PReD-Bench/PRed-Bench huggingface dataset:
Inhibition of Mitofusin-2 Promotes Cardiac Fibroblast Activation via the PERK/ATF4 Pathway and Reactive Oxygen Species
Authors: Jing Qu
Wenchao Wu
Xiaojing Liu
Lixing Yuan
Song Lei
Yanguo Xin
Xiaojiao Wang
Journal: Oxidative Medicine and Cellular Longevity (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Mitofusin-2; cardiac fibroblast activation; TGF-β1; hypertrophic heart tissues; siMfn2
Affiliations: Department of Cardiology, West China Hospital, Sichuan University, Chengdu 610041, China., Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China., Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China., Public Laboratory of West China Second University Hospital, Sichuan University, Chengdu 610041, China.

Abstract:  Mitofusin-2 (Mfn2) is a key outer mitochondrial membrane protein, which maintains normal mitochondrial dynamics and function. However, its role in cardiac fibroblast activation remains poorly understood. In the present study, a rat model of transverse aortic constriction (TAC) was established to observe the cardiac fibroblast activation in vivo. TGF-β1 treatment for 24 hours was used to induce cardiac fibroblast activation in vitro. As a result, the expression of Mfn2 decreased in the hypertrophic heart tissues and cardiac fibroblasts treated with TGF-β1. siMfn2 and adenovirus were applied to mediate Mfn2 gene silencing and overexpression in cardiac fibroblasts to elucidate the relationship between Mfn2 and cardiac fibroblast activation, as well as the possible underlying mechanisms. Knockdown of Mfn2 further promoted TGF-β1-induced cardiac fibroblast activation, while forced expression of Mfn2 attenuated this pathological reaction. The PERK/ATF4 pathway, one of the branches of endoplasmic reticulum (ER) stress, was identified to be involved in this process. Knockdown and overexpression of Mfn2 lead to aggravation or alleviation of the PERK/ATF4 pathway. Blocking this pathway by silencing ATF4 with siATF4 attenuated the pathological process. During the activation of cardiac fibroblasts, knockdown of Mfn2 also increased the production of reactive oxygen species (ROS), while ROS scavenger N-acetyl-l-cysteine (NAC) could attenuate the effect caused by knockdown of Mfn2. Our data suggested that inhibition of Mfn2 could promote cardiac fibroblast activation by activating the PERK/ATF4 signaling pathway and increasing the generation of ROS. 

Retracted: No

PubPeer comments:
 Figure 4A u2013 more similar than expected ![file] , 
 #1 Hi there, Thanks for your comment. We are sorry to make this mistake, and we will contact with the journal editor and replace our original WB band. If necessary we could provide our original raw data. Thanks. , 
 #2 The original band is as below:![file] . Yanguo Xin ,
Oscillatory phosphorylation of yeast Fus3 MAP kinase controls periodic gene expression and morphogenesis
Authors: Zoe Hilioti
Marcus D Goncalves
Lee Bardwell
Andre Levchenko
Adriel Bergmann
Walid Sabbagh Jr
Saurabh Paliwal
Journal: Current Biology (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Signal-transduction networks; dynamic behavior; oscillations; MAPK; Fus3
Affiliations: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.

Abstract:  Signal-transduction networks can display complex dynamic behavior such as oscillations in the activity of key components [1-6], but it is often unclear whether such dynamic complexity is actually important for the network's regulatory functions [7, 8]. Here, we found that the mitogen-activated protein kinase (MAPK) Fus3, a key regulator of the yeast mating-pheromone response, undergoes sustained oscillations in its phosphorylation and activation state during continuous pheromone exposure. These MAPK activity oscillations led to corresponding oscillations in mating-gene expression. Oscillations in MAPK activity and gene expression required the negative regulator of G protein signaling Sst2 and partially required the MAPK phosphatase Msg5. Peaks in Fus3 activation correlated with periodic rounds of cell morphogenesis, with each peak preceding the formation of an additional mating projection. Preventing projection formation did not eliminate MAPK oscillation, but preventing MAPK oscillation blocked the formation of additional projections. A mathematical model was developed that reproduced several features of the observed oscillatory dynamics. These observations demonstrate a role for MAPK activity oscillation in driving a periodic downstream response and explain how the pheromone signaling pathway, previously thought to desensitize after 1-3 hr, controls morphology changes that continue for a much longer time. 

