PReD-Bench/PRed-Bench huggingface dataset:
Preclinical Evaluation of Chimeric Antigen Receptor–Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer
Authors: Yong-Sheng Wang
Lin Jiang
Hong-Feng Gou
Yong Huang
You-Ling Gong
Wei Wang
Xiao Yang
Bing-Lan Zhang
Dan Li
Yu-Quan Wei
Di-Yuan Qin
Xiao Liang
Journal: Human Gene Therapy (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EpCAM; cancer immunotherapy; chimeric antigen receptor; colorectal cancer.
Affiliations: Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China, Department of Gastroenterology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China., Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China, Department of Medical Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China

Abstract:  Chimeric antigen receptor-modified T cells (CAR-T cells) have emerged as a promising cancer immunotherapy for solid tumors. Epithelial cell adhesion molecule (EpCAM) is overexpressed in a variety of tumors and is recognized as a biomarker for circulating tumor cells and cancer stem cells, representing an attractive target for adoptive T-cell immunotherapy. This study generated third-generation CAR-T cells with redirected specificity to EpCAM (EpCAM CAR-T) by lentiviral vector. The study demonstrated that EpCAM CAR-T cells can elicit lytic cytotoxicity to target cells in an EpCAM-dependent manner and secrete cytotoxic cytokines, including interferon gamma and tumor necrosis factor alpha. Furthermore, adoptive transfer of EpCAM CAR-T cells significantly delayed tumor growth and formation in xenograft models. In addition, the safety evaluation showed that CAR-T cells have no systemic toxicity in mice. The data confirmed the antitumor ability and safety of CAR-T cells targeting EpCAM and may provide a new target for CAR-T cell therapies in treating solid tumors. 

Retracted: No

PubPeer comments:
 Heart tissue image (Mock) in Figure 6 appears to be the same as heart image (CAR-T) in Figure 7, rotated 90u2070 CCW and cropped differently. *** ![file] , 
 Journal contacted me to indicate they are investigating. , 
 ![file] , 
 ![file] ,
Uvangoletin induces mitochondria-mediated apoptosis in HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances
Authors: Yiqun Zhang
Yalin Wang
Li Zhang
Zhenhua Qiao
Rong Gong
Bo Jiang
Chunxia Dong
Zhuanzhen Zheng
Yanping Ma
Guoxia Li
Wenliang Chen
Yujin Lu
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: uvangoletin; cytotoxic effect; HL-60 cells; apoptosis; anti-apoptotic proteins
Affiliations: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China., Shanxi Academy of Medical Sciences, Shanxi University Hospital, Taiyuan 030001, P.R. China., Department of Hematology, the Second People's Hospital of Shanxi Province, Taiyuan 030001, P.R. China.

Abstract:  This study investigated the cytotoxic effect of uvangoletin on HL-60 cells, and the effects of uvangoletin on myelosuppression, leucopenia, gastrointestinal tract disturbances and the possible cytotoxic mechanisms by using CCK-8, flow cytometry, western blot, xenograft, cyclophosphamide-induced leucopenia, copper sulfate-induced emesis and ethanol-induced gastric mucosal lesions assays. The results of CCK-8, flow cytometry and western blot assays indicated that uvangoletin showed the cytotoxic effect on HL-60 cells and induced the apoptosis of HL-60 cells by downregulating the expression levels of anti-apoptotic proteins (Survivin, Bcl-xl and Bcl-2), upregulating the expression levels of pro-apoptotic proteins (Smac, Bax, Bad, c-caspase-3 and c-caspase-9), and promoting the release of cytochrome c from mitochondria to cytoplasm. Further, the results of xenograft assay suggested that uvangoletin inhibited the HL-60-induced tumor growth without adverse effect on body weight of nude mice in vivo by regulating the expression levels of above apoptotic proteins. The results indicated that the reductions of WBCs count and thighbone marrow granulocytes percentage in cyclophosphamide-induced leucopenia assay, the incubation period and number of emesis in copper sulfate-induced emesis assay and the gastric mucosal lesions in ethanol-induced gastric mucosal lesions assay were not exacerbated or reversed by uvangoletin. In conclusion, the research preliminarily indicated that uvangoletin induced apoptosis of HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances, and the pro-apoptotic mechanisms may be related to mitochondria-mediated apoptotic pathway. 

Retracted: No

PubPeer comments:
 Figure 3. * Some groups of data points look more similar to each other than expected, accounting for mirroring or width compression. Shown with boxes of the same color - there might be more. ![file] ,
The ubiquitously expressed Csk adaptor protein Cbp is dispensable for embryogenesis and T-cell development and function
Authors: Alexander Tarakhovsky
Masato Okada
Marc-Werner Dobenecker
Christian Schmedt
Journal: Molecular and Cellular Biology (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Src family kinase; Csk; Csk-binding protein; PAG; membrane adaptor
Affiliations: Laboratory of Lymphocyte Signaling, The Rockefeller University, 1230 York Avenue, Box 301, New York, NY 10021, USA. 

