SLN were prepared by homogenization method and characterized by size, zeta potential, entrapment efficiency and stability, transmission electron microscopy (TEM), X-ray diffraction (XRD) and in vitro release study. Microplate analysis and flow cytometry techniques were used for cytotoxicity and apoptosis study. The physical characterization showed the suitability of method of preparation. TEM and XRD study revealed the spherical nature and entrapment of curcumin in amorphous form, respectively. The cytotoxicity, ROS and cell uptake was found to be increased considerably with Tf-C-SLN compared to curcumin solubilized surfactant solution (CSSS) and curcumin-loaded SLN (C-SLN) suggesting the targeting effect. AnnexinV-FITC/PI double staining, DNA analysis and reduced mitochondrial potential confirmed the apoptosis. The flow cytometric studies revealed that the anticancer activity of curcumin is enhanced with Tf-C-SLN compared to CSSS and C-SLN, and apoptosis is the mechanism underlying the cytotoxicity. The present study indicated the potential of Tf-C-SLN in enhancing the anticancer effect of curcumin in breast cancer cells in vitro. 

Retracted: No

PubPeer comments:
 Figure 6 appears to have two sets of images which overlap, after images resized (aspect ratio adjusted). *** ![file] *** Showing example transformation ![file] ,
HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
Authors: Madeline M Keenen
David Brown
Harrison Khoo
Geeta J Narlikar
Christopher R Carlson
Stephan W Grill
Bo Huang
Sy Redding
Roman Renger
Lucy D Brennan
Journal: eLife (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: biochemistry; chemical biology; chromatin organization; heterochromatin; human
Affiliations: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States, Tetrad Graduate Program, University of California, San Francisco, San Francisco, United States, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, Department of Mechanical Engineering, Johns Hopkins University, Baltimore, United States, Department of Physiology, University of California, San Francisco, San Francisco, United States, Chan Zuckerberg Biohub, San Francisco, United States, Cluster of Excellence Physics of Life, Technische Universität Dresden, Dresden, Germany, Marine Biological Laboratory, Woods Hole, United States

Abstract:  In mammals, HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here, we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1β. Finally, we find that differences in each HP1 paralog's DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale. 

Retracted: No

PubPeer comments:
 A published paper (2018) has been cribbed partially from their other one (2016) and festooned with citations to the authors own work. **NO REFERENCE is given for the images (for the paper in 2016) shown below.** An example article is shown at the very end below for a better understanding. ![file] ,
Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
Authors: J O Thomas
T Kouzarides
J F Partridge
P Zegerman
A J Bannister
E A Miska
R C Allshire
Journal: Nature (2001)
Discipline: Multidisciplinary
Keywords: Heterochromatin protein 1; HP1; gene silencing; chromo domain; Swi6
Affiliations: Wellcome/CRC Institute and Department of Pathology, University of Cambridge, UK.

Abstract:  Heterochromatin protein 1 (HP1) is localized at heterochromatin sites where it mediates gene silencing. The chromo domain of HP1 is necessary for both targeting and transcriptional repression. In the fission yeast Schizosaccharomyces pombe, the correct localization of Swi6 (the HP1 equivalent) depends on Clr4, a homologue of the mammalian SUV39H1 histone methylase. Both Clr4 and SUV39H1 methylate specifically lysine 9 of histone H3 (ref. 6). Here we show that HP1 can bind with high affinity to histone H3 methylated at lysine 9 but not at lysine 4. The chromo domain of HP1 is identified as its methyl-lysine-binding domain. A point mutation in the chromo domain, which destroys the gene silencing activity of HP1 in Drosophila, abolishes methyl-lysine-binding activity. Genetic and biochemical analysis in S. pombe shows that the methylase activity of Clr4 is necessary for the correct localization of Swi6 at centromeric heterochromatin and for gene silencing. These results provide a stepwise model for the formation of a transcriptionally silent heterochromatin: SUV39H1 places a 'methyl marker' on histone H3, which is then recognized by HP1 through its chromo domain. This model may also explain the stable inheritance of the heterochromatic state. 

Retracted: No

PubPeer comments:
 Fig. 2A: Seems to be more similar than expected (in red). ![file] Contrast enhanced: ![file] ,