PReD-Bench/PRed-Bench huggingface dataset:
An antimitotic and antivascular agent BPR0L075 overcomes multidrug resistance and induces mitotic catastrophe in paclitaxel-resistant ovarian cancer cells
Authors: Jun Wu
Hsing-Pang Hsieh
Erxi Wu
Tian-Li Wang
Xiaolei Wang
Xinli Liu
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Paclitaxel; ovarian cancer; resistance; BPR0L075; antimitotic
Affiliations: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas, United States of America.

Abstract:  Paclitaxel plays a major role in the treatment of ovarian cancer; however, resistance to paclitaxel is frequently observed. Thus, new therapy that can overcome paclitaxel resistance will be of significant clinical importance. We evaluated antiproliferative effects of an antimitotic and antivascular agent BPR0L075 in paclitaxel-resistant ovarian cancer cells. BPR0L075 displays potent and broad-spectrum cytotoxicity at low nanomolar concentrations (IC50 = 2-7 nM) against both parental ovarian cancer cells (OVCAR-3, SKOV-3, and A2780-1A9) and paclitaxel-resistant sublines (OVCAR-3-TR, SKOV-3-TR, 1A9-PTX10), regardless of the expression levels of the multidrug resistance transporter P-gp and class III β-tubulin or mutation of β-tubulin. BPR0L075 blocks cell cycle at the G2/M phase in paclitaxel-resistant cells while equal concentration of paclitaxel treatment was ineffective. BPR0L075 induces cell death by a dual mechanism in parental and paclitaxel-resistant ovarian cancer cells. In the parental cells (OVCAR-3 and SKOV-3), BPR0L075 induced apoptosis, evidenced by poly(ADP-ribose) polymerase (PARP) cleavage and DNA ladder formation. BPR0L075 induced cell death in paclitaxel-resistant ovarian cancer cells (OVCAR-3-TR and SKOV-3-TR) is primarily due to mitotic catastrophe, evidenced by formation of giant, multinucleated cells and absence of PARP cleavage. Immunoblotting analysis shows that BPR0L075 treatment induced up-regulation of cyclin B1, BubR1, MPM-2, and survivin protein levels and Bcl-XL phosphorylation in parental cells; however, in resistant cells, the endogenous expressions of BubR1 and survivin were depleted, BPR0L075 treatment failed to induce MPM-2 expression and phosphorylation of Bcl-XL. BPR0L075 induced cell death in both parental and paclitaxel-resistant ovarian cancer cells proceed through caspase-3 independent mechanisms. In conclusion, BPR0L075 displays potent cytotoxic effects in ovarian cancer cells with a potential to overcome paclitaxel resistance by bypassing efflux transporters and inducing mitotic catastrophe. BPR0L075 represents a novel microtubule therapeutic to overcome multidrug resistance and trigger alternative cell death by mitotic catastrophe in ovarian cancer cells that are apoptosis-resistant. 

Retracted: No

PubPeer comments:
 Figures 5 and 6. * Red, green, orange, and blue boxes: several panels look more similar to each other than expected. Reported to the journal in October 2015, but no action as of today. ![file] ,
miR-526b-3p functions as a tumor suppressor in colon cancer by regulating HIF-1α
Authors: Jian Zhao
Jian Xu
Jianhui Jia
Jian Wang
Rui Zhang
Journal: American journal of translational research (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HIF-1α; colon cancer; glycolysis; miR-526b-3p.
Affiliations: Department of Colorectal Surgery, Liaoning Cancer Hospital & Institute Shenyang, China., Department of RadioTherapy, Liaoning Cancer Hospital & Institute Shenyang, China.

Abstract:  HIF-1α is an important transcriptional factor, which plays roles in cancer development and progression. But its regulation by miRNAs is not clear. Here, to investigate the regulation of HIF-1α by miRNAs, miRNAs were predicted and miR-526b-3p was verified as a regulator of HIF-1α in colon cancer cells. Using TaqMan RT-PCR analysis, we analyzed the expression of miR-526b-3p in tumor tissues and cell lines and found that miR-526b-3p was consistently under-expressed in cancer tissues and cell lines compared with their normal controls. When miR-526b-3p was induced into the colon cancer cells, cell proliferation, metastasis and glycolysis of colon cancer cells were suppressed. We also found that miR-526b-3p was down-regulated in metastatic colon cancer tissues and negatively with HIF-1α mRNA in colon cancer tissues. In a summary, miR-526b-3p plays as a tumor suppressor by down-regulation of HIF-1α expression in colon cancer and may be a new diagnosis or therapeutic target. 

