PReD-Bench/PRed-Bench huggingface dataset:
Genistein induces apoptosis in ovarian cancer cells via different molecular pathways depending on Breast Cancer Susceptibility gene-1 (BRCA1) status
Authors: Priya Srinivas
S Nair Rakesh
Thankappan Ratheeshkumar
Gopala Srinivas
Karedath Abdul Aziz Thasni
Mani Shankar Babu
Asoke Banerji
Gopakumaran Rojini
Journal: European Journal of Pharmacology (2008)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: BRCA1; BRCA2; genistein; chemoprevention; estrogen receptor
Affiliations: Molecular Therapeutic Laboratory, Division of Cancer Biology, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram 695 014, Kerala, India.

Abstract:  It has been reported that Breast Cancer Susceptibility gene-1 &amp; 2 (BRCA1 &amp; 2 are potential molecular targets for chemoprevention by isoflavone genistein (4' 5, 7-trihydroxy isoflavone), in breast and prostate cancer cells. It is also known that BRCA1 has inhibitory activity on estrogen receptor-alpha and genistein's action on cells is mainly through modulation of estrogen receptor activity. The action of genistein with respect to BRCA1 status in ovarian cancer cells has not been reported so far. Therefore in this study, we analyzed the action of genistein on BRCA1 antisense blocked (AS4) and unblocked (NEO) BG-1 ovarian cancer cells. We found that genistein induced comparable cytotoxic effect in both AS4 and NEO cells, but through different pathways. We found that genistein induces caspase 8 dependent apoptotic pathway in NEO cells. Genistein inhibits estrogen receptor-alpha and activates BARD1 in BRCA1 blocked cells and induces estrogen receptor-beta and FAS in presence of BRCA1. It can be concluded that even though there is no difference in the extent of cell death or apoptosis, the molecular mechanism of action of genistein in inducing apoptosis is different in BRCA1 blocked and unblocked cells. This could partially explain the beneficial effects of genistein in both wild type and mutated BRCA1 estrogen receptor positive tumors. 

Retracted: No

PubPeer comments:
 Figure 3B immunoblot images have some unusual editing and cropping. The images were suspected to be obtained from different membranes. The area in the yellow box is an additional pasting. Could the authors show their uncropped images to clarify? ![file] ,
Multifunctional Alginate Hydrogel Protects and Heals Skin Defects in Complex Clinical Situations
Authors: Danping Liu
Fangxin Ta
Zhongkai Fan
Dongyan Bao
Dezhi Zhang
Wei Lu
Zheng Zhang
Journal: ACS Omega (2020)
Discipline: CHEMISTRY
Keywords: Skin defects; soft tissue damage; fractures; medical technology; functional exercises
Affiliations: Department of Orthopaedic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Liaoning 121001, PR China, Basic Medical College, Jinzhou Medical University, Liaoning 121001, PR China, Health Management Center, The First Affiliated Hospital of Jinzhou Medical University, Liaoning 121001, PR China

Abstract:  Skin defects, soft tissue damage, and fractures often occur simultaneously in severe trauma. Under current medical technology, fractures can be quickly fixed by internal or external repair techniques, and early functional exercises can be performed. However, skin defects heal over a long time and can even be difficult to heal. Functional exercise may cause cutting of fresh granulation to break and impair wound healing. Functional exercise and wound healing seem to contradict each other. In this study, an alginate hydrogel was developed. With self-healing characteristics, the hydrogel tightly adhered to the wound and could self-heal breaks in the gel caused by functional exercises. These characteristics enable this hydrogel to be used in complex clinical situations to solve sports rehabilitation and skin defect repair problems. In addition, this hydrogel can slowly release strontium ions, promote angiogenesis and collagen deposition in the wound, and quickly heal the wound. 

Retracted: No

PubPeer comments:
 In Figure 3a, two micrographs have been duplicated and presented as something else. ![file] ,
Effects of HIF-1α on diabetic retinopathy angiogenesis and VEGF expression
Authors: F-L Lv
D Zhang
G-H Wang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HIF-1α; VEGF; angiogenesis; diabetic retinopathy; rats
Affiliations: Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong, China. .

Abstract:  Objective: To investigate the effect of hypoxia inducing factor (HIF)-1α on the expression of vascular endothelial growth factor (VEGF) and angiogenesis in diabetic retinopathy. Patients and methods: 8-week healthy SD rats were used for the experiments. Under systemic anesthesia condition, control rats received a saline injection into the left ocular body (control A group), and 2 μl antisense oligonucleotides (ASODN) (10 μmol/L) into right eye (control B group). Model rats received a saline injection into the left eye (model A group), and 2 μl ASODN (10 μmol/L) into the right eye (model B group). Rats received an intraocular injection of HIF-1α ASODN for 2, 4, and 6 weeks (A1, A2, A3, B1, B2, B3, respectively). Retinal vessel development was observed by ADP staining. Vascular endothelial cells penetrating retinal inner membrane were counted. Immunohistochemistry was used to detect expressions of VEGF and HIF-1α proteins in the retina. Results: Prominent angiogenesis and hyperplasia were found in model A group. Relatively fewer newly formed vessels were shown in model group B. However, no significant change of retinal vascular morphology was presented in control group. Of note, the vascular endothelial cell counts, VEGF and HIF-1α contents were significantly increased in model group (p &lt; 0.05). After treatment with HIF-1α ASODN, lower endothelial cell counts was found in model B group (p &lt; 0.05 comparing to model A). VEGF expression in model B group was significantly decreased, among which, model B3 was observed with lower cell counts than model B1 or B2 (p &lt; 0.05 comparing to model A). Injection of HIF-1α ASODN significantly suppressed HIF-1α level in model B in a time-dependent manner. Conclusions: Retinal angiogenesis is closely related with increasing level of HIF-1α. Inhibition of HIF-1α suppressed VEGF expression and deterred angiogenesis in a time-dependent manner. This provided novel insights for treating diabetic retinopathy. 

