PReD-Bench/PRed-Bench huggingface dataset:
RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1
Authors: Bin-Bin Du
Tian-Kang Guo
Wei-Sheng Zhang
Zheng-Xia Wang
Lai-Yuan Li
Xiong-Fei Yang
Xiang-Yong Hao
Yi-Feng Chen
Tao Wang
Zhi-Wei Wu
Journal: Cancer medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: RAPTOR; URB1; colorectal cancer; cyclinA2; mTORC1
Affiliations: The First School of Clinical Medicine, Lanzhou University, Lanzhou, China., Department of Colorectal Surgery, Gansu Provincial People's Hospital, Lanzhou, China., Department of Otolaryngology, The Second Hospital of Lanzhou University, Lanzhou, China., The School of Preclinical Medicine, Gansu University of Chinese Medicine, Lanzhou, China., Department of General surgery, Gansu Provincial People's Hospital, Lanzhou, China.

Abstract:  Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)-URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC. 

Retracted: No

PubPeer comments:
 there are many areas of very similar data patterns between the flow cytometry graphs in Figure 3B, e.g. ![file] there are some extra points in some of the apparently duplicated data areas and small differences in data density in some of the similar patterns. It would be reassuring to readers if the raw numerical data were posted to PubPeer. , 
 the 400x area for the high expression RAPTOR image shown in Figure 1H is not a magnified view of the corresponding boxed 40X area ![file] , 
 following up on social media tip, Figure 2 F has duplicated areas ![file] , 
 ![](http: )![file] ![file] Figure 6 F has overlapping regions within the URB1 column; RAPTOR and sh-NC both appear to the the same image shifted with RAPTOR being manipulated to be darker ,
An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness
Authors: Daniel D Billadeau
Qiang Guo
Yu-Qing Lv
Saverio Bellusci
Xiaokun Li
Jing Bai
Zhenkun Lou
Wei Wang
Li Ding
Jin-San Zhang
Jiayu Liu
Ruo Yang
Rui Han
Mei-Yu Quan
Yaxin Cai
Journal: Frontiers in Cell and Developmental Biology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FGFR; SOX2; pancreatic cancer; sphere-formation assay; stemness.

Abstract:  Cancer stemness is associated with high malignancy and low differentiation, as well as therapeutic resistance of tumors including pancreatic ductal adenocarcinoma (PDAC). Fibroblast growth factors (FGFs) exert pleiotropic effects on a variety of cellular processes and functions including embryonic stem cell pluripotency and cancer cell stemness via the activation of four tyrosine kinase FGF receptors (FGFRs). FGF ligands have been a major component of the cocktail of growth factors contained in the cancer stemness-inducing (CSI) and organoid culture medium. Although FGF/FGFR signaling has been hypothesized to maintain cancer stemness, its function in this process is still unclear. We report that inhibition of FGF/FGFR signaling impairs sphere-forming ability of PDAC in vitro, and knocking down FGFR1 and FGFR2 decreased their tumorigenesis abilities in vivo. Mechanistically, we demonstrated that SOX2 is down-regulated upon loss of FGFR signaling. The overexpression of SOX2 in SOX2-negative cells, which normally do not display stemness capabilities, is sufficient to induce spheroid formation. Additionally, we found that AKT phosphorylation was reduced upon FGFR signaling inhibition. The inhibition of AKT using specific pharmacological inhibitors in the context of CSI medium leads to the loss of spheroid formation associated with loss of SOX2 nuclear expression and increased degradation. We demonstrate that an FGFR/AKT/SOX2 axis controls cancer stemness in PDAC and therefore may represent an important therapeutic target in the fight against this very aggressive form of cancer. 

Retracted: No

PubPeer comments:
 October 2020 Corrigendum, found here: https: www.frontiersin.org articles 10.3389 fcell.2020.594589 full It reads:  In the original article, there was a mistake in Figures 2C, 6B, and S3C as published. The control tubulin immunoblot shown in Figure S3C and microscopy of sphere-formation assay in Figures 2C and 6B were redundantly used. The corrected Figures 2C, 6B, and S3C appear below. , 
 The current PDF contains the newly replaced images, not the originals. I could not find the original supplemental figure but the original PDF was available. Here is a comparison of the original Figures 2C (now replaced), 3C, and 6C (now replaced), in which three panels appear to show overlaps with each other, with some distortion of the aspect ratios. ![file] ,
Combinatorial Peptide Microarray Synthesis Based on Microfluidic Impact Printing
Authors: Ruiwu Liu
Gaomai Yang
Jiannan Li
Paolo Disano
Wenwu Xiao
Siwei Zhao
Tingrui Pan
Kit S Lam
Journal: ACS Combinatorial Science (2019)
Discipline: CHEMISTRY
Keywords: cancer targeting; integrin binding; microfluidic; peptide microarrays; peptide synthesis
Affiliations: Department of Biomedical Engineering , University of California , Davis , California 95616-5270 , United States., Department of Biomedical Engineering , Tufts University , Boston , Massachusetts 02155 , United States., Department of Biochemistry and Molecular Medicine , University of California , Davis , California 95817 , United States.

