PReD-Bench/PRed-Bench huggingface dataset:
Distinct roles of Mus81, Yen1, Slx1-Slx4, and Rad1 nucleases in the repair of replication-born double-strand breaks by sister chromatid exchange
Authors: Kirk T Ehmsen
Miguel G Blanco
Andrés Aguilera
Cristina Tous
Wolf-Dietrich Heyer
Sandra Muñoz-Galván
Stephen C West
Erin K Schwartz
Journal: Molecular and Cellular Biology (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DNA double-strand breaks; homologous recombination; sister chromatid recombination; structure-selective endonucleases; Yen1
Affiliations: Centro Andaluz de Biología Molecular y Medicina Regenerativa, Universidad de Sevilla-CSIC, Seville, Spain, London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, United Kingdom, Department of Microbiology, University of California, Davis, California, USA

Abstract:  Most spontaneous DNA double-strand breaks (DSBs) arise during replication and are repaired by homologous recombination (HR) with the sister chromatid. Many proteins participate in HR, but it is often difficult to determine their in vivo functions due to the existence of alternative pathways. Here we take advantage of an in vivo assay to assess repair of a specific replication-born DSB by sister chromatid recombination (SCR). We analyzed the functional relevance of four structure-selective endonucleases (SSEs), Yen1, Mus81-Mms4, Slx1-Slx4, and Rad1, on SCR in Saccharomyces cerevisiae. Physical and genetic analyses showed that ablation of any of these SSEs leads to a specific SCR decrease that is not observed in general HR. Our work suggests that Yen1, Mus81-Mms4, Slx4, and Rad1, but not Slx1, function independently in the cleavage of intercrossed DNA structures to reconstitute broken replication forks via HR with the sister chromatid. These unique effects, which have not been detected in other studies unless double mutant combinations were used, indicate the formation of distinct alternatives for the repair of replication-born DSBs that require specific SSEs. 

Retracted: No

PubPeer comments:
 May 2017 Correction found here: https: mcb.asm.org content 37 11 e00161-17 It reads:  * Fig. 2A: The representative Southern image uploaded for WT + mus81-dd-MMS4 was incorrect. By mistake the image uploaded was the same one used to illustrate the WT + MUS81-MMS4 control. The corrected image of the WT + mus81-dd-MMS4 Southern blot is shown below. We apologize for this unintentional error, which did not impact the results or conclusions of the study.* Here is the original Figure 2A, with the duplication marked in red. ![file] I thank the authors for correcting this error. This paper was part of a structured search for image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long ,
Loss of p73 promotes dissemination of Myc-induced B cell lymphomas in mice
Authors: Ute M Moll
Alice Nemajerova
Lorenz Trümper
Oleksi Petrenko
Gustavo Palacios
Journal: Journal of Clinical Investigation (2010)
Discipline: CLINICAL MEDICINE
Keywords: Emu-myc mice; lymphomas; p53; p73; tumor suppressor
Affiliations: Department of Pathology, Stony Brook University, Stony Brook, New York 11794, USA.

Abstract:  Mice engineered to express c-Myc in B cells (Emu-myc mice) develop lethal lymphomas in which the gene encoding the p53 tumor suppressor is frequently mutated. Whether the p53 homolog p73 also functions as a tumor suppressor in vivo remains controversial. Here we have shown that p73 loss does not substantially affect disease onset and mortality in Emu-myc mice. However, it does alter the phenotype of the disease. Specifically, p73 loss decreased nodal disease and increased widespread extranodal dissemination. We further found that p53 acted as the dominant tumor suppressor during the onset of Emu-myc-driven B cell lymphomagenesis, while p73 modulated tumor dissemination and extranodal growth. Immunophenotyping and expression profiling suggested that p73 loss allowed increased maturation of malignant B cells and deregulated genes involved in lymphocyte homing and dissemination of human lymphomas. Consistent with this, p73 expression was frequently downregulated in a large cohort of human mature aggressive B cell lymphomas, and both the incidence and degree of p73 downregulation in these tumors correlated with their extranodal dissemination status. These data indicate that p73 is a modifier of Myc-driven lymphomas in mice, favoring tumor dissemination, and suggest that p73 could be a biomarker for human B cell lymphoma dissemination, a notion that can now be tested in clinicopathologic correlation studies. 

Retracted: No

PubPeer comments:
null, 
null, 
 Left section figure 3C. https: imgur.com D7jLW2s , 
 #3 Even the background noise around these two lanes has unexpected similarities. Could the corresponding author comment or, ideally, provide the uncropped originals? *** ![file] ,
Circ_0000515 drives the progression of hepatocellular carcinoma by regulating MAPK10
Authors: R Yuan
H Li
C-M Li
H-B Wang
J Wei
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: circ_0000515; hepatocellular carcinoma; clinical significance; molecular mechanism; differential expression
Affiliations: Department of Liver and Infectious Diseases, Liver Disease Research Center, the Second People's Hospital of Yunnan Province, Kunming, China. .

