PReD-Bench/PRed-Bench huggingface dataset:
RETRACTED ARTICLE: Effects of chronic treatment with the eNOS stimulator Impaza on penis length and sexual behaviors in rats with a high baseline of sexual activity
Authors: X Chu
O I Epstein
S A Sergeeva
E S Zhavbert
I A Kheyfets
A Agmo
J L Dugina
Journal: International Journal of Impotence Research (2014)
Discipline: CLINICAL MEDICINE
Keywords: Endothelial nitric oxide synthase (eNOS); Impaza; sexual behavior; penis length; rats
Affiliations: Department of Psychology, University of Tromsø, Tromsø, Norway., OOO "NPF "Materia Medica Holding", Moscow, Russia.

Abstract:  Endothelial nitric oxide synthase (eNOS) has an important role in erection, and it also affects aspects of sexual behavior. In this experiment, we determined whether a compound enhancing the activity of eNOS, Impaza, could stimulate any aspect of sexual behavior and increase penis length in rats with a high baseline of sexual activity. For comparison, the PDE5 inhibitor sildenafil was included. Male rats were orally treated with Impaza or sildenafil for 28 days. Impaza (3 ml kg(-1)) was given daily while sildenafil (3 mg kg(-1)) was given twice weekly. Tests for sexual incentive motivation and copulatory behavior were performed just before drug treatment and at days 7, 14 and 28 of treatment. In addition, the length of the protruding penis at mount, intromission and ejaculation was measured. Impaza but not sildenafil increased penis length at mount after 14 and 28 days of treatment. The compounds failed to modify sexual incentive motivation or copulatory behavior. It is suggested that Impaza enhanced intracavernous pressure, as such a pressure increase is the most likely explanation for enhanced penis length at mount. This effect, together with an absence of motivational actions, suggests that Impaza may be the most valuable treatment for erectile dysfunction. 

Retracted: Yes

PubPeer comments:
 https: www.discovermagazine.com the-sciences the-strange-case-of-the-homeopathic-sex-enhancer Also, https: retractionwatch.com 2020 07 01 coming-up-short-journal-retracts-penis-enlargement-paper-after-realizing-it-was-homeopathy The Editor has retracted this article because there are u201cconcerns about the scientific validity of the study. Specifically, the reagent is diluted beyond the point to which any active molecules are expected to be present and there is no molecular analysis to support the presence of molecules at these dilutions. These concerns have caused the Editor to lose faith in the reliability of the findings. All authors disagree with this retraction.u201c Competing interests (apparently in original): ESZ (Research Associate), JLD (Head of Preclinical Development), IAK (Senior Research Associate), SAS (Chief Scientific Officer) have paid positions in OOO u201cNPF u201cMateria Medica Holdingu201d, OIE is the General Director and the owner of the company above mentioned. XC and Au00c5 are employees of the University of Tromsu00f8 and have no financial interests in OOO u201cNPF u201cMateria Medica Holdingu201d. ,
Tubulin-destabilizing agent BPR0L075 induces vascular-disruption in human breast cancer mammary fat pad xenografts
Authors: Xiaolei Wang
Hsing-Pang Hsieh
Ralph P Mason
Haley Beck
Xinli Liu
Li Liu
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: BPR0L075; tubulin-binding agent; antimitotic; antiangiogenic; breast cancer
Affiliations: Cancer Imaging Program, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

Abstract:  BPR0L075, 6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole, is a tubulin-binding agent that inhibits tubulin polymerization by binding to the colchicine-binding site. BPR0L075 has shown antimitotic and antiangiogenic activity in vitro. The current study evaluated the vascular-disrupting activity of BPR0L075 in human breast cancer mammary fat pad xenografts using dynamic bioluminescence imaging. A single dose of BPR0L075 (50 mg/kg, intraperitoneally (i.p.)) induced rapid, temporary tumor vascular shutdown (at 2, 4, and 6 hours); evidenced by rapid and reproducible decrease of light emission from luciferase-expressing orthotopic MCF7 and MDA-MB-231 breast tumors after administration of luciferin substrate. A time-dependent reduction of tumor perfusion after BPR0L075 treatment was confirmed by immunohistological staining of the perfusion marker Hoechst 33342 and tumor vasculature marker CD31. The vasculature showed distinct recovery within 24 hours post therapy. A single i.p. injection of 50 mg/kg of BPR0L075 initially produced plasma concentrations in the micromolar range within 6 hours, but subsequent drug distribution and elimination caused BPR0L075 plasma levels to drop rapidly into the nanomolar range within 24 h. Tests with human umbilical vein endothelial (HUVEC) cells and tumor cells in culture showed that BPR0L075 was cytotoxic to both tumor cells and proliferating endothelial cells, and disrupted pre-established vessels in vitro and ex vivo. In conclusion, BPR0L075 caused rapid, albeit, temporary tumor vascular shutdown and led to reduction of tumor perfusion in orthotopic human breast cancer xenografts, suggesting that this antimitotic agent may be useful as a vascular-disrupting cancer therapy. 

