PReD-Bench/PRed-Bench huggingface dataset:
NADPH oxidase and the degeneration of dopaminergic neurons in parkinsonian mice
Authors: Cecília C Café-Mendes
Marina S Hernandes
Luiz R G Britto
Journal: Oxidative Medicine and Cellular Longevity (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Oxidative stress; Parkinson's disease; NADPH oxidase; Nox; 6-hydroxydopamine
Affiliations: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-900 SP, Brazil.

Abstract:  Several lines of investigation have implicated oxidative stress in Parkinson's disease (PD) pathogenesis, but the mechanisms involved are still unclear. In this study, we characterized the involvement of NADPH oxidase (Nox), a multisubunit enzyme that catalyzes the reduction of oxygen, in the 6-hydroxydopamine- (6-OHDA-) induced PD mice model and compared for the first time the effects of this neurotoxin in mice lacking gp91(phox-/-), the catalytic subunit of Nox2, and pharmacological inhibition of Nox with apocynin. Six-OHDA induced increased protein expression of p47(phox), a Nox subunit, in striatum. gp91(phox-/-) mice appear to be completely protected from dopaminergic cell loss, whereas the apocynin treatment conferred only a limited neuroprotection. Wt mice treated with apocynin and gp91(phox-/-) mice both exhibited ameliorated apomorphine-induced rotational behavior. The microglial activation observed within the striatum and the substantia nigra pars compacta (SNpc) of 6-OHDA-injected Wt mice was prevented by apocynin treatment and was not detected in gp91(phox-/-) mice. Apocynin was not able to attenuate astrocyte activation in SN. The results support a role for Nox2 in the 6-OHDA-induced degeneration of dopaminergic neurons and glial cell activation in the nigrostriatal pathway and reveal that no comparable 6-OHDA effects were observed between apocynin-treated and gp91(phox-/-) mice groups. 

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. ,
Magnesium-Zinc-Calcium-Vitamin D Co-supplementation Improves Hormonal Profiles, Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Mehri Jamilian
Maryam Maktabi
Zatollah Asemi
Journal: Biological Trace Element Research (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Endocrine profiles; Inflammation; Polycystic ovary syndrome; Supplementation.
Affiliations: Endocrinology and Metabolism Research Center, Department of Gynecology and Obstetrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran., Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran. .

Abstract:  Data on the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS) are scarce. The objective of this study was to assess the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress in women with PCOS. Sixty PCOS women were randomized into two groups and treated with 100 mg magnesium, 4 mg zinc, 400 mg calcium plus 200 IU vitamin D supplements (n = 30), or placebo (n = 30) twice a day for 12 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were assessed at baseline and at end-of-treatment. After the 12-week intervention, compared with the placebo, magnesium-zinc-calcium-vitamin D co-supplementation resulted in significant reductions in hirsutism (-2.4 ± 1.2 vs. -0.1 ± 0.4, P &lt; 0.001), serum high sensitivity C-reactive protein (-0.7 ± 0.8 vs. +0.2 ± 1.8 mg/L, P &lt; 0.001), and plasma malondialdehyde (-0.4 ± 0.3 vs. +0.2 ± 1.0 μmol/L, P = 0.01), and a significant increase in plasma total antioxidant capacity concentrations (+46.6 ± 66.5 vs. -7.7 ± 130.1 mmol/L, P = 0.04). We failed to find any significant effect of magnesium-zinc-calcium-vitamin D co-supplementation on free androgen index, and other biomarkers of inflammation and oxidative stress. Overall, magnesium-zinc-calcium-vitamin D co-supplementation for 12 weeks among PCOS women had beneficial effects on hormonal profiles, biomarkers of inflammation, and oxidative stress. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A149 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 18 publications have an expression of concern, and 6 have been retracted. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
Genetic alterations of the NRP/B gene are associated with human brain tumors
Authors: Shalom Avraham
Hava Karsenty Avraham
Xing-Qun Liang
Shuxian Jiang
Journal: Oncogene (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: brain tumors; genetic alterations; oncogenes; tumor suppressor genes; nuclear matrix
Affiliations: Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115, USA.

Abstract:  Nearly all brain tumors develop following the progressive accumulation of genetic alterations of oncogenes and tumor suppressor genes (such as p53 and retinoblastoma protein). Furthermore, aberrations in the nuclear matrix often contribute to genomic instabilities and the development of cancer. We have previously shown that nuclear-restricted protein/brain (NRP/B), a member of the BTB/Kelch repeat family, is a nuclear matrix protein normally expressed in neurons but not in astrocytes, and that it is an early and specific marker of neurons during the development of the central nervous system. Here, we show aberrant expression of NRP/B in human brain tissues. NRP/B is expressed in the cytoplasm of human brain tumor cells (glioblastoma, GBM) arising from astrocytes. NRP/B mutations (13 mutations in the Kelch domains, two in the intervening sequence (IVS) domain and two in the BTB domain) were detected in brain tumor cell lines (A-172, CCF-STTG1, SK-N-SH and U87-MG) and in primary human malignant GBM tissues (eight samples). More importantly, we found that NRP/B mutants, but not wild-type (wt) NRP/B, increased the activation of ERK and consequently promoted cell proliferation, attenuated caspase activation and suppressed the cellular apoptosis induced by the stressful stimulus cisplatin (10 microM). These events were observed to occur via a p53-mediated pathway. In addition, while wt NRP/B was associated with actin, mutations in the Kelch domains of NRP/B led to its reduced binding affinity to actin. Thus, alterations and gene mutations within the NRP/B gene may contribute to brain tumorigenesis by promoting cell proliferation, suppressing apoptosis and by affecting nuclear cytoskeleton dynamics. 