Retracted: No

PubPeer comments:
  Figure 1. Retinal slide staining images. A, Control group; B, Model group A; C, Model group B1; D, Model group B2; E, Model group B3. B, C, D overlap. ![file] ,
Volasertib suppresses the growth of human hepatocellular carcinoma and
Authors: Yao Chen
Meng-Ning Wei
Yong Li
Kun Wang
Yang Yang
Di-Wei Zheng
Zhi Shi
You-Qiu Xue
Xing Wei
Jian-Ge Qiu
Qi-Wei Jiang
Jin-Ming Di
Wen-Ji Zhang
Jia-Rong Huang
Journal: American journal of cancer research (2016)
Discipline: CLINICAL MEDICINE
Keywords: Hepatocellular carcinoma; ROS; apoptosis; volasertib.
Affiliations: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China., Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering MedicineGuangzhou 510632, Guangdong, China; Center for Clinic Immunology, Third Hospital at Sun Yat-sen UniversityGuangzhou 510630, China., Department of Gastrointertinal Surgery & General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences Guangzhou, Guangdong 510080, China., Department of Urology, The 3rd Affiliated Hospital of Sun Yat-sen University Guangzhou, Guangdong 510630, China.

Abstract:  Hepatocellular carcinoma (HCC) is the sixth most frequent malignant tumor with poor prognosis, and its clinical therapeutic outcome is poor. Volasertib, a potent small molecular inhibitor of polo-like kinase 1 (PLK1), is currently tested for treatment of multiple cancers in the clinical trials. However, the antitumor effect of volasertib on HCC is still unknown. In this study, our data show that volasertib is able to induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the spindle abnormalities in human HCC cells. Furthermore, volasertib also increases the intracellular reactive oxidative species (ROS) levels, and pretreated with ROS scavenger N-acety-L-cysteine partly reverses volasertib-induced apoptosis. Moreover, volasertib markedly inhibits the subcutaneous xenograft growth of HCC in nude mice. Overall, our study provides new therapeutic potential of volasertib on hepatocellular carcinoma. 

Retracted: Yes

PubPeer comments:
 Figure 5A: duplication of microscopy data. ![file] , 
 2020 retraction. https: www.ncbi.nlm.nih.gov pmc articles PMC7269776 Falsfied materials and or data reported in this publication had been detected by a knowledgeable reader and subsequently confirmed by further investigation of editorial office. Therefore, the entire article has been retracted in accordance with this journalu2019s policy and Editorial decision. ,
Pegylated protein encapsulated multivesicular liposomes: a novel approach for sustained release of interferon alpha
Authors: P N Gupta
A Rawat
M Rawat
S Mahor
S P Vyas
Journal: Drug development and industrial pharmacy (2006)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Hepatitis C; viral chemotherapy; interferon alpha-2a; polyethylene glycol modification; multivesicular liposomes
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya Sagar, MP, India. 

Abstract:  Hepatitis C viral chemotherapy suffers from a relatively short half-life of the interferon alpha-2a (IFN alpha). To address this issue, we investigated the effects of polyethylene glycol modification and their subsequent encapsulation in multivesicular liposomes (MVLs), on the release properties of IFN alpha. In the present study, interferon-alpha was conjugated with methoxy-polyethylene glycol (mPEG, MW 5000). Prepared IFN alpha-mPEG5000 conjugate (IFN alpha-mPEG5000) was purified with size exclusion chromatography. The relative in vitro anti-viral activity of pegylated interferon alpha-2a was found to 87.9% of the unmodified IFN alpha. Pegylated IFN alpha encapsulated multivesicular liposomes were prepared by double emulsification technique followed by evaporation of organic solvents from chloroform ether spherules suspended in water. Prepared MVLs were then characterized for shape, size, vesicle count, encapsulation efficiency, and in vitro release rate. In process stability studies of pegylated IFN alpha protein exhibited better stability when exposed to chloroform: diethyl ether (1:1 ratio) mixture as well as variable vortexing time as compared to native IFN alpha. Relatively high percentage of encapsulation of protein ( approximately 75%) was achieved. In vitro release profile of pegylated IFN alpha-mPEG5000 containing MVLs in the PBS showed lower initial burst release with sustained and incomplete release over a period of 1 week. In contrast, native IFN alpha entrapped MVLs were observed as higher initial burst release, i.e., nearly 35% followed by almost complete release. The results confirmed the possibility of multivesicular liposomes as a long-acting or sustained-release delivery system using a combination of pegylation and encapsulation technique for controlled delivery of interferon alpha. 