Retracted: No

PubPeer comments:
 Figure 1. * Red boxes: The 24h timepoint for the left experiment looks like the 0h timepoint for the right experiment. These should be different mice - or perhaps I am not understanding the experiments well? * Green boxes: In the left experiment, the 2h 4h 6h 24h timepoints all look very similar, as if the mouse has not moved or was attended to in a 24h time frame. Can the authors please clarify? ![file] , 
 Figure 2 * Cyan boxes: The 24h timepoint for the left experiment looks like the 0h timepoint for the right experiment. These should be different mice. * Orange boxes: In the left experiment, the 4h 6h timepoints look very similar Can the authors please clarify? ![file] , 
 Figure 5C. * Pink boxes: In the CTR row, the 0h and 24h timepoints look like differently stretched versions of each other ![file] ,
RPLP1, a crucial ribosomal protein for embryonic development of the nervous system
Authors: Sergi Guerrero
Laura Perucho
Zhao-Qi Wang
Matilde E LLeonart
Santiago Ramón y Cajal
Ana Artero-Castro
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Ribosomal proteins; Rplp1; tumorigenesis; development; tissue homeostasis
Affiliations: Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany., Oncology and Pathology Group, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain., Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany; Faculty of Biology and Pharmacy, Friedrich Schiller University of Jena, Jena, Germany.

Abstract:  Ribosomal proteins are pivotal to development and tissue homeostasis. RP Large P1 (Rplp1) overexpression is associated with tumorigenesis. However, the physiological function of Rplp1 in mammalian development remains unknown. In this study, we disrupted Rplp1 in the mouse germline and central nervous system (Rplp1CNSΔ). Rplp1 heterozygosity caused body size reductions, male infertility, systemic abnormalities in various tissues and a high frequency of early postnatal death. Rplp1CNSΔ newborn mice exhibited perinatal lethality and brain atrophy with size reductions of the neocortex, midbrain and ganglionic eminence. The Rplp1 knockout neocortex exhibited progenitor cell proliferation arrest and apoptosis due to the dysregulation of key cell cycle and apoptosis regulators (cyclin A, cyclin E, p21CIP1, p27KIP1, p53). Similarly, Rplp1 deletion in pMEFs led to proliferation arrest and premature senescence. Importantly, Rplp1 deletion in primary mouse embryonic fibroblasts did not alter global protein synthesis, but did change the expression patterns of specific protein subsets involved in protein folding and the unfolded protein response, cell death, protein transport and signal transduction, among others. Altogether, we demonstrated that the translation "fine-tuning" exerted by Rplp1 is essential for embryonic and brain development and for proper cell proliferation. 

Retracted: No

PubPeer comments:
null, 
 ![file] ,
Pleuromutilin Inhibits Proliferation and Migration of A2780 and Caov-3 Ovarian Carcinoma Cells and Growth of Mouse A2780 Tumor Xenografts by Down-Regulation of pFAK2
Authors: Xiaoli Ma
Sijing Li
Bo Zhang
Yuan Li
Jiumei Cheng
Journal: Medical Science Monitor (2020)
Discipline: CLINICAL MEDICINE
Keywords: Pleuromutilin; ovarian carcinoma cells; migration; proliferation; tumor xenografts
Affiliations: Department of Minimally Invasive Gynecological Centre, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China (mainland)., Department of Perinatal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China (mainland)., Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China (mainland).

Abstract:  BACKGROUND Pleuromutilin is a natural tricyclic, derived from the fungus, Pleurotus mutilus. This study aimed to investigate the effects of pleuromutilin on migration and proliferation of A2780 and Caov-3 human ovarian carcinoma cells and the growth of A2780 tumor xenografts in mice and the molecular mechanisms involved. MATERIAL AND METHODS A2780 and Caov-3 human ovarian carcinoma cells were cultured with and without 40, 160, and 200 μM of pleuromutilin. The Edu fluorescence assay, the wound-healing assay, and Matrigel were used to measure A2780 and Caov-3 cell proliferation, migration, invasion, and adhesion in vitro, respectively. Western blot measured protein levels of FAK, p-FAK, MMP-2, and MMP-9. A2780 cells were injected subcutaneously into mice to determine the effects of pleuromutilin on the growth of tumor xenografts. RESULTS Pleuromutilin significantly reduced A2780 and Caov-3 cell proliferation at 48 h in a dose-dependent manner (P&lt;0.05), and at 200 μM, pleuromutilin reduced cell proliferation by 21.43% and 23.65%, respectively. Treatment of A2780 cells with pleuromutilin significantly reduced cell migration, invasion, and adhesion and the expression of p-FAK, MMP-2, and MMP-9 compared with untreated controls. In the mouse tumor xenograft model, treatment with pleuromutilin significantly reduced tumor size compared with the untreated group and inhibited tumor metastasis to the intestine, spleen, and peritoneal cavity. CONCLUSIONS In A2780 and Caov-3 human ovarian carcinoma cells, pleuromutilin inhibited cell proliferation, migration, invasion, and adhesion in a dose-dependent manner, and reduced tumor growth and metastases in a mouse A2780 cell tumor xenograft model. 

Retracted: Yes

PubPeer comments:
 Figure 5A. * Some cells or groups of cells appear to be visible multiple times. ![file] , 
 Figure 6A. * Some cells or groups of cells appear to be visible multiple times. ![file] , 
 Figure 7A. * Some cells or groups of cells appear to be visible multiple times. ![file] , 
 The email for the corresponding author, Jiumei Cheng, is a surprising choice: CorneliaRiveradfy12@gmail.com , 
 Retracted [21 January 2021] .  ABSTRACT: Some cells or groups of cells in figures appear to be visible multiple times. Because the manuscript contains non-credible results this journal is retracting the above publication. ,
Effect of tumor suppressor PTEN gene on apoptosis and cell cycle of human airway smooth muscle cells
Authors: Wenyan Lai
Liang Luo
Xiefei Qi
Yuan Qi Gong
Yaling Luo
Haibing Lan
Journal: Molecular and Cellular Biochemistry (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ASMCs; PTEN gene; apoptosis; proliferation; PI3K/Akt
Affiliations: Department of Medical Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhong Shan Er Road, Guangzhou, People's Republic of China.