Retracted: No

PubPeer comments:
 Figure 3c. Much more similar than you would expect. https: imgur.com HAwYHYM , 
 Figure 2b. Much more similar than you would expect. https: imgur.com MnlmYkT , 
 Figure 4b. Much more similar than you would expect. https: imgur.com EkMVIuo , 
 #1 Figure 3c. Actin blots. Much more similar than you would expect. https: imgur.com weURlW5 ,
shRNA-mediated silencing of hTERT suppresses proliferation and promotes apoptosis in osteosarcoma cells
Authors: P Chen
J Wang
M-Z Gong
W-L Gu
D-Q Li
Journal: Cancer Gene Therapy (2017)
Discipline: CLINICAL MEDICINE
Keywords: shRNA; hTERT; osteosarcoma cells; proliferation; apoptosis
Affiliations: Department of Trauma Orthopedics, The Second Hospital of Shandong University, Jinan, China., Department of Operating Theatre, The Second Hospital of Shandong University, Jinan, China.

Abstract:  In this study, we aim to explore the effects of short hairpin RNAs (shRNAs) targeting human telomerase reverse transcriptase (hTERT) on the proliferation and apoptosis of osteosarcoma cells. After the synthesis of shRNA that target hTERT, osteosarcoma cells were assigned into three experimental groups-shRNA group, scramble group and blank group. The transcription and expressions of the hTERT gene in transfected cells were measured with quantitative real-time polymerase chain reaction and western blotting. Cell proliferation in each group was detected by Cell Counting Kit-8 assay. Cell cycle and rates of apoptosis were measured by flow cytometry. Expressions of apoptosis-related proteins, caspase-9 and caspase-3, were detected by western blotting. Telomerase activity was measured by PCR enzyme-linked immunosorbent assay. Results show that both the mRNA and protein expressions of hTERT were significantly lowered after the transfection of hTERT-shRNA. The proliferation capacity of transfected osteosarcoma MG-63, SaOS2 and U2OS cells in the shRNA group was lower than that in the blank group. We also found changes and differences in the amount of cells throughout the cell cycle. All cells in the G0/G1 phase increased in numbers, whereas the number of cells in the S phase were reduced, with elevated apoptosis rates. Expressions of apoptosis-related proteins, caspase-9 and caspase-3, were increased and telomerase activity was decreased in the transfected shRNA group (all P&lt;0.05). Our results showed that shRNA targeting of the hTERT gene was able to inhibit cell proliferation and promote apoptosis of osteosarcoma cells by reducing the telomerase activity. 

Retracted: No

PubPeer comments:
 *[left]* Figs 3b, 7c. *[right]* Fig 3B from [Feng Qiu (2018)] . ![file] The latter thread links to other manifestations of these blots. ,
A multi-ingredient nutritional supplement enhances exercise training-related reductions in markers of systemic inflammation in healthy older men
Authors: Adrian Chabowski
Kirsten E Bell
Dinesh Kumbhare
Michael A Zulyniak
Stuart M Phillips
Gianni Parise
Tim Snijders
Journal: Applied Physiology Nutrition and Metabolism (2018)
Discipline: CLINICAL MEDICINE
Keywords: acides gras polyinsaturés oméga-3; calcium; creatine; créatine; entraînement par intervalle d’intensité élevée
Affiliations: Department of Kinesiology, McMaster University, Hamilton, ON L8S 4L8, Canada., Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada., Department of Physiology, Medical University of Bialystok, 15-222 Bialystok, Poland.

Abstract:  We evaluated whether twice-daily consumption of a multi-ingredient nutritional supplement (SUPP) would reduce systemic inflammatory markers following 6 weeks of supplementation alone (phase 1), and the subsequent addition of 12 weeks of exercise training (phase 2) in healthy older men, in comparison with a carbohydrate-based control (CON). Tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations were progressively reduced (P-time &lt; 0.05) in the SUPP group. No change in TNF-α or IL-6 concentrations was observed in the CON group. 

Retracted: No

PubPeer comments:
 Copy pasted from https: cdnsciencepub.com doi 10.1139 apnm-2020-0763 :  Publication: Applied Physiology, Nutrition, and Metabolism u2022 28 September 2020 Ref.: Appl. Physiol. Nutr. Metab. 43(3): 299u2013302 (2018) dx.doi.org 10.1139 apnm-2017-0533. The authors wish to correct the conflict of interest statement as follows: In addition, S.M.P. and G.P. were inventors on a Canadian patent 3052324 and US patent application 62 466,557. Both authors hold equity in Exerkine, the company that owns the patent. S.M.P. reports that all proceeds from his equity share of Exerkine are donated to charity. See https: retractionwatch.com 2021 02 12 eleven-papers-corrected-after-nutrition-prof-fails-to-disclose-patent-company-ties for backgrounds. ,
A ubiquitin-proteasome pathway for the repair of topoisomerase I-DNA covalent complexes
Authors: Shyamal D Desai
Chao-Po Lin
Yi Lisa Lyu
Leroy F Liu
Yi Ban
Journal: Journal of Biological Chemistry (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Topoisomerase I; DNA cleavage complexes; camptothecins; Top1 down-regulation; transcription arrest
Affiliations: Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