Retracted: No

PubPeer comments:
 Identified by another reader. Correction addresses the issue with figure 3E, but seems hard to justify. *** ![file] ,
Patched1 haploinsufficiency severely impacts intermediary metabolism in the skin of Ptch1+/−/ODC transgenic mice
Authors: Mahendra Kashyap
Changzhao Li
Arianna L Kim
Levy Kopelovich
Shaida A Andrabi
Shahid M Mukhtar
David R Bickers
Mohammad Athar
Bharat Mishra
Zhiping Weng
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: Heritable cancers; Gorlin syndrome; Ptch1 haploinsufficiency; BCCs; murine model
Affiliations: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA., Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA., Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA., Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA., Department of Dermatology, Columbia University, New York, NY, USA., Department of Medicine, Weill Cornell Medical College, New York, NY, USA. ., Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA. .

Abstract:  The study of dominantly heritable cancers has provided insights about tumor development. Gorlin syndrome (GS) is an autosomal dominant disorder wherein affected individuals develop multiple basal cell carcinomas (BCCs) of the skin. We developed a murine model of Ptch1 haploinsufficiency on an ornithine decarboxylase (ODC) transgenic background (Ptch1+/-/ODCt/C57BL/6) that is more sensitive to BCCs growth as compared with Ptch1+/+/ODCt/C57BL/6 littermates. Ptch1+/-/ODCt/C57BL/6 mice show an altered metabolic landscape in the phenotypically normal skin, including restricted glucose availability, restricted ribose/deoxyribose flow and NADPH production, an accumulation of α-ketoglutarate, aconitate, and citrate that is associated with reversal of the tricarboxylic acid cycle, coupled with increased ketogenic/lipogenic activity via acetyl-CoA, 3-hydroybutyrate, and cholesterol metabolites. Also apparent was an increased content/acetylation of amino-acids, glutamine and glutamate, in particular. Accordingly, metabolic alterations due to a single copy loss of Ptch1 in Ptch1+/-/ODCt/C57BL/6 heterozygous mice may provide insights about the cancer prone phenotype of BCCs in GS patients, including biomarkers/targets for early intervention. 

Retracted: No

PubPeer comments:
 Figure 3 Panel C has 2 identical graphs. ![file] Although the graphs are the same they have different p values, which should not be possible. ,
Understanding the role of growth factors in modulating stem cell tenogenesis
Authors: Sang-Jin Lee
James J Yoo
Anthony Atala
Rui L Reis
Ana I Gonçalves
Márcia T Rodrigues
Manuela E Gomes
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Tendon injuries; Cell-based approaches; Stem cells; Growth factors; Tenogenic differentiation
Affiliations: 3B's Research Group, Department of Polymer Engineering, Univ. of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal ; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal., Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.