Abstract:  Objective: To explore the expression pattern and clinical significance of circ_0000515 in hepatocellular carcinoma (HCC), as well as the molecular mechanism. Patients and methods: Fifty HCC patients were recruited, and their cancer tissues and adjacent normal ones were collected for detecting the differential expression of circ_0000515. The relationship between circ_0000515 and clinical parameters in HCC patients was analyzed. Circ_0000515 knockdown model was generated by lentivirus transfection in Hep3B and MHCC88H cells that were highly expressed with circ_0000515. Regulatory effects of circ_0000515 on phenotypes of Hep3B and MHCC88H cells were examined by Cell Counting Kit-8 (CCK-8) and transwell assay. Target gene of circ_0000515 was verified by Dual-Luciferase reporter assay, and its involvement in HCC progression was detected by rescue experiments. In vivo xenograft model was generated in nude mice aiming to elucidate the role of circ_0000515 in regulating HCC growth. Results: Circ_0000515 was highly expressed in HCC tissues and cell lines. High level of circ_0000515 predicted advanced stage, high incidence of lymphatic metastasis, and low disease-free survival and overall survival in HCC. Knockdown of circ_0000515 attenuated proliferative and migratory abilities in Hep3B and MHCC88H cells. MAPK10, as the target gene binding circ_0000515, was negatively regulated by circ_0000515. Rescue experiments and in vivo xenograft model both indicated that circ_0000515 aggravated the malignant progression of HCC by targeting MAPK10. Conclusions: Circ_0000515 is upregulated in HCC tissues and cell lines. It can be used for predicting tumor staging, lymphatic metastasis, and prognosis in HCC. Circ_0000515 aggravates the malignant progression of HCC by downregulating MAPK10. 

Retracted: No

PubPeer comments:
 I assume that the 54 cases of hepatocellular carcinoma used here is the same sample featured in [E et al (2019)] and [Yang et al (2019)] to study LOC105372579 (and miR-4316 FOXP4 signaling) and CACNA1Gu2010AS1 (and the miRu20102392 C1orf61 pathway), respectively. The present Fig 1D ( Bioinformatics analysis of aberrantly expressed lncRNAs in HCC tissues according to GSE113850 ) appears to be the same heatmap shown in those papers, though with a different color-palette, and this time re-ordered to place probe IVGNh05758 at the top. ![file] ![] I am wondering whether the order of probes in the heatmap(s) means anything, or is perhaps arbitrary. Did the authors investigate any other candidate lncRNAs besides these three? The possibility arises that multiple comparisons have affected the significance of the present results. ,
CD8(+)IL-17(+) T Cells Mediate Neutrophilic Airway Obliteration in T-bet-Deficient Mouse Lung Allograft Recipients
Authors: Iulia Popescu
Hannah L Miller
Mauricio Rojas
Tiffany A Coon
Elizabeth A Lendermon
Melanie Levine
Yutong Zhao
Nathaniel M Weathington
Jing Zhao
Jeffrey M Dodd-o
Nayra Cardenes
John F McDyer
Christopher P O&#x27;Donnell
Sudipto Ganguly
Journal: American Journal of Respiratory Cell and Molecular Biology (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: IL-17; T-bet; acute rejection; mouse orthotopic lung transplant; neutrophils.
Affiliations: 1 Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.

Abstract:  Acute cellular rejection is a known risk factor for the development of obliterative bronchiolitis, which limits the long-term survival of lung transplant recipients. However, the T cell effector mechanisms in both of these processes remain incompletely understood. Using the mouse orthotopic lung transplant model, we investigated whether C57BL/6 T-bet(-/-) recipients of major histocompatibility complex (MHC)-mismatched BALB/c lung grafts develop rejection pathology and allospecific cytokine responses that differ from wild-type mice. T-bet(-/-) recipients demonstrated vigorous allograft rejection at 10 days, characterized by neutrophilic inflammation and predominantly CD8(+) T cells producing allospecific IL-17 and/or IFN-γ, in contrast to IFN-γ-dominant responses in WT mice. CD4(+) T cells produced IL-17 but not IFN-γ responses in T-bet(-/-) recipients, in contrast to WT controls. Costimulation blockade using anti-CD154 Ab significantly reduced allospecific CD8(+)IFN-γ(+) responses in both T-bet(-/-) and WT mice but had no attenuating effect on lung rejection pathology in T-bet(-/-) recipients or on the development of obliterative airway inflammation that occurred only in T-bet(-/-) recipients. However, neutralization of IL-17A significantly attenuated costimulation blockade-resistant rejection pathology and airway inflammation in T-bet(-/-) recipients. In addition, CXCL1 (neutrophil chemokine) was increased in T-bet(-/-) allografts, and IL-17 induced CXCL1 from mouse lung epithelial cells in vitro. Taken together, our data show that T-bet-deficient recipients of complete MHC-mismatched lung allografts develop costimulation blockade-resistant rejection characterized by neutrophilia and obliterative airway inflammation that is predominantly mediated by CD8(+)IL-17(+) T cells. Our data support T-bet-deficient mouse recipients of lung allografts as a viable animal model to study the immunopathogenesis of small airway injury in lung transplantation. 

Retracted: No

PubPeer comments:
 Some duplication ![file] ,
Synthesis, thermal decomposition and dielectric behavior of bis(thiourea)silver(I)nitrate
Authors: Sivakumar, N.
Kanagathara, N.
Gayathri, K.
Krishnan, P.
Anbalagan, G.
Journal: Journal of Thermal Analysis and Calorimetry (2014)
Discipline: CHEMISTRY
Keywords: Semi-organic; Crystal growth; X-ray diffraction; Orthorhombic system; Non-centrosymmetric