Abstract:  In this Research Article, a novel inkjet printing technique, micro impact printing (MI printing), is applied for the first time to combinatorial peptide microarray synthesis on amine functionalized microdisc arrays through standard Fmoc chemistry. MI printing shows great advantages in combinatorial peptide microarray synthesis compared with other printing techniques, including (1) a disposable cartridge; (2) a small spot size (80 μm) increases array density; (3) minimal loading volume (0.6 μL) and dead volume (&lt;0.1 μL), reduce chemical waste; and (4) multiplexibility of 5 channels/cartridge and capacity of multiple cartridges. Using this synthesis platform, a tetrapeptide library with 625 permutations was constructed and then applied for the screening of ligands targeting α4β1 integrin on Jurkat cells. 

Retracted: No

PubPeer comments:
 In the commented article the papers of Furka et al. [1] and Lam et al. [2] are cited as the sources of OBOC libraries. In the Corrigendum to u2018Tumor-targeting peptides from combinatorial librariesu2019 however, published in Adv. Drug Del. Rew. in 2017 one can read that the split-mix strategy of Furka et al. [1] is used for the synthesis of OBOC libraries. ![file] This means that Lam et al. [2] are not inventors of the synthesis of OBOC libraries. Why is cited again the Lam et al. paper in the commented article? Kit S. Lam who is corresponding author in both articles may give an answer. 1.tFurka, A.; Sebestyen, F.; Asgedom, M.; Dibo, G. General-Method for Rapid Synthesis of Multicomponent Peptide Mixtures. Int. J. Pept. Protein Res. 1991, 37 (6), 487u2212493. 2.tLam, K. S.; Salmon, S. E.; Hersh, E. M.; Hruby, V. J.; Kazmierski, W. M.; Knapp, R. J. A New Type of Synthetic Peptide Library for Identifying Ligand-Binding Activity. Nature 1991, 354 (6348), 82u221284. ,
AnnexinA5 Might Suppress the Phenotype of Human Gastric Cancer Cells via ERK Pathway
Authors: Yunzhe Ci
Meichuan Li
Xiaojie Wang
Yina Zhao
Huan Wang
Xin Li
Jialu Zhang
Yarui Dai
Journal: Frontiers in Oncology (2021)
Discipline: CLINICAL MEDICINE
Keywords: ERK pathway; anexinA5; apoptosis; gastric cancer; invasion
Affiliations: Histology and Embryology Department, Chengde Medical University, Chengde, China.

Abstract:  Gastric cancer is one of the most fatal diseases around the world. However, the mechanism of the development of gastric cancer is still not clarified. In addition, the anticancer drugs have cytotoxicity with different degrees. AnnexinA5, a member of the annexin family, has a great binding ability with the membrane phospholipid in a calcium dependent manner and is involved in the development of various cancers. This study aims to explore the influence of annexinA5 on human gastric cancer cells and whether it has the potential to be an auxiliary treatment to gastric cancer. In this study, the role of annexinA5 was detected from both the endogenous and the exogenous aspects on the gastric cancer cell lines MGC-803 and MKN-45. The cells were divided into a knockdown group in which RNA interference technique was used to suppress annexinA5 expression and a protein-supplementing group in which annexinA5 protein was added in the culture supernatant. After the suppression ratio of RNA interference was determined and the IC50 of annexinA5 protein was decided respectively, the cells' proliferation was detected by MTT assay, colony formation assay, and the expression of PCNA. FCM assay and PI staining methods were applied to test cell apoptosis and necrosis. To investigate whether ANXA5 influence cell metastasis, wound healing assay and transwell assay were employed. To further detect the mechanism of annexinA5 action, the signal pathway was examined with Western Blot method. When ANXA5 gene was knocked down, cell proliferation and metastasis were promoted, while cell apoptosis was suppressed. On the other hand, after the annexinA5 protein was applied to the gastric cancer cells, cell proliferation and metastasis were inhibited, while cell apoptosis and necrosis were promoted. AnnexinA5 played its role via ERK signal pathway. ANXA5 acted as tumor suppressor gene in the gastric cancer by suppressing ERK signal pathway and has the potentiality to be an auxiliary anticancer agent. 

Retracted: No

PubPeer comments:
 Fig. 1H and Fig. 3D contain two WB bands shown in red boxes which appear more similar than expected. ![file] , 
 Fig. 1E and Fig. 3A contain two duplicate migration images which represent different treatments. ![file] ,
Immunohistochemical Evaluation of p63, E-Cadherin, Collagen I and III Expression in Lower Limb Wound Healing under Honey
Authors: Jyotirmoy Chatterjee
Raunak Kumar Das
Santanu Dhara
Ananya Barui
Shyamal Kumar Basu
Provas Banerjee
Journal: Evidence-based Complementary and Alternative Medicine (2011)
Discipline: CLINICAL MEDICINE
Keywords: Honey; occlusive dressing; nonhealing wounds; traumatic; lower limb
Affiliations: School of Medical Science & Technology, Indian Institute of Technology, Kharagpur 721302, India., School of Medical Science & Technology, Indian Institute of Technology, Kharagpur 721302, India, Banerjee’s Biomedical Research Foundation, Sainthia 731234, India

Abstract:  Honey is recognized traditionally for its medicinal properties and also appreciated as a topical healing agent for infected and noninfected wounds. This study evaluates impact of honey-based occlusive dressing on nonhealing (nonresponding to conventional antibiotics) traumatic lower limb wounds (n = 34) through clinicopathological and immunohistochemical (e.g., expression of p63, E-cadherin, and Collagen I and III) evaluations to enrich the scientific validation. Clinical findings noted the nonadherence of honey dressing with remarkable chemical debridement and healing progression within 11-15 days of postintervention. Histopathologically, in comparison to preintervention biopsies, the postintervention tissues of wound peripheries demonstrated gradual normalization of epithelial and connective tissue features with significant changes in p63(+) epithelial cell population, reappearance of membranous E-cadherin (P &lt; .0001), and optimum deposition of collagen I and III (P &lt; .0001). Thus, the present study for the first time reports the impact of honey on vital protein expressions in epithelial and connective tissues during repair of nonhealing lower limb wounds. 