Abstract:  Current treatments for tendon injuries often fail to fully restore joint biomechanics leading to the recurrence of symptoms, and thus resulting in a significant health problem with a relevant social impact worldwide. Cell-based approaches involving the use of stem cells might enable tailoring a successful tendon regeneration outcome. As growth factors (GFs) powerfully regulate the cell biological response, their exogenous addition can further stimulate stem cells into the tenogenic lineage, which might eventually depend on stem cells source. In the present study we investigate the tenogenic differentiation potential of human- amniotic fluid stem cells (hAFSCs) and adipose-derived stem cells (hASCs) with several GFs associated to tendon development and healing; namely, EGF, bFGF, PDGF-BB and TGF-β1. Stem cells response to biochemical stimuli was studied by screening of tendon-related genes (collagen type I, III, decorin, tenascin C and scleraxis) and proteins found in tendon extracellular matrix (ECM) (Collagen I, III, and Tenascin C). Despite the fact that GFs did not seem to influence the synthesis of tendon ECM proteins, EGF and bFGF influenced the expression of tendon-related genes in hAFSCs, while EGF and PDGF-BB stimulated the genetic expression in hASCs. Overall results on cellular alignment morphology, immunolocalization and PCR analysis indicated that both stem cell source can be biochemically induced towards tenogenic commitment, validating the potential of hASCs and hAFSCs for tendon regeneration strategies. 

Retracted: No

PubPeer comments:
 Figure 2 appears to include at least three sets of repeated images. Two sets in the upper panel, one set in the lower panel. Marked with red cyan and magenta respectively. *** ![file] *** ![file] ,
SMAR1 forms a ternary complex with p53-MDM2 and negatively regulates p53-mediated transcription
Authors: Sanchari Kar
Samit Chattopadhyay
Siddhartha Roy
Srijata Mukherjee
Kadreppa Sreenath
Lakshminarasimhan Pavithra
Kazuyasu Sakaguchi
Journal: Journal of molecular biology (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: tumor suppressor protein p53; autoregulatory feedback loop; negative regulator MDM2; N-terminal phosphorylations; C-terminal acetylations
Affiliations: National Centre for Cell Science, Ganeshkhind, Pune 411007, India.

Abstract:  The intra-cellular level of tumor suppressor protein p53 is tightly controlled by an autoregulatory feedback loop between the protein and its negative regulator MDM2. The role of MDM2 in down-regulating the p53 response in unstressed conditions and in the post-stress recovery phase is well documented. However, interplay between the N-terminal phosphorylations and C-terminal acetylations of p53 in this context remains unclear. Here, we show that an MAR binding protein SMAR1 interacts with MDM2 and the Ser15 phosphorylated form of p53, forming a ternary complex in the post stress-recovery phase. This triple complex formation between p53, MDM2 and SMAR1 results in recruitment of HDAC1 to deacetylate p53. The deacetylated p53 binds poorly to the target promoter (p21), which results in switching off the p53 response, essential for re-entry into the cell cycle. Interestingly, the knock-down of SMAR1 using siRNA leads to a prolonged cell-cycle arrest in the post stress recovery phase due to ablation of p53-MDM2-HDAC1 interaction. Thus, the results presented here for the first time highlight the role of SMAR1 in masking the active phosphorylation site of p53, enabling the deacetylation of p53 by HDAC1-MDM2 complex, thereby regulating the p53 transcriptional response during stress rescue. 

Retracted: No

PubPeer comments:
 ![file] , 
 ![file] , 
 #1 ![file] , 
 #2 ![file] ,
TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth
Authors: Ze-Liang Li
Jian-Bin Bi
Chui-Ze Kong
Zhe Zhang
Sheng-Lin Gao
Xian-Kui Liu
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: TRPM7; bladder cancer; tumorigenesis; overexpressed; recurrence
Affiliations: Institute of Urology, Department of Urology, The First Affiliated Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.

Abstract:  Recent findings suggest that the melastatin transient receptor potential channel 7 (TRPM7) is overexpressed in many types of cancers and is involved in tumorigenesis. However, its expression pattern and the potential role in bladder cancer remain unclear. The aim of the present study was to investigate the expression status of TRPM7 and its relationship with the development of bladder cancer. In the present study, we observed that the expression of TRPM7 was significantly elevated in bladder cancer tissues compared with that noted in the adjacent non-tumor tissues. Furthermore, increased TRPM7 expression was significantly associated with recurrence, metastasis and prognosis. In addition, after knockdown of the expression of TRPM7 by siRNA, the proliferation and the motility of T24 and 5637 cells were obviously inhibited, and downregulation of TRPM7 was found to play an important role in bladder cancer cell apoptosis. In conclusion, our findings suggest that TRPM7 plays an important role in bladder cancer, and TRPM7 may serve as a potentially unfavorable factor and novel target for human bladder cancer. 