Abstract:  Regulation of Src family kinase (SFK) activity is indispensable for a functional immune system and embryogenesis. The activity of SFKs is inhibited by the presence of the carboxy-terminal Src kinase (Csk) at the cell membrane. Thus, recruitment of cytosolic Csk to the membrane-associated SFKs is crucial for its regulatory function. Previous studies utilizing in vitro and transgenic models suggested that the Csk-binding protein (Cbp), also known as phosphoprotein associated with glycosphingolipid microdomains (PAG), is the membrane adaptor for Csk. However, loss-of-function genetic evidence to support this notion was lacking. Herein, we demonstrate that the targeted disruption of the cbp gene in mice has no effect on embryogenesis, thymic development, or T-cell functions in vivo. Moreover, recruitment of Csk to the specialized membrane compartment of "lipid rafts" is not impaired by Cbp deficiency. Our results indicate that Cbp is dispensable for the recruitment of Csk to the membrane and that another Csk adaptor, yet to be discovered, compensates for the loss of Cbp. 

Retracted: No

PubPeer comments:
 ![file] ![file] ,
Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways
Authors: Qin Wang
Zheng Bao
Huiyan Qiang
Shigang Yin
Alexander Teichmann
Jinyue Zhang
Heinrich Wieland
Lanyang Gao
Danli Zhu
Jing Jia
Journal: Frontiers in Oncology (2021)
Discipline: CLINICAL MEDICINE
Keywords: PI3K/Akt/FOXO pathways; USP7; deubiquitinating enzyme; melanoma; quantitative proteomics.
Affiliations: Sichuan Provincial Center for Gynaecology and Breast Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, China., Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China., Laboratory of Nervous System Disease and Brain Functions, The Affiliated Hospital of Southwest Medical University, Luzhou, China., Department of Outpatient, The Affiliated Hospital of Southwest Medical University, Luzhou, China., Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China., Laboratory of Anesthesiology, Southwest Medical University, Luzhou, China.

Abstract:  The ubiquitin-specific protease 7 (USP7), as a deubiquitinating enzyme, plays an important role in tumor progression by various mechanisms and serves as a potential therapeutic target. However, the functional role of USP7 in melanoma remains elusive. Here, we found that USP7 is overexpressed in human melanoma by tissue microarray. We performed TMT-based quantitative proteomic analysis to evaluate the A375 human melanoma cells treated with siRNA of USP7. Our data revealed specific proteins as well as multiple pathways and processes that are impacted by USP7. We found that the phosphatidylinositol-3-kinases/Akt (PI3K-Akt), forkhead box O (FOXO), and AMP-activated protein kinase (AMPK) signaling pathways may be closely related to USP7 expression in melanoma. Moreover, knockdown of USP7 in A375 cells, particularly USP7 knockout using CRISPR-Cas9, verified that USP7 regulates cell proliferation in vivo and in vitro. The results showed that inhibition of USP7 increases expression of the AMPK beta (PRKAB1), caspase 7(CASP7), and protein phosphatase 2 subunit B R3 isoform (PPP2R3A), while attenuating expression of C subunit of vacuolar ATPase (ATP6V0C), and peroxisomal biogenesis factor 11 beta (PEX11B). In summary, these findings reveal an important role of USP7 in regulating melanoma progression via PI3K/Akt/FOXO and AMPK signaling pathways and implicate USP7 as an attractive anticancer target for melanoma. 

Retracted: No

PubPeer comments:
 The microscopy data presented in Figure 1 show no proof of extracellular vesicles. Without markers for extracellular vesicles, the presented stuff can be anything. Furthermore, the Western immublot of CD63 show no smearing, which is usual for this protein, indicating that it is not CD63. ![file] ,
Atrasentan increased the expression of klotho by mediating miR-199b-5p and prevented renal tubular injury in diabetic nephropathy
Authors: Wen-Ling Kang
Gao-Si Xu
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Atrasentan; Diabetic nephropathy; miR-199b-5p; Klotho; Renal tubular injury
Affiliations: Medical Center of the Graduate School, Nanchang University, Nanchang 330000, China., Department of Nephrology, People's Hospital of Xinyu City, Xinyu 338000, China., Department of Nephrology, Second Affiliated Hospital, Nanchang University, Nanchang 330006 China.

Abstract:  Atrasentan is a promising therapy for treating diabetic nephropathy (DN). Here we evaluated whether atrasentan down-regulated the miR-199b-5p expression, thereby increasing klotho and preventing renal tubular injury in DN. One-hundred patients with type 2 diabetes mellitus (T2DM) and 40 healthy subjects were included. A DN mice model was established by an injection of streptozotocin (STZ). Human renal proximal tubular epithelial HK-2 cells were exposed to high glucose (20 mmol/L). Treated the mice and HK-2 cells with atrasentan, and we then investigated whether and how miR-199b-5p and Klotho were involved in preventing renal tubular injury in DN. In patients, the serum miR-199b-5p level increased and the klotho concentration decreased in accordance with elevated albuminuria. Atrasentan down-regulated miR-199b-5p and up-regulated klotho of the DN mice and HK-2 cells exposed to high glucose. High glucose promoted the binding of histone H3 to the miR-199b-5p promoter, and atrasentan canceled this effect. MiR-199b-5p targeted the 3' UTR of klotho. Overexpression of miR-199b-5p canceled the effects of atrasentan on klotho expression and apoptosis of renal tubular cells in both in vivo and in vitro. The increased serum klotho, mediated by miR-199b-5p, is a possible mechanism by which atrasentan prevents renal tubular injury in DN. 