Retracted: No

PubPeer comments:
 duplication, rotated, horizontally + vertically flipped ![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. ,
E2F1 is crucial for E2F‐dependent apoptosis
Authors: Kristian Helin
Eros Lazzerini Denchi
Journal: EMBO reports (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: pRB; E2F transcription factors; apoptosis; E2F3; E2F1
Affiliations: Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy., Department of Experimental Oncology, European Institute of Oncology  Via Ripamonti 435 20141 Milan Italy, Biotech Research &amp; Innovation Centre (BRIC)  Fruebjergvej 3 2100 Copenhagen Denmark

Abstract:  Loss of the retinoblastoma protein, pRB, leads to apoptosis, and several results have suggested that this is dependent on the E2F transcription factors. However, so far, the ability of the different E2F family members to contribute to apoptosis is controversial. Here, we show that ectopic expression of E2F3 results in apoptosis in both primary mouse fibroblasts and transgenic mice. Apoptosis induced by E2F3 is associated with the accumulation of E2F1 and, strikingly, we found that E2F3-induced apoptosis is dependent on E2F1. On the basis of these results, we propose that the accumulation of crucial levels of E2F1 activity, and not total E2F activity, is essential for the induction of apoptosis in response to a deregulated pRB pathway. These results are consistent with previous findings that E2F1, but not other E2Fs, can have tumour-suppressing activities. 

Retracted: No

PubPeer comments:
 Figure 1C, two images that are supposed to describe different cell types come from same sample, as they partially overlap (red boxes), although vertical dimension has been slightly modified. Could the authors please comment? ![file] , 
 Figure 3B: there are two duplications here. Orange boxes: same image rotated 90 deg. Blue boxes: same image rotated 180 deg. Could the authors please comment? ![file] , 
 Figure 2B, much more similar than expected (pink boxes). Could the authors please post the scan of the blots at high resolution and take away any concern? ![file] , 
 There is also self plagiarism: Figure 1 includes an image reused in another publication from same group (purple boxes). Of note, in this other publication the image was duplicated in Fig 3A and 3B (below). ![file] ,
Effect of miR-200c on migration and proliferation of breast cancer MDA-MB-231 cells and BT-549 cells and the possible mechanism
Authors: Y Ma
Y Lei
X-F Wang
Y Liu
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-200c; breast cancer; migration; proliferation; MDA-MB-231
Affiliations: Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an, P.R. China. .

Abstract:  Objective: This study was designed to investigate the effects of miR-200c on the migration and proliferation of breast cancer MDA-MB-231 cells and BT-549 cells and the possible mechanisms. Materials and methods: The effects of miR-200c on the proliferation and migration of highly invasive human breast cancer MDA-MB-231 and BT-549 cells were investigated by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) MTT and wound-healing assay. Effects of miR-200c on the expression of adhesion molecules in cells of 2 cell lines were examined by Western blot. Results: MTT assay showed that miR-200c could inhibit the proliferation of MDA-MB-231 and BT-549 cells. Wound-healing assay results showed that miR-200c could inhibit the migration of MDA-MB-231 and BT-549 cells. Western blot results showed that miR-200c up-regulated the expression of E-cadherin protein and down-regulated the expression of Vimentin protein. Conclusions: The results showed that miR-200c can inhibit the proliferation of highly invasive human breast cancer cells and may inhibit cell migration by up-regulating the expression of E-cadherin protein and down-regulating the expression of Vimentin protein. 

Retracted: No

PubPeer comments:
 Withdrawn. The journal does not provide any details beyond  This article has been withdrawn. The Publisher apologizes for any inconvenience this may cause. The original paper PDF has been removed from the journal s website. ,
The transcriptional activity of the CCAAT-binding factor CBF is mediated by two distinct activation domains, one in the CBF-B subunit and the other in the CBF-C subunit
Authors: B de Crombrugghe
F Coustry
S N Maity
S Sinha
Journal: Journal of Biological Chemistry (1996)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CBF; transcription activation; heterotrimeric; recombinant subunits; DNA complex
Affiliations: Department of Molecular Genetics, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract:  CBF-A, CBF-B, and CBF-C together form the heterotrimeric mammalian CCAAT-binding factor, CBF, which binds to DNA to form a CBF-DNA complex. Here we examined the transcription activation function of CBF in an in vitro reconstituted system using the three purified recombinant CBF subunits expressed in Escherichia coli. Two of the subunits, CBF-A and CBF-C, were coexpressed and purified as a CBF-A/CBF-C complex. Addition of the three wild-type recombinant CBF subunits to EL4 cell nuclear extracts depleted of CBF stimulated transcription 5-20-fold from proalpha2(1) collagen promoters and 10-fold from the Rous sarcoma virus long terminal repeat. Two CBF deletion mutants, one containing full-length CBF-A and CBF-C and a CBF-B lacking the NH2-terminal residues 1-224, and the other containing full- length CBF-A and CBF-B and a CBF-C lacking the COOH-terminal residues 114-309, also stimulated transcription from these promoters, but the level of activation was reduced to half that obtained with the full-length CBF subunits. In contrast, a CBF deletion mutant protein containing full-length CBF-A and deleted forms of both CBF-B and CBF-C showed very little transcription activation from these promoters. Hence, this study demonstrates that the heterotrimeric CBF protein consists of two transcription activation domains, one present in CBF-B and the other in CBF-C, and that the two domains act additively in the in vitro assay. The activation domains of both CBF-B and CBF-C, which are rich in glutamine and hydrophobic residues, showed amino acid sequence similarities with each other and with the glutamine-rich activation domain of transcription factor Sp1. 