Retracted: No

PubPeer comments:
 Figure 13 and 14 contain an enormous number of overlapping regions, clearly photoshop (or similar) was used extensively to construct these images. I ve added a few coloured boxes to get things started. Would the authors please comment? ![file] ,
DosS Is required for the complete virulence of mycobacterium tuberculosis in mice with classical granulomatous lesions
Authors: Smriti Mehra
David R Sherman
Nadia A Golden
Peter J Didier
Xavier Alvarez
Tianhua Niu
Ryan S Kissee
Cecily C Midkiff
Deepak Kaushal
Uma S Gautam
Jyothi Rengarajan
Amanda McGillivray
Journal: American Journal of Respiratory Cell and Molecular Biology (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Mycobacterium tuberculosis; hypoxia; latency; response regulator; sensor kinase.
Affiliations: Divisions of 1 Bacteriology and Parasitology.

Abstract:  Mycobacterium tuberculosis (Mtb) must counter hypoxia within granulomas to persist. DosR, in concert with sensor kinases DosS and DosT, regulates the response to hypoxia. Yet Mtb lacking functional DosR colonize the lungs of C57Bl/6 mice, presumably owing to the lack of organized lesions with sufficient hypoxia in that model. We compared the phenotype of the Δ-dosR, Δ-dosS, and Δ-dosT mutants to Mtb using C3HeB/FeJ mice, an alternate mouse model where lesions develop hypoxia. C3HeB/FeJ mice were infected via aerosol. The progression of infection was analyzed by tissue bacterial burden and histopathology. A measure of the comparative global immune responses was also analyzed. Although Δ-dosR and Δ-dosT grew comparably to wild-type Mtb, Δ-dosS exhibited a significant defect in bacterial burden and pathology in vivo, accompanied by ablated proinflammatory response. Δ-dosS retained the ability to induce DosR. The Δ-dosS mutant was also attenuated in murine macrophages ex vivo, with evidence of reduced expression of the proinflammatory signature. Our results show that DosS, but not DosR and DosT, is required by Mtb to survive in C3HeB/FeJ mice. The attenuation of Δ-dosS is not due to its inability to induce the DosR regulon, nor is it a result of the accumulation of hypoxia. That the in vivo growth restriction of Δ-dosS could be mimicked ex vivo suggested sensitivity to macrophage oxidative burst. Anoxic caseous centers within tuberculosis lesions eventually progress to cavities. Our results provide greater insight into the molecular mechanisms of Mtb persistence within host lungs. 

Retracted: No

PubPeer comments:
 Legend (not fully clear) does not explain duplication ![file] , 
 Retraction: https: pubmed.ncbi.nlm.nih.gov 31647877 , 
 EXPRESSION OF CONCERN: The authors have informed the Journal that they have become aware that some of the data in this article may be unreliable. Therefore, we have added this expression of concern while the situation is being reviewed , 
 Retraction in Retraction: Isoniazid and Rifapentine Treatment Eradicates Persistent Mycobacterium tuberculosis in Macaques. [No authors listed] Am J Respir Crit Care Med. 2021 Apr 15;203(8):1045. doi: 10.1164 rccm.v203retraction1. , 
 https: ori.hhs.gov content case-summary-kaushal-deepak , 
 See https: retractionwatch.com 2022 08 03 leading-primate-researcher-admits-to-faking-data-in-nih-grant-applications-paper for some backgrounds about this retraction. ,
Liposomal valinomycin mediated cellular K+ leak promoting apoptosis of liver cancer cells
Authors: Qian-Wen Zhang
Xiang Qin
Xing-Hua Xia
Ting-Ting Zhai
Mirza Muhammad Faran Ashraf Baig
Tian-Qi Zhang
Journal: Journal of Controlled Release (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Apoptosis; Cancer therapy; Ionophore; Potassium ion efflux; Valinomycin, liposomes.
Affiliations: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China., State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China. Electronic address: .