Abstract:  It is well established that hyperplasia and decreased apoptosis of airway smooth muscle cells (ASMCs) play an important role in the asthmatic airway remodeling. Tumor suppressor PTEN gene with phosphatase activity plays an important regulatory role in embryonic development, cell proliferation, and apoptosis, cell cycle regulation, migration (invasion) of the cytoskeleton. We hypotheses that PTEN gene could affect the growth and viability of ASMCs through the regulation of PI3K/Akt, MAPK, and cell cycle-related gene expression. We constructed a recombinant adenovirus to transfect ASMCs. Cells were divided into the overexpression of PTEN gene group (Ad-PTEN-GFP), negative control group (Ad-GFP), and blank control group (DMEM). The cell apoptosis of ASMCs were evaluated by Hoechst-33342 staining and PE-7AAD double-labeled flow cytometry. The cell cycle distribution was observed by flow cytometry with PI staining. The expression of PTEN, p-Akt, total-Akt, p-ERK1/2, total-ERK1/2, cleaved-Caspases-3, Caspases-9, p21, and Cyclin D1 were tested by the Western blotting. Our study revealed that overexpression of PTEN gene did not induce apoptosis of human ASMCs cultured in vitro. However, overexpression of PTEN inhibited proliferation of human ASMCs cultured in vitro and was associated with downregulation of Akt phosphorylation levels, while did not affect ERK1/2 phosphorylation levels. Moreover, overexpression of PTEN could induce ASMCs arrested in the G0/G1 phase through the downregulation of Cyclin D1 and upregulation of p21 expressions. 

Retracted: No

PubPeer comments:
 Figure 6. * Red boxes: Three lanes in the b-actin panels in Figure 6C and 6D look similar to each other but do not quite represent the same experiments * Green boxes: The b-actin panel in Figure 6A looks similar to the GAPDH panel in Figure 6B. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. I would love to hear from the authors if the journal ever contacted them in the past five years. ![file] ,
NIMA-related kinase 2 regulates hepatocellular carcinoma cell growth and proliferation
Authors: Ying-Fei Li
Hui Yang
Xiao-Bo Lai
Bo Shen
Hong-Li Huang
Yu-Qiang Nie
Chuang-Yu Cao
Zhi-Qiang Feng
Journal: Oncology Letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: Nek2; cancer proliferation; hepatocellular carcinoma; wnt/β-catenin.
Affiliations: Department of Gastroenterology and Hepatology, The First Municipal People's Hospital of Guangzhou, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China., Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China., Department of Gastroenterology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510282, P.R. China.

Abstract:  NIMA-related kinase 2 (Nek2) is often upregulated in human cancer and is important in regulating the cell cycle and gene expression, and maintaining centrosomal structure and function. The present study aimed to investigate the expression pattern, clinical significance, and biological function of Nek2 in hepatocellular carcinoma (HCC). mRNA and protein levels of Nek2 were examined in HCC and corresponding normal liver tissues. The MTT and soft agar colony formation assays, and flow cytometry were employed to assess the roles of Nek2 in cell proliferation and growth. In addition, western blot analysis was performed to assess the expression of cell cycle- and proliferation-related proteins. The results revealed that Nek2 was upregulated in HCC tissues and cell lines. The clinical significance of Nek2 expression was also analyzed. Inhibiting Nek2 expression by siRNA suppressed cell proliferation, growth, and colony formation in hepatocellular carcinoma cell line HepG2 cells, induced cell cycle arrest in the G2/M phase by retarding the S-phase, and promoted apoptosis. Furthermore, Nek2 depletion downregulated β-catenin expression in HepG2 cells and diminished expression of Myc proto-oncogene protein (c-Myc), cyclins D1, B1, and E and cyclin-dependent kinase 1, whilst increasing protein levels of p27. This demonstrates that overexpression of Nek2 is associated with the malignant evolution of HCC. Targeting Nek2 may inhibit HCC cell growth and proliferation through the regulation of β-catenin by the Wnt/β-catenin pathway and therefore may be developed as a novel therapeutic strategy to treat HCC. 

Retracted: No

PubPeer comments:
 Image concerns in this paper were found during a systematic search of papers in Spandidos journals for possible duplicated images. Figure 4B. * Blue boxes: The  Blank and  NC panels look unexpectedly similar. ![file] , 
 Figure 5. * Red boxes: The Nek2 and CycE panels look unexpectedly similar. ![file] ,
Acute exercise reverses aged-induced impairments in insulin signaling in rodent skeletal muscle
Authors: José R Pauli
Juliana C Moraes
José A C de Almeida Leme
Eliete Luciano
José B C Carvalheira
Patricia O Prada
Eduardo R Ropelle
Mario J A Saad
Cláudio Teodoro De Souza
Adelino S R da Silva
Dennys Esper Cintra
Lício A Velloso
Journal: Mechanisms of Ageing and Development (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: insulin resistance; aging; exercise; pIRS-1Ser307; JNK
Affiliations: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas - UNICAMP, Campinas, SP, Brazil. 