Abstract: New semi-organic bis(thiourea)silver(I)nitrate (TuAgN) single crystals have been grown from slow evaporation solution growth technique. Single crystal X-ray diffraction study reveals that the crystal belongs to orthorhombic system with the non-centrosymmetric space group C2221 and the calculated cell parameters are a&nbsp;=&nbsp;33.3455 (6) \xc5, b&nbsp;=&nbsp;45.2957 (7) \xc5, c&nbsp;=&nbsp;20.3209 (5) \xc5, α&nbsp;=&nbsp;β&nbsp;=&nbsp;γ&nbsp;=&nbsp;90°, and V&nbsp;=&nbsp;30692.8 (10) \xc5 3. The thermal stability and decomposition behavior of TuAgN compound have been studied by thermogravimetric analysis at three different heating rates 5, 10, and 15&nbsp;°C&nbsp;min\u22121. The effective activation energy (E a) and pre-exponential factor (ln A) of thermal decomposition of thiourea from TuAgN compound at three different heating rates are estimated by model free methods: Arrhenius, Flynn–Wall, Kissinger, and Kim–Park. The calculated effective activation energies were found to vary with the fraction (α) reacted. The compensation effect between the (ln A) and (E a) has also been studied. Dielectric properties of TuAgN crystal have been studied in a wide range of frequencies and temperatures. AC conductivity has also been carried out.

Retracted: No

PubPeer comments:
 The authors are requested to clarify if the title crystal in this paper is the same as the one reported by Sivakumar et al in Spectrochim Acta (for details pl. see https: pubpeer.com publications 530F18967B33B61CE47B52304FB2A7) on a so called poly bis (thiourea) silver (I) nitrate single crystal whose unit cell is exactly same as that of the title crystal. Authors are requested to clarify for not using the term poly in this case despite the same unit cell and also same procedure of crystal growth. Which of the following names is the correct? bis(thiourea)silver(I)nitrate or poly bis (thiourea) silver (I) nitrate. ,
Knockdown of long non-coding RNA HOXD-AS1 inhibits the progression of osteosarcoma
Authors: Jianwu Zhao
Rongpeng Dong
Haohan Zhou
Mingyang Kang
Shuang Zheng
Dezhi Zhao
Yang Qu
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HOXD-AS1; Osteosarcoma; Proliferation; STAT3; lncRNA.
Affiliations: Department of Orthopaedics, the Second Hospital of Jilin University, #218 Ziqiang Street, Changchun 130041, China., Department of Orthopaedics, the Second Hospital of Jilin University, #218 Ziqiang Street, Changchun 130041, China. Electronic address: .

Abstract:  Long non-coding RNA HOXD-AS1 (HOXD-AS1) has recently been shown to be involved in the development and progression of multiple cancers. However, the expression, significance, and biological function of HOXD-AS1 in osteosarcoma (OS) remain unknown. Here, we found that the expression level of HOXD-AS1 was significantly upregulated in OS tissues and cells. Furthermore, high expression of HOXD-AS1 was positively associated with the clinical and pathological characteristics of OS, including tumor stage and lymph node metastasis, and negatively correlated with overall survival rate. in vitro assays confirmed that knockdown of HOXD-AS1 suppressed cell proliferation, colony formation, migration, and invasion, and promoted cell cycle arrest at G1 stage and apoptosis in OS cells. in vivo assays confirmed that knockdown of HOXD-AS1 significantly decreased tumor growth in xenograft mice, and decreased tumor size and weight. Importantly, we also showed that knockdown of HOXD-AS1 significantly reduced signal transducer and activator of transcription 3 and its target protein (CyclinD1, Bcl-2, and MMP-2) expression in vitro and in vivo. Moreover, overexpression of STAT3 could reverse the suppression of proliferation ability induced by sh-HOXD-AS1 in U2OS cells. Collectively, our data indicated that HOXD-AS1 might be an oncogenic long non-coding RNA (lncRNA) and might be a potential attractive therapeutic target for OS. 

Retracted: No

PubPeer comments:
 *[above]* Fig 5B.  Photographs of tumors derived from U2OS cells 30 days after injection . *[below]* Fig 5B from [Li et al (2018)] .  Images of tumor tissues in the sh-LINC00152 and sh-NC groups . ![file] Could the authors of either paper comment on the appearance of the same tumors in both? (albeit differently identified, in a different arrangement, and at a different scale). ,
The potency of lncRNA MALAT1/miR-155/CTLA4 axis in altering Th1/Th2 balance of asthma
Authors: Zhijun Liang
Fenglian Tang
Journal: Bioscience reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CTLA-4; T-bet/Gata3 ratio; Th1/Th2 balance; asthma; lncRNA MALAT1
Affiliations: Department of Respiratory Medicine, Affiliated Hospital of Jining Medical University, Jining City 272000, Shandong Province, China

Abstract:  Objectives: The present study examined if the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-155/CTLA-4 axis was involved in modifying Th1/Th2 balance, a critical indicator for asthma progression. Methods: Altogether 772 asthma patients and 441 healthy controls were recruited, and their blood samples were collected to determine expressional levels of MALAT1, miR-155, CTLA-4, T-bet, GATA3, Th1-type cytokines and Th2-type cytokines. The CD4+ T cells were administered with pcDNA3.1-MALAT1, si-MALAT1, miR-155 mimic and miR-155 inhibitor to assess their effects on cytokine release. The luciferase reporter gene assay was also adopted to evaluate the sponging relationships between MALAT1 and miR-155, as well as between miR-155 and CTLA-4. Results: Over-expressed MALAT1 and under-expressed miR-155 were more frequently detected among asthma patients who showed traits of reduced forced expiratory failure volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) and FEV1% of predicted (P&lt;0.05). Moreover, MALAT1 expression was negatively expressed with the Th1/Th2 and T-bet/GATA3 ratios, yet miR-155 expression displayed a positively correlation with the ratios (P&lt;0.05). Additionally, the IFN-γ, IL-2 and T-bet levels were reduced under the influence of pcDNA3.1-MALAT1 and miR-155 inhibitor, while levels of IL-4, IL-10 and GATA3 were raised under identical settings (P&lt;0.05). Furthermore, MALAT1 constrained expression of miR-155 within CD4+ T cells by sponging it, and CTLA-4 could interfere with the effects of MALAT1 and miR-155 on Th1/Th2 balance and T-bet/Gata3 ratio (P&lt;0.05). Conclusion: MALAT1 sponging miR-155 was involved with regulation of Th1/Th2 balance within CD4+ T cells, which might aid to develop therapies for amelioration of asthmatic inflammation. 