Retracted: No

PubPeer comments:
 Fig 3,  Photomicrograph Showing Phase Contrast Image of IFN au2013mPEG5000 Encapsulated MVLs at 400X Magnification. ![file] Two pairs of MVLs are implausibly similar. ,
Endotoxemia accelerates diaphragm dysfunction in ventilated rabbits
Authors: Tao Yu
Federico Longhini
Yingzi Huang
Ling Liu
Haibo Qiu
Fengmei Guo
Yi Yang
Chun Pan
Journal: Journal of Surgical Research (2016)
Discipline: CLINICAL MEDICINE
Keywords: Diaphragm; Endotoxemia; Lipopolysaccharide; Microcirculation; Sepsis.
Affiliations: Department of Critical Care Medicine, Zhong-Da Hospital, Southeast University, Nanjing, China., Department of Anesthesiology and Intensive Care Unit, Wannan Medical College First Affiliated Hospital, Yijishan Hospital, Wuhu, China., Department of Translational Medicine, Eastern Piedmont University "A. Avogadro", Novara, Italy., Department of Critical Care Medicine, Zhong-Da Hospital, Southeast University, Nanjing, China. Electronic address: .

Abstract:  Background: Ventilators may induce diaphragm dysfunction, and most of the septic population who are admitted to the intensive care unit require mechanical ventilation. However, there is no evidence that sepsis accelerates the onset of ventilator-induced diaphragm dysfunction or affects the microcirculation. Our study investigated whether lipopolysaccharide (LPS)-induced endotoxemia accelerated diaphragm dysfunction in ventilated rabbits by evaluating microcirculation, lipid accumulation, and diaphragm contractility. Methods: After anesthesia and tracheostomy, 25 invasively monitored and mechanically ventilated New Zealand white rabbits were randomized to control (n = 5), controlled mechanical ventilation (CMV) (n = 5), pressure support ventilation (PSV; n = 5), CMV or PSV with LPS-induced endotoxemia (CMV-LPS and PSV-LPS, respectively; n = 5 for each). Rabbits were anesthetized and ventilated for 24 h, except the control rabbits (30 min). Diaphragmatic contractility was evaluated using neuromechanical and neuroventilatory efficiency. We evaluated the following at the end of the protocol: (1) diaphragm microcirculation; (2) lipid accumulation; and (3) diaphragm muscular fibers structure. Results: Diaphragm contractility, microcirculation, lipid accumulation, and fiber structures were severely compromised in endotoxemic animals after 24 h compared to nonendotoxemic rabbits. Moreover, a slight but significant increase in lipid accumulation was observed in CMV and PSV groups compared with controls (P &lt; 0.05). Conclusions: Endotoxemia accelerates the diaphragm dysfunction process in ventilated rabbits, affects the microcirculation, and results in diaphragmatic lipid accumulation and contractility impairment. 

Retracted: No

PubPeer comments:
 Figure 3B appears to have 2 images which overlap. *** ![file] ,
Regulation of MAP Kinase–Directed Mitogenic and Protein Kinase B–Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells
Authors: Andrew J Irving
Clare Stretton
Simon Hastings
Harinder S Hundal
Ken Mackie
Jonathan S Hundal
Christopher Lipina
Journal: Diabetes (2010)
Discipline: CLINICAL MEDICINE
Keywords: endocannabinoid system; ECS; feeding behavior; energy balance; lipogenesis
Affiliations: Division of Molecular Physiology, James Black Centre, College of Life Sciences, University of Dundee, Dundee, Scotland.

Abstract:  Objective: The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behavior and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic beta-cells, and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells. Research design and methods: Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)-protein kinase B (PKB) and extracellular signal-related kinases 1/2 (ERK1/2)-directed signaling were determined. Results: Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent mitogen-activated protein (MAP) kinase (ERK1/2) and the canonical PI 3-kinase/PKB signaling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase- and PKB-directed signaling. Conclusions: Our study provides evidence that signaling via cannabinoid receptors can significantly modulate mitogenic and metabolic signaling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism. 

Retracted: Yes

PubPeer comments:
 Fig.2B, Fig.2D, Fig.3B: The experimental conditions are different *WIN*, *AC*, *JW* incubations, respectively. However, there is partial overlap in the ERK1 2 panels. ![file] ![file] ![file] , 
 2021 retraction. https: diabetes.diabetesjournals.org content early 2021 06 17 db21-rt08a ![file] ,
FBX8 Acts as an Invasion and Metastasis Suppressor and Correlates with Poor Survival in Hepatocellular Carcinoma
Authors: Yudan Qiao
Yanqing Ding
Feifei Wang
Xiaoli Ren
Li Liang
Yi Ding
Jianmei Wang
Wenhui Ma
Xiaojing Zhang
Jiang Yu
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: FBX8; hepatocellular carcinoma; prognosis; cell proliferation; invasion
Affiliations: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, People's Republic of China ; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou City, Guangdong Province, People's Republic of China.