Abstract:  The insulin resistance associated with aging is improved by exercise, but the molecular mechanisms of this improvement are not fully understood. We investigated whether the improvement in insulin action, associated with acute exercise in old rats is dependent on the modulation of pIRS-1Ser307, JNK, IkBalpha and PTP-1B. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45min rest period. Sixteen hours after the exercise, the rats were killed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the reduction in glucose disappearance rate (Kitt), observed in aged rats, was restored at 16h after exercise. Aging led to an increase in Ser307 phosphorylation of IRS-1, and this was reversed by exercise in the skeletal muscle, in parallel with a reduction in pJNK and IkBalpha degradation. Moreover, aging induced an increase in the expression of PTP-1B and attenuated insulin signaling in the muscle of rats, a phenomenon that was reversed by exercise. Interestingly, the decrease in PTP-1B expression in the muscle of exercised old rats was accompanied by an increase in SIRT1 expression. These results provide new insights into the mechanisms by which exercise restores insulin sensitivity during aging. 

Retracted: No

PubPeer comments:
 Figure 1C vs Figure 1E u2013 similarities are observed: ![file] , 
 Last author [calling for] new research integrity office at Unicamp. ,
Dissociation between bone resorption and bone formation in osteopenic transgenic mice
Authors: M Amling
M Priemel
D A Corral
G Karsenty
R Baron
S Fuchs
P Ducy
E Loyer
Journal: Proceedings of the National Academy of Sciences of the United States of America (1998)
Discipline: Multidisciplinary
Keywords: Bone remodeling; osteoclast; osteoblast; bone resorption; bone formation
Affiliations: Department of Molecular Genetics, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Abstract:  Bone mass is maintained constant in vertebrates through bone remodeling (BR). BR is characterized by osteoclastic resorption of preexisting bone followed by de novo bone formation by osteoblasts. This sequence of events and the fact that bone mass remains constant in physiological situation lead to the assumption that resorption and formation are regulated by each other during BR. Recent evidence shows that cells of the osteoblastic lineage are involved in osteoclast differentiation. However, the existence of a functional link between the two activities, formation and resorption, has never been shown in vivo. To define the role of bone formation in the control of bone resorption, we generated an inducible osteoblast ablation mouse model. These mice developed a reversible osteopenia. Functional analyses showed that in the absence of bone formation, bone resorption continued to occur normally, leading to an osteoporosis of controllable severity, whose appearance could be prevented by an antiresorptive agent. This study establishes that bone formation and/or bone mass do not control the extent of bone resorption in vivo. 

Retracted: No

PubPeer comments:
 ![file] Sections from same bone duplicated, shown as two different mice. ,
MiR-182 inhibits the epithelial to mesenchymal transition and metastasis of lung cancer cells by targeting the Met gene
Authors: Hongyu Liu
Hongbing Zhang
Yongwen Li
Chenlong Zhao
Xin Li
Yaguang Fan
Ying Li
Jinghao Liu
Jun Chen
Journal: Molecular carcinogenesis (2018)
Discipline: CLINICAL MEDICINE
Keywords: epithelial to mesenchymal transition (EMT); lung cancer; metastasis; miR-182.
Affiliations: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment; Tianjin Lung Cancer Institute; Tianjin Medical University General Hospital; Tianjin China, Department of Lung Cancer Surgery; Tianjin Medical University General Hospital; Tianjin China

Abstract:  The microRNA miR-182, belonging to the miR-183 family, is one of the most frequently studied cancer-related oncogenic miRNAs that is dysregulated in various cancer tissues, and it plays a crucial role in tumorigenesis and tumor progression. Studies revealed that miR-182 might function as an oncogenic or tumor suppressor miRNA in different tissues. However, the role of miR-182 in the development of lung cancer remains largely unknown. miR-182 expression in tumor samples from 58 patients, normal lung tissue samples, and lung cancer cell lines were evaluated by qRT-PCR. Survival curves were analyzed using the Kaplan-Meier method and compared with a log-rank test. Our study demonstrated that miR-182 is frequently downregulated in metastatic NSCLC cells compared with primary tumor tissues. Over-expression of miR-182 significantly inhibited the migration and invasion of lung cancer cells and promoted the expression of the epithelial marker (E-cadherin) in addition to reducing the levels of Snail in lung cancer cells. Further studies demonstrated that miR-182 negatively regulated Met via direct binding to the Met 3'-untranslated region (3'-UTR). Furthermore, we found that miR-182 suppressed the phosphorylation of AKT and the nuclear accumulation of Snail, a transcription factor that promotes the epidermal to mesenchymal transition (EMT). Moreover, miR-182 could repress cell migration, invasion, and EMT of lung cancer cells induced by hepatocyte growth factor (HGF). miR-182 might suppress the EMT and metastasis via inactivation of Met/AKT/Snail in non-small cell lung cancer (NSCLC) cells, which implicates miR-182 may be useful as a new therapeutic target in NSCLC. 

Retracted: No

PubPeer comments:
 There is something odd about the western blots in this paper. This is exemplified by Figure 7, shown below. Not only do the band shapes change going from convex to concave, but the lane distances appear to spread apart and magically come back together again. Continuing the pattern, the background is completely absent in every other image and highly granulated in every other. The background pattern for p-AKT moreover suggests that the bands have been stretched compared to the pattern on p-p38. Finally, the p-p38 image clearly has a transparent image (with the blots?) slapped slightly askew over another image (the background?). ![file] I would be very curious to see the original scan for these blots. Could the authors provide an explanation to what is going on here? ,
Spreading depression triggers headache by activating neuronal Panx1 channels
Authors: Emine Eren-Koçak
Sefik Evren Erdener
Yasemin Gursoy-Ozdemir
Hulya Karatas
Zümrüt Duygu Sen
Sevda Lule
Turgay Dalkara
Journal: Science (2013)
Discipline: Multidisciplinary
Keywords: migraine; cortical spreading depression; trigeminal afferents; Pannexin1; caspase-1
Affiliations: Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.