Retracted: No

PubPeer comments:
 In Figure 2F, the GATA3 and IL-10 bands appear unexpectedly similar. *** ![file] *** ![file] ,
The Effect of Dietary Supplements Containing Green Tea, Capsaicin and Ginger Extracts on Weight Loss and Metabolic Profiles in Overweight Women: A Randomized Double-Blind Placebo-Controlled Clinical Trial
Authors: Sara Taheri
Narjes Farzin
Mohsen Taghizadeh
Zatollah Asemi
Mahnaz Mahlouji
Hossein Akbari
Fatemeh Karamali
Journal: Annals of Nutrition and Metabolism (2017)
Discipline: CLINICAL MEDICINE
Keywords: Dietary supplements; Insulin resistance; Overweight; Weight loss.
Affiliations: Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Abstract:  Background: This study was conducted to determine the effects of dietary supplements containing green tea, capsaicin and ginger extracts on weight loss and metabolic profiles among overweight women. Methods: This randomized double-blind placebo-controlled clinical trial was implemented among 50 overweight women. Participants were randomly divided into 2 groups. Group A received dietary supplements containing 125 mg green tea, 25 mg capsaicin and 50 mg ginger extracts (n = 25) group B received placebos (n = 25) twice with lunch and twice with dinner daily for 8 weeks. Results: Compared with placebo, taking dietary supplements containing green tea, capsaicin and ginger resulted in a significant decrease in weight (-1.8 ± 1.5 vs. +0.4 ± 1.2 kg, respectively, p &lt; 0.001) and body mass index (BMI; -0.7 ± 0.5 vs. +0.1 ± 0.5 kg/m2, respectively, p &lt; 0.001). In addition, subjects who received green tea, capsaicin and ginger co-supplements had significantly decreased serum insulin concentrations (-2.6 ± 3.9 vs. -0.6 ± 2.0 µIU/mL, p = 0.02), homeostatic model of assessment for insulin resistance (-0.5 ± 0.8 vs. -0.05 ± 0.6, p = 0.01), and increased quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. +0.001 ± 0.01, p = 0.008) and plasma glutathione (GSH) levels (+73.8 ± 120.6 vs. -28.3 ± 193.4 µmol/L, p = 0.03) compared with the placebo. Conclusions: Our study indicated that taking green tea, capsaicin and ginger co-supplements for 8 weeks among overweight women had beneficial effects on weight, BMI, markers of insulin metabolism and plasma GSH levels. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A117 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
Ryanodine receptors are expressed and functionally active in mouse spermatogenic cells and their inhibition interferes with spermatogonial differentiation
Authors: Carla Boitani
Mario Stefanini
Rossella Puglisi
Vincenzo Sorrentino
Pieranna Chiarella
Journal: Journal of Cell Science (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ryanodine receptors; calcium release channels; male germ cells; maturation; isoforms
Affiliations: Department of Histology and Medical Embryology and Centro di Eccellenza Biologia e Medicina Molecolare, University of Rome La Sapienza, Via A. Scarpa 14, 00161 Roma, Italy.

Abstract:  Ryanodine receptors (RyRs) are intracellular calcium release channels that are highly expressed in striated muscle and neurons but are also detected in several non-excitable cells. We have studied the expression of the three RyR isoforms in male germ cells at different stages of maturation by western blot and RT-PCR. RyR1 was expressed in spermatogonia, pachytene spermatocytes and round spermatids whereas RyR2 was found only in 5- to 10-day-old testis but not in germ cells. RyR3 was not revealed at the protein level, although its mRNA was detected in mixed populations of germ cells. Caffeine, a known agonist of RyRs, was able to induce release of Ca(2+) from intracellular stores in spermatogonia, pachytene spermatocytes and round spermatids, but not spermatozoa. Treatment with high doses of ryanodine, which are known to block RyR channel activity, reduced spermatogonial proliferation and induced meiosis in in vitro organ cultures of testis from 7-day-old mice. In conclusion, the results presented here indicate that RyRs are present in germ cells and that calcium mobilization through RyR channels could participate to the regulation of male germ maturation. 

Retracted: No

PubPeer comments:
 More similar than expected. Could authors check it please? ![file] ,
Mechanisms underlying p53 regulation of PIK3CA transcription in ovarian surface epithelium and in ovarian cancer
Authors: Nelly Auersperg
Gordon B Mills
Wyeth W Wasserman
David Arenillas
Peter C K Leung
Sandra E Dunn
Arezoo Astanehe
Barry R Davies
Journal: Journal of Cell Science (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p53; PIK3CA; ovarian carcinomas; tumorigenesis; transcriptional inhibition
Affiliations: Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.