Retracted: No

PubPeer comments:
 Fig 3.  Low expression of miR-526b-3p is positively correlated with clinic features of colon cancer. A. miR-526b-3p was down-regulated in various colon cancer tissues. B. miR-526b-3p was down-regulated in metastatic colon cancer tissues. C. miR-526b-3p was related to colon cancer features in clinic. D. HIF-1u03b1 mRNA expression was negatively with miR-526b-3p expression in colon cancer tissues . ![file] It appears that the expression of miR-526b-3p in 86 cases of colon cancer ranges from about 1 to 19 in (D). When the cases are grouped by clinical grade (C), the values range from a **negative** value (or values) in the T4 group, up to 17 in the T1 group. When cases are dichotomised into metastatic and non-metastatic groups (B), values range from about 0.5 to about 11.5. When lumped together for comparison with controls (A), they range from negative expression up to an extreme of about 4. Am I missing something? ,
Fucosterol exhibits selective antitumor anticancer activity against HeLa human cervical cell line by inducing mitochondrial mediated apoptosis, cell cycle migration inhibition and downregulation of m-TOR/PI3K/Akt signalling pathway
Authors: Meng Xia
Shuqin Chen
Aiyue Chen
Peng Guo
Hongye Jiang
Jie Li
Yinguang Li
Shuzhong Yao
Journal: Oncology Letters (2018)
Discipline: CLINICAL MEDICINE
Keywords: ROS; apoptosis; cervical carcinoma; chemotherapy; fucosterol.
Affiliations: Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510086, P.R. China.

Abstract:  Cervical cancer greatly contributes to cancer-associated mortalities worldwide. The growing incidence of cervical cancer is of primary concern, and has signaled the need for multiple treatment options. Despite preliminary responses to chemotherapy and/or surgical interventions, the tumors consistently relapse. Previously, natural products gained attention for their diverse bioactivities, which include however are not limited to, neuroprotective, antimicrobial and anticancer effects. The present study evaluated the anticancer activity of fucosterol against a panel of human cancer cell lines. Results indicated that fucosterol exhibited selective inhibitory activity against human HeLa cervical cancer cell line with an IC50 of 40 µM. Fucosterol also induced apoptosis in HeLa cells and prompted reactive oxygen species mediated alterations in mitochondrial membrane potential. It triggered cell cycle arrest of HeLa cells at G2/M check point and exerted inhibitory effects on cell migration. The activation of the phosphoinositide-3-kinase (PI3K)/AKT Serine/Threonine Kinase 1 (AKT)/mechanistic target of Rapamycin (mTOR) pathway is important in cancer tumorigenesis, progression and chemotherapy resistance. The results demonstrated that fucosterol significantly inhibited the expression levels of key proteins of the PI3K/Akt/mTOR signaling pathway. Overall, the results of the present study suggest that fucosterol may prove beneficial in the management of cervical cancer. 

Retracted: No

PubPeer comments:
 *[right]* Figure 5 from [Jiang et al (2018)] .  Cell migration inhibitory potential of fucosterol at IC50 concentration (40 u00b5M) in human cervical cancer cell . *[left]* Figure 6 from [He et al (2018)] .  The effect of the IC50 concentration of arglabin on cell (A) migration and (B) invasion. The Figure depicts that arglabin inhibits cell invasion in a concentration-dependent manner . ![file] ,
SDF-1α upregulation by atorvastatin in rats with acute myocardial infarction via nitric oxide production confers anti-inflammatory and anti-apoptotic effects
Authors: Anping Cai
Yugang Dong
Shaoqi Rao
Danqing Yu
Dongdan Zheng
Yuli Huang
Ruofeng Qiu
Weiyi Mai
Yingling Zhou
Yingqing Feng
Journal: Journal of Biomedical Science (2012)
Discipline: CLINICAL MEDICINE
Keywords: atorvastatin; SDF-1α; AMI; rats; eNOS
Affiliations: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.

Abstract:  Background: The effects of atorvastatin on SDF-1α expression under acute myocardial infarction (AMI) are still unclear. Therefore, our present study is to investigate the roles and mechanisms of atorvastatin treatment on SDF-1α expression in rats with AMI. Methods: Male Sprague-Dawley rats were underwent permanent coronary artery ligation and randomly assigned into four groups as follow: blank control (B), atorvastatin (A), atorvastatin plus L-NAME (A+L-NAME), and atorvastatin plus AMD3100 (A+AMD3100). Rats underwent similar procedure but without ligation were used as group sham operated (S). Atorvastatin (10mg/Kg/d body weight) was administrated by gavage to rats in three atorvastatin treated groups, and L-NAME (40 mg/Kg/d body weight) or AMD3100 (5mg/Kg/d body weight) was given to group A+L-NAME or A+AMD3100, respectively. Results: Comparing with group B, NO production, SDF-1α and CXCR4 expression were significantly up-regulated in three atorvastatin treated groups at the seventh day. However, the increments of SDF-1α and CXCR4 expression in group A+L-NAME were reduced when NO production was inhibited by L-NAME. Anti-inflammatory and anti-apoptotic effects of atorvastatin were offset either by decrease of SDF-1α and CXCR4 expression (by L-NAME) or blockage of SDF-1α coupling with CXCR4 (by AMD3100). Expression of STAT3, a cardioprotective factor mediating SDF-1α/CXCR4 axis induced cardiac protection, was up-regulated most significantly in group A. The effects of atorvastatin therapy on cardiac function were also abrogated either when SDF-1α and CXCR4 expression was diminished or the coupling of SDF-1α with CXCR4 was blocked. Conclusion: SDF-1α upregulation by atorvastatin in rats with AMI was, at least partially, via the eNOS/NO dependent pathway, and SDF-1α upregulation and SDF-1α coupling with CXCR4 conferred anti-inflammatory and anti-apoptotic effects under AMI setting which we speculated that ultimately contributed to cardiac function improvement. 