Abstract:  The initial phase in the development of a migraine is still poorly understood. Here, we describe a previously unknown signaling pathway between stressed neurons and trigeminal afferents during cortical spreading depression (CSD), the putative cause of migraine aura and headache. CSD caused neuronal Pannexin1 (Panx1) megachannel opening and caspase-1 activation followed by high-mobility group box 1 (HMGB1) release from neurons and nuclear factor κB activation in astrocytes. Suppression of this cascade abolished CSD-induced trigeminovascular activation, dural mast cell degranulation, and headache. CSD-induced neuronal megachannel opening may promote sustained activation of trigeminal afferents via parenchymal inflammatory cascades reaching glia limitans. This pathway may function to alarm an organism with headache when neurons are stressed. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
null, 
null, 
 Let s repost my original concern about Figure 1. Although the erratum states something about a higher exposure, the 3 bands on the right all look very similar (marked with red boxes), albeit at different exposures and orientation. One could argue if an Erratum would suffice to address this. ![file] , 
 My concerns about Figure 2 did not survive the PubPeer upgrade, but are worth uploading again. Several elements in Figure 2C appear to be visible multiple times within the same photo. The Erratum said  In Fig. 2, panel C has been revised to remove the annotations in the background. It appears that elements from the original panel D are also visible in the original panel C, not once but multiple times, and in different locations and orientations. ![file] ,
RETRACTED ARTICLE: TGF-β is associated with poor prognosis and promotes osteosarcoma progression <i>via</i> PI3K/Akt pathway activation
Authors: Chuan Zhang
Kun Ma
Wuyin Li
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PI3K/mTOR pathway; TGF-β; apoptosis; invasion/migration; osteosarcoma
Affiliations: Luoyang Orthopaedic Hospital of Henan Province and Orthopaedic Hospital of Henan Province, Luoyang, Henan, P. R. China

Abstract:  Transforming growth factor beta (TGF-β) is a multifunctional cytokine with important functions in cell proliferation and differentiation. TGF-β is highly expressed in several types of cancers and promotes tumor invasion and metastasis. However, the role of TGF-β in osteosarcoma progression is poorly understood. In the present study, we found that TGF-β is highly expressed in osteosarcoma cells and tissues, and is associated with high Ennecking stage (P = 0.033), metastasis, and recurrence. TGF-β-knockdown osteosarcoma cell lines were established using siRNA (si-TGF-β). Cells transfected with si-TGF-β exhibited significantly reduced proliferation, migration/invasion, and colony formation abilities, and increased levels of cell apoptosis. In addition, si-TGF-β treatment reduced spheroid size, the ratio of CD133-positive cells, and expression of SOX-2, Nanog, and Oct-3/4 in osteosarcoma cells. Mechanistically, PI3K/mTOR phosphorylation is inhibited by TGF-β knockdown. Pretreatment with 25 µM LY294002, a PI3K-specific inhibitor, further enhanced the si-TGF-β-induced suppression of osteosarcoma progression. Taken together, these results reveal a novel role for TGF-β in osteosarcoma progression and modulation of stemness-related traits and indicate that TGF-β may be of value as a therapeutic target for the treatment of osteosarcoma. 

Retracted: Yes

PubPeer comments:
 There seems to be some discrepancy between the reporting of the number of samples included in the main figures and the source data. For example, in Table S4 there are 27 human cases listed, and in figure legends for Fig 5H and Fig 5I it states that n=14 PMC+ and n=13 PMC- cases were analysed, but in Data File S1 showing the source data for Fig 5H has n=14 PMC+ and n=16 PMC- and source data for Fig 5I has n=15 PMC+ and n=14 PMC-. The stats in the figure legend (5H p=0.0089 and 5I p=0.0039) match with the result if you do a 2-tailed t-test of the data from the source files with the larger n s, so the data in the source file must be what was used for the analysis. Fig 5E has n=10 for PABPN1- in Source file and only 10 data points in the graph in the figure, but states n=11 in the figure legend. It states in the methods section that there were total of 31 AD cases in the study - so details on 4 of these are missing from the Table S4, and some of them must have been excluded from some of the studies, and it appears the n values stated in the figure legends are sometimes incorrect. ,
Ginsenoside Rb1 Alleviates Oxidative Low-Density Lipoprotein-Induced Vascular Endothelium Senescence via the SIRT1/Beclin-1/Autophagy Axis
Authors: Bin Zhou
Baoshun Hao
Guangyao Shi
Shujie Yu
Min Wang
Zhiming Song
Xiaoxian Qian
Lin Wu
Dinghui Liu
Chaodong Wu
Jieming Zhu
Yong Liu
Journal: Journal of cardiovascular pharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ox-LDL; endothelium senescence; atherosclerosis; Ginsenoside Rb1; HUVECs
Affiliations: Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China., Department of Cardiology, The First Affiliated Hospital of Henan University, Kaifeng, Henan, China., Department of Nutrition and Food Science, Texas A&M University, College Station, TX., Institute Integrated Traditional Chinese and Western Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