Abstract:  Reversible topoisomerase I (Top1)-DNA cleavage complexes are the key DNA lesion induced by anticancer camptothecins (e.g. topotecan and irinotecan) as well as structurally perturbed DNAs (e.g. oxidatively damaged DNA, UV-irradiated DNA, alkylated DNA, uracil-substituted DNA, mismatched DNA, gapped and nicked DNA, and DNA with abasic sites). Top1 cleavage complexes arrest transcription and trigger transcription-dependent degradation of Top1, a phenomenon termed Top1 down-regulation. In the current study, we have investigated the role of Top1 down-regulation in the repair of Top1 cleavage complexes. Using quiescent (serum-starved) human WI-38 cells, camptothecin (CPT) was shown to induce Top1 down-regulation, which paralleled the induction of DNA single-strand breaks (SSBs) (assayed by comet assays) and ATM autophosphorylation (at Ser-1981). Interestingly, Top1 down-regulation, induction of DNA SSBs and ATM autophosphorylation were all abolished by the proteasome inhibitor MG132. Furthermore, studies using immunoprecipitation and dominant-negative ubiquitin mutants have suggested a specific requirement for the assembly of Lys-48-linked polyubiquitin chains for CPT-induced Top1 down-regulation. In contrast to the effect of proteasome inhibition, inactivation of PARP1 was shown to increase the amount of CPT-induced SSBs and the level of ATM autophosphorylation. Together, these results support a model in which Top1 cleavage complexes arrest transcription and activate a ubiquitin-proteasome pathway leading to the degradation of Top1 cleavage complexes. Degradation of Top1 cleavage complexes results in the exposure of Top1-concealed SSBs for repair through a PARP1-dependent process. 

Retracted: No

PubPeer comments:
 ![file] ,
Effects of High-dose Vitamin E Supplementation on Markers of Cardiometabolic Risk and Oxidative Stress in Patients with Diabetic Nephropathy: a Randomized Double-blinded Controlled Trial
Authors: Esmat Aghadavod
Alireza Soleimani
Zatollah Asemi
Gholamali Hamidi
Akbar Heidari
Fariba Keneshlou
Journal: Iranian journal of kidney diseases (2018)
Discipline: CLINICAL MEDICINE
Keywords: Diabetic nephropathy; Vitamin E supplementation; Cardiometabolic risk; Oxidative stress; Lipid profile
Affiliations: Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran. .

Abstract:  Introduction: Patients with diabetic nephropathy (DN) may benefit from vitamin E's antilipid and antioxidant activities. This study aimed to evaluate the effects of high-dose vitamin E supplementation on markers of cardiometabolic risk and oxidative stress in patients with DN. Materials and methods: This randomized controlled trial was carried out on 54 patients with DN that were randomly divided into 2 groups to receive vitamin E supplement (800 IU/d) or placebo for 12 weeks. Fasting blood samples were obtained at baseline and after the 12-week intervention to determine markers of cardiometabolic risk and oxidative stress. Results: Vitamin E supplementation, compared with the placebo, resulted in a significant reduction in serum total cholesterol (-14.3 ± 29.9 mg/dL versus -0.8 ± 13.1 mg/L, P = .03), low-density lipoprotein cholesterol (-16.4 ± 28.5 mg/dL versus 0.1 ± 17.2 mg/L, P = .01), and ratio of total cholesterol to high-density lipoprotein cholesterol ratio (-0.5 ± 0.7 versus 0.1 ± 0.5, P = .001), and a significant elevation in vitamin E levels (39.7 ± 12.4 nmol/mL versus -0.5 ± 1.3 nmol/mL, P &lt; .001) and high-density lipoprotein cholesterol levels (1.4 ± 3.7 versus -2.1 ± 5.1 mg/L, P = .006). It also resulted in a significant elevation in plasma glutathione levels. Conclusions: Our study demonstrated that high-dose vitamin E supplementation for 12 weeks had favorable effects on lipid profile and glutathione levels of patients with DN, except for triglycerides, very low-density lipoprotein cholesterol, nitric oxide, and total antioxidant capacity levels. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A125 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern, and 2 have been retracted. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
MicroRNA-101 suppresses migration and invasion via targeting vascular endothelial growth factor-C in hepatocellular carcinoma cells
Authors: Xiaoming Fan
Zhenyu Liu
Jingjie Wang
Yuqing Mao
Bing Zou
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: hepatocellular carcinoma; invasion; microRNA-101; migration; vascular endothelial growth factor-C.
Affiliations: Department of Gastroenterology and Hepatology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China; Department of Gastroenterology and Hepatology, Shenzhen Hospital, Peking University, Shenzhen, Guangdong 518036, P.R. China., Department of Gastroenterology and Hepatology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China., Department of Gastroenterology and Hepatology, Shenzhen Hospital, Peking University, Shenzhen, Guangdong 518036, P.R. China.

Abstract:  MicroRNAs (miRNAs) are a class of non-coding RNAs 18-25 nucleotides in length, which play important roles in the regulation of cancer progression through gene silencing. miRNA (miR)-101 has been suggested to be associated with hepatocellular carcinoma (HCC). However, the detailed role of miR-101 in HCC metastasis and the underlying mechanism remain largely unclear. The present study demonstrated that the expression of miR-101 was significantly reduced in HCC tissues compared with that in matched normal adjacent tissues. miR-101 was also found to be downregulated in four HCC cell lines compared with its expression in a normal liver cell line. Vascular endothelial growth factor (VEGF)-C was further identified as a direct target of miR-101, and the protein expression of VEGF-C was downregulated by miR-101 in HepG2 HCC cells. Furthermore, the overexpression of miR-101 and the knockdown of VEGF-C significantly inhibited HepG2 cell migration and invasion, while restoration of VEGF-C reversed the inhibitory effect of miR-101 overexpression on HepG2 cell migration and invasion. Finally, the expression of VEGF-C was notably increased in HCC tissues and cell lines. These findings suggest that miR-101 exerts a suppressive effect on HCC cell migration and invasion, at least in part through the direct inhibition of VEGF-C protein expression. Therefore, the miR-101/VEGF-C axis may serve as a potential therapeutic target for HCC metastasis. 