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. ,
Cytokine-mediated up-regulation of CD55 and CD59 protects human hepatoma cells from complement attack
Authors: O B Spiller
S Rodríguez De Córdoba
B P Morgan
O Criado-García
Journal: Clinical and experimental immunology (2000)
Discipline: IMMUNOLOGY
Keywords: Hepatic parenchymal cells; acute-phase cytokines; complement regulatory proteins; membrane complement regulators; hepatoma cell line
Affiliations: Complement Biology Group, Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, UK. 

Abstract:  Hepatic parenchymal cells respond in many different ways to acute-phase cytokines. Some responses may protect against damage by liver-derived inflammatory mediators. Previous investigations have shown that cytokines cause increased secretion by hepatoma cells of soluble complement regulatory proteins, perhaps providing protection from complement attack. More important to cell protection are the membrane complement regulators. Here we examine, using flow cytometry and Northern blotting, the effects of different cytokines, singly or in combination, on expression of membrane-bound complement regulators by a hepatoma cell line. The combination of tumour necrosis factor-alpha, IL-1beta, and IL-6 caused increased expression of CD55 (three-fold) and CD59 (two-fold) and decreased expression of CD46 at day 3 post-exposure. Interferon-gamma reduced expression of CD59 and strongly antagonized the up-regulatory effects on CD59 mediated by the other cytokines. Complement attack on antibody-sensitized hepatoma cells following a 3-day incubation with the optimum combination of acute-phase cytokines revealed increased resistance to complement-mediated lysis and decreased C3b deposition. During the acute-phase response there is an increased hepatic synthesis of the majority of complement effector proteins. Simultaneous up-regulation of expression of CD55 and CD59 may serve to protect hepatocytes from high local concentrations of complement generated during the acute-phase response. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,
One‐pot green synthesis and structural characterisation of silver nanoparticles using aqueous leaves extract of Carissa carandas : antioxidant, anticancer and antibacterial activities
Authors: Deepika Singh
Vikas Kumar
Ujendra Komal
Ekta Yadav
Manvendra Singh
Amita Verma
Neha Falls
Journal: IET Nanobiotechnology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Green synthesis; Silver nanoparticles; Carissa carandas leaves; Bioactive molecules; Fourier transforms infrared spectroscopy
Affiliations: Department of Pharmaceutical ScienceFaculty of Health SciencesSam Higginbottom University of Agriculture, Technology &amp; SciencesAllahabadUP 211007India, Natural Product Drug Discovery LaboratoryDepartment of Pharmaceutical SciencesFaculty of Health SciencesSam Higginbottom University of Agriculture, Technology &amp; SciencesAllahabadUP 211007India, Department of Computer SciencesHMFA Institute of Engineering and TechnologyHandia, AllahabadUPIndia, Department of Mechanical &amp; Industrial EngineeringIndian Institute of TechnologyRoorkeeUttrakhandIndia, Bio‐organic &amp; Medicinal Chemistry Research LaboratoryDepartment of Pharmaceutical SciencesFaculty of Health SciencesSam Higginbottom University of Agriculture, Technology &amp; SciencesAllahabadUP 211007India

Abstract:  Facile green synthesis of silver nanoparticles (AgNPs) using an aqueous extract of Carissa carandas (C. carandas) leaves was studied. Fabrication of AgNPs was confirmed by the UV-visible spectroscopy which gives absorption maxima at 420 nm. C. carandas leaves are the rich source of the bioactive molecules, acts as a reducing and stabilising agent in AgNPs, confirmed by Fourier transforms infrared spectroscopy. The field emission scanning electron microscope revealed the spherical shape of biosynthesised AgNPs. A distinctive peak of silver at 3 keV was determined by energy dispersive X-ray spectroscopy. X-ray diffraction showed the facecentred cubic structure of biosynthesised AgNPs and thermal stability was confirmed by the thermogravimetric analysis. Total flavonoid and total phenolic contents were evaluated in biosynthesised AgNPs. Biosynthesised AgNPs showed free radical scavenging activities against 2, 2-diphenyl-1-picrylhydrazyl test and ferric reducing antioxidant power assay. In vitro cytotoxicity against hepatic cell lines (HUH-7) and renal cell lines (HEK-293) were also assessed. Finally, biosynthesised AgNPs were scrutinised for their antibacterial activity against methicillin-resistant Staphylococcus aureus, Shigella sonnei, Shigella boydii and Salmonella typhimurium. This study demonstrated the biofabrication of AgNPs by using C. carandas leaves extract and a potential in vitro biological application as antioxidant, anticancer and antibacterial agents. 

Retracted: No

PubPeer comments:
 blots in Figures 2 and 5 outlined in red boxes appear to be identical although labeled as different things ![file] , 
 it appears that the same beta-actin was used for both Figures 5 and 6 although Figure 5 is stretched relative to Fig 6 ![file] , 
 #2 Lanes are consistent so that looks reasonable. ,
Clinical study on local application of low-dose insulin for promoting wound healing after operation for deep burns
Authors: Ming Zeng
Yan Zhi
Wei Zhang
Wenjun Liu
Jinxiong Xu
Journal: Experimental and Therapeutic Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: deep burn; heat shock protein-90; interleukin-1 CD31 immunohistochemistry; low-dose insulin; transforming growth factor-β
Affiliations: Department of Burns, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.