Retracted: No

PubPeer comments:
null, 
 Figure 5B. Much more similar than you would expect even though the treatments are different. https: imgur.com qRPIJ7u ,
Assessment of HIV-1 integration in tissues and subsets across infection stages
Authors: Vincent H Wu
John K Everett
Santiago Ávila-Ríos
Perla M Del Rio Estrada
Mauricio González-Navarro
Frederic D Bushman
Michael R Betts
Fernanda Torres-Ruiz
Christopher L Nobles
Leticia Kuri-Cervantes
Kevin McCormick
Son Nguyen
Gustavo Reyes-Terán
Journal: JCI Insight (2020)
Discipline: CLINICAL MEDICINE
Keywords: AIDS/HIV; Cellular immune response; Immunology; T cells.
Affiliations: Department of Microbiology and., Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.

Abstract:  The integration of HIV DNA into the host genome contributes to lifelong infection in most individuals. Few studies have examined integration in lymphoid tissue, where HIV predominantly persists before and after antiretroviral treatment (ART). Of particular interest is whether integration site distributions differ between infection stages with paired blood and tissue comparisons. Here, we profiled HIV integration site distributions in sorted memory, tissue-resident, and/or follicular helper CD4+ T cell subsets from paired blood and lymphoid tissue samples from acute, chronic, and ART-treated individuals. We observed minor differences in the frequency of nonintronic and nondistal intergenic sites, varying with tissue and residency phenotypes during ART. Genomic and epigenetic annotations were generally similar. Clonal expansion of cells marked by identical integration sites was detected, with increased detection in chronic and ART-treated individuals. However, overlap between or within CD4+ T cell subsets or tissue compartments was only observed in 8 unique sites of the 3540 sites studied. Together, these findings suggest that shared integration sites between blood and tissue may, depending on the tissue site, be the exception rather than the rule and indicate that additional studies are necessary to fully understand the heterogeneity of tissue-sequestered HIV reservoirs. 

Retracted: No

PubPeer comments:
 There are several issues with the way the authors estimate heterogeneity in their phylogenetic analysis: 1. there is no simulation study to show the ability of the method to detect this signal using similar data, 2. parameters related to heterogeneity are not estimated (the parameters estimated are the initial number of infected hosts, the date of origin of the epidemic and the change after March 19), 3. it is assumed that the effect of the superspreading behavior on the transmission rate (tau) is a function of the proportion of superspreaders (p_h), which has an unclear motivation (it would seem simpler to set the effect of superspreading tau and rescale beta) and could affect the results (see point 1 about the need for a simulation study). Overall, this makes the reported effect of superspreading on epidemic spread uncertain. ,
Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell-mediated lung inflammation
Authors: Qian Li
Xiongfei Xu
Xuetao Cao
Sheng Xia
Zhenhong Guo
Journal: European Journal of Immunology (2008)
Discipline: IMMUNOLOGY
Keywords: tissue microenvironment; immune cells; DC; pulmonary stromal microenvironment; lung
Affiliations: Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, P. R. China.

Abstract:  The tissue microenvironment may affect the development and function of immune cells such as DC. Whether and how the pulmonary stromal microenvironment can affect the development and function of lung DC need to be investigated. Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such regulatory DC exist in the lung and what is the effect of the pulmonary stromal microenvironment on the generation of DCreg. Here we demonstrate that murine pulmonary stromal cells can drive immature DC, which are regarded as being widely distributed in the lung, to proliferate and differentiate into a distinct subset of DCreg, which express high levels of CD11b but low levels of MHC class II (I-A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E2 (PGE2) and suppress T-cell proliferation. The natural counterpart of DCreg in the lung with similar phenotype and regulatory function has been identified. Pulmonary stroma-derived TGF-beta is responsible for the differentiation of immature DC to DCreg, and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation. Moreover, DCreg can induce the generation of CD4+CD25+Foxp3+ Treg. Importantly, infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation in vivo. Therefore, the pulmonary microenvironment may drive the generation of DCreg, thus contributing to the maintenance of immune homoeostasis and the control of inflammation in the lung. 