Retracted: No

PubPeer comments:
 Figure 1J and Figure 7H appear to have an image which overlaps, although it appears that they are described differently. Note: I did not find a caption that included the description of 1J, but perhaps I missed that. *** ![file] ![file] *** ![file] ,
Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson&rsquo;s disease
Authors: Luisa Ugedo
Jose Luis Pedraz
Jose Angel Ruiz-Ortega
Jose Vicente Lafuente
Harkaitz Bengoetxea
Rosa Maria Hernández
Catalina Requejo
Manoli Igartua
Enara Herrán
Asier Aristieta
Journal: International Journal of Nanomedicine (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 6-OHDA; PLGA; nanoparticles; neuroregeneration; neurotrophic factors

Abstract:  Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease. 

Retracted: No

PubPeer comments:
 Figure 2A seems very similar to a figure used in a previous paper from the same group (http: doi.org 10.1016 j.jconrel.2013.04.028). Could the authors please check? ![file] ,
Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia
Authors: Chul Woo Yang
Ki-Hwan Han
Myung-Shik Lee
Sun Ah Nam
Hyang Kim
Sang Hee Park
Arum Choi
Yong Kyun Kim
Yu-Mi Kim
Jin Kim
Wan-Young Kim
Hong Lim Kim
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: hypokalemia; aquaporin 2; autophagy; Atg7; IMCD cells
Affiliations: Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea., Institute of Clinical Medicine Research of Bucheon St. Mary's Hospital, Bucheon, Korea., Integrative Research Support Center, College of Medicine, The Catholic University of Korea, Seoul, Korea., Division of Nephrology, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Korea., Department of Anatomy, Ewha Womans University School of Medicine, Seoul, Korea., Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea., Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul, Korea., Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea. ., Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. .

Abstract:  Prolonged hypokalemia induces a decrease of urinary concentrating ability via down-regulation of aquaporin 2 (AQP2); however, the precise mechanisms remain unknown. To investigate the role of autophagy in the degradation of AQP2, we generated the principal cell-specific Atg7 deletion (Atg7Δpc) mice. In hypokalemic Atg7-floxed (Atg7f/f) mice, huge irregular shaped LC3-positive autophagic vacuoles accumulated mainly in inner medullary collecting duct (IMCD) cells. Total- and pS261-AQP2 were redistributed from apical and subapical domains into these vacuoles, which were not co-localized with RAB9. However, in the IMCD cells of hypokalemic Atg7Δpc mice, these canonical autophagic vacuoles were markedly reduced, whereas numerous small regular shaped LC3-negative/RAB9-positive non-canonical autophagic vacuoles were observed along with diffusely distributed total- and pS261-AQP2 in the cytoplasm. The immunoreactivity of pS256-AQP2 in the apical membrane of IMCD cells was markedly decreased, and no redistribution was observed in both hypokalemic Atg7f/f and Atg7Δpc mice. These findings suggest that AQP2 down regulation in hypokalemia was induced by reduced phosphorylation of AQP2, resulting in a reduction of apical plasma labeling of pS256-AQP2 and degradation of total- and pS261-AQP2 via an LC3/ATG7-dependent canonical autophagy pathway. 

Retracted: No

PubPeer comments:
 Much more similar than expected ![file] ,
Novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing hydrazone fragment as potent and selective anticancer agents
Authors: Yuhao Li
Chenhao Xu
Pengfei Jia
Wen Zhao
Jiadi Peng
Hui Qiao
Guanjun Dong
Kai Sun
Wenjuan Zhou
Hongmin Liu
Journal: Bioorganic Chemistry (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Anti-prostatic; Apoptosis; EGFR; Hydrazone; ROS
Affiliations: State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University School of Pharmaceutical Sciences and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China., State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University School of Pharmaceutical Sciences and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China; Department of Pathology, Oslo University Hospital, Faculty of Medicine, University of Oslo, Oslo 0379, Norway., State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University School of Pharmaceutical Sciences and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China. Electronic address: .

Abstract:  In this paper, based on molecular hybridization, a series of [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing hydrazine was synthesized and their antiproliferative activities against 5 cancer cell lines (MGC-803, PC3, PC9, EC9706 and SMMC-7721) were evaluated. We found that most of them exhibited obvious growth inhibition effects on these tested cancer cells, especially compound 34 on PC3 cells (IC50 = 26.25 ± 0.28 nM). Meanwhile, compound 34 displayed best selectivity on PC3, compared with the other cancer cell lines, as well as excellent selectivity towards normal cell lines (Het-1A, L02 and GES-1). Further investigations demonstrated that 34 could significantly inhibit PC3 cells' colony formation, increase cellular ROS content, suppress EGFR expression and induce apoptosis. Our findings indicate that 34 may serve as a novel lead compound for the discovery of more triazolopyrimidine derivatives with improved anticancer potency and selectivity. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,
MicroRNA-187 exerts tumor-suppressing functions in osteosarcoma by targeting ZEB2
Authors: Dongxu Zhao
Jie Xing
Dan Fei
Kunchi Zhao
Hongping Yuan
Journal: American journal of cancer research (2016)
Discipline: CLINICAL MEDICINE
Keywords: Osteosarcoma; ZEB2; miR-187; proliferation.
Affiliations: Department of Ultrasonographic, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, P. R. China., Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, P. R. China., Department of Nephrology, The Fourth Hospital of Jilin University Changchun 130000, Jilin, P. R. China.