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the corresponding author. It has been found that Fig 2B contains manipulated components, and Fig 5A partially overlaps with Fig 6 of a published paper authored by Mirza Muhammad Faran Ashraf Baig, et, al., The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors, J. Pharm. Anal. 11 (2021) 174-182, https://doi.org/10.1016/j.jpha.2020.10.003. The corresponding author indicated that they cannot guarantee the integrity of the images in the manuscript, as well as the conclusions of the paper. As a result, the Editor-in-Chief has decided to retract the paper. The corresponding author deeply regrets the circumstances and apologizes to the scientific community for not having detected this prior to publication. 

Retracted: Yes

PubPeer comments:
 Figure 2A. https: imgur.com DmaVNld , 
 Figure 3B. Much more similar than expected. https: imgur.com y69Dezl ,
Dihydroartemisinin Induces Growth Arrest and Overcomes Dexamethasone Resistance in Multiple Myeloma
Authors: Meral Beksac
Jinjun Qian
Ying Chen
Artur Jurczyszyn
Dongqing Yang
Rui Li
Yuqi Zhu
Ye Yang
Sixia Zhong
Chunyan Gu
Journal: Frontiers in Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: artemisinin; dexamethasone; dihydroartemisinin; drug resistance; multiple myeloma.
Affiliations: The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China., School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China., Department of Internal Medicine, University of Iowa, Iowa City, IA, United States., Department of Hematology, Collegium Medicum, Jagiellonian University, Kraków, Poland., Department of Hematology, School of Medicine, Ankara University, Ankara, Turkey., Key Laboratory for Combination of Acupuncture and Chinese Materia Medica of Chinese Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.

Abstract:  The discovery of artemisinin (ART) for malaria treatment won the 2015 Nobel Prize in Medicine, which inspired the rediscovery and development of ART for the treatment of other diseases including cancer. In this study, we investigated the potential therapeutic effect of ART and dihydroartemisinin (DHA) on multiple myeloma (MM) cells including primary MM cells and in 5TMM3VT mouse model. Both in vitro and in vivo experiments showed that DHA might be a more promising anti-MM agent with significantly improved efficacy compared to ART. Mechanistic analyses suggested that DHA activated the mitochondrial apoptotic pathway by interacting with ferrous (Fe2+) ions and oxygen to produce reactive oxygen species (ROS). Intriguingly, DHA could reverse the upregulated expression of B-cell lymphoma 2 (Bcl-2) protein, a typical mitochondrial apoptotic marker, induced by dexamethasone (Dexa) in MM. We further demonstrated that DHA treatment could overcome Dexa resistance and enhance Dexa efficacy in MM. Additionally, DHA combined with Dexa resulted in increased ROS production and cytochrome C translocation from the mitochondria to the cytoplasm, resulting in alterations to the mitochondrial membrane potential and caspase-mediated apoptosis. In summary, our study demonstrated that DHA was superior to ART in MM treatment and overcame Dexa resistance both in vitro and in vivo, providing a promising therapeutic strategy for MM therapy. 

Retracted: No

PubPeer comments:
 Fig 3C, the 2 loading controls bare striking resemblence, although they look somehow different in vertical dimension. the image quality was also quite poor. Can the authors post high resolution un-cropped original images to help clarify? Thanks. ![file] ,
Inhibition of PLK4 might enhance the anti-tumour effect of bortezomib on glioblastoma via PTEN/PI3K/AKT/mTOR signalling pathway
Authors: Yan Sun
Jiuhong Ma
Chao Xu
Hongming Ji
Yue Tu
Lina Wang
Jing Wang
Rui Cheng
Guijun Jia
Chunhong Wang
Jinrui Ren
Dengpeng Ren
Journal: Journal of cellular and molecular medicine (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PLK4; PTEN/PI3K/AKT/mTOR signalling pathway; bortezomib; glioblastoma.
Affiliations: Department of neurosurgeryShanxi academy of medical scienceShanxi Bethune Hospital Taiyuan China, Department of neurosurgery Central Hospital of Yuncheng city Yuncheng China, Neurological intensive care unitSpecial medical center of PAP Tianjin China, Department of neurosurgery Shanxi people's hospital Taiyuan China