Abstract:  Transplanted free skin flaps are often needed to treat deep burns; their survival, however, is less than optimal. This study examined whether local low-dose insulin injections can promote flap survival and wound healing after surgery. A total of 165 patients who underwent free skin flap transplantation for simple deep burns were enrolled in the study and divided into 5 groups of 33 patients each: Blank control group (no local subcutaneous drug injections), saline control group (saline injections), low-dose insulin group (0.5 units regular insulin injections), medium-dose group (1.0 units regular insulin injections) and high-dose group (2.0 units regular insulin injections). Wound healing and flap survival conditions were assessed and compared among groups. The best wound healing rate found was that of the low-dose insulin injection group where all the parameters measured improved significantly: The healing time was shorter; the blood flow volume, the flap survival, the number of fibroblasts and new vessels increased; the re-epithelialization occurred faster; the infiltration of inflammatory cells was reduced; the expression levels of heat shock protein-90, vascular endothelial growth factor, transforming growth factor-β and interleukin-1 were higher; and the plasma glucose levels only fluctuated slightly. The results clearly demonstrate that a local low-dose insulin regime after flap transplantation can accelerate the healing time and improve the surgical outcome without exerting detrimental secondary effects on the glucose plasma level of deep burn patients. 

Retracted: No

PubPeer comments:
 Figure 1 and Figure 3 appear to have some images which overlap, or are repeated. Of greatest concern, the images in Figure 1 are not exact duplicates, and may have been edited. *** Figure 1 ![file] *** Figure 3 ![file] , 
 I have no idea what is going on with Fig 3. The 14-day Saline Control and Low-dose panels differ from the 7-day versions only in the duplication of a segment of each image. ![file] ,
Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast
Authors: Matthias Heinemann
Athanasios Litsios
Mattia Rovetta
Johan Hekelaar
Katarzyna Buczak
Marten Exterkate
Alexander Schmidt
Georg Hubmann
Alexandros Papagiannakis
Daphne H E W Huberts
Hanna M Terpstra
Andreas Milias-Argeitis
Paolo Guerra
Journal: Nature Cell Biology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Saccharomyces cerevisiae; Cln3; cell cycle; protein production rate; metabolic dynamics
Affiliations: Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands., Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Proteomics Core Facility, Biozentrum, University of Basel, Basel, Switzerland., Department of Biology, Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Heverlee, Belgium., Center for Microbiology, VIB, Heverlee, Belgium., Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands., Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands. .

Abstract:  In the unicellular eukaryote Saccharomyces cerevisiae, Cln3-cyclin-dependent kinase activity enables Start, the irreversible commitment to the cell division cycle. However, the concentration of Cln3 has been paradoxically considered to remain constant during G1, due to the presumed scaling of its production rate with cell size dynamics. Measuring metabolic and biosynthetic activity during cell cycle progression in single cells, we found that cells exhibit pulses in their protein production rate. Rather than scaling with cell size dynamics, these pulses follow the intrinsic metabolic dynamics, peaking around Start. Using a viral-based bicistronic construct and targeted proteomics to measure Cln3 at the single-cell and population levels, we show that the differential scaling between protein production and cell size leads to a temporal increase in Cln3 concentration, and passage through Start. This differential scaling causes Start in both daughter and mother cells across growth conditions. Thus, uncoupling between two fundamental physiological parameters drives cell cycle commitment. 

Retracted: No

PubPeer comments:
 ![file] , 
 ![file] , 
 Figures 2A and 2C overlapping. ![file] ,
MicroRNA-198 inhibits metastasis of thyroid cancer by targeting H3F3A
Authors: L Kong
J Fang
L-M He
J-M Zhu
H-L Dai
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-198; thyroid cancer; H3F3A; tumor progression; qRT-PCR
Affiliations: Department of General Surgery, Chinese PLA 988 Hospital, Zhengzhou, China. .

Abstract:  Objective: This study was designed to investigate the role of microRNA-198 in thyroid cancer (TCa) progression. Patients and methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to examine microRNA-198 and H3F3A levels in tumor tissue specimens and paracancerous ones collected from 50 patients with TCa, and the interplay between microRNA-198 or H3F3A and some clinical indicators or prognosis of TCa patients was analyzed as well. MicroRNA-198 and H3F3A overexpression models were constructed using lentivirus in TCa cell lines TPC-1 and BHP2-7, and the impacts of microRNA-198 on TCa cell functions were evaluated by using cell counting kit-8 (CCK-8), plate clone formation, and transwell assays. Finally, recovery investigations were conducted to explore the underlying mechanisms as well as the interaction between microRNA-198 and H3F3A. Results: QRT-PCR indicated that in tumor tissues of TCa patients, microRNA-198 showed a remarkably lower expression than in adjacent normal tissue samples. Compared with patients with high expression of microRNA-198, those with microRNA-198 low expression had more advanced tumor stage, larger tumor size, higher lymph node metastasis rate, and lower overall survival rate. Meanwhile, the results of research on H3F3A were just opposite to the above observations on microRNA-198. In in vitro cell experiments, overexpression of microRNA-198 significantly weakened the proliferation and migration ability of thyroid tumor cells. Besides, Luciferase reporter gene experiment revealed that H3F3A was a specific target gene for microRNA-198. Moreover, qRT-PCR indicated that H3F3A and microRNA-198 were negatively correlated in thyroid carcinoma tissues. In addition, compared with NC group, overexpression of H3F3A markedly enhanced the migration and proliferative capacity of TCa cells. Lastly, recovery experiment revealed a mutual regulation between microRNA-198 and H3F3A, the two of which may together participate in the malignant progression of TCa. Conclusions: MicroRNA-198 is remarkably reduced in TCa and inhibits malignant progression of TCa by regulating H3F3A. Meanwhile, microRNA-198 is remarkably associated with pathological stage, tumor size, lymph node metastasis, and poor prognosis of TCa. 