Retracted: No

PubPeer comments:
 Figure 2E appears to have a band with a repeated smear. Could the authors please provide the original uncropped scan? I did not check elsewhere. *** ![file] *** Closeup showing some common background features. ![file] , 
 Dear Actinopolyspora Biskrensisuff0c Thank you very much for your comments, and sorry to bother you with this problem.Upon receipt of your query, we re-check our manuscripts and raw data carefully, and I can provide the the original uncropped scan as belowuff0c ![file] ![file] Thank you four attention and help. Sincerely Hong qiong Fan ,
TRIM59 knockdown blocks cisplatin resistance in A549/DDP cells through regulating PTEN/AKT/HK2
Authors: Hongxu Liu
Rong He
Journal: Gene (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cisplatin resistance; Glycolysis; NSCLC; TRIM59.
Affiliations: Department of Thoracic Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, PR China., Department of Thoracic Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, PR China. Electronic address: .

Abstract:  Cisplatin is commonly used for lung cancer treatment. However, acquire resistance to cisplatin results in reduced therapy efficacy. Tripartite motif-containing 59 (TRIM59), acting as an oncogene in non-small cell lung cancer (NSCLC), induces chemoresistance in breast cancer cells. Here, the mechanism by which TRIM59 mediates cisplatin resistance was determined. We demonstrated that cisplatin-resistant NSCLC cell line (A549/DDP) had higher expression of TRIM59 than its parental cell line (A549). As indicated by cell apoptosis assay, TRIM59 overexpression in A549 cells resulted in an increased cisplatin resistance, while TRIM59 downregulation in A549/DDP cells led to an decreased cisplatin resistence. A549/DDP cells with TIMR59 knockdown was more sensitive to cisplatin treatment in a xenograft model. Moreover, A549/DDP cells exhibited increased glucose uptake, lactate production, and hexokinase 2 (HK2, an important glycolytic pathway enzyme) expression than A549 cells. The glycolysis was increased by TRIM59 overexpression in A549 cell, and decreased by TRIM59 knockdown in A549/DDP cells. 3-Bromopyruvate Acid (3-BrPA), an inhibitor of HK2, significantly enhanced cisplatin-sensitivity in A549 cells overexpressing TRIM59. Furthermore, both TRIM59 and HK2 expression was higher in cisplatin-resistant NSCLC tissues than in non-resistant ones, and mRNA expression of these two molecules was positively correlated in NSCLC tissues. The changes of PTEN and phosphorylation of AKT (p-AKT), a critical upstream regulator of HK2, were also consistent with HK2 expression. Immunoprecipiation experiments showed the interaction between TRIM59 and PTEN in A549/DDP cells, and that TRIM59 knockdown suppressed the ubiquitination of PTEN. Collectively, the present study indicates that TRIM59 knockdown reverses high glycolysis rate and cisplatin resistance in A549/DDP cells through the regulation of PTEN/AKT/HK2 and may provide insights into overcoming cancer resistance to cisplatin treatment. 

Retracted: No

PubPeer comments:
 Figure 1B and 1C. Four panels appear to look very similar to each other, but the labels suggest they are different experiments. From the figure legend: * B shows: (B) A549 cells were transduced with TRIM59 overexpression virus (TRIM OE) or control virus (Vector) for 24 h, and then treated with 0 or 20 u03bcM cisplatin for 24 h. * C shows: (C) A549 DDP cells were transduced with TRIM59 shRNAs (shTRIM-1 and shTRIM-2) or control shRNA (shNC) for 24 h, and then treated with 0 or 20 u03bcM cisplatin for 24 h. ![file] ,
Rapamycin induces autophagy in the melanoma cell line M14 via regulation of the expression levels of Bcl-2 and Bax
Authors: DI Wu
Jinggang Shen
Meihua Zhou
Yan Lu
Xue Li
Journal: Oncology Letters (2013)
Discipline: CLINICAL MEDICINE
Keywords: Cancer therapy; rapamycin; melanoma; autophagy; proliferation
Affiliations: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029,  P.R. China.

Abstract:  Cancer therapy with rapamycin has been successfully implemented for kidney cancer, glioblastoma and prostate cancer. However, there are few studies concerning the effects of rapamycin on the treatment of human melanoma. In this study, we investigated whether rapamycin may be a promising strategy for the effective treatment of melanoma and explored the possible mechanism for this by culturing M14 cells in vitro and treating with rapamycin at three concentrations (10, 50 or 100 nmol/l). MDC and LC3B staining, western blot analysis, flow cytometry and transmission electron microscopy were employed. We revealed that rapamycin induced autophagy and inhibited the proliferation of M14 cells in a concentration-dependent manner, Furthermore, western blot analysis revealed an upregulated expression of Bcl-2 and downregulated expression of Bax in M14 cells. In conclusion, rapamycin induced autophagy and inhibited the growth of M14 cells. The mechanism may involve regulation of the expression of Bcl-2 family proteins. Rapamycin appears to be a promising strategy for the effective treatment of melanoma. 