Abstract:  Oxidative low-density lipoprotein (ox-LDL) induces endothelium senescence and promotes atherosclerosis. Ginsenoside Rb1 (gRb1) has been proved to protect human umbilical vein cells (HUVECs), but its effect on ox-LDL-induced endothelium senescence and the underlying mechanism remains unknown. This study is to explore the involvement of the SIRT1/Beclin-1/autophagy axis in the effect of gRb1 on protecting endothelium against ox-LDL-induced senescence. Hyperlipidemia of Sprague Dawley rats was induced by high-fat diet, and gRb1 was intraperitoneal injected. A senescence model of HUVECs induced by ox-LDL was also established. The results showed that gRb1 alleviated hyperlipidemia-induced endothelium senescence and ox-LDL-induced HUVECs senescence. GRb1 also restored the reductions in SIRT1 and autophagy, which were involved in the anti-senescence effects. Beclin-1 acetylation was reduced, and the correlation between SIRT1 and Beclin-1 was increased by gRb1. Results of our study demonstrated the anti-senescence function of gRb1 against hyperlipidemia in the endothelium, and the underlying mechanism involves the SIRT1/Beclin-1/autophagy axis. 

Retracted: No

PubPeer comments:
 Fig 2(e)  Senescence cells were dyed blue-green (positive staining) by SA-u03b2-gal staining (scale bar, 200u00b5m) . Fig 3(e)  80u00b5M ginsenoside Rb1 was added to the medium 30min before ox-LDL, and ... SA-u03b2-gal staining (scale bar, 200u00b5m) ... of different groups showed that cells senescence induced by ox-LDL was alleviated by 80u00b5M ginsenoside Rb1. ![file] There may be some mistake. The CONtrol panel from 3(e) matches a treatment group in 2(e), apart from a greater blue-green signal in the latter. Could the authors check? Here with increased contrast: ![file] ,
Cellular senescence bypass screen identifies new putative tumor suppressor genes
Authors: D H Beach
C Blanco-Aparicio
S Ramon Y Cajal
J F M Leal
M Lleonart
A Cascón
M V Guijarro
J Fominaya
A Carnero
M Robledo
M E Castro
Journal: Oncogene (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Senescence; genetic screen; tumorigenesis; regulatory genes; cellular lifespan
Affiliations: Experimental Therapeutics Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.

Abstract:  Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. To identify new senescence regulatory genes that might play a role in tumorigenesis, we have designed and performed a large-scale antisense-based genetic screen in primary mouse embryo fibroblasts (MEFs). Out of this screen, we have identified five different genes through which loss of function partially bypasses senescence. These genes belong to very different biochemical families: csn2 (component of the Cop9 signalosome), aldose reductase (a metabolic enzyme) and brf1 (subunit of the RNA polymerase II complex), S-adenosyl homocysteine hydrolase and Bub1. Inactivation, at least partial, of these genes confers resistance to both p53- and p16INK4a-induced proliferation arrest. Furthermore, such inactivation inhibits p53 but not E2F1 transcriptional activity and impairs DNA-damage-induced transcription of p21. Since the aim of the screen was to identify new regulators of tumorigenesis, we have tested their inactivation in human tumors. We have found, either by northern blot or quantitative reverse transcriptase-PCR analysis, that the expression of three genes, Csn2, Aldose reductase and Brf1, is lost at different ratios in tumors of different origins. These genes are located at common positions of loss of heterogeneity (15q21.2, 7q35 and 14q32.33); therefore,we have measured genomic losses of these specific genes in different tumors. We have found that Csn2 and Brf1 also show genomic losses of one allele in different tumors. Our data suggest that the three genes identified in the genome-wide loss-of-function genetic screen are putative tumor suppressors located at 15q21.2; 7q35 and 14q32.33. 

Retracted: No

PubPeer comments:
 Figure 2c. BRF1 set of panels. Rightmost lane p21 panel appears to have its own rectangle. ![file] ,
Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway
Authors: Ariel Erental
Idith Sharon
Hanna Engelberg-Kulka
Journal: PLoS Biology (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PCD; apoptosis; Escherichia coli; mazEF; toxin-antitoxin system
Affiliations: Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Abstract:  In eukaryotes, the classical form of programmed cell death (PCD) is apoptosis, which has as its specific characteristics DNA fragmentation and membrane depolarization. In Escherichia coli a different PCD system has been reported. It is mediated by the toxin-antitoxin system module mazEF. The E. coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. mazEF-mediated cell death is a population phenomenon requiring the quorum-sensing pentapeptide NNWNN designated Extracellular Death Factor (EDF). mazEF is triggered by several stressful conditions, including severe damage to the DNA. Here, using confocal microscopy and FACS analysis, we show that under conditions of severe DNA damage, the triggered mazEF-mediated cell death pathway leads to the inhibition of a second cell death pathway. The latter is an apoptotic-like death (ALD); ALD is mediated by recA and lexA. The mazEF-mediated pathway reduces recA mRNA levels. Based on these results, we offer a molecular model for the maintenance of an altruistic characteristic in cell populations. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 I agree with this finding. ,
Transforming Growth Factor-beta Regulation of Ephrin Type-A Receptor 4 Signaling in Breast Cancer Cellular Migration
Authors: Suhad Ali
Jean-Jacques Lebrun
Ibrahim Y Hachim
Julien Boudreault
Halema Haiub
Lucie Canaff
Mahmood Y Hachim
Manuel Villatoro
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Breast cancer; tumor subtypes; prognosis; basal-like breast cancer; Transforming growth factor-beta (TGFβ)
Affiliations: Department of Medicine, McGill University Health Center, Cancer Research Program, Montreal, QC, H4A 3J1, Canada., Sharjah Institute for Medical Research, University of, Sharjah, UAE., Department of Medicine, McGill University Health Center, Cancer Research Program, Montreal, QC, H4A 3J1, Canada. .