Retracted: No

PubPeer comments:
 Figure 6. * Blue boxes: The HOB stained panels from 14 days and 21 days appear to show an overlap. ![file] ,
Toll-like receptor 10 (TLR10) exhibits suppressive effects on inflammation of prostate epithelial cells
Authors: Yu Ding
Duan Guo
Shi Qiu
Yu Fan
Tao Lin
Zhuang Tang
Qiang Wei
Lu Yang
Ping Tan
Journal: Asian Journal of Andrology (2019)
Discipline: CLINICAL MEDICINE
Keywords: TLR10; Toll-like receptor 2 (TLR2); benign prostatic hyperplasia; inflammation.
Affiliations: Department of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu 610041, China., Department of Core Facility, West China Hospital of Sichuan University, Chengdu 610041, China., Department of Urology, Sun Yat-Sen Memorial Hospital of Zhongshan University, Guangzhou 510120, China., Department of Palliative Medicine, West China Fourth Affiliated Hospital of Sichuan University, Chengdu 610041, China.

Abstract:  Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phospho-nuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were downregulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were involved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells. 

Retracted: No

PubPeer comments:
 Figure 3A u2013 actin bands are more similar than expected ![file] Zoom: ![file] ,
LncRNA ASMTL-AS1/microRNA-1270 differentiate prognostic groups in gastric cancer and influence cell proliferation, migration and invasion
Authors: Jian Wang
Zhenhe Song
Journal: Bioengineered (2022)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ASMTL-AS1; gastric cancer; invasion; miR-1270; migration.
Affiliations: Department of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China, Department of Laboratory, Yidu Central Hospital of Weifang, Weifang, Shandong, China

Abstract:  The objective of this study was to determine the expression levels of ASMTL-AS1 and miR-1270 in gastric cancer, and to explore whether ASMTL-AS1 and miR-1270 is associated with cancer prognosis and progression or not. ASMTL-AS1 and miR-1270 expression were quantified in gastric cancer tissues and adjacent normal tissues (n = 167) and cell lines. The potential of ASMTL-AS1 and miR-1270 as prognostic biomarkers was evaluated by the receiver operating characteristic (ROC) curve, Kaplan-Meier, and multivariate Cox regression analyses. The binding between ASMTL-AS1 and miR-1270 was verified by the Luciferase reporter assay and RNA pull-down assay. Functional roles of ASMTL-AS1/miR-1270 on cells were investigated in HGC-27 and NCI-N87 cells by MTS viability, Transwell migration, and Matrigel invasion assay. ASMTL-AS1 was significantly downregulated while miR-1270 was upregulated in gastric cancer tissues as compared with normal tissue and cell lines. According to the studies, ASMTL-AS1 and miR-1270 were related to unfavorable clinical parameters, such as the advanced TNM stage. Downregulated ASMTL-AS1 and upregulated miR-1270 were associated with reduced 5-year overall survival. Functional studies suggested that ASMTL-AS1 inhibits proliferation, migration, and invasion of HGC-27 and NCI-N87 cells by regulation of miR-1270. In summary, ASMTL-AS1 and miR-1270 are associated with poor prognosis of patients with gastric cancer. ASMTL-AS1 inhibited gastric cancer progression by regulating miR-1270. Therefore, ASMTL-AS1/miR-1270 may be a potential prognostic biomarker and novel strategy for gastric cancer targeted therapy. 

Retracted: No

PubPeer comments:
 Can the authors please provide the approval number for the use of patient material in this study? In the references, four of them are published in Bioengineered. Two of them where published in 2020, same issue, the other two in 2021, same issue. This indicates that there references are added only for one purpose: to pump up the journal impact factor. Furthermore, there is no funding associated with this publication, which is common for most of the papers published in issue 1, 2022, Bioengineered. ![file] ,
WITHDRAWN: Performance of cartilage cells in different types of mandibular condylar fractures
Authors: Tuerdi Maimaitituxun
Zhitao Yao
Wei An
Journal: Bioscience reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Mandibular condylar fracture; apoptosis; cartilage cells; osteogenesis; rehabilitation.
Affiliations: The First Affiliated Hospital, Xinjiang Medical University, Urumqi, China.

Abstract:  The Accepted Manuscript version of this article (published on 10 June 2020) was withdrawn on 2 July 2020 due to concerns over data validity. 