Abstract:  MicroRNA-187 (miR-187) has been reported to be involved in the occurrence and development of several types of cancers; however, a role for miR-187 in osteosarcoma (OS) has not yet been reported. Here, miR-187 was found to be significantly downregulated in OS cell lines and tissue samples, and decreased miR-187 expression was shown to be correlated closely with the TNM stage and lymph node metastasis. miR-187 overexpression suppressed OS cell proliferation, colony formation, migration, invasion, and epithelial-mesenchymal transition (EMT). Mechanically, zinc finger E-box binding homeobox 2 (ZEB2) was shown to serve as a direct target of miR-187 in OS cells and the overexpression of ZEB2 rescued the miR-187-induced suppression of proliferation, colony formation, migration, and invasion in OS cells. In clinical OS specimens, ZEB2 expression levels were elevated and were inversely correlated with miR-187 expression. These results suggest that miR-187 functions as a tumor suppressor in OS, partially by targeting ZEB2, and that miR-187 can serve as a promising candidate for OS. 

Retracted: Yes

PubPeer comments:
 Fig. 2C. Red and yellow boxes: Image duplication. Blue box: Image overlap. ![file] , 
 Thank you for ingforming me, I will check the original data and response to it. ,
Pancreatic Stellate Cells Promote Tumor Progression by Promoting an Immunosuppressive Microenvironment in Murine Models of Pancreatic Cancer
Authors: Lei Yang
Yuzhen Zhuo
Qi Zhang
Botao Wang
Ximo Wang
Shukun Zhang
Lihua Cui
Lanqiu Zhang
Caixia Li
Journal: Pancreas (2020)
Discipline: CLINICAL MEDICINE
Keywords: Pancreatic ductal adenocarcinoma; Pancreatic stellate cells; Tumor microenvironment; Immunosuppressive; Orthotopic mouse model
Affiliations: From the Institute of Integrated Traditional Chinese and Western Medicine, Tianjin Nankai Hospital., Nankai Clinical College, Tianjin Medical University., Graduate School, Tianjin Medical University, Tianjin, China.

Abstract:  Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer with poor prognosis. Pancreatic stellate cells (PSCs) play a vital role in PDAC development. The aim of this study was to explore tumor microenvironment response to PSCs in an orthotopic pancreatic cancer mouse model and to assess if PSCs secreted factors that can facilitate an immunosuppressive microenvironment. Methods: Pancreatic ductal adenocarcinoma orthotopic tumor model, derived from coinjection of Panc02 cells plus PSCs, was used to investigate tumor proliferation, metastasis, and the population of immune cells in vivo, including regulatory T cells, M2-type macrophages, myeloid-derived suppressor cells, CD8 T cells, CD4 T cells, M1-type macrophages, natural killer (NK), and NK T cells. Results: Pancreatic stellate cells promoted PDAC growth not only induced cell proliferation and metastasis, but also significantly increased the suppressive immune cell population of regulatory T cells, M2-type macrophages, and myeloid-derived suppressor cells. In addition, PSCs decreased the immune cell population of CD8 T, CD4 T cells, and M1-type macrophages in the spleen and tumor tissues of the tumor-bearing mice. Moreover, PSCs decreased the population of NK and NK T cells in the tumor tissues. Conclusions: Our findings support PSCs playing multiple roles in PDAC development via promoting immunosuppressive microenvironment. 

Retracted: No

PubPeer comments:
 Figure 2E and 2F might shares similar cytometry results, and some pattern matching ![file] , 
 Retraction notice [1 February 2019] .  Ji F, Chen B, Du R, Zhang M, Liu YJ, Ding Y. International Journal of Clinical and Experimental Pathology. 2019;12:113-122. Multiple frauds in this paper have been discovered by a knowledgeable party and subsequently confirmed by the Editorial Office. Therefore, the entire article has been retracted in accordance with this journalu2019s policy and editorial decision. ,
A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus
Authors: Qi Liu
Qianqian Yuan
Yan Li
Xi Li
Xianli Bian
Shijun Wei
Jiangxia Li
Wenjie Sun
Qiji Liu
Feng Long
Pengyu Li
Shang Gao
Fei Gao
Ruonan Duan
Journal: Journal of clinical immunology (2019)
Discipline: IMMUNOLOGY
Keywords: K63-linked ubiquitin; NF-κB; TNFAIP3; TRAF6; blood-brain barrier
Affiliations: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Basic Medical Sciences, No. 44 West Wenhua Road, Jinan, 250012, Shandong, China., Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China., Department of Rheumatology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China., Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Basic Medical Sciences, No. 44 West Wenhua Road, Jinan, 250012, Shandong, China. .