Abstract:  Inactivation of the transcription factor and tumor suppressor p53, and overexpression or mutational activation of PIK3CA, which encodes the p110alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), are two of the most common deleterious genomic changes in cancer, including in ovarian carcinomas. We investigated molecular mechanisms underlying interactions between these two mediators and their possible roles in ovarian tumorigenesis. We identified two alternate PIK3CA promoters and showed direct binding of and transcriptional inhibition by p53 to one of these promoters. Conditional suppression of functional p53 increased p110alpha transcripts, protein levels and PI3K activity in immortalized, non-tumorigenic ovarian surface epithelial (OSE) cells, the precursors of ovarian carcinoma. Conversely, overexpression of p53 by adenoviral infection and activation of p53 by gamma-irradiation both diminished p110alpha protein levels in normal OSE and ovarian cancer cells. The demonstration that p53 binds directly to the PIK3CA promoter and inhibits its activity identifies a novel mechanism whereby these two mediators regulate cellular functions, and whereby inactivation of p53 and subsequent upregulation of PIK3CA might contribute to the pathophysiology of ovarian cancer. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
null, 
 #4 2020 Expression of Concern. https: pubmed.ncbi.nlm.nih.gov 32917731 ,
Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer
Authors: Sourobh Maji
Jitendra K Thakur
Neha Nagpal
Giorgio Durante
Shivani Sharma
Manuela Ferracin
Ritu Kulshreshtha
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: Mediator complex; miRNAs; MED1; breast cancer; prognosis
Affiliations: Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, 110016, India., Children's Hospital, Harvard Medical School, Boston, MA, USA., National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi, 110067, India., Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126, Bologna, Italy., National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi, 110067, India. ., Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, 110016, India. .

Abstract:  Mediator complex has been extensively shown to regulate the levels of several protein-coding genes; however, its role in the regulation of miRNAs in humans remains unstudied so far. Here we show that MED1, a Mediator subunit in the Middle module of Mediator complex, is overexpressed in breast cancer and is a negative prognostic factor. The levels of several miRNAs (miR-100-5p, -191-5p, -193b-3p, -205-5p, -326, -422a and -425-5p) were found to be regulated by MED1. MED1 induces miR-191/425 cluster in an estrogen receptor-alpha (ER-α) dependent manner. Occupancy of MED1 on estrogen response elements (EREs) upstream of miR-191/425 cluster is estrogen and ER-α-dependent and ER-α-induced expression of these miRNAs is MED1-dependent. MED1 mediates induction of cell proliferation and migration and the genes associated with it (JUN, FOS, EGFR, VEGF, MMP1, and ERBB4) in breast cancer, which is abrogated when used together with miR-191-inhibition. Additionally, we show that MED1 also regulates the levels of direct miR-191 target genes such as SATB1, CDK6 and BDNF. Overall, the results show that MED1/ER-α/miR-191 axis promotes breast cancer cell proliferation and migration and may serve as a novel target for therapy. 

Retracted: No

PubPeer comments:
 Figure 5B shows a sharp area of transition, more evident when image is brightened. Top: 5B brightness enhanced; Bottom: Figure 5 *** ![file] *** ![file] , 
 In this Figure 5, all the inputs are shown towards right hand side. See Figures 5D and 5G. In order to maintain the uniformity, input in Figure 5B is also shown towards right side. The original gel picture is pasted here. The very first lane of input has been moved towards right of IgG in the Figure 5B . ![file] ,
Evaluation of pyruvate decarboxylase‐negative Saccharomyces cerevisiae strains for the production of succinic acid
Authors: Ahmed Zahoor
Felix T F Küttner
Lars M Blank
Birgitta E Ebert
Journal: Engineering in Life Sciences (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CRISPR‐Cas9; dicarboxylic acids; metabolic engineering; succinic acid; yeast.
Affiliations: Institute of Applied Microbiology – iAMBAachen Biology and Biotechnology – ABBtRWTH Aachen University Aachen Germany

Abstract:  Dicarboxylic acids are important bio-based building blocks, and Saccharomyces cerevisiae is postulated to be an advantageous host for their fermentative production. Here, we engineered a pyruvate decarboxylase-negative S. cerevisiae strain for succinic acid production to exploit its promising properties, that is, lack of ethanol production and accumulation of the precursor pyruvate. The metabolic engineering steps included genomic integration of a biosynthesis pathway based on the reductive branch of the tricarboxylic acid cycle and a dicarboxylic acid transporter. Further modifications were the combined deletion of GPD1 and FUM1 and multi-copy integration of the native PYC2 gene, encoding a pyruvate carboxylase required to drain pyruvate into the synthesis pathway. The effect of increased redox cofactor supply was tested by modulating oxygen limitation and supplementing formate. The physiologic analysis of the differently engineered strains focused on elucidating metabolic bottlenecks. The data not only highlight the importance of a balanced activity of pathway enzymes and selective export systems but also shows the importance to find an optimal trade-off between redox cofactor supply and energy availability in the form of ATP. 

Retracted: No

PubPeer comments:
 Figure 1 is incorrect in showing an NADH being consumed in the fumC reaction. This is a redox neutral dehydration. ,
MiR-101 inhibits cell proliferation and invasion of pancreatic cancer through targeting STMN1
Authors: Yinan Chen
Kai Nie
Hong Yu
Yongxin Xiao
Lin Zhu
Journal: Cancer Biomarkers (2018)
Discipline: CLINICAL MEDICINE
Keywords: MiR-101; STMN1; invasion; pancreatic cancer; proliferation.
Affiliations: Department of Radiology, Dongfang Hospital Affiliated to Shanghai Tongji University, Shanghai, China, Department of Radiology, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China, Department of Radiology, Shanghai Changzheng Hospital Affiliated to the Second Military Medical University, Shanghai, China