Abstract:  Background: F-box only protein 8 (FBX8), a novel component of F-box proteins, is lost in several cancers and has been associated with invasiveness of cancer cells. However, its expression pattern and role in the progression of hepatocellular carcinoma remain unclear. This study investigated the prognostic significance of FBX8 in hepatocellular carcinoma samples and analyzed FBX8 function in hepatocellular carcinoma cells by gene manipulation. Methodology: The expression of FBX8 was detected in 120 cases of clinical paraffin-embedded hepatocellular carcinoma tissues, 20 matched pairs of fresh tissues and five hepatocellular carcinoma cell lines by immunohistochemistry with clinicopathological analyses, real-time RT-PCR or Western blot. The correlation of FBX8 expression with cell proliferation and invasion in five HCC cell lines was analyzed. Moreover, loss of function and gain of function assays were performed to evaluate the effect of FBX8 on cell proliferation, motility, invasion in vitro and metastasis in vivo. Conclusions: We found that FBX8 was obviously down-regulated in HCC tissues and cell lines (P&lt;0.05). The FBX8 down-regulation correlated significantly with poor prognosis, and FBX8 status was identified as an independent significant prognostic factor. Over-expression of FBX8 decreased proliferation, migration and invasion in HepG2 and 97H cells, while knock-down of FBX8 in 7721 cells showed the opposite effect. FBX8 negatively correlated with cell proliferation and invasion in 7701, M3, HepG2 and 97H cell lines. In vivo functional assays showed FBX8 suppressed tumor growth and pulmonary metastatic potential in mice. Our results indicate that down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma treatment. 

Retracted: No

PubPeer comments:
 Figure 4E appears to have two images which overlap. *** ![file] ,
Androgen regulation of parathyroid hormone-related peptide production in human prostate cancer cells
Authors: Helena Pizzi
Luisa Carpio
Julienne Gladu
Shafaat A Rabbani
David Goltzman
Dengshun Miao
Journal: Endocrinology (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PTHrP; hypercalcemia; malignancies; prostate cancer; androgens
Affiliations: Department of Medicine, McGill University Health Centre, Montréal, Québec H3A 1A1, Canada.

Abstract:  PTHrP is the major pathogenetic factor for hypercalcemia in several malignancies including prostate cancer. In the current study, we have assessed the ability of androgens to regulate PTHrP production in androgen-insensitive human prostate cancer cells PC-3 and cells transfected with androgen receptor (PC-3T). Androgen responsiveness caused a marked decrease in PC-3T cell growth, and treatment of these cells with dihydrotestosterone led to inhibition of PTHrP production. These inhibitory effects were readily reversed by androgen receptor antagonist flutamide. To determine the effect of androgens on tumor growth and PTHrP production in vivo, PC-3 and PC-3T cells were injected into the right flank of male BALB/c nu/nu mice. Animals inoculated with PC-3 and PC-3T cells developed palpable tumors at wk 2 and 4, respectively. Inoculation of PC-3T cells into castrated animals resulted in rapid tumor growth in PC-3T tumors, effects that were reversed in PC-3T tumors grown in castrated hosts. Using PTHrP promoter luciferase reporter, a 30% decrease in luciferase activity was seen following treatment with dihydrotestosterone. These results indicate that PC-3 cell growth correlates inversely with androgen sensitivity and directly with PTHrP production in vitro and in vivo, androgens can regulate PTHrP production, and the androgen effect on PTHrP is mediated at least in part by transcriptional regulation via the androgen receptor. 

Retracted: No

PubPeer comments:
 Figure 2A. much more similar than expected. ![file] ,
Diagnostic and prognostic values of KLK11 in nasopharyngeal carcinoma
Authors: T-J Yuan
Y-Y Huang
X-L Li
H-L Bi
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: KLK11; nasopharyngeal carcinoma; diagnostic value; prognostic value; qRT-PCR
Affiliations: Department of Maxillofacial Surgery, Weifang People's Hospital, Weifang, China. .

Abstract:  Objective: This study aims to clarify potential diagnostic and prognostic values of KLK11 in nasopharyngeal carcinoma (NPC). Patients and methods: KLK11 levels in 81 primary NPC tissues, 24 recurrent NPC tissues, and 60 nasopharyngeal tissues with chronic mucosal inflammation were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, receiver operating characteristic (ROC) curves were depicted for assessing the diagnostic value of KLK11 in primary and recurrent NPC. Next, correlation between KLK11 level and pathological indexes of NPC patients was analyzed by Chi-square test. Enrolled NPC patients were followed up for 5 years, and the follow-up data were recorded to determine the potential influence of KLK11 on overall survival by Kaplan-Meier method. In addition, Cox regression model was applied for assessing factors that could affect prognosis of NPC patients. Results: It was found that KLK11 level was higher in primary NPC tissues than that in nasopharyngeal tissues with chronic mucosal inflammation. In recurrent NPC tissues, KLK11 was upregulated relative to primary ones. In addition, ROC curves revealed a certain diagnostic value of KLK11 in NPC. Overall survival was worse in primary and recurrent NPC patients expressing a high level of KLK11. By analyzing the pathological indexes of NPC patients, KLK11 level was found to be correlated with age, T stage, and clinical stage of NPC patients. Furthermore, KLK11 level was found to be the risk factor influencing the survival of NPC patients. Conclusions: KLK11 is upregulated in NPC tissues, and unfavorable to the prognosis of NPC. Besides, it can be utilized as a potential hallmark for diagnosing NPC. 

Retracted: No

PubPeer comments:
 From the Methods:  A total of 81 primary NPC tissues, 24 recurrent NPC tissues and 60 nasopharyngeal tissues with chronic mucosal inflammation confirmed by biopsy were collected from Weifang Peopleu2019s Hospital from May 2016 to December 2018. Figure 2 from this paper showed that the 81 primary NPC patients were followed for 5 years (60 months). How can that have been done if the patients were enrolled less than 5 years before publication of this paper? ![file] ,
Protein kinase D1 mediates stimulation of DNA synthesis and proliferation in intestinal epithelial IEC-18 cells and in mouse intestinal crypts
Authors: Robert Kui
Carlos Huang
Enrique Rozengurt
Nora Rozengurt
James Sinnett-Smith
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: protein kinase D1; intestinal epithelial cell proliferation; G(q)-coupled receptor agonists; gene silencing; transgenic mice
Affiliations: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, CURE: Digestive Diseases Research Center and Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.