Retracted: No

PubPeer comments:
 I declare no competing interests. Jean-Paul Moatti is married to Yolande Obadia, who is chairing the Fundation behind Raoult s institute. This is a huge conflict of interest. , 
 ![file] ,
Escheriosome-mediated cytosolic delivery of PLK1-specific siRNA: potential in treatment of liver cancer in BALB/c mice
Authors: Ahmad Nadeem
Arun Chauhan
Swaleha Zubair
Sajid Ali Ansari
Mohammad Yunus Ansari
Owais Mohammad
Journal: Nanomedicine (2014)
Discipline: CLINICAL MEDICINE
Keywords: anticancer efficacy; escheriosome-based formulation; PLK1-specific siRNA; liver cancer; BALB/c mice

Abstract:  Aim: In the present study, the anticancer efficacy of a novel escheriosome-based formulation of PLK1-specific siRNA was evaluated against liver cancer in BALB/c mice. Materials &amp; methods: The escheriosome-based siRNA nanoparticles were prepared using lipids isolated from Escherichia coli. The escheriosomes were characterized for size, surface charge and stability. The anticancer potential of PLK1-specific siRNA formulation was ascertained on the basis of expression of pro-/anti-apoptotic factors and histopathological studies. Results: The escheriosome-entrapped siRNA was found to be released in surrounding milieu in a sustained manner. The nanoformulation was successful in modulating proapoptotic factors and eventually helped in better survival of the treated animals. Conclusion: Our data demonstrate the efficacy of systemically administered siRNA in the treatment of experimental liver cancer. This novel therapeutic strategy may be applicable to a broad range of cancers in patients with the obstinate form of the disease. 

Retracted: No

PubPeer comments:
 Figure 4A. * Red boxes: in the p53wt panel, lanes 2, 3, and 5 all appear to share similar features, although the top or bottom parts differ. * Yellow boxes: Some similarities between lanes 2 and 3 in the p53mut panel appear to be visible * Green boxes: In the Bax panel, bands in lanes 1 and 3 both share similarities ![file] ,
Circular RNA Plasmacytoma Variant Translocation 1 (CircPVT1) knockdown ameliorates hypoxia-induced bladder fibrosis by regulating the miR-203/Suppressor of Cytokine Signaling 3 (SOCS3) signaling axis
Authors: Teng Li
Shaojin Zhang
Lingang Cui
Guoxian Zhang
Yan Wang
Yi Xing
Yinsheng Wei
Qingwei Wang
Journal: Bioengineered (2022)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bladder fibrosis; bladder outlet obstruction; circular rna; hypoxia; microRNA
Affiliations: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Abstract:  The effects of circular RNAs (circRNAs) on bladder outlet obstruction (BOO)-induced hypertrophy and fibrogenesis in rats and hypoxia-induced bladder smooth muscle cell (BSMC) fibrosis remain unclear. This study aimed to determine the regulatory role of circRNAs in the phenotypic changes in BSMCs in BOO-induced rats.circRNAmicroarray and real-time PCR were used to explore differentiated expressed circRNAs. Bioinformatics analyses and dual-luciferase reporter were performed to identify the targets for circRNA PVT1 (circPVT1). BOO was performed to establish a bladder fibrosis animal model. The circPVT1 and suppressor of cytokine signaling 3 (SOCS3) expression levels were upregulated (p = 0.0061 and 0.0328, respectively), whereas the microRNA-203a (miR-203) level was downregulated in rats with bladder remodeling (p=0.0085). Bioinformatics analyses and dual-luciferase reporter assay results confirmed that circPVT1 sponges miR-203 and that the latter targets the 3'-untranslated region of SOCS3. Additionally, circPVT1 knockdown alleviated BOO-induced bladder hypertrophy and fibrogenesis. Furthermore, hypoxia was induced in BSMCs to establish a cell model of bladder fibrosis. Hypoxia induction in BSMCs resulted in upregulated circPVT1 and SOCS3 levels (p = 0.0052) and downregulated miR-203 levels. Transfection with circPVT1 and SOCS3 shRNA ameliorated hypoxia-induced transforming growth factor-β (TGF-β1), TGFβR1, α-smooth muscle actin, fibrotic growth factor, extracellular matrix subtypes, BSMC proliferation, and apoptosis-associated cell injury, whereas co-transfection with miR-203 inhibitor counteracted the effect of circPVT1 shRNA on these phenotypes.These findings revealed a novel circRNA regulator of BOO-associated bladder wall remodeling and hypoxia-induced phenotypic changes in BMSCs by targeting the miR-203-SOCS3 signaling axis. 

Retracted: No

PubPeer comments:
 This article is full of non-scientific and odd phrases, indicating that the  authors do not have any experience. The paper is citing three other Bioengineered papers. Interestingly, all of them are from the same issue, indicating that they are put up just for the purpose to increase the journal impact factor. This behaviour is seen in many Bioengineered papers. ![file] ,
Conformational and sequential epitopes on the human granulocyte-colony stimulating factor molecule (hG-CSF) and their role in binding to human placenta receptors
Authors: L P Roguin
C H Carbonetto
V J Marino
A E Sterin-Prync
Journal: Cytokine (2001)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Monoclonal antibodies; hG-CSF; cytokine orientation; receptors; human placenta
Affiliations: Facultad de Farmacia y Bioquímica, Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Junin 956-1113 Buenos Aires, Argentina.