Abstract:  MiRNAs regulated most genes expression, which were proved important in various tumors. In this study, we want to investigate miR-101 effect and molecular mechanism on pancreatic cancer (PC), the research about this was blank now. RT-PCR analysis showed that miR-101 expression was declined in PC. MTT assay found that miR-101 mimic suppressed cell viability, while suppressing miR-101 facilitated cell proliferation. Transwell assay showed that miR-101 mimic inhibited cell invasion, but promoted cell invasion by miR-101 inhibitor. With TargetScanHuman's help, we verified STMN1 as a specific target of miR-101 and luciferase reporter assay was carried out to further confirm this discovery. STMN1 expression was reduced by miR-101 mimic and increased by miR-101 inhibitor. We next found that STMN1 was elevated in PC and its expression was negatively correlated with miR-101 expression. Furthermore, STMN1 siRNA curbed cell proliferation and invasion, which was opposite to miR-101 inhibitor effect on PC progression and STMN1 siRNA attenuated miR-101 inhibitor effect on cell proliferation and invasion. In conclusion, miR-101 inhibited PC cell proliferation and invasion via regulating STMN1, which provided a potential therapeutic for PC patients. 

Retracted: No

PubPeer comments:
 Fig. 2.  miR-101u2019 suppressive effect on PC cell proliferation and invasion. Fig 5  (C) Relative invaded cells detected in PC two cell lines after inhibiting miR-101, silencing STMN1 and inhibiting both miR-101 and STMN1 . ![file] Con-mimic and miR-101 mimic displaying advanced mimicry skills. ,
Development and evaluation of a sensitive and specific assay for diagnosis of human toxocariasis by use of three recombinant antigens (TES-26, TES-30USM, and TES-120)
Authors: Norhaida Che Azmi
Rahmah Noordin
Suharni Mohamad
Journal: Journal of Clinical Microbiology (2009)
Discipline: MICROBIOLOGY
Keywords: Toxocariasis diagnosis; Recombinant antigens; IgG4 ELISA; Specificity; Sensitivity
Affiliations: Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Penang, Malaysia.

Abstract:  Diagnosis of human toxocariasis currently relies on serologic tests that use Toxocara excretory-secretory (TES) antigen to detect immunoglobulin G (IgG) antibodies to the larvae. In general, however, these assays do not have adequate specificity for use in countries in which other soil-transmitted helminths are endemic. The use of recombinant antigens in these assays, however, is promising for improving the specificity of the diagnosis of toxocariasis. Toward this goal, we developed an IgG4 enzyme-linked immunosorbent assay (ELISA) involving three recombinant antigens: rTES-30USM (previously produced), rTES-26, and rTES-120. The latter two antigens were produced by reverse transcription-PCR cloning; subcloned into glutathione S-transferase (GST)-tagged and His-tagged prokaryotic expression vectors, respectively; and expressed in Escherichia coli. The recombinant proteins were subsequently purified by affinity chromatography using GST and His-Trap resins. The diagnostic potential of each purified recombinant antigen was tested with various immunoglobulin classes (IgG, IgM, and IgE) and IgG subclasses. The IgG4 ELISA was determined to have the highest specificity and was further evaluated using a panel of serum samples. The rTES-26 IgG4 ELISA showed 80.0% (24/30 samples positive) sensitivity, and both the rTES-30USM IgG4 ELISA and rTES-120 IgG4 ELISA had 93.0% (28/30) sensitivity. Combined use of rTES-120 and rTES-30 IgG4 ELISA for the diagnosis of toxocariasis provided 100% sensitivity. The specificities of rTES-26, rTES-30USM, and rTES-120 antigens were 96.2%, 93.9%, and 92.0%, respectively. These results indicate that the development of a diagnostic test using the three recombinant antigens will allow for more-accurate detection of toxocariasis. 

Retracted: No

PubPeer comments:
 Concerns about Figures 1 and 3 were reported to the journal in April 2014, but the journal did not take any action, so I am posting them here. Figure 1. * Purple boxes: Lanes 3 and 4 look remarkably similar, although with different vertical compression ratios. ![file] , 
 Figure 3. * Green arrows: Sharp vertical transitions suggestive of splicing. * Red boxes: In Figure 3a, lanes 5 and 8 look remarkably similar. ![file] ,
Fibronectin Stimulates Non–Small Cell Lung Carcinoma Cell Growth through Activation of Akt/Mammalian Target of Rapamycin/S6 Kinase and Inactivation of LKB1/AMP-Activated Protein Kinase Signal Pathways
Authors: ShouWei Han
Jesse Roman
Fadlo R Khuri
Journal: Cancer research (2006)
Discipline: CLINICAL MEDICINE
Keywords: Akt; mTOR; p70S6K; lung carcinoma; fibronectin
Affiliations: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. 