Abstract:  We examined whether protein kinase D1 (PKD1), the founding member of a new protein kinase family, plays a critical role in intestinal epithelial cell proliferation. Our results demonstrate that PKD1 activation is sustained, whereas that of PKD2 is transient in intestinal epithelial IEC-18 stimulated with the G(q)-coupled receptor agonists angiotensin II or vasopressin. PKD1 gene silencing utilizing small interfering RNAs dramatically reduced DNA synthesis and cell proliferation in IEC-18 cells stimulated with G(q)-coupled receptor agonists. To clarify the role of PKD1 in intestinal epithelial cell proliferation in vivo, we generated transgenic mice that express elevated PKD1 protein in the intestinal epithelium. Transgenic PKD1 exhibited constitutive catalytic activity and phosphorylation at the activation loop residues Ser(744) and Ser(748) and on the autophosphorylation site, Ser(916). To examine whether PKD1 expression stimulates intestinal cell proliferation, we determined the rate of crypt cell DNA synthesis by detection of 5-bromo-2-deoxyuridine incorporated into the nuclei of crypt cells of the ileum. Our results demonstrate a significant increase (p &lt; 0.005) in DNA-synthesizing cells in the crypts of two independent lines of PKD1 transgenic mice as compared with non-transgenic littermates. Morphometric analysis showed a significant increase in the length and in the total number of cells per crypt in the transgenic PKD1 mice as compared with the non-transgenic littermates (p &lt; 0.01). Thus, transgenic PKD1 signaling increases the number of cells per crypt by stimulating the rate of crypt cell proliferation. Collectively, our results indicate that PKD1 plays a role in promoting cell proliferation in intestinal epithelial cells both in vitro and in vivo. 

Retracted: No

PubPeer comments:
 ![file] ,
LncRNA-SNHG16 predicts poor prognosis and promotes tumor proliferation through epigenetically silencing p21 in bladder cancer
Authors: Dong Yue
Jing Xu
Xianxiang Cao
Journal: Cancer Gene Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: lncRNA; SNHG16; bladder cancer; prognosis; cell proliferation
Affiliations: Urology Department, Affiliated hospital of jining medical college, Shandong, 272000, China., Urology Department, Affiliated hospital of jining medical college, Shandong, 272000, China. .

Abstract:  More and more evidences have ensured the crucial functions of long non-coding RNAs (lncRNAs) in multiple tumors. It has been discovered that lncRNA-SNHG16 is involved in many tumors. Even so, it is still necessary to study SNHG16 comprehensively in bladder cancer. In terms of our study, the level of SNHG16 both in the tumor tissues and cell lines was measured and the relationship among SNHG16, clinicopathological traits and prognosis was explored. Interference assays were applied to determine the biological functions of SNHG16. It was discovered that the level of SNHG16 was evidently enhanced both in tissues and cell lines of bladder cancer. Patients with highly expressed SNHG16 suffered from poor overall survival. Multivariable Cox proportional hazards regression analysis implied that highly expressed SNHG16 could be used as an independent prognostic marker. It could be known from functional assays that silenced SNHG16 impaired cell proliferation, owing to the effects of SNHG16 on cell cycle and apoptosis. Finally, mechanism experiments revealed that SNHG16 could epigenetically silence the expression of p21. The facts above pointed out that lncRNA-SNHG16 might be quite vital for the diagnosis and development of bladder cancer, and could even become an important therapeutic target for bladder cancer. 

Retracted: No

PubPeer comments:
 Figure 3: several flow cytometry plots appear unexpectedly similar. Some regions with similarities identified in image below. *** ![file] , 
 This paper still figures at the top of the list for  The best of Cancer Gene Therapy 2018-2019 . , 
 This paper figures as No 1 on the list of  The best of Cancer Gene Therapy 2018-2019 . It has been cited 33 times so far. ![file] ,
CCAAT/Enhancer-binding protein beta DNA binding is auto-inhibited by multiple elements that also mediate association with p300/CREB-binding protein (CBP)
Authors: Maria Miller
Peter F Johnson
Jon D Shuman
Sook Lee
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ras GTPases; CCAAT/enhancer-binding protein (C/EBPbeta); oncogenic H-Ras(V12); senescence; growth arrest
Affiliations: Laboratory of Cancer Prevention, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702-1201, USA.