Retracted: No

PubPeer comments:
 There is overlap both within Figure 3 and between Figure 3 and Figure 5 ![file] , 
 The article has been withdrawn The notice from the publisher:  The Accepted Manuscript version of this article (published on 10 June 2020) was withdrawn on 2 July 2020 due to concerns over data validity. https: portlandpress.com bioscirep article doi 10.1042 BSR20193919 225237 WITHDRAWN-Performance-of-cartilage-cells-in?searchresult=1 ,
Development of hRad51–Cas9 nickase fusions that mediate HDR without double-stranded breaks
Authors: David R Liu
Wei-Hsi Yeh
Holly A Rees
Journal: Nature Communications (2019)
Discipline: Multidisciplinary
Keywords: DNA breaks; end-joining processes; insertions; deletions; rearrangements
Affiliations: Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA., Howard Hughes Medical Institute, Harvard University, Cambridge, MA, 02142, USA., Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138, USA., Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA, 02115, USA., Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. ., Howard Hughes Medical Institute, Harvard University, Cambridge, MA, 02142, USA. ., Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138, USA. .

Abstract:  In mammalian cells, double-stranded DNA breaks (DSBs) are preferentially repaired through end-joining processes that generally lead to mixtures of insertions and deletions (indels) or other rearrangements at the cleavage site. In the presence of homologous DNA, homology-directed repair (HDR) can generate specific mutations, albeit typically with modest efficiency and a low ratio of HDR products:indels. Here, we develop hRad51 mutants fused to Cas9(D10A) nickase (RDN) that mediate HDR while minimizing indels. We use RDN to install disease-associated point mutations in HEK293T cells with comparable or better efficiency than Cas9 nuclease and a 2.7-to-53-fold higher ratio of desired HDR product:undesired byproducts. Across five different human cell types, RDN variants generally result in higher HDR:indel ratios and lower off-target activity than Cas9 nuclease, although HDR efficiencies remain strongly site- and cell type-dependent. RDN variants provide precision editing options in cell types amenable to HDR, especially when byproducts of DSBs must be minimized. 

Retracted: No

PubPeer comments:
 Sequencing data [PRJNA515942] still not submitted (been 6months+) - else it would have shown that nickases have DSBs, the [Prime-editor follow up paper] . , 
 Apologize, the sequencing data is there. Brain fade I guess. Will analyze the data and get back , 
 And as expected, DSBs abound in this study. Undoubtedly, there is a lot of work here - 2000+ sequencing samples. But most of them have integrations of the plasmid at the gRNA edited site. In fact, there are off-target integrations too. Here is the [updated pre-print] - and the [sequencing data] . I wonder how such a paper (and the [Prime-editor] ) can not be retracted. This is bizarre science. ,
Epithelial-mesenchymal transition markers and HER3 expression are predictors of elisidepsin treatment response in breast and pancreatic cancer cell lines
Authors: Miguel Aracil
Javier Hernández-Losa
Cristina Teixidó
Santiago Ramón y Cajal
Rosó Marés
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Elisidepsin; antiproliferative activity; tumor cell lines; epithelial-mesenchymal transition (EMT); HER family receptors
Affiliations: Molecular Pathology Group, Vall d'Hebron Research Institute, Universidad Autonoma of Barcelona, Barcelona, Spain.

Abstract:  Elisidepsin (elisidepsin trifluoroacetate, Irvalec®, PM02734) is a new synthetic depsipeptide, a result of the PharmaMar Development Program that seeks synthetic products of marine origin-derived compounds. Elisidepsin is a drug with antiproliferative activity in a wide range of tumors. In the present work we studied and characterized the mechanisms associated with sensitivity and resistance to elisidepsin treatment in a broad panel of tumor cell lines from breast and pancreas carcinomas, focusing on different factors involved in epithelial-mesenchymal transition (EMT) and the use of HER family receptors in predicting the in vitro drug response. Interestingly, we observed that the basal protein expression levels of EMT markers show a significant correlation with cell viability in response to elisidepsin treatment in a panel of 12 different breast and pancreatic cancer cell lines. In addition, we generated three elisidepsin treatment-resistant cell lines (MCF-7, HPAC and AsPC-1) and analyzed the pattern of expression of different EMT markers in these cells, confirming that acquired resistance to elisidepsin is associated with a switch to the EMT state. Furthermore, a direct correlation between basal HER3 expression and sensitivity to elisidepsin was observed; moreover, modulation of HER3 expression levels in different cancer cell lines alter their sensitivities to the drug, making them more resistant when HER3 expression is downregulated by a HER3-specific short hairpin RNA and more sensitive when the receptor is overexpressed. These results show that HER3 expression is an important marker of sensitivity to elisidepsin treatment. 

Retracted: No

PubPeer comments:
 Figure 5. Reported to the journal in 2014. Several panels appear to look similar to each other. The b-actin panels (marked in lime green and blue) are probably representing the same experiment, so this is not of concern, but the other 2 sets of bands (marked in red and darker green) are not expected to look so similar. Dashed lines represent mirrored images. ![file] Close up view: ![file] ,
Multi-level interactions between the nuclear receptor TRα1 and the WNT effectors β-catenin/Tcf4 in the intestinal epithelium
Authors: Seham Skah
Imtiaz Nisar Lone
Maria Sirakov
Dimitar Angelov
Michelina Plateroti
Julien Nadjar
Journal: PloS one (2012)
Discipline: Multidisciplinary
Keywords: Intestinal homeostasis; signaling pathways; tumorigenesis; thyroid hormone nuclear receptor TRα1; WNT pathway
Affiliations: Institut de Génomique Fonctionnelle de Lyon, Lyon, France.