Abstract:  Monoclonal antibodies (mAbs) named 8C2 and 6E3, directed against the recombinant human granulocyte colony-stimulating factor (hG-CSF), were used as probes to study the cytokine orientation on its binding to receptors from human placenta. Competition enzyme linked immunoabsorbent assays (ELISA) revealed that mAb 8C2 would be directed to a linear epitope, whereas mAb 6E3 would delimit a more assembled epitope. Gel-filtration high performance liquid chromatography (HPLC) of the immune complexes formed by incubating [(125)I]hG-CSF with each mAb showed that epitope 8C2, but not 6E3, was altered after cytokine iodination. In addition, mAb 6E3 completely inhibited [(125)I]hG-CSF binding to human placental microsomes. Although [(125)I]mAb 6E3 was unable to bind to preformed hG-CSF-receptor complexes, [(125)I]mAb 8C2 did recognize hG-CSF previously bound to receptors, suggesting that epitope 8C2 would remain accessible in the hG-CSF-receptor complex. To identify the cytokine region defined by mAbs, hG-CSF was digested with different proteolytic enzymes: Arg-C, Glu-C, trypsin and alpha chymotrypsin. Immunoreactivity of the resulting peptides was examined by Western blot and their sequences were established by Edman degradation. Results showed that mAb 6E3 would be directed to a conformation-dependent epitope located close to the hG-CSF binding domain and included into the sequence 1-122/123, whereas mAb 8C2 recognized the region 41-58, which represents a linear epitope left exposed after cytokine binding to receptors from human placenta. 

Retracted: No

PubPeer comments:
 Concern about Figure 6. * The backgrounds of the strips, in particular those in panel B, all look remarkably similar, and the bands appear to have been painted on, with no connection or bleeding into the background * Red circles: The three narrow bands in lanes 2-4 of panel B look remarkably similar Reported to the journal in October 2015, but no action was taken. ![file] , 
 Figure 8: * Blue boxes: background similarities ![file] ,
Relative Retinal Blood Flow: A Novel and Informative Measure of Unilateral Retinal Vein Occlusion Severity
Authors: Colin A Lemire
Jorge G Arroyo
Brendan Seto
Purva Atreay
Rachelle Koch
Nina Hazra
Keiko Yamada
Journal: Translational Vision Science & Technology (2021)
Discipline: CLINICAL MEDICINE
Keywords: retinal vascular blood flow; central retinal vein occlusion; branch retinal vein occlusion; relative blood flow; laser speckle flowgraphy
Affiliations: Division of Ophthalmology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Abstract:  Purpose: This study quantifies retinal vascular blood flow affected by unilateral central or branch retinal vein occlusion (CRVO or BRVO). We created a new, unitless metric for the severity of these diseases-relative blood flow (RBF)-and contextualized it with subject demographics, ocular presentation, and systemic conditions. Finally, we explored its efficacy as a predictor of future outcomes. Methods: Data were collected from 20 control subjects and 32 clinically diagnosed CRVO (n = 15) or BRVO (n = 17) patients. We used laser speckle flowgraphy to quantify blood flow as mean blur rate and present RBF as the ratio between the blood flow in a subject's diseased and undiseased eyes. Because of our demonstration that blood flow has high intrapatient (between eyes and over time) but low interpatient correlation in eyes of healthy subjects, any differences between eyes can be attributed to the disease. These data were correlated with subject demographics and disease characteristics. Results: In CRVO and BRVO eyes, average blood flow decreased by 26% and 7%, respectively. In CRVO, occlusion duration, central macular thickness, intraocular pressure, diabetes, previous laser and injection treatments, and injection within three months after measurement were significantly associated with RBF. In BRVO, no significant associations with RBF were found. Conclusions: Blood flow in CRVO and BRVO was reduced compared to the unaffected fellow eye in most patients. RBF was useful in determining the severity of RVOs and predicting future treatment needs. Translational relevance: RBF is a promising new and informative metric for quantifying the severity of unilateral RVOs. 

Retracted: Yes

PubPeer comments:
 Retracted [March 2022] .  After publication of the above article, a serious issue related to lack of Institutional Review Board (IRB) approval for the research procedures was brought to the attention of the journal by the IRB, and has been corroborated by the corresponding author. It was therefore agreed that this article should be retracted. One of 8 papers or communications retracted for similar reasons. ![file] ,
Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells
Authors: Kedar Hastak
Munna L Agarwal
Hasan Mukhtar
Sanjay Gupta
Mukesh K Agarwal
Nihal Ahmad
Journal: Oncogene (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: green tea polyphenols; prostate carcinogenesis; apoptosis; EGCG; p53
Affiliations: Department of Environmental Health Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.

Abstract:  We have recently shown that oral consumption of green tea polyphenols inhibits prostate carcinogenesis in transgenic mouse model of prostate cancer and suggested that induction of apoptosis in prostate cancer cells is responsible for these effects. Much of the chemopreventive effects of green tea are attributed to its major polyphenolic constituent (-) epigallocatechin-3-gallate (EGCG). In the present study, we report that EGCG-induced apoptosis in human prostate carcinoma LNCaP cells is mediated via modulation of two related pathways: (a) stabilization of p53 by phosphorylation on critical serine residues and p14ARF-mediated downregulation of murine double minute 2(MDM2) protein, and (b) negative regulation of NF-kappaB activity, thereby decreasing the expression of the proapoptotic protein Bcl-2. EGCG-induced stabilization of p53 caused an upregulation in its transcriptional activity, thereby resulting in activation of its downstream targets p21/WAF1 and Bax. Thus, EGCG had a concurrent effect on two important transcription factors p53 and NF-kappaB, causing a change in the ratio of Bax/Bcl-2 in a manner that favors apoptosis. This altered expression of Bcl-2 family members triggered the activation of initiator capsases 9 and 8 followed by activation of effector caspase 3. Activation of the caspases was followed by poly (ADP-ribose) polymerase cleavage and induction of apoptosis. Taken together, the data indicate that EGCG induces apoptosis in human prostate carcinoma cells by shifting the balance between pro- and antiapoptotic proteins in favor of apoptosis. 