Abstract:  Purpose: Genome-wide association study of systemic lupus erythematosus (SLE) revealed tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) as a susceptibility gene. Here, we report a de novo mutation in TNFAIP3 in a Chinese patient with neuropsychiatric SLE (NPSLE). Methods: Whole exome sequencing was performed for the patient and healthy members from the family. Suspected pathogenic variants were further analyzed and co-segregation was confirmed by Sanger sequencing. Real-time PCR and western blot were performed with peripheral blood mononuclear cells (PBMCs) and patient-derived T cells. Transfected HEK293T cells, human umbilical vein endothelial cells, normal human astrocytes, and microglia were used for in vitro studies. Results: A de novo frameshift mutation in TNFAIP3 was found in the NPSLE patient. Western blot analysis showed activated NF-κB and mitogen-activated protein kinase pathways. Real-time PCR revealed elevated expression of pro-inflammatory cytokines. On immunoprecipitation assay, the mutant A20 altered the K63-linked ubiquitin level of TRAF6 via its ubiquitin-editing function. Conclusions: The mutant A20 may play a role in weakening the tight junction of the blood-brain barrier to cause neurologic symptoms. We report a rare variant of TNFAIP3 in a patient with NPSLE and reveal its autoimmune disease-causing mechanism in both peripheral tissues and the central nervous system. 

Retracted: No

PubPeer comments:
 Correction to: Journal of Clinical Immunology 39:795u2013804(2019) https: doi.org 10.1007 s10875-019-00695-4 Fig. 4a in Manuscript ID#JOCI-D-19-00318 has been revised due to the replacement of immunoblot lane of u03b2-catenin by Zo-1 in NHA group. Please see below corrected version. *** ![file] , 
 The misuse of the WB band in figure 4 was found 3 months after publication. So we contact editor for replacement. ,
IL-10 gene-modified dendritic cells-induced type 1 T regulatory cells inhibit graft-versus-host disease while preserving graft-versus-leukemia effect
Authors: Siguo Hao
Fang Huang
Weiwei Hu
Jiangbo Wan
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Dendritic cells; Graft-versus-host disease; Graft-versus-leukemia; IL-10; Type 1 regulatory T cells.
Affiliations: Department of Hematology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medcine, Shanghai 200092, PR China., Department of Hematology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medcine, Shanghai 200092, PR China. Electronic address: .

Abstract:  To explore the role of type 1 regulatory T (Tr1) cells in allogeneic bone marrow transplantation (allo-BMT), we generated Tr1 cells from naïve CD4+ T cells in donor mice that were subjected to stimulation of recipient interleukin (IL)-10 gene-modified dendritic cells (DCs). In animal models, the severity of graft-versus-host disease (GVHD) in the group co-infused with DC-induced Tr1 cells was markedly milder than that in the groups without infusion of Tr1 cells. Moreover, the co-infusion Tr1 cells significantly prolonged the leukemia-free survival in tumor-bearing mice. Besides, Tr1-induced cells mediated the shift from T helper (Th)1 to Th2 cytokines in allo-BMT recipients. In Conclusions, our findings suggest that IL-10 gene-modified DC-induced Tr1 cells could inhibit GVHD while maintaining Graft-versus-leukemia (GVL) through mediating the shift of Th1/Th2 cytokines in an allo-BMT mice model. 

Retracted: No

PubPeer comments:
 Figure 3E appears to have two images which overlap. *** ![file] ,
Suppression of Bcl-xL expression by a novel tumor-specific RNA interference system inhibits proliferation and enhances radiosensitivity in prostatic carcinoma cells
Authors: Shi-Yin Cheng
Ke Dong
Hui-Zhong Zhang
San-Hua Wei
Xi Wang
Ping Gao
Rui Wang
Fang Lin
Journal: Cancer Chemotherapy and Pharmacology (2008)
Discipline: CLINICAL MEDICINE
Keywords: Bcl-xL; anti-apoptotic; prostatic carcinoma; RNA interference; survivin promoter
Affiliations: Research Center, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, 710038 Xi'an, Shaanxi Province, China.

Abstract:  Bcl-xL, a novel member of anti-apoptotic Bcl-2 family that play important roles in regulating cell survival and apoptosis, is frequently overexpressed in various kinds of human cancers, including prostatic carcinoma. To explore its possibility as a therapeutic target for prostatic carcinoma, we developed a novel tumor-specific RNA interference system by using survivin promoter and employed it to suppress exogenous reporters (LUC and EGFP) and endogenous gene Bcl-xL expression and analyzed its phenotypes. We found that expression of exogenous reporters (LUC and EGFP) was specifically inhibited in tumor cells but not in normal cells. We also observed that the specific inhibition of Bcl-xL in human prostatic carcinoma cells (PC3) strongly suppressed in vitro cell proliferation and in vivo tumorigenicity. We observed significant apoptosis induction and radiosensitivity enhancement in PC3 cells by the RNA interference-mediated suppression of Bcl-xL expression. All these results indicate that inhibition of Bcl-xL expression can result in potent antitumor activity and radiosensitization in human prostatic carcinoma. 