Retracted: No

PubPeer comments:
 ![file] some panels of figure 1b and figure 1c appear to show an area of overlap. , 
 ![file] There seems to be more problems in the figures of this paper. In Figure 4. This anomaly is more clearly shown in the reversed phase photograph. ,
Acetonic extract of Buxus sempervirens induces cell cycle arrest, apoptosis and autophagy in breast cancer cells
Authors: Lauriane Fritsch
Véronique Joliot
Julien Pontis
Ouardia Ait-Mohamed
Djebbar Atmani
Slimane Ait-Si-Ali
Souhila Medjkane
Valentine Battisti
Aazdine Lamouri
Christine Fahy
Mohamed Rholam
Catherine Redeuilh
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: Plants; anti-cancer drugs; Buxus sempervirens; breast cancer cell lines; cytotoxic activity
Affiliations: Laboratoire de Biochimie Appliquée, Faculté des Sciences de la Nature et de la vie, Université de Béjaia, Béjaia, Algeria. 

Abstract:  Plants are an invaluable source of potential new anti-cancer drugs. Here, we investigated the cytotoxic activity of the acetonic extract of Buxus sempervirens on five breast cancer cell lines, MCF7, MCF10CA1a and T47D, three aggressive triple positive breast cancer cell lines, and BT-20 and MDA-MB-435, which are triple negative breast cancer cell lines. As a control, MCF10A, a spontaneously immortalized but non-tumoral cell line has been used. The acetonic extract of Buxus sempervirens showed cytotoxic activity towards all the five studied breast cancer cell lines with an IC(50) ranging from 7.74 µg/ml to 12.5 µg/ml. Most importantly, the plant extract was less toxic towards MCF10A with an IC(50) of 19.24 µg/ml. Fluorescence-activated cell sorting (FACS) analysis showed that the plant extract induced cell death and cell cycle arrest in G0/G1 phase in MCF7, T47D, MCF10CA1a and BT-20 cell lines, concomitant to cyclin D1 downregulation. Application of MCF7 and MCF10CA1a respective IC(50) did not show such effects on the control cell line MCF10A. Propidium iodide/Annexin V double staining revealed a pre-apoptotic cell population with extract-treated MCF10CA1a, T47D and BT-20 cells. Transmission electron microscopy analyses indicated the occurrence of autophagy in MCF7 and MCF10CA1a cell lines. Immunofluorescence and Western blot assays confirmed the processing of microtubule-associated protein LC3 in the treated cancer cells. Moreover, we have demonstrated the upregulation of Beclin-1 in these cell lines and downregulation of Survivin and p21. Also, Caspase-3 detection in treated BT-20 and T47D confirmed the occurrence of apoptosis in these cells. Our findings indicate that Buxus sempervirens extract exhibit promising anti-cancer activity by triggering both autophagic cell death and apoptosis, suggesting that this plant may contain potential anti-cancer agents for single or combinatory cancer therapy against breast cancer. 

Retracted: No

PubPeer comments:
 Figure 3C and 5. * Some panels appear to show overlapping areas, as shown here with boxes of the same color. ![file] ,
LINC00483 is regulated by IGF2BP1 and participates in the progression of breast cancer
Authors: Y-S Qiao
B-H Jin
J-H Zhou
B Zhao
Y-Q Wu
Journal: European review for medical and pharmacological sciences (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: LINC00483; breast cancer; mechanism of action; RNA immunoprecipitation; IGF2BP1

Abstract:  Objective: To explore the role of long intergenic non-coding ribonucleic acid 483 (LINC00483) in the development of breast cancer (BC) and its possible mechanism of action. Patients and methods: LINC00483 expression level in BC tissues and cell lines was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). The association between LINC00483 expression and survival rate of BC patients was analyzed using Kaplan-Meier survival analysis. The binding relation between LINC00483 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was verified via RNA immunoprecipitation (RIP) and RNA pull-down assays. The expression of IGF2BP1 in BC patients was determined using qRT-PCR. Moreover, the role of LINC00483 on the proliferative ability of BC cells was detected via cell counting kit-8 (CCK8) and 5-Ethynyl-2'-deoxyuridine (EdU) assays. Whether LINC00483 exerts its effects under the regulation of IGF2BP1 was verified via reversal assay. Results: The results of qRT-PCR showed that LINC00483 had a significantly high expression in BC tissues and corresponding cell lines, and it rose with the increase in tumor stage, which was higher in patients with metastasis. CCK8/EdU assay revealed that the proliferative ability of MDA-MB-231 and MCF-7 cell lines was enhanced by overexpression of LINC00483. It was confirmed by RIP and pull-down assays that IGF2BP1 could bind to LINC00483, and the expression of LINC00483 was significantly promoted after up-regulation of IGF2BP1. It was found via qRT-PCR that the expression of IGF2BP1 evidently rose in BC patients, which was positively related with the expression level of LINC00483. The results of reversal assay manifested that the function of LINC00483 on cell proliferation was regulated by IGF2BP1. Conclusions: LINC00483 has a significantly higher expression in BC tissues than that in para-carcinoma tissues, and its effect of promoting proliferation of BC cells may be regulated by IGF2BP1. 