Abstract:  Intestinal homeostasis results from complex cross-regulation of signaling pathways; their alteration induces intestinal tumorigenesis. Previously, we found that the thyroid hormone nuclear receptor TRα1 activates and synergizes with the WNT pathway, inducing crypt cell proliferation and promoting tumorigenesis. Here, we investigated the mechanisms and implications of the cross-regulation between these two pathways in gut tumorigenesis in vivo and in vitro. We analyzed TRα1 and WNT target gene expression in healthy mucosae and tumors from mice overexpressing TRα1 in the intestinal epithelium in a WNT-activated genetic background (vil-TRα1/Apc mice). Interestingly, increased levels of β-catenin/Tcf4 complex in tumors from vil-TRα1/Apc mice blocked TRα1 transcriptional activity. This observation was confirmed in Caco2 cells, in which TRα1 functionality on a luciferase reporter-assay was reduced by the overexpression of β-catenin/Tcf4. Moreover, TRα1 physically interacted with β-catenin/Tcf4 in the nuclei of these cells. Using molecular approaches, we demonstrated that the binding of TRα1 to its DNA target sequences within the tumors was impaired, while it was newly recruited to WNT target genes. In conclusion, our observations strongly suggest that increased β-catenin/Tcf4 levels i) correlated with reduced TRα1 transcriptional activity on its target genes and, ii) were likely responsible for the shift of TRα1 binding on WNT targets. Together, these data suggest a novel mechanism for the tumor-promoting activity of the TRα1 nuclear receptor. 

Retracted: No

PubPeer comments:
 The authors have not mentioned the permission letter no. of PCCF and just mentioned that they have been issued a permission as they have done in multiple other publications. This can be done by anybody and any data can be provided. Again the authors fail to inform which areas they have collected the snakes from and what was their age and was any permission taken from the ethical committee. Was their protocol of not feeding the snakes for 7 days approved by the CPCSEA guidelines? ![file] ![file] ,
TEAD mediates YAP-dependent gene induction and growth control
Authors: Weiquan Li
Jiandie D Lin
Siming Li
Zhi-Chun Lai
Arul M Chinnaiyan
Jianjun Yu
Jindan Yu
Li Li
Bin Zhao
Kun-Liang Guan
Cun-Yu Wang
Xin Ye
Journal: Genes & Development (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: YAP; TEAD; Hippo pathway; oncogene; CTGF
Affiliations: Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA.

Abstract:  The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent gene expression. TEAD is also required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition. CTGF is identified as a direct YAP target gene important for cell growth. Moreover, the functional relationship between YAP and TEAD is conserved in Drosophila Yki (the YAP homolog) and Scalloped (the TEAD homolog). Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar than expected. https: imgur.com WCtYv6j ,
Trichosanthin suppresses HeLa cell proliferation through inhibition of the PKC/MAPK signaling pathway
Authors: Ping Wang
Ji-Cheng Li
Hui Yan
Li-Li Chen
Journal: Cell Biology and Toxicology (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Trichosanthin; TCS; HeLa cell proliferation; apoptotic pathway; cAMP response element binding protein
Affiliations: Institute of Cell Biology, Zhejiang University, Hangzhou, China.

Abstract:  Trichosanthin (TCS) possesses a broad spectrum of biological and pharmacological activities, including anti-tumor activities. Our previous studies have shown that TCS inhibits HeLa cell proliferation by activating the apoptotic pathway. In particular, the transcriptional factor cAMP response element binding (CREB) protein plays a pivotal role in apoptotic HeLa cells. However, no information, to date, is available about the signaling pathways involved in the inhibition of cell proliferation induced by TCS. The present study showed that PKA and PKC activities were significantly inhibited by TCS treatment. However, specific inhibitor of PKA activity failed to affect the inhibition of HeLa cell proliferation induced by TCS, even in the presence of cAMP agonists. In contrast, PKC activator/inhibitor significantly attenuated/enhanced the inhibitory effect of TCS on cell proliferation. In particular, the reversed effect of cAMP agonist on cell proliferation was partly prevented by PKC, ERK1/2, and p38 MAPK blockade. Consistent with these results, the reversed effect of cAMP agonists on CREB phosphorylation was significantly decreased by inhibitors of these kinases, but not PKA inhibitor. Therefore, our results suggested that HeLa cell proliferation was inhibited by TCS via suppression of PKC/MAPK signaling pathway. 

Retracted: No

PubPeer comments:
 the loading controls in Fig 4 5 look like a combination of 3 reused blobs. Can the authors upload their original films to clarify? ![file] ,
Facial recognition technology can expose political orientation from naturalistic facial images
Authors: Michal Kosinski
Journal: Scientific Reports (2021)
Discipline: Multidisciplinary
Keywords: Facial recognition technology; political orientation; algorithm; similarity; liberal
Affiliations: Stanford University, Stanford, CA, 94305, USA. .