Abstract:  Breast cancer consists of a range of tumor subtypes with different clinical characteristics, disease prognosis, and treatment-response. Luminal breast cancer has the best prognosis while basal-like breast cancer (BLBC) represents the worst subtype. Transforming growth factor-beta (TGFβ) plays a prominent role in stimulating the migration and invasion of malignant breast cancer cells contributing to tumor progression. In this study, we identified the Ephrin type-A receptor 4 (EPHA4) as a novel target of TGFβ in breast cancer. Moreover, we show that TGFβ induction of EPHA4 gene expression is specific to basal-like tumors and is required for TGFβ-mediated cell migration. We further addressed the mechanism and found EPHA4 to be required for TGFβ-mediated cell migration in breast cancer through TGFβ-induced short term and long term activation of RhoGTPases. Finally, our data revealed a strong association between high EPHA4 expression and advanced tumor stage, aggressive BLBC molecular subtype and poor prognosis. Importantly, we found significant co-expression of EPHA4 and the TGFβ receptor type-2 (TGFβR2) in breast cancer subtypes associated with increased tumor relapse and drug resistance. Together, this study highlight the important role of the TGFβ/EPHA4 signaling axis in mediating tumor aggressiveness and poor patient survival in human breast cancer. 

Retracted: No

PubPeer comments:
 The lower panel of figure 5 A appears to have two images which overlap. *** Closeup ![file] *** ![file] , 
 #1 Here s another look at this probable overlap. Will contact the journal today. *** ![file] ,
Prevention of dystrophic pathology in severely affected dystrophin/utrophin-deficient mice by morpholino-oligomer-mediated exon-skipping
Authors: Dave Powell
Ryszard Kole
Aurélie Goyenvalle
Kay E Davies
Sue Fletcher
Arran Babbs
Steve D Wilton
Journal: Molecular Therapy (2010)
Discipline: CLINICAL MEDICINE
Keywords: Duchenne muscular dystrophy; DMD; exon-skipping; dystrophin gene; Antisense-mediated
Affiliations: MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.

Abstract:  Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by mutations in the dystrophin gene that result in the absence of functional protein. Antisense-mediated exon-skipping is one of the most promising approaches for the treatment of DMD because of its capacity to correct the reading frame and restore dystrophin expression, which has been demonstrated in vitro and in vivo. In particular, peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) have recently been shown to induce widespread high levels of dystrophin expression in the mdx mouse model. Here, we report the efficiency of the PPMO-mediated exon-skipping approach in the utrophin/dystrophin double-knockout mouse (dKO) mouse, which is a much more severe and progressive mouse model of DMD. Repeated intraperitoneal (i.p.) injections of a PPMO targeted to exon 23 of dystrophin pre-mRNA in dKO mice induce a near-normal level of dystrophin expression in all muscles examined, except for the cardiac muscle, resulting in a considerable improvement of their muscle function and dystrophic pathology. These findings suggest great potential for PPMOs in systemic treatment of the DMD phenotype. 

Retracted: No

PubPeer comments:
null, 
null, 
 Two images in Figure 1c appear unexpectedly similar. *** With enhanced brightness ![file] ,
Enhancement of Soft Tissue Sarcoma Cell Radiosensitivity by Poly(ADP-ribose) Polymerase-1 Inhibitors
Authors: Lorenzo Livi
Carlotta Becherini
Angela Silvano
Giulia Salvatore
Domenico Campanacci
Daniela Greto
Pietro Garlatti
Icro Meattini
Luca Dominici
Chiara Gerini
Isacco Desideri
Pierluigi Bonomo
Camilla Delli Paoli
Monica Mangoni
Silvia Scoccianti
Mauro Loi
Mariangela Sottili
Giovanni Beltrami
Journal: Radiation Research (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Soft tissue sarcomas; PARP-1 inhibitors; radiosensitization; DNA damage; clonogenic assays
Affiliations: Department of a   Biomedical, Experimental and Clinical Sciences "Mario Serio", Section of Radiation Oncology, University of Florence, Largo Brambilla 3, 50134 Florence, Italy., d   Istituto Toscano Tumori, via Taddeo Alderotti 26/N, 50139 Florence, Italy., epartment of, b   Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy., c   Department of Orthopaedic Oncology, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 3, 50134 Florence, Italy and.