Retracted: No

PubPeer comments:
 ![file]  A total of 32 cases of BC tissues and corresponding para-carcinoma tissues were surgically resected from BC patients in Chifeng Municipal Hospital from May 2017 to June 2019. Yet these survival curves show the patients were monitored for 100+ months. Have the authors been time travelling? , 
 The corresponding author here, Bo Zhao, affiliated to Department of Nuclear Medicine, Changhai Hospital, Second Military Medical University, Shanghai, provides an email address at Portland Community College for correspondence (in the name of Martin Brandon). ![file] Is this some kind of mistake? ,
Glucose deprivation induced upregulation of phosphoenolpyruvate carboxykinase modulates virulence in Leishmania donovani
Authors: Ruby Singh
Ajay Kumar
Pradeep Das
Abhishek Mandal
Kislay Kumar Sinha
Sudha Verma
Ayan Kumar Ghosh
Abul Hasan Sardar
Sushmita Das
Kumar Abhishek
Bidyut Purkait
Savita Saini
Ashish Kumar
Journal: Molecular Microbiology (2016)
Discipline: MICROBIOLOGY
Keywords: Leishmania donovani; glucose starvation; virulence; survival; metacyclogenesis
Affiliations: Department of Biotechnology; National Institute of Pharmaceutical Education and Research (NIPER); Hajipur Bihar India, Division of Molecular Biology; Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Indian Council of Medical Research; Patna Bihar India, Department of Microbiology; All India Institute of Medical Sciences; Patna Bihar India

Abstract:  Various physiological stimuli trigger the conversion of noninfective Leishmania donovani promastigotes to the infective form. Here, we present the first evidence of the effect of glucose starvation, on virulence and survival of these parasites. Glucose starvation resulted in a decrease in metabolically active parasites and their proliferation. However, this was reversed by supplementation of gluconeogenic amino acids. Glucose starvation induced metacyclogenesis and enhanced virulence through protein kinase A regulatory subunit (LdPKAR1) mediated autophagy. Glucose starvation driven oxidative stress upregulated the antioxidant machinery, culminating in increased infectivity and greater parasitic load in primary macrophages. Interestingly, phosphoenolpyruvate carboxykinase (LdPEPCK), a gluconeogenic enzyme, exhibited the highest activity under glucose starvation to regulate growth of L. donovani by alternatively utilising amino acids. Deletion of LdPEPCK (Δpepck) decreased virulent traits and parasitic load in primary macrophages but increased autophagosome formation in the mutant parasites. Furthermore, Δpepck parasites failed to activate the Pentose Phosphate Pathway shunt, abrogating NADPH/NADP+ homoeostasis, conferring increased susceptibility towards oxidants following glucose starvation. In conclusion, this study showed that L. donovani undertakes metabolic rearrangements via gluconeogenesis under glucose starvation for acquiring virulence and its survival in the hostile environment. 

Retracted: No

PubPeer comments:
 Concern about Figure 5A: * The results state that:  *Semiquantitative PCR analysis did not show any significant difference in the expression of the gluconeogenic pathway genes LdPEPCK, LdPPDK or LdFBPase in GS and GR parasites (Fig. 5A).* * However, most of the bands in these four gel strips are separated by sharp background transitions, and several bands look similar to each other, as shown with arrows of the same color. * Image contrast enhanced to bring out details. ![file] Concerns supported by Fiji false-color imaging: ![file] ,
A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis
Authors: Roland Nilsson
Vishal M Gohil
Zareen Gauhar
Joshua M Baughman
Vamsi K Mootha
Daniel H Arlow
Journal: PLoS genetics (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Oxidative phosphorylation; ATP biosynthesis; Gene regulation; Expression screening; Regulators
Affiliations: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.

Abstract:  The human oxidative phosphorylation (OxPhos) system consists of approximately 90 proteins encoded by nuclear and mitochondrial genomes and serves as the primary cellular pathway for ATP biosynthesis. While the core protein machinery for OxPhos is well characterized, many of its assembly, maturation, and regulatory factors remain unknown. We exploited the tight transcriptional control of the genes encoding the core OxPhos machinery to identify novel regulators. We developed a computational procedure, which we call expression screening, which integrates information from thousands of microarray data sets in a principled manner to identify genes that are consistently co-expressed with a target pathway across biological contexts. We applied expression screening to predict dozens of novel regulators of OxPhos. For two candidate genes, CHCHD2 and SLIRP, we show that silencing with RNAi results in destabilization of OxPhos complexes and a marked loss of OxPhos enzymatic activity. Moreover, we show that SLIRP plays an essential role in maintaining mitochondrial-localized mRNA transcripts that encode OxPhos protein subunits. Our findings provide a catalogue of potential novel OxPhos regulators that advance our understanding of the coordination between nuclear and mitochondrial genomes for the regulation of cellular energy metabolism. 

Retracted: No

PubPeer comments:
 At least two of the flow cytometry images are re-samplings re-gatings of the same population. They are very small, but I have highlighted three identical regions. ![file] Have the authors uploaded the wrong images? ,
Repression of the Transactivating Capacity of the Oncoprotein PLAG1 by SUMOylation
Authors: Els L D Delvaux
Marcela V Chavez
Frederik Van Dyck
Wim J M Van de Ven
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PLAG1; transcription factors; SUMOylation; oncoprotein; transactivation
Affiliations: Laboratory for Molecular Oncology, Department for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Herestraat 49, B-3000 Leuven, Belgium.