Abstract:  Ubiquitous facial recognition technology can expose individuals' political orientation, as faces of liberals and conservatives consistently differ. A facial recognition algorithm was applied to naturalistic images of 1,085,795 individuals to predict their political orientation by comparing their similarity to faces of liberal and conservative others. Political orientation was correctly classified in 72% of liberal-conservative face pairs, remarkably better than chance (50%), human accuracy (55%), or one afforded by a 100-item personality questionnaire (66%). Accuracy was similar across countries (the U.S., Canada, and the UK), environments (Facebook and dating websites), and when comparing faces across samples. Accuracy remained high (69%) even when controlling for age, gender, and ethnicity. Given the widespread use of facial recognition, our findings have critical implications for the protection of privacy and civil liberties. 

Retracted: No

PubPeer comments:
 https: twitter.com cfiesler status 1351307867102605313 , 
 https: statmodeling.stat.columbia.edu 2021 08 09 controversy-over-facial-recognition-technology-can-expose-political-orientation-from-naturalistic-facial-images ,
Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding
Authors: Daniel D Carson
Amantha Thathiah
Carl P Blobel
Journal: Journal of Biological Chemistry (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MUC1 clearance; embryo implantation; uterine epithelium; protease; shedding
Affiliations: Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, USA.

Abstract:  MUC1 clearance from the uterine epithelial cell surface is a prerequisite for the creation of an environment conducive to embryo implantation. In some species, reduced mRNA levels along with metabolic turnover account for loss of MUC1 during the receptive phase throughout the uterine epithelium. In other species, MUC1 is rapidly lost solely at the site of blastocyst attachment, suggesting the action of a protease. Correlative studies also indicate the presence of soluble forms of MUC1 in cell culture supernatants in vitro and in bodily fluids in vivo. To characterize the proteolytic activity mediating MUC1 release, shedding of MUC1 was analyzed in a human uterine epithelial cell line (HES) that abundantly expresses and readily sheds MUC1. MUC1 release was stimulated by phorbol 12-myristate 13-acetate and was markedly inhibited by the synthetic peptide hydroxamate metalloprotease inhibitor, tumor necrosis factor-alpha protease inhibitor (TAPI), as well as by an endogenous inhibitor of matrix metalloproteases, tissue inhibitor of metalloproteases (TIMP)-3. These characteristics along with studies conducted with cell lines genetically deficient in various ADAMs (for a disintegrin and metalloprotease) identified tumor necrosis factor-alpha converting enzyme (TACE)/ADAM 17 as a MUC1 sheddase. Furthermore, both TACE and MUC1 were expressed in human uterine epithelia during the receptive phase, and co-immunoprecipitation experiments revealed a physical interaction between TACE and MUC1 in HES cells. These studies establish a proteolytic mechanism for MUC1 clearance from a human uterine epithelial cell line and identify TACE as a MUC1 sheddase. 

Retracted: No

PubPeer comments:
 Figure 4C. Splicing between plus and minus treatments. ![file] ,
Differential Regulation of Soluble and Membrane-Bound Inorganic Pyrophosphatases in the Photosynthetic Bacterium Rhodospirillum rubrum Provides Insights into Pyrophosphate-Based Stress Bioenergetics
Authors: Rosa L López-Marqués
José R Pérez-Castiñeira
Aurelio Serrano
Manuel Losada
Journal: Journal of Bacteriology (2004)
Discipline: MICROBIOLOGY
Keywords: inorganic pyrophosphatases; Rhodospirillum rubrum; regulation; environmental growth conditions; anaerobic phototrophic batch cultures
Affiliations: Instituto de Bioquímica Vegetal y Fotosíntesis, Universidad de Sevilla-CSIC, 41092 Seville, Spain

Abstract:  Soluble and membrane-bound inorganic pyrophosphatases (sPPase and H(+)-PPase, respectively) of the purple nonsulfur bacterium Rhodospirillum rubrum are differentially regulated by environmental growth conditions. Both proteins and their transcripts were found in cells of anaerobic phototrophic batch cultures along all growth phases, although they displayed different time patterns. However, in aerobic cells that grow in the dark, which exhibited the highest growth rates, Northern and Western blot analyses as well as activity assays demonstrated high sPPase levels but no H(+)-PPase. It is noteworthy that H(+)-PPase is highly expressed in aerobic cells under acute salt stress (1 M NaCl). H(+)-PPase was also present in anaerobic cells growing at reduced rates in the dark under either fermentative or anaerobic respiratory conditions. Since H(+)-PPase was detected not only under all anaerobic growth conditions but also under salt stress in aerobiosis, the corresponding gene is not invariably repressed by oxygen. Primer extension analyses showed that, under all anaerobic conditions tested, the R. rubrum H(+)-PPase gene utilizes two activator-dependent tandem promoters, one with an FNR-like sequence motif and the other with a RegA motif, whereas in aerobiosis under salt stress, the H(+)-PPase gene is transcribed from two further tandem promoters involving other transcription factors. These results demonstrate a tight transcriptional regulation of the H(+)-PPase gene, which appears to be induced in response to a variety of environmental conditions, all of which constrain cell energetics. 

Retracted: No

PubPeer comments:
 Figure 4A: two bands seems as they are duplicated (blue graphs), and red arrow points to a visible splice. In neighbouring blot, orange arrow points to a strange discontinuity, indicating a putative splice or other kind of manipulation. Could the authors please comment, and eventually post the uncropped scans of blots at higher resolution? ![file] , 
 #1 I wish to better highlight my concerns on Figure 4A: ![file] ,