Abstract:  Signaling through Ras GTPases controls the activity of many transcription factors including CCAAT/enhancer-binding protein (C/EBPbeta), which regulates oncogenic H-Ras(V12)-induced senescence and growth arrest. Here we report that C/EBPbeta (LAP) DNA binding is inhibited by N-terminal sequences and derepressed by oncogenic Ras signaling. Sequence and mutational analyses showed that auto-repression involves two LXXLF (phiXXphiphi)-like motifs (LX1 and LX2) and a third element, auto-inhibitory domain (AID), located within conserved region CR5. LX1 is a critical component of the transactivation domain and has been shown to mediate C/EBPbeta binding to the TAZ2 region of p300/CREB-binding protein coactivators. C/EBPbeta auto-repression also involves a C-terminal regulatory domain (CRD) adjacent to the leucine zipper. CRD contains a third phiXXphiphi motif (LX3) and a short sequence, KQL, which has similarity to a region in the protein-binding site of TAZ2. The C/EBPbeta N- and C-terminal domains physically associate in a manner that requires the basic region and CRD. We propose a model in which the regulatory sequences form a hydrophobic core that reciprocally inhibits DNA binding and transactivation. We also suggest a mechanism for C/EBPbeta derepression involving several recently identified modifications within AID and CRD. Finally, we show that association of activated C/EBPbeta with p300/CREB-binding protein requires the LX2 and AID auto-inhibitory elements. Thus, the N-terminal regulatory elements have dual roles in auto-inhibition and coactivator binding. 

Retracted: No

PubPeer comments:
 Looks like lane 1-2 in Fig. 6A and lane 1 in Fig.6C donu2019t exist. They were only blank backgrounds sliced from other images. ![file] ,
M1/M2 macrophages and associated mechanisms in congenital bicuspid aortic valve stenosis
Authors: Wen Chen
Liangpeng Li
Rui Wang
Xin Chen
Zhifei Ma
Journal: Experimental and Therapeutic Medicine (2014)
Discipline: CLINICAL MEDICINE
Keywords: congenital bicuspid aortic valve; inflammation; macrophage; neovascularization; tricuspid aortic valve.
Affiliations: Department of Thoracic and Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.

Abstract:  The aim of this study was to observe macrophage infiltration in congenital bicuspid aortic valve (CBAV) stenosis. M1/M2 macrophage distribution, inflammatory cytokine expression and the role of M1 macrophages during CBAV stenosis were also explored. The experimental and control groups comprised 30 severely stenotic CBAVs and 30 severely stenotic tricuspid aortic valves (TAVs), respectively. Histological and morphological changes were assessed using hematoxylin-eosin (HE) staining and mRNA levels of vascular endothelial growth factor (VEGF) were examined using the quantitative polymerase chain reaction. Nonspecific, M1 and M2 macrophages were monitored using cluster of differentiation (CD)68, inducible nitric oxide synthase (iNOS) and CD163 staining, respectively. Endothelial nitric oxide synthase (eNOS), interleukin (IL)-10, arginase (Arg)-1 and macrophage colony-stimulating factor (M-CSF) were also examined using immunohistochemical staining. Of note, HE staining revealed a higher cell density and neovascularization was more common in CBAVs than TAVs. At the mRNA level, VEGF expression was two-fold higher in CBAVs relative to that in TAVs (P=0.02). Furthermore, CD68 and iNOS were significantly higher in CBAVs compared with TAVs (P=0.029 and 0.021, respectively), while CD163 expression was lower in CBAVs (P=0.033). In addition, eNOS expression was higher and Arg-1, IL-10 and M-CSF expression were lower in CBAVs compared with TAVs (all P&lt;0.0001). The present study suggested that CBAVs are associated with a higher total and M1 macrophage density and a lower M2 macrophage density than TAVs, and that M1 macrophage infiltration may contribute to calcification of CBAVs. 

Retracted: No

PubPeer comments:
 unexpected 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. ,
Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin
Authors: Peng Xia
Jianwu Zhao
Su Pan
Shanyong Zhang
Yang Qu
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: XIAP; inhibitors of apoptosis; osteosarcoma; metastasis; chemotherapeutic drugs
Affiliations: Department of Orthopedics, The Second Hospital of Jilin University, Nanguan, Changchun, Jilin 130042, P.R. China.

Abstract:  X-chromosome-linked inhibitor of apoptosis protein (XIAP) is an important member of the inhibitors of apoptosis (IAP) family. It has been shown that XIAP promotes the invasion, metastasis, growth and survival of malignant cells, and confers resistance to some chemotherapeutic drugs in various types of cancer. However, little is known regarding its detailed role in osteosarcoma (OS). In the present study, we first investigated the expression of XIAP in OS tissues, and an increased expression of XIAP in OS tissues compared to adjacent non-tumor tissue was identified. Additionally, its expression level correlated with key pathological characteristics including clinical stage, tumor size and metastasis. Subsequently, small interfering RNA (siRNA) was used to block XIAP expression to evaluate the effect of XIAP siRNA on cell proliferation, colony formation, cell cycle, apoptosis, tumorigenicity, and the combined effects of doxorubicin or cisplatin in OS cell lines (MG63 cells). Downregulation of XIAP expression using the RNA silencing approach efficiently decreased cell proliferation and colony formation, and induced cell apoptosis and cell cycle in the G0/G1 stage. In addition, this downregulation inhibited tumor growth in a nude murine model. The resuls also showed that treatment with XIAP-shRNA in combination with doxorubicin or cisplatin enhanced chemosensitivity. These results suggested that XIAP may aid the diagnosis of OS and may be an effective strategy for gene therapy of this disease. 