Abstract:  The Akt/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K) pathway is considered a central regulator of protein synthesis and of cell proliferation, differentiation, and survival. However, the role of the Akt/mTOR/p70S6K pathway in lung carcinoma remains unknown. We previously showed that fibronectin, a matrix glycoprotein highly expressed in tobacco-related lung disease, stimulates non-small cell lung carcinoma (NSCLC) cell growth and survival. Herein, we explore the role of the Akt/mTOR/p70S6K pathway in fibronectin-induced NSCLC cell growth. We found that fibronectin stimulated the phosphorylation of Akt, an upstream inducer of mTOR, and induced the phosphorylation of p70S6K1 and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), two downstream targets of mTOR in NSCLC cells (H1792 and H1838), whereas it inhibited the phosphatase and tensin homologue deleted on chromosome 10, a tumor suppressor protein that antagonizes the phosphatidylinositol 3-kinase/Akt signal. In addition, treatment with fibronectin inhibited the mRNA and protein expression of LKB1 as well as the phosphorylation of AMP-activated protein kinase (AMPKalpha), both known to down-regulate mTOR. Rapamycin, an inhibitor of mTOR, blocked the fibronectin-induced phosphorylation of p70S6K and 4E-BP1. Akt small interfering RNA (siRNA) and an antibody against the fibronectin-binding integrin alpha5beta1 also blocked the p70S6K phosphorylation in response to fibronectin. In contrast, an inhibitor of extracellular signal-regulated kinase 1/2 (PD98095) had no effect on fibronectin-induced phosphorylation of p70S6K. Moreover, the combination of rapamycin and siRNA for Akt blocked fibronectin-induced cell proliferation. Taken together, these observations suggest that fibronectin-induced stimulation of NSCLC cell proliferation requires activation of the Akt/mTOR/p70S6K pathway and is associated with inhibition of LKB1/AMPK signaling. 

Retracted: No

PubPeer comments:
 Figure 1D. Much more similar than you would expect. https: imgur.com k3JGkca , 
 https: retractionwatch.com 2015 08 11 eighth-retraction-published-for-former-physiology-researcher ,
Cryptanshinone Inhibits the Glycolysis and Inhibits Cell Migration Through PKM2/β-Catenin Axis in Breast Cancer
Authors: Hsin-An Chen
Chang-Wei Li
Haoran Wu
Chih-Ming Su
Shin-Han Tsai
Jiefeng Zhou
Shicong Du
Yu-Ting Yeh
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: PKM2; breast cancer; cryptotanshinone; glycolysis; migration.
Affiliations: Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan., Ningbo AJcore Biosciences Inc, High-tech Zone, Ningbo City, People's Republic of China., Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan., Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan., Ningbo AllBiolife Biotech Inc, High-tech Zone, Ningbo City, People's Republic of China., Department of Emergency Medicine, Shuang Ho Hospital, Taipei Medical University, Institute of Injury Prevention and Control, Taipei Medical University, Taipei City, Taiwan., Information Technology Office, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

Abstract:  Background: Breast cancer is one of the most prevalent gynecologic malignancies worldwide. Despite the high sensitivity in response to chemotherapy, drug resistance occurred frequently in clinical treatment. Cryptotanshinone (CTS) is a herbal medicine and has been identified as an anti-inflammatory and anti-oxidative drug. Methods: In vitro assays, including the cell proliferation assay, colony formation assay, Western blot analysis, transwell migration/invasion assays, and cell scratch assay were used to explore the biological activities and working mechanism of CTS. Breast cancer cells were also transfected with PKM2 expressing vectors to define the molecular mechanisms involved in CTS-mediated anti-tumor activity. Results: We found that CTS shows anti-proliferative effects and decreases the clonogenic ability of breast cancer cells. We also found that CTS inhibited the migration and invasion activity of MCF-7 and MDA-MB-231 cells by different analyzed methods. CTS also downregulated the levels of glycolysis-related proteins, such as PKM2, LDHA, and HK2. In addition, overexpression of PKM2 recovered CTS-mediated suppression of cell proliferation, colony formation, and cell mobility of breast cancer cells. We also found PKM2 was significantly overexpressed in tumor tissues and invasive ductal breast carcinoma compared to normal tissues and patients with high PKM2 expression had worse overall survival and metastasis-free survival outcomes. Conclusion: CTS inhibited the proliferation, migration, and invasion of breast cancer cells. The involved mechanism may refer to the downregulation of the PKM2/β-catenin axis. 

Retracted: No

PubPeer comments:
 In Figure 5F same micrograph has been used three times for three different conditions. ![file] ,
P38 alpha mitogen-activated protein kinase sensitizes cells to apoptosis induced by different stimuli
Authors: Amparo Valladares
Concetta Ambrosino
Susana Zuluaga
Manuel Benito
Angel R Nebreda
Almudena Porras
Alberto M Alvarez
Emma Black
Journal: Molecular Biology of the Cell (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p38 alpha; apoptosis; signaling pathway; cellular responses; stress
Affiliations: Departamento de Bioquimica y Biologia Molecular II (Centro Mixto UCM/CSIC), UCM, Ciudad Universitaria, 28040 Madrid, Spain, European Molecular Biology Laboratory, 69117 Heidelberg, Germany, Centro de Citometría de Flujo y Microscopía Confocal, Facultad de Farmacia, UCM, Ciudad Universitaria, 28040 Madrid, Spain

Abstract:  p38 alpha mitogen-activated protein (MAP) kinase is a broadly expressed signaling molecule that participates in the regulation of cellular responses to stress as well as in the control of proliferation and survival of many cell types. We have used cell lines derived from p38 alpha knockout mice to study the role of this signaling pathway in the regulation of apoptosis. Here, we show that cardiomyocytes and fibroblasts lacking p38 alpha are more resistant to apoptosis induced by different stimuli. The reduced apoptosis of p38 alpha-deficient cells correlates with decreased expression of the mitochondrial proapoptotic protein Bax and the apoptosis-inducing receptor Fas/CD-95. Cells lacking p38 alpha also have increased extracellular signal-regulated kinase (ERKs) MAP kinase activity, and the up-regulation of this survival pathway seems to be at least partially responsible for the reduced levels of apoptosis in the absence of p38 alpha. Phosphorylation of the transcription factor STAT3 on Ser-727, mediated by the extracellular signal-regulated kinase MAP kinase pathway, may contribute to the decrease in both Bax and Fas expression in p38 alpha-/- cells. Thus, p38 alpha seems to sensitize cells to apoptosis via both up-regulation of proapoptotic proteins and down-regulation of survival pathways. 