Retracted: No

PubPeer comments:
 Figure 4C. * Some cells or groups of cells appear to be visible multiple times within the same photo. Shown with boxes of the same color. ![file] ,
SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin
Authors: Zongguang Zhou
Qin Wang
Meijuan Huang
Yi Liu
Chunlei Li
Lin Cheng
Yong Peng
Rong Xiang
Shuang Zhang
Yuquan Wei
Xueliang Cui
Hongxin Deng
Ying Mao
Junfeng Zhang
Lei Dai
Xun Hu
Dechao Yu
Jinliang Yang
Yang Yang
Xin Zhang
Xiaolan Su
Qingnan Wang
Hanshuo Yang
Yi Lin
Ping Fan
Journal: Nature Communications (2016)
Discipline: Multidisciplinary
Keywords: SARI; tumorigenesis; angiogenesis; VEGF; ceruloplasmin
Affiliations: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China., Huaxi Biobank, West China Hospital, Sichuan University, Chengdu, Sichuan 610093, China., Department of Thoracic Oncology, Tumour Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China., Department of Immunology, Nankai University School of Medicine, Tianjin 300071, China., Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Abstract:  SARI, also called as BATF2, belongs to the BATF family and has been implicated in cancer cell growth inhibition. However, the role and mechanism of SARI in tumour angiogenesis are elusive. Here we demonstrate that SARI deficiency facilitates AOM/DSS-induced colonic tumorigenesis in mice. We show that SARI is a novel inhibitor of colon tumour growth and angiogenesis in mice. Antibody array and HUVEC-related assays indicate that VEGF has an essential role in SARI-controlled inhibition of angiogenesis. Furthermore, Co-IP/PAGE/mass spectrometry indicates that SARI directly targets ceruloplasmin (Cp), and induces protease degradation of Cp, thereby inhibiting the activity of the HIF-1α/VEGF axis. Tissue microarray results indicate that SARI expression inversely correlates with poor clinical outcomes in colon cancer patients. Collectively, our results indicate that SARI is a potential target for therapy by inhibiting angiogenesis through the reduction of VEGF expression and is a prognostic indicator for patients with colon cancer. 

Retracted: No

PubPeer comments:
 The GAPDH results in Figure 1G and Figure 4D were seemingly exposed different times using the same membrane, and the photo was rotated. ![file] ![file] ,
Evolution-guided discovery of antibiotics that inhibit peptidoglycan remodelling
Authors: Kalinka Koteva
Nicholas Waglechner
Brian K Coombes
Yen-Pang Hsu
Aline A Fiebig-Comyn
Wenliang Wang
Gerard D Wright
Michael S Van Nieuwenhze
Yves V Brun
Elizabeth J Culp
David Sychantha
Journal: Nature (2020)
Discipline: Multidisciplinary
Keywords: Antibiotic crisis; Drug-resistant infections; Actinomycetes; Genome sequencing; Biosynthetic gene clusters
Affiliations: M. G. DeGroote Institute for Infectious Disease Research, David Braley Centre for Antibiotic Discovery, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada., Department of Chemistry, Indiana University, Bloomington, IN, USA., Department of Biology, Indiana University, Bloomington, IN, USA., Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada., M. G. DeGroote Institute for Infectious Disease Research, David Braley Centre for Antibiotic Discovery, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. .

Abstract:  Addressing the ongoing antibiotic crisis requires the discovery of compounds with novel mechanisms of action that are capable of treating drug-resistant infections1. Many antibiotics are sourced from specialized metabolites produced by bacteria, particularly those of the Actinomycetes family2. Although actinomycete extracts have traditionally been screened using activity-based platforms, this approach has become unfavourable owing to the frequent rediscovery of known compounds. Genome sequencing of actinomycetes reveals an untapped reservoir of biosynthetic gene clusters, but prioritization is required to predict which gene clusters may yield promising new chemical matter2. Here we make use of the phylogeny of biosynthetic genes along with the lack of known resistance determinants to predict divergent members of the glycopeptide family of antibiotics that are likely to possess new biological activities. Using these predictions, we uncovered two members of a new functional class of glycopeptide antibiotics-the known glycopeptide antibiotic complestatin and a newly discovered compound we call corbomycin-that have a novel mode of action. We show that by binding to peptidoglycan, complestatin and corbomycin block the action of autolysins-essential peptidoglycan hydrolases that are required for remodelling of the cell wall during growth. Corbomycin and complestatin have low levels of resistance development and are effective in reducing bacterial burden in a mouse model of skin MRSA infection. 