Retracted: No

PubPeer comments:
 Figure 3a. Much more similar than expected. https: imgur.com Ap75hCJ ,
Circulating micro RNA ‐590‐5p functions as a liquid biopsy marker in non‐small cell lung cancer
Authors: Rajeev Kumar Seam
Karen M Vasquez
Manjit Kaur Rana
Hridayesh Prakash
Manish Gupta
Aklank Jain
Akanksha Khandelwal
Journal: Cancer Science (2020)
Discipline: CLINICAL MEDICINE
Keywords: STAT3; circulating miRNA; liquid biopsy; miR-590-5p; non-small cell lung cancer.
Affiliations: Department of Biochemistry and Microbial Sciences, Central University of Punjab, Bathinda, Punjab, India., Department of Radiation Oncology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India., Department of Pathology, Advanced Cancer Institute, Bathinda, Punjab, India., Institute of Virology and Immunology, Amity University, Noida, Uttar Pradesh, India., Division of Pharmacology and Toxicology, College of Pharmacy, Dell Pediatric Research Institute, The University of Texas at Austin, Austin, TX, USA., Department of Animal Sciences, Central University of Punjab, Bathinda, Punjab, India.

Abstract:  Despite the availability of various diagnostic procedures, a tissue biopsy is still indispensable for the routine diagnosis of lung cancer. However, inaccurate diagnoses can occur, leading to inefficient cancer management. In this context, use of circulating microRNAs (miRNAs) may serve as diagnostic tools as liquid biopsies, and as biomarkers to better understand the molecular mechanisms involved in the progression of cancer. We identified miR-590-5p as a potential prognostic marker in the progression of non-small cell lung cancer (NSCLC). We were able to detect this miRNA in blood plasma samples of NSCLC patients through quantitative real-time PCR. Our data showed an ~7.5-fold downregulation of miR-590-5p in NSCLC patients compared to healthy controls, which correlated with several clinicopathological features. Further, overexpression of miR-590-5p led to decreased cell viability, proliferation, colony formation, migration, and invasion potential of lung cancer cells, whereas its knockdown showed the opposite effect. In addition, the levels of several proteins involved in the epithelial-to-mesenchymal transition negatively correlated with miR-590-5p levels in lung adenocarcinoma cells and tumors of NSCLC patients. Further, dual-luciferase reporter assays identified STAT3 as a direct target of miR-590-5p, which negatively regulated STAT3 activation and its downstream signaling molecules (eg, Cyclin D1, c-Myc, Vimentin, and β-catenin) involved in tumorigenesis. Taken together, our study suggests that miR-590-5p functions as a tumor suppressor in NSCLC through regulating the STAT3 pathway, and may serve as a useful biomarker for the diagnosis/prognosis of NSCLC, and as a potential therapeutic target for the treatment of NSCLC. 

Retracted: No

PubPeer comments:
 Figure 4A appears to have overlapping images. While I understand that images taken at 24 hours and 48 hours should be *similar*, they shouldn t be exactly the same as they appear here. Perhaps a mistake? ![file] The authors could resolve this by posting the original uncropped images. ,
Replication Study: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44
Authors: Beibei Tang
Xuefei Yan
Biao Chen
Elizabeth Iorns
Timothy M Errington
Huajun Yang
Alexandria Denis
Rachel Tsui
Reproducibility Project: Cancer Biology
Nicole Perfito
Yongli Shan
Journal: eLife (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: LAPC4; Reproducibility Project: Cancer Biology; cancer biology; human; metascience
Affiliations: Crown Biosciences Inc, Science & Technology Innovation Park, Taicang, China., Science Exchange, Palo Alto, United States., Center for Open Science, Charlottesville, United States.

Abstract:  As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Li et al., 2015), that described how we intended to replicate selected experiments from the paper 'The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44' (Liu et al., 2011). Here we report the results. We found the microRNA, miR-34a, was expressed at twice the level in CD44+ prostate cancer cells purified from xenograft tumors (LAPC4 cells) compared to CD44- LAPC4 cells, whereas the original study reported miR-34a was underexpressed in CD44+ LAPC4 cells (Figure 1B; Liu et al., 2011). When LAPC4 cells engineered to express miR-34a were injected into mice, we did not observe changes in tumor growth or CD44 expression; however, unexpectedly miR-34a expression was lost in vivo. In the original study, LAPC4 cells expressing miR-34a had a statistically significant reduction in tumor regeneration and reduced CD44 expression compared to control (Figure 4A and Supplemental Figures 4A,B and 5C; Liu et al., 2011). Furthermore, when we tested if miR-34a regulated CD44 through binding sites in the 3'UTR we did not find a statistically significant difference, whereas the original study reported miR-34a decreased CD44 expression that was partially abrogated by mutation of the binding sites in the CD44 3'UTR (Figure 4D; Liu et al., 2011). Finally, where possible, we report meta-analyses for each result. 