Retracted: No

PubPeer comments:
 Figure 5A. Much more similar than expected. ![file] ,
Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting
Authors: Awesh K Yadav
Sunil K Jain
Shyam S Pancholi
Amol Paharia
Gopal Rai
Govind P Agrawal
Journal: AAPS PharmSciTech (2007)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Eudragit-coated pectin microspheres; colon targeting; 5-fluorouracil; emulsion dehydration method; encapsulation efficiencies
Affiliations: Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, India.

Abstract:  An objective of the present investigation was to prepare and evaluate Eudragit-coated pectin microspheres for colon targeting of 5-fluorouracil (FU). Pectin microspheres were prepared by emulsion dehydration method using different ratios of FU and pectin (1:3 to 1:6), stirring speeds (500-2000 rpm) and emulsifier concentrations (0.75%-1.5% wt/vol). The yield of preparation and the encapsulation efficiencies were high for all pectin microspheres. Microspheres prepared by using drug:polymer ratio 1:4, stirring speed 1000 rpm, and 1.25% wt/vol concentration of emulsifying agent were selected as an optimized formulation. Eudragit-coating of pectin microspheres was performed by oil-in-oil solvent evaporation method using coat:core ratio (5:1). Pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size distribution, swellability, percentage drug entrapment, and in vitro drug release in simulated gastrointestinal fluids (SGF). The in vitro drug release study of optimized formulation was also performed in simulated colonic fluid in the presence of 2% rat cecal content. Organ distribution study in albino rats was performed to establish the targeting potential of optimized formulation in the colon. The release profile of FU from Eudragit-coated pectin microspheres was pH dependent. In acidic medium, the release rate was much slower; however, the drug was released quickly at pH 7.4. It is concluded from the present investigation that Eudragit-coated pectin microspheres are promising controlled release carriers for colon-targeted delivery of FU. 

Retracted: No

PubPeer comments:
 Figure 1.  Scanning electron photomicrographs of (A) Pectin microspheres (original magnification x422) and (B) Eudragit-coated pectin microsphere (original magnification x3.06K). MS indicates microspheres. ![file] Fig 1 from [Bilthare Jain (2013)](http: www.ijpaonline.info index.php ijpaonline article view 29) - no DOI or PMID, so not indexed in PubPeer.  (B) SEM Photomicrograph of eudragit-S100 coated starch microspheres (650X) ![file] Are they pectin microspheres and Eudragit-coated **pectin** microspheres, or a single group of eudragit-coated **starch** microspheres? Perhaps the original 2007 authors or the 2013 authors can tell us. ,
Airway Resistance Caused by Sphingomyelin Synthase 2 Insufficiency in Response to Cigarette Smoke
Authors: Ziyad Elgamal
Yeun-Po Chiang
Patrick Geraghty
Chongmin Huan
Xian-Cheng Jiang
Hannah Goldenberg
Nathalie Baumlin
Gayatri Gupta
Melissa Rivas
Abdoulaye Dabo
Christopher Railwah
Begum Ahmed
Matthias Salathe
Michael D Kim
Apurav A Panwala
Justin Poon
Robert Foronjy
Raj Wadgaonkar
Journal: American Journal of Respiratory Cell and Molecular Biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Akt phosphorylation; airway restriction; cigarette smoke; protease; sphingomyelin synthase.
Affiliations: Division of Pulmonary and Critical Care Medicine, Department of Medicine., Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas; and., Department of Cell Biology, and., Department of Surgery, State University of New York Downstate Medical Center, Brooklyn, New York., VA Medical Center, Brooklyn, New York.

Abstract:  Sphingomyelin synthase is responsible for the production of sphingomyelin (SGM), the second most abundant phospholipid in mammalian plasma, from ceramide, a major sphingolipid. Knowledge of the effects of cigarette smoke on SGM production is limited. In the present study, we examined the effect of chronic cigarette smoke on sphingomyelin synthase (SGMS) activity and evaluated how the deficiency of Sgms2, one of the two isoforms of mammalian SGMS, impacts pulmonary function. Sgms2-knockout and wild-type control mice were exposed to cigarette smoke for 6 months, and pulmonary function testing was performed. SGMS2-dependent signaling was investigated in these mice and in human monocyte-derived macrophages of nonsmokers and human bronchial epithelial (HBE) cells isolated from healthy nonsmokers and subjects with chronic obstructive pulmonary disease (COPD). Chronic cigarette smoke reduces SGMS activity and Sgms2 gene expression in mouse lungs. Sgms2-deficient mice exhibited enhanced airway and tissue resistance after chronic cigarette smoke exposure, but had similar degrees of emphysema, compared with smoke-exposed wild-type mice. Sgms2-/- mice had greater AKT phosphorylation, peribronchial collagen deposition, and protease activity in their lungs after smoke inhalation. Similarly, we identified reduced SGMS2 expression and enhanced phosphorylation of AKT and protease production in HBE cells isolated from subjects with COPD. Selective inhibition of AKT activity or overexpression of SGMS2 reduced the production of several matrix metalloproteinases in HBE cells and monocyte-derived macrophages. Our study demonstrates that smoke-regulated Sgms2 gene expression influences key COPD features in mice, including airway resistance, AKT signaling, and protease production. 

Retracted: No

PubPeer comments:
 Are these the same controls in different experiments? ![file] ,