Abstract:  Soft tissue sarcomas (STS) are aggressive tumors with a poor prognosis. Poly(ADP-ribose) polymerase (PARP)-1 inhibitors (PARPi) enhance the cytotoxic effects of radiation. In this study, we evaluated the effect of PARPi on survival and DNA damage of irradiated STS cells. For clonogenic assays, STS cell lines were irradiated with or without olaparib, iniparib or veliparib pretreatment. The effect of PARP inhibition on γ-H2AX and Rad51 foci formation, on PARP-1, phospho-ERK and cleaved caspase-3 protein expression and on cell cycle progression was evaluated on irradiated rhabdomyosarcoma cells pretreated with olaparib. The results from this work showed that PARPi induced significant radiosensitization in STS cells. Rhabdomyosarcoma cells showed the highest increase in radiosensitivity, with a radiosensitization enhancement ratio at 50% survival (ER50) of 3.41 with veliparib. All PARPi exerted a synergistic effect when combined with radiation. Fibrosarcoma cells showed an ER50 of 2.29 with olaparib. Leiomyosarcoma and liposarcoma cells showed their highest ER50 with veliparib (1.71 and 1.84, respectively). In rhabdomyosarcoma, olaparib enhanced the formation of radiation-induced γ-H2AX/Rad51 foci and PARP-1 cleavage, induced slightly increased expression of cleaved caspase-3 and reduced phospho-ERK expression. Moreover, the combination of olaparib and radiation resulted in a significantly enhanced cell cycle arrest in the G2/M phase compared to the two treatments alone. In conclusion, we have shown that PARPi are potent radiosensitizers of human STS cells. These results support the pursuit of further investigations into the effects of PARPi combined with radiation on STS. 

Retracted: No

PubPeer comments:
 In this study they use Iniparib as a PARP inhibitor. It s not a PARP inhibitor, and the results are therefore misleading. This was known back in 2012: https: clincancerres.aacrjournals.org content 18 2 510 https: clincancerres.aacrjournals.org content 18 6 1655 ,
Sperm methylome alterations following yoga‐based lifestyle intervention in patients of primary male infertility: A pilot study
Authors: Rajeev Kumar
Surabhi Srivastava
Rima Dada
Sofia Banu
Shilpa Bisht
Rashmi U Pathak
Rakesh K Mishra
Journal: Andrologia (2020)
Discipline: CLINICAL MEDICINE
Keywords: RRBS; male infertility; methylome; sperm quality; yoga.
Affiliations: Lab for Molecular Reproduction and Genetics Anatomy Department All India Institute of Medical Sciences New Delhi India, CSIR‐Centre for Cellular and Molecular Biology Hyderabad India, Department of Urology All India Institute of Medical Sciences New Delhi India

Abstract:  A majority of the cases of primary male infertility are idiopathic with the underlying molecular mechanisms contributing to the pathophysiology as yet unknown. Effects of the environment can alter the sperm epigenome thereby impacting male reproductive health. Epigenetic mechanisms are crucial to understanding health and disease, and methylome alterations are now known to have far-reaching clinical implications. Here, we report the results from our pilot study, a first of its kind analysis of the effect of the traditional practice of yoga on human sperm quality. We find marked improvement in sperm characteristics in patients of idiopathic male infertility following a supervised 21-day yoga regimen. Furthermore, next-generation sequencing-based methylome analysis reveals alterations in the sperm epigenome of these patients. We find that the practice of yoga is associated with DNA methylation changes at nearly 400 genes, 147 of which were hypermethylated while 229 were hypomethylated. These included promoters of several genes linked to maintenance of fertility and genomic integrity. This novel piece of work draws a direct link between positive lifestyle practices and male reproductive health. 

Retracted: No

PubPeer comments:
 In Figure 7, three different micrographs have been duplicated and presented as something else. ![file] ,
Multipotent mesenchymal stem cells in lung fibrosis
Authors: Luca Tamo
Katrin E Hostettler
Michael Tamm
Didier Lardinois
Michael Roth
Petra Khan
Thomas Geiser
Amiq Gazdhar
Spasenija Savic
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: Stem cells; Mesenchymal stem cells (MSC); Lung disease; Fibrotic lung diseases; Emphysema
Affiliations: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland., Clinics of Respiratory Medicine, University Hospital Basel, University of Basel, Basel, Switzerland., Division of Pulmonary Medicine, University Hospital Bern, Bern, Switzerland., Department of Pathology, University Hospital Basel, University of Basel, Basel, Switzerland., Division of Thoracic Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.

Abstract:  Rationale: Stem cells have been identified in the human lung; however, their role in lung disease is not clear. We aimed to isolate mesenchymal stem cells (MSC) from human lung tissue and to study their in vitro properties. Methods: MSC were cultured from lung tissue obtained from patients with fibrotic lung diseases (n = 17), from emphysema (n = 12), and normal lungs (n = 3). Immunofluorescence stainings were used to characterize MSC. The effect of MSC-conditioned media (MSC-CM) on fibroblast proliferation and on lung epithelial wound repair was studied. Results: Expression of CD44, CD90, and CD105 characterized the cells as MSC. Moreover, the cells stained positive for the pluripotency markers Oct3/4 and Nanog. Positive co-stainings of chemokine receptor type 4 (CXCR4) with CD44, CD90 or CD105 indicated the cells are of bone marrow origin. MSC-CM significantly inhibited the proliferation of lung fibroblasts by 29% (p = 0.0001). Lung epithelial repair was markedly increased in the presence of MSC-CM (+ 32%). Significantly more MSC were obtained from fibrotic lungs than from emphysema or control lungs. Conclusions: Our study demonstrates enhanced numbers of MSC in fibrotic lung tissue as compared to emphysema and normal lung. The cells inhibit the proliferation of fibroblasts and enhance epithelial repair in vitro. Further in vivo studies are needed to elucidate their potential role in the treatment of lung fibrosis. 

Retracted: No

PubPeer comments:
 Fig 2 I looks identical to 2 E after lowering brightness ![file] , 
 the linked Erratum from the Journal is non-relevant to the data correction, and does not provide explanations for the suspected stretching and duplicated-usage of raw microscope data. ,