Retracted: Yes

PubPeer comments:
 In Fig 11 the control image appears to overlap with the G sample for 50u03bcg. Original images shown to indicate placement, then enlarged images of control image and G sample to illustrate similarity. The original images are of different brightness contrast coloring. I believe there is a difference in dimensions too, but I was unable to match. *** ![file] , 
 PLease compare *[at right]* Figure 3(B)  HRTEM image... of Sample A with *[at left]* Fig.5(a)  TEM images ... of HA from  Strontium and ciprofloxacin modified hydroxyapatites as functional grafts for bone prostheses [(Sangeetha et al. 2018)] . ![file] , 
 Figure 11 also appears to have another image overlap in 11A (purple boxes). The aspect ratio and coloring seem to be different. ![file] ,
4-Hydroxynonenal modulation of p53 family gene expression in the SK-N-BE neuroblastoma cell line
Authors: Paola Costelli
Stefania Pizzimenti
Giuseppina Barrera
Stefano Laurora
Cristina Toaldo
Federica Briatore
Mario U Dianzani
Paola Bardini
Patrizia Reffo
Oliviero Danni
Elena Tamagno
Journal: Free Radical Biology and Medicine (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HNE; lipid peroxidation; tumor cells; p53; p21
Affiliations: Department of Experimental Medicine and Oncology, Section of General Pathology, University of Turin, Corso Raffaello 30, 10125 Turin, Italy.

Abstract:  4-Hydroxynonenal (HNE), a product of lipid peroxidation, inhibits proliferation of several tumor cells. The p53 tumor suppressor protein plays a critical role in cell cycle control, by inducing p21 expression, and in apoptosis, by inducing bax expression. Recently, two other proteins with many p53-like properties, TAp73 (p73) and TAp63 (p63), have been discovered. SK-N-BE human neuroblastoma cells express the three p53 family proteins and can be used for the study of their induction. We investigated HNE action in the control of proliferation, differentiation, and apoptosis in SK-N-BE cells and the HNE effect on the expression of p53, p63, p73, p21, bax, and G1 cyclins. Retinoic acid (RA) was used as a positive control. HNE inhibited cell proliferation without inducing differentiation; it decreased S-phase cells and increased the number of apoptotic cells. RA reduced the proportion of S-phase cells and did not induce apoptosis. HNE increased p53, p73, p63, p21, and bax expression at different time points. HNE reduced cyclin D2 expression and the phosphorylation of pRb protein. Our results demonstrated that HNE inhibits SK-N-BE cell proliferation by increasing the expression of p53 family proteins and p53 target proteins which modulate cell cycle progression and apoptosis. 

Retracted: No

PubPeer comments:
 Two bands in Figure 1B appear unexpectedly similar. The the authors please share the original data? *** ![file] ,
Eicosapentaenoic acid (EPA) induced apoptosis in HepG2 cells through ROS–Ca2+–JNK mitochondrial pathways
Authors: Xiaohong Cao
Lihua Hou
Xiaolei Ma
Dai Cheng
Lirong Han
Yuanyuan Zhang
Wentao Qi
Chunling Wang
Journal: Biochemical and Biophysical Research Communications (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Apoptosis; Ca(2+); Eicosapentaenoic acid; Mitochondrial; ROS.
Affiliations: Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457, People's Republic of China., Academy of State Administration of Grain, No.11 Baiwanzhuang Avenue, Xicheng District, Beijing, 100037, People's Republic of China., Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457, People's Republic of China. Electronic address: .

Abstract:  Eicosapentaenoic acid (EPA), a well-known dietary n-3 PUFAS, has been considered to inhibit proliferation of tumor cells. However, the molecular mechanism related to EPA-induced liver cancer cells apoptosis has not been reported. In this study, we investigated the effect of EPA on HepG2 cells proliferation and apoptosis mechanism through mitochondrial pathways. EPA inhibited proliferation of HepG2 cells in a dose-dependent manner and had no significant effect on the cell viability of humor normal liver L-02 cells. It was found that EPA initially evoked ROS formation, leading to [Ca(2+)]c accumulation and the mitochondrial permeability transition pore (MPTP) opening; EPA-induced HepG2 cells apoptosis was inhibited by N-acetylcysteine (NAC, an inhibitor of ROS), 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM, a chelator of calcium) and CsA (inhibitor of MPTP). The relationship between ROS production, the increase of cytoplasmic Ca and MPTP opening was detected. It seems that ROS may act as an upstream regulator of EPA-induced [Ca(2+)]c generation, moreover, generation of ROS, overload of mitochondrial [Ca(2+)]c, and JNK activated cause the opening of MPTP. Western blotting results showed that EPA elevated the phosphorylation status of JNK, processes associated with the ROS generation. Simultaneously, the apoptosis induced by EPA was related to release of cytochrome C from mitochondria to cytoplasm through the MPTP and activation of caspase-9 and caspase-3. These results suggest that EPA induces apoptosis through ROS-Ca(2+)-JNK mitochondrial pathways. 