Abstract:  Human pleomorphic adenoma gene 1 (PLAG1), a developmentally regulated proto-oncogene, is consistently rearranged and overexpressed in pleomorphic salivary gland adenomas and lipoblastomas with 8q12 translocations. Together with PLAGL1 and PLAGL2, PLAG1 belongs to a subfamily of C(2)H(2) zinc finger transcription factors that activate transcription through binding to the bipartite consensus sequence GRGGC(N)(6-8)GGG. Ectopic expression of PLAG1 deregulates target genes and presumably results in uncontrolled cell proliferation. To gain insight into molecular mechanisms regulating PLAG transcriptional capacity, we searched for interaction partners using the yeast two-hybrid system and confirmed these by glutathione S-transferase pull-down. Ubiquitin-conjugating enzyme 9 (UBC9) and protein inhibitor of activated STAT (PIAS) proteins were first identified as genuine interacting partners of mouse PlagL2. Because UBC9 and PIAS are components of the small ubiquitin-related modifier (SUMO) modification pathway, we hypothesized that PLAG proteins could be SUMOylated. Here, we report results obtained for founding family member PLAG1. Its endogenous SUMOylation was demonstrated, and SUMOylation of PLAG1 was further investigated in cells co-transfected with PLAG1 and SUMO-1 DNA or a SUMO-1 mutant form and similarly examined in the presence or absence of DNA encoding the various PIAS proteins. Using anti-PLAG1 antibodies, we discovered single and double SUMO-1-modified forms of PLAG1. By mutating predicted SUMO consensus sites, we defined two important target lysines for SUMOylation in PLAG1, Lys-244 and Lys-263. Moreover, mutation of both SUMO consensus sequences, resulting in inhibition of SUMOylation, led to a significant increase of the transactivation capacity of PLAG1. Nuclear distribution of PLAG1 was not measurably influenced. Our results suggest a direct repression of the transactivating capacity of the oncoprotein PLAG1 by SUMOylation. 

Retracted: No

PubPeer comments:
 (A) and (B) of FIGURE 2 are obviously not from the same patient. The size of the nipple and areola is completely different, and the skin color is also different. ![file] ,
A pneumocyte-macrophage paracrine lipid axis drives the lung toward fibrosis
Authors: Jennifer Madenspacher
Raymond B Penn
Mani Kavuru
Dilip Shah
Michael B Fessler
Michelle Duong
Ross Summer
Bo Lu
William Stafstrom
Caleb B Kallen
Kenneth Walsh
Freddy Romero
Journal: American Journal of Respiratory Cell and Molecular Biology (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: alveolar macrophages; foam cells; oxidized phospholipids; pulmonary fibrosis; type II pneumocytes.
Affiliations: 1 Center for Translational Medicine and Jane and Leonard Korman Lung Center., 2 Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina; and., 3 Bodine Cancer Center, and., 4 Department of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, Pennsylvania., 5 Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.

Abstract:  Lipid-laden macrophages, or "foam cells," are observed in the lungs of patients with fibrotic lung disease, but their contribution to disease pathogenesis remains unexplored. Here, we demonstrate that fibrosis induced by bleomycin, silica dust, or thoracic radiation promotes early and sustained accumulation of foam cells in the lung. In the bleomycin model, we show that foam cells arise from neighboring alveolar epithelial type II cells, which respond to injury by dumping lipids into the distal airspaces of the lungs. We demonstrate that oxidized phospholipids accumulate within alveolar macrophages (AMs) after bleomycin injury and that murine and human AMs treated with oxidized phosphatidylcholine (oxPc) become polarized along an M2 phenotype and display enhanced production of transforming growth factor-β1. The direct instillation of oxPc into the mouse lung induces foam cell formation and triggers a severe fibrotic reaction. Further, we show that reducing pulmonary lipid clearance by targeted deletion of the lipid efflux transporter ATP-binding cassette subfamily G member 1 increases foam cell formation and worsens lung fibrosis after bleomycin. Conversely, we found that treatment with granulocyte-macrophage colony-stimulating factor attenuates fibrotic responses, at least in part through its ability to decrease AM lipid accumulation. In summary, this work describes a novel mechanism leading to foam cell formation in the mouse lung and suggests that strategies aimed at blocking foam cell formation might be effective for treating fibrotic lung disorders. 

Retracted: No

PubPeer comments:
 Figure 7A. Much more similar than expected. https: imgur.com 3f4R8yG ,
Selective silencing of the hypoxia-inducible factor 1 target gene BNIP3 by histone deacetylation and methylation in colorectal cancer
Authors: H Turley
A L Harris
S Fox
A L Bacon
Journal: Oncogene (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hypoxia; HIF-1; HIF-2; BNIP3; colorectal cancer
Affiliations: Laboratory of Molecular Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Cancer Research UK, Oxford, UK.

Abstract:  Hypoxia, via the hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2), upregulates many genes involved in cell survival. However, proapoptotic pathways are also induced. BCL-2/adenovirus E1B-19 kDa-interacting protein 3 (BNIP3) represents a paradigm of a cell death protein that is hypoxically upregulated via HIF-1 in most cancers. We found that in contrast to many other cell types, 6/8 colorectal cancer (CRC) cell lines show little hypoxic induction of BNIP3 despite an intact HIF signalling system. Colorectal tumour tissue also loses BNIP3 expression relative to matched normal samples. Downregulation of hypoxic BNIP3 in CRC cells was independent of the expression of other BCL-2 family members, or BNIP3L. That BNIP3 plays a functional role in hypoxic survival in CRC cells was demonstrated by the fact that CRC cell lines that do not upregulate BNIP3 or have been treated with BNIP3 RNA interference were insensitive to hypoxia-induced cell death. Promoter methylation and histone deacetylation were shown to silence BNIP3 in these CRC cell lines. Of significance, hypoxic induction of BNIP3 was restored in 4/6 cell lines by trichostatin-A treatment alone. These data suggest that BNIP3 plays an important role in hypoxic cell death and epigenetic mechanisms selectively silence its expression in CRC. 