Retracted: No

PubPeer comments:
 Author response to the replication here: https: pubpeer.com publications 6C60EA3640C6E18ACC355530FB9C7A#2 , 
 If this study was conducted in China, whereas the original study was conducted in the US, surely the reagents might be different. How do the authors factor in this into the issue of u201cirreproducibilityu201d of the original results? ,
QuPath: The global impact of an open source digital pathology system
Authors: P Maxwell
M Salto-Tellez
M P Humphries
Journal: Computational and Structural Biotechnology Journal (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Artificial Intelligence; Computational Pathology; Digital Pathology; Image Analysis; QuPath.
Affiliations: Precision Medicine Centre of Excellence, The Patrick G Johnston Centre for Cancer Research, Queen's University, Belfast, UK., Integrated Pathology Programme, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.

Abstract:  QuPath, originally created at the Centre for Cancer Research &amp; Cell Biology at Queen's University Belfast as part of a research programme in digital pathology (DP) funded by Invest Northern Ireland and Cancer Research UK, is arguably the most wildly used image analysis software program in the world. On the back of the explosion of DP and a need to comprehensively visualise and analyse whole slides images (WSI), QuPath was developed to address the many needs associated with tissue based image analysis; these were several fold and, predominantly, translational in nature: from the requirement to visualise images containing billions of pixels from files several GBs in size, to the demand for high-throughput reproducible analysis, which the paradigm of routine visual pathological assessment continues to struggle to deliver. Resultantly, large-scale biomarker quantification must increasingly be augmented with DP. Here we highlight the impact of the open source Quantitative Pathology &amp; Bioimage Analysis DP system since its inception, by discussing the scope of scientific research in which QuPath has been cited, as the system of choice for researchers. 

Retracted: No

PubPeer comments:
 There is a false statement in the abstract, repeated with a typo corrected in the introduction. The article states,  QuPathu2026 is arguably the most [wildly widely] used image analysis software program in the world. No evidence is provided for this statement, and it can be readily falsified. For example, Figure 3 of the paper shows ~250 citations of QuPath in 2020, whereas there are more than 34,000 citations of ImageJ in that time period, listed by Google Scholar: https: scholar.google.com scholar?q=%22imagej%22 hl=en as_sdt=0%2C22 as_ylo=2020 as_yhi=2020 , 
 Pete Bankhead claims he wrote this software. He is not an author of this paper. https: twitter.com petebankhead status 1357697513596346371 , 
 Supporting evidence for code contribution for the QuPath project is logged in Github: https: github.com qupath qupath graphs contributors , 
 What exactly is the  software credit claimed by the author? If the primary developer and current open-source maintainer are not an author on this paper, are there truly  no known ... personal relationships that could have appeared to influence the work reported in this paper. ![file] ,
Biogenic platinum nanoparticles using black cumin seed and their potential usage as antimicrobial and anticancer agent
Authors: Mehmet Cengiz Baloglu
Fulya Gülbagca
Mehmet Nuri Atalar
Mehmet Hakkı Alma
Aysenur Aygun
Buket Ustaoglu
Lutfiye Yildiz Ozer
Yasemin Celik Altunoglu
Fatih Sen
Journal: Journal of pharmaceutical and biomedical analysis (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Antibacterial; Anticancer; Biogenic platinum nanoparticles; HeLa cervical cancer lines; MDA-MB-231
Affiliations: Sen Research Group, Department of Biochemistry, University of Dumlupınar, 43000 Kütahya, Turkey., Department of Chemical Engineering, Khalifa University of Science and Technology, Masdar Institute, Masdar City, 54224, Abu Dhabi, United Arab Emirates., Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, 37150, Turkey., Department of Biochemistry, University of Igdir, 76000 Igdir, Turkey. Electronic address: ., Department of Environmental, Faculty of Engineering, University of Igdir, 76000 Igdir, Turkey., Sen Research Group, Department of Biochemistry, University of Dumlupınar, 43000 Kütahya, Turkey. Electronic address: .

Abstract:  Herein, the biogenic platinum nanoparticles (Pt NPs) were synthesized by using black cumin seed (Nigella sativa L.) extract as a reducing agent. The biogenic platinum nanoparticles synthesized by black cumin seed extract was characterized in detail by Transmission Electron Microscopy (TEM), UV-vis spectrophotometer, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS). According to TEM analysis, Pt nanoparticles have spherical shapes and sizes between 1-6 nm. Moreover, the biogenic Pt NPs was assessed for its cytotoxicity effect on MDA-MB-231 breast and HeLa cervical cancer lines and their antibacterial effect against selected strains of gram-positive and negative bacteria. The cytotoxicity and bacterial tests showed the effectiveness of biogenic Pt nanoparticles. Dose-dependent toxicity effects were shown in the MDA-MB-231 breast and HeLa cervical cancer lines (IC50: 36.86 μg/mL and 19.83 μg/mL, respectively). In addition, Pt NPs showed high zone diameters against gram-positive and gram-negative bacteria at concentrations of 100 and 500 μg/ml. These results contribute to the development of the pharmaceutical industry as a potential antibacterial and anticancer agent. 

Retracted: No

PubPeer comments:
 Would the authors be so kind as to upload the images from the original gel scan? The shape and shading of the B-actin band suggest that perhaps this was run on a separate gel. Thank you. *** ![file] ,