Retracted: No

PubPeer comments:
 There appears to have been an error in the preparation of figure 2b. *** ![file] *** ![file] ,
Long Noncoding RNA H19 Inhibits Cell Viability, Migration, and Invasion Via Downregulation of IRS-1 in Thyroid Cancer Cells
Authors: Qingao Bu
Weimin Xu
Haixia Liu
Diwen Sun
Peng Wang
Guoqing Liu
Journal: Technology in Cancer Research & Treatment (2017)
Discipline: CLINICAL MEDICINE
Keywords: apoptosis; cell proliferation; insulin receptor substrate 1; long noncoding RNA H19; thyroid cancer.
Affiliations: 1 Department of Mammary Gland and Thyroid Surgery, Shengli Oilfield Central Hospital, Dongying, People's Republic of China., 2 Department of Endocrinology, Shengli Oilfield Central Hospital, Dongying, People's Republic of China., 3 Department of Anesthesiology, Shengli Oilfield Central Hospital, Dongying, People's Republic of China.

Abstract:  Thyroid cancer is a common endocrine gland malignancy which exhibited rapid increased incidence worldwide in recent decades. This study was aimed to investigate the role of long noncoding RNA H19 in thyroid cancer. Long noncoding RNA H19 was overexpressed or knockdown in thyroid cancer cells SW579 and TPC-1, and the expression of long noncoding RNA H19 was detected by real-time polymerase chain reaction. The cell viability, migration, and invasion were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, Transwell assay, and wound healing assay, respectively. Furthermore, cell apoptosis was analyzed by flow cytometry, and expressions of some factors that were related to phosphatidyl inositide 3-kinases/protein kinase B and nuclear factor κB signal pathway were measured by Western blotting. This study revealed that cell viability and migration/invasion of SW579 and TPC-1 were significantly decreased by long noncoding RNA H19 overexpression compared with the control group ( P &lt; .05), whereas cell apoptosis was statistically increased ( P &lt; .001). Meanwhile, cell viability and migration/invasion were significantly increased after long noncoding RNA H19 knockdown ( P &lt; .05). Furthermore, long noncoding RNA H19 negatively regulated the expression of insulin receptor substrate 1 and thus effect on cell proliferation and apoptosis. Insulin receptor substrate 1 regulated the activation of phosphatidyl inositide 3-kinases/AKT and nuclear factor κB signal pathways. In conclusion, long noncoding RNA H19 could suppress cell viability, migration, and invasion via downregulation of insulin receptor substrate 1 in SW579 and TPC-1 cells. These results suggested the important role of long noncoding RNA H19 in thyroid cancer, and long noncoding RNA H19 might be a potential target of thyroid cancer treatment. 

Retracted: Yes

PubPeer comments:
 Fig. 4D contains a set of image duplication. ![file] , 
 Again, Fig. 9A contains a set of WB image duplication. ![file] ,
Downregulation of Bmi-1 is associated with suppressed tumorigenesis and induced apoptosis in CD44⁺ nasopharyngeal carcinoma cancer stem-like cells
Authors: Xiaoyan Liu
Juan Hu
Daojun Li
Qiao Huang
Weihong Chen
Xinhua Xu
Jin Su
Yang Liu
Jinghua Ren
Lidan Sun
Mingqian Lu
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Bmi-1; CD44+; nasopharyngeal carcinoma; cancer stem-like cells; shRNA
Affiliations: The First College of Clinical Medical Science, China Three Gorges University and Department of Oncology, Yichang Central People's Hospital, Yichang, Hubei 443003, P.R. China., Oncology Institute, China Three Gorges University, Yichang, Hubei 443003, P.R. China., Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China., Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Department of Medical College, China Three Gorges University, Yichang, Hubei 443002, P.R. China.

Abstract:  Bmi-1 (B-cell-specific Moloney murine leukemia virus insertion site 1) is a member of the Polycomb group gene (PcG) family, which is involved in the proliferation, migration and tumorigenesis of several types of cancer stem cells (CSCs). However, its precise role and mechanism in CD44+ nasopharyngeal carcinoma (NPC) cancer stem-like cells (CSC-LCs) remain poorly understood. In our previous study, we successfully silenced Bmi-1 by short hairpin RNA (shRNA) in CD44+ NPC CSC-LCs and obtained stable Bmi-1 knockdown (KD) cell lines. In the present study, we tested the cell proliferation by CCK-8 assay and apoptosis by ﬂow cytometry. Scratch wound healing assay, together with Transwell migration and invasion assays were used to measure the migration and invasion capacity. We further evaluated the tumorigenicity of CD44+ NPC CSC-LCs transfected with Bmi-1 shRNA in vivo. Based on our results, knockdown of Bmi-1 by shRNA resulted in the inhibition of tumor proliferation, migration and invasion in vitro, followed by cell apoptosis. In addition, our results preliminarily demonstrated that inhibition of Bmi-1 expression by shRNA increased tumor apoptosis through the p16INK4a-p14ARF-p53 pathway. Bmi-1 silencing in CD44+ NPC CSC-LCs also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of Bmi-1 in the occurrence and development of NPC. Based on our findings, regulation of Bmi-1 in CD44+ NPC CSC-LCs may provide a potential molecular target for the therapy of NPC, and targeted silencing of Bmi-1 by shRNA may have clinical future implications in NPC therapy. 