Retracted: No

PubPeer comments:
 Figure 4a. Much more similar than expected. Legend states  Each Western blot is representative of at least three independent experiments. Same western for beta-tubulin appears 3 times. ![file] , 
 #1 Thank you for pointing this out. I agree and most likely explanation is researcher error with so many gels to compare [13 cell lines, normoxia and hypoxia, HIF1, HIF2 ,CA9, BNIP3, GLUT1, loading control]. However, this was one out of 13 cell lines studied, all of which showed hypoxia induction of key proteins such as HIF1 and HIF2 and the other 12 had appropriate loading controls. On balance therefore this error does not influence any conclusions. ,
Herpes simplex virus type 1 blocks the apoptotic host cell defense mechanisms that target Bcl-2 and manipulates activation of p38 mitogen-activated protein kinase to improve viral replication
Authors: J Conner
M Koffa
G Zachos
J B Clements
C M Preston
Journal: Journal of Virology (2001)
Discipline: MICROBIOLOGY
Keywords: HSV-1; apoptosis; Bcl-2; mutant viruses; ICP27
Affiliations: <!--label omitted: 1-->Institute of Virology, University of Glasgow,1 and, <!--label omitted: 3-->MRC Virology Unit, Institute of Virology,3 Glasgow G11 5JR, and, <!--label omitted: 2-->School of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA,2 United Kingdom

Abstract:  Wild-type (wt) herpes simplex virus type 1 (HSV-1) suppresses cell death. We investigated the apoptotic pathways triggered during infection with mutant viruses tsk and 27lacZ (which lack functional ICP4 and ICP27 viral proteins, respectively) and examined the mechanisms used by wt HSV-1 to protect against programmed cell death induced by the DNA-damaging compound cisplatin. In our studies, we used BHK and HeLa cells, with similar results. We suggest that a decrease in the levels of Bcl-2 protein is a key event during apoptosis induced by the mutant viruses and that Bcl-2 levels are targeted by (i) a decrease of bcl-2 RNA, (ii) caspase-related proteolysis, and (iii) p38 mitogen-activated protein kinase (p38MAPK)-dependent destabilization of Bcl-2 protein. We show that wt HSV-1, but not the mutant viruses, maintains bcl-2 RNA and protein levels during infection and protects from the cisplatin-induced decrease in bcl-2 RNA; our data suggest that both ICP27 and ICP4 are required for this function. Additionally, wt HSV-1 evades but does not actively block activation of caspases. Although wt HSV-1 induces p38MAPK activation during infection, it prevents p38MAPK-dependent destabilization of Bcl-2 and exploits p38MAPK stimulation to enhance transcription of specific viral gene promoters to increase viral yields. 

Retracted: No

PubPeer comments:
 A new notion of **hesitant probabilistic fuzzy linguistic sets** is coined for decision making and some aggregation operations are introduced. It is obvious that the operations defined in Definition 8 and Definition 9 are by no means idempotent. Property 2 is invalid. ![file] ![file] ,
Long non‑coding RNA LINC00152 promotes tumorigenesis via sponging miR‑193b‑3p in osteosarcoma
Authors: Yue Wang
Wubin He
Pinduan Liu
Yanyan Lu
Journal: Oncology Letters (2019)
Discipline: CLINICAL MEDICINE
Keywords: LINC00152; cancer; long non-coding RNA; miR-193b-3p; noncoding RNA
Affiliations: Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China., Bio-Therapeutics Laboratory, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China., Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.

Abstract:  The majority of the human genome has been revealed to be non-protein-coding, which are transcribed into noncoding RNAs (ncRNA), RNAs which are not translated into protein. Long non-coding RNAs (lncRNAs), including LINC00152, may be associated with the pathogenesis of different types of cancer. LINC00152 serves as an endogenous sponge by binding to micro-RNAs (miRNAs) and inhibiting their activity. The current study revealed that LINC00152 is overexpressed in osteosarcoma cells, leading to increased cell proliferation, and decreased G0/G1 cell cycle arrest and apoptosis. The binding of miR-193b-3p to LINC00152 was demonstrated by dual-luciferase assay, and led to miR-193b-3p downregulation in osteosarcoma cells. Knockdown of LINC00152 revealed an antitumorigenic effect by reducing cell proliferation and increasing G0/G1 arrest and apoptosis. Inhibiting miR-193b-3p reversed the effects of LINC00152 knockdown. These results suggested that LINC00152 binds to miR-193b-3p and reduces its expression level, leading to increased cell proliferation and decreased G0/G1 cell cycle arrest and apoptosis in osteosarcoma cells. 

Retracted: No

PubPeer comments:
 Fig 3A.  Transwell invasion assay was conducted to observe the invasive cells in HeLa cells. ![file] Other manifestations include Fig 3C of [Zhang et al (2017)] :  Transwell invasion assays were conducted to observe the invasive cells in SW1990 and PANC-1 cells . ![] Figure 5 of [Nie et al (2017)] .  miR-138 counteracts the effect of HOTAIR in promoting the metastasis of PC. A. The invasive cells were detected by Transwell invasion assays in PCNA-1 cells transfected with HOTAIR-siRNA or HOTAIR scramble together with or miR-138 inhibitor . ![] , 
 Fig 2C.  Cell apoptosis was detected using the flow cytometry . ![file] Please compare the panel marked with a light brown box with Fig 2E of [Zhang et al (2017)] .  Flow cytometry was performed to determine the percentages of apoptosis in SW1990 and PANC-1 cells . ![] Fig 2G of [Gao et al (2017)] .  Cell apoptosis was measured by flow cytometry . ![] ,