Retracted: No

PubPeer comments:
 Figure 1C. * Red boxes: In the 24h panel, the same cell appears to be visible twice. ![file] ,
The production of an efficient visible light photocatalyst for CO oxidation through the surface plasmonic effect of Ag nanoparticles on SiO2@α-Fe2O3 nanocomposites
Authors: Thomas C-K Yang
Nadarajan Arjun
Shih-Wen Chen
Kasimayan Uma
Guan-Ting Pan
Journal: RSC Advances (2018)
Discipline: CHEMISTRY
Keywords: photo deposition; noble Ag nanoparticles; core-shell structure; SiO2@α-Fe2O3 nanocomposite spheres; CO photo oxidation catalyst
Affiliations: Centre for Precision Analysis and Research Center, National Taipei University of Technology, Taipei, Taiwan 106, Department of Chemical Engineering and Biotechnology

Abstract:  A process for the photo deposition of noble Ag nanoparticles on a core-shell structure of SiO2@α-Fe2O3 nanocomposite spheres was performed to produce a CO photo oxidation catalyst. The structural analyses were carried out for samples produced using different Ag metal nanoparticle weight percentages on SiO2@α-Fe2O3 nanocomposite spheres by X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), UV-vis spectroscopy, Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR). A computational study was also performed to confirm the existence of the synergic effect of surface plasmon resonance (SPR) for different weight percentages of Ag on the SiO2@α-Fe2O3 nanocomposites. The mechanism for CO oxidation on the catalyst was explored using diffuse reflectance infrared Fourier transform spectroscopy (DRFIT). The CO oxidation results for the Ag (2 wt%)-SiO2@α-Fe2O3 nanocomposite spheres showed 48% higher photocatalytic activity than α-Fe2O3 and SiO2@α-Fe2O3 at stable temperature. 

Retracted: No

PubPeer comments:
 Fig. 1 XRD spectra of SiO2, a-Fe2O3, SiO2@a-Fe2O3 and 1, 2 and 3 wt% Ag deposited SiO2@a-Fe2O3 nanocomposites. Regions with identical background noise. Four copies in red frame. ![file] , 
 #1 ![file] ,
Retracted: Influence of p53 in the transition of myotrophin-induced cardiac hypertrophy to heart failure
Authors: Amit Vasanji
David Young
Subha Sen
Sagartirtha Sarkar
Biswajit Das
Sudhiranjan Gupta
Journal: Cardiovascular Research (2010)
Discipline: CLINICAL MEDICINE
Keywords: myotrophin; p53; cardiac hypertrophy; heart failure; transgenic mice
Affiliations: Department of Molecular Cardiology-NB50, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.,  Department of Molecular Cardiology-NB50, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA,  Biomedical Imaging and Analysis Core, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA

Abstract:  Aims: Cardiac-specific overexpression of myotrophin (myo) protein in transgenic (myo-Tg) mice results in hypertrophy at 4 weeks that progresses to heart failure (HF) by 36 weeks. Gene profiling showed that p53 expression increases as hypertrophy worsens to HF, suggesting that p53 may influence myo-induced HF. We aimed to define how the p53 signalling cascade affects the spectrum of cardiac hypertrophy (CH)/HF. Methods and results: Immunoblot analysis showed that in myo-Tg mice (Mus musculus), upregulation of p53 occurs only when hypertrophy transitions to HF (16 weeks onward). To elucidate the role of p53, a double-Tg mouse line (p53(-/-)/myo(+/+)) was developed by crossing myo-Tg mice with p53-null mice. A significant reduction in cardiac mass with improved cardiac function was observed in p53(-/-)/myo(+/+) mice, suggesting that absence of p53 prevents hypertrophy from turning into HF. Analysis via real-time reverse-transcription PCR revealed changes in transcripts of the p53 pathway in p53(-/-)/myo(+/+) mice. Ingenuity Pathway Analysis indicated that cross-talk among several key nodal molecules (e.g. cyclin-dependent kinase inhibitor 1A, caspase-3, nuclear factor kappa-light-chain enhancer of activated B cells etc.) may play a regulatory role in the transition of CH to HF. Conclusion: Our data provide evidence, for the first time, that the coherence of p53 with myo plays an active role during the transition of CH to HF in a model of HF induced by myo overexpression. Transition from CH to HF can be prevented in the absence of p53 in myo-induced hypertrophy. Therefore, deletion/inhibition of p53 could be a therapeutic strategy to prevent CH from transitioning to HF. 

Retracted: No

PubPeer comments:
 ![file] , 
 2021 retraction. https: academic.oup.com cardiovascres advance-article doi 10.1093 cvr cvab131 6245632 An expression of concern was issued by the Journal following an institutional investigation about the data presented in Figures 1A and 7. The ESC Journals Family Ethics Committee reviewed the institutionu2019s report and the authors responses, including that the authors were unable to provide the Journal with original figures and data. The Committee ultimately agreed with the institutionu2019s recommendation, so the Editors have agreed to retract this article. ,
The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM
Authors: M G Roncarolo
R Geha
J E De Vries
J Sayos
L Notarangelo
S van Schaik
X Zhang
C Wu
M Morra
N Wang
D Allen
G Aversa
H Oettgen
C Terhorst
Journal: Nature (1998)
Discipline: Multidisciplinary
Keywords: B-cell; T-cell; antigen receptors; ligand; receptor-ligand pair
Affiliations: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. 

Abstract:  In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw150), which is present on the surface of B and T cells, forms such a receptor-ligand pair as it is a self-ligand. We now show that a T-cell-specific, SLAM-associated protein (SAP), which contains an SH2 domain and a short tall, acts as an inhibitor by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. The gene encoding SAP maps to the same area of the X chromosome as the locus for X-linked lymphoproliferative disease (XLP) and we found mutations in the SAP gene in three XLP patients. Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SLAM, leading to an inability to control B-cell proliferation caused by Epstein-Barr virus infections. 

Retracted: No

PubPeer comments:
 Figure 4a. Much more similar than expected. ![file] ![file] ,