Retracted: No

PubPeer comments:
 Figure 4. * Tumors and mice in panels A look quite similar to those in panels B. The mice appear in a different order. Maybe I am not quite understanding this, but panels A and B represent the same or overlapping experiments? The labeling is different and the experiments are separately described, so I am not quite sure. ![file] ,
A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability
Authors: Elisabetta Tabolacci
Valentina Mercaldo
Francesca Zalfa
Claudia Bagni
Boris Eleuteri
Kirsten S Dickson
Alessandra di Penta
Silvia De Rubeis
Pietro Chiurazzi
Giovanni Neri
Seth G N Grant
Journal: Nature neuroscience (2007)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Fragile X syndrome; FMRP; mRNA stability; PSD-95; synaptic signaling
Affiliations: Dipartimento di Biologia, Università Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy.

Abstract:  Fragile X syndrome (FXS) results from the loss of the fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates a variety of cytoplasmic mRNAs. FMRP regulates mRNA translation and may be important in mRNA localization to dendrites. We report a third cytoplasmic regulatory function for FMRP: control of mRNA stability. In mice, we found that FMRP binds, in vivo, the mRNA encoding PSD-95, a key molecule that regulates neuronal synaptic signaling and learning. This interaction occurs through the 3' untranslated region of the PSD-95 (also known as Dlg4) mRNA, increasing message stability. Moreover, stabilization is further increased by mGluR activation. Although we also found that the PSD-95 mRNA is synaptically localized in vivo, localization occurs independently of FMRP. Through our functional analysis of this FMRP target we provide evidence that dysregulation of mRNA stability may contribute to the cognitive impairments in individuals with FXS. 

Retracted: No

PubPeer comments:
 2020 retraction. https: translational-medicine.biomedcentral.com articles 10.1186 s12967-020-02266-3 The Editor-in-Chief and the publisher have retracted this article [1]. An investigation by the Lithuanian Bioethics Committee concluded that, contrary to the statements in the article, the study described was not conducted in the Vilnius City Clinical Hospital and the Commission of Medical Ethics did not issue any approval for such a study. Additionally, investigation by the State Health Care Accreditation Agency of the Ministry of Health revealed that the records of the patients described in this study could not be located and verified. The Lithuanian Bioethics Committee therefore concluded that the data are unreliable. The Ombudsperson for Academic Ethics and Procedures conducted a follow up investigation and affirmed that the information presented with respect to the location of the study, the ethical approval, and the period of data collection was fictional but was provided as if it was true, i.e. this information was fabricated. Adas Darinskas and Thomas E. Ichim disagree with this retraction. The other authors did not respond to any correspondence about this retraction. Reference 1. Darinskas A, Paskevicius M, Apanavicius G, Vilkevicius G, Labanauskas L, Ichim TE, Rimdeika R. Stromal vascular fraction cells for the treatment of critical limb ischemia: a pilot study. J Transl Med. 2017;15:143. https: doi.org 10.1186 s12967-017-1243-3 ,
The tissue transglutaminase: a potential target regulating MDR in breast cancer
Authors: Y Han
Y-Z Zhang
Z-L Yang
K Cheng
Y-T Hua
X-H Wang
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Multi-drug resistance; tTG; breast cancer; MDR; CD44
Affiliations: School of Medicine, Shandong University, Jinan, China. .

Abstract:  Objective: Multi-drug resistance (MDR) is the main obstacle influencing the anti-tumor effect in breast cancer. To date, no proper potential targets are found to overcome MDR. Here, tTG was explored to show whether it is a potential target to regulate MDR in breast cancer. Materials and methods: tTG was silenced by small interfere siRNA. After that, the mRNA level of CD44, CD24, LRP, MRP and MDR1 were detected by RT-PCR. The Western blot analysis was used to detect the expression of LRP, P-gp and MRP. In addition, the impact of tTG on cell apoptosis, as well as cell proliferation were observed. Finally, to evaluate the role of tTG in BALB/c nude mice, the growth of tumor was performed, and the immunohistochemistry analysis was used to observe the expression of LRP, P-gp and MRP in vivo. Results: In MCF-7/ADR, Compared to MCF-7, tTG expression was highly increased. After silencing tTG, the mRNA level and the protein level of P-gp, MRP, LRP were both differently decreased. The mRNA level of CD44 and CD24 was also down-regulated after silencing tTG. In addition, the cell proliferation was significantly inhibited in the ADR + tTG siRNA+Adriamycin group (p&lt;0.05), and the tumor growth was prevented in a time-dependent situation. Cell apoptosis was significantly strengthened in the ADR+tTG siRNA+Adriamycin group (p&lt;0.05). In vivo, the growth of tumors was reduced after silencing tTG, and the LRP, P-gp and MRP expression were significantly down-regulated in ADR + tTG SiRNA +adriamycin group (p&lt;0.05). Conclusions: It is concluded that the tTG may be a potential target regulating the MDR by regulating LRP, P-gp and MRP expression as well as the expression of CD44CD24 to improve the MDR in breast cancer. 

Retracted: No

PubPeer comments:
 Figure 4A. * Red boxes: Two panels representing different experiments appear to show an overlap, if one of them is rotated and stretched differently. ![file] ,