Abstract:  Glioblastoma (GBM) is one of the most common aggressive cancers of the central nervous system in adults with a high mortality rate. Bortezomib is a boronic acid-based potent proteasome inhibitor that has been actively studied for its anti-tumour effects through inhibition of the proteasome. The proteasome is a key component of the ubiquitin-proteasome pathway that is critical for protein homeostasis, regulation of cellular growth, and apoptosis. Overexpression of polo-like kinase 4 (PLK4) is commonly reported in tumour cells and increases their invasive and metastatic abilities. In this study, we established a cell model of PLK4 knockdown and overexpression in LN-18, A172 and LN-229 cells and found that knockdown of PLK4 expression enhanced the anti-tumour effect of bortezomib. We further found that this effect may be mediated by the PTEN/PI3K/AKT/mTOR signalling pathway and that the apoptotic and oxidative stress processes were activated, while the expression of matrix metalloproteinases (MMPs) was down-regulated. Similar phenomenon was observed using in vitro experiments. Thus, we speculate that PLK4 inhibition may be a new therapeutic strategy for GBM. 

Retracted: No

PubPeer comments:
 Dublicated FACS blots in Fig 3: ![file] Apart from that, how could Western blots be quantified? Blots are heavily overloaded and exposure is far from beeing linear, e.g. Fig 5: ![file] ,
Curcumin and linseed oil co-delivered in phospholipid nanoemulsions enhances the levels of docosahexaenoic acid in serum and tissue lipids of rats
Authors: B R Lokesh
D Sugasini
Journal: Prostaglandins Leukotrienes and Essential Fatty Acids (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bioavailability; Curcumin; Docosahexaenoic Acid; Linseed oil; Nanoemulsion
Affiliations: Department of Lipid Science and Traditional Foods, CSIR-Central Food Technological Research Institute, Mysore 570020, India. Electronic address: .

Abstract:  Docosahexaenoic acid (DHA) is an important long chain omega-3 polyunsaturated fatty acid (PUFA) primarily found in marine fishes. The diets of vegetarian population do not contain preformed DHA, but they can derive it from shorter chain α-linolenic acid (ALA) found in plant oils. However, the conversion efficiency of ALA to DHA is minimal in human adults. This may cause insufficiency of DHA in the vegetarian population. Curcumin, diferuloyl methane found in the spice turmeric, has the potential to increase the formation of DHA from ALA by activating the enzymes FADS2 and elongase 2. The present study was designed to prepare curcumin nanoemulsion using phospholipid core material (Lipoid™) and exploring the possibility of enhancing its bioavailability and its impact on DHA levels in rats. Curcumin was dissolved in coconut oil (CNO, MCFA rich), Sunflower oil (SNO, n-6 PUFA rich) or Linseed oil (LSO, n-3 PUFA rich) and nanoemulsions were prepared after mixing with Lipoid™ using high pressure homogenizer. The nanoemulsions were fed to weaning rats for 60 days along with AIN-93 diets. Rats fed nanoemulsion containing curcumin in LSO showed high levels of curcumin in serum liver, heart and brain. Significant increase in DHA levels of serum and tissue lipids were observed in rats given LSO with curcumin in nanoemulsions. Therefore, supplementation of diets with ALA rich LSO and curcumin could increase DHA concentrations in serum, liver, heart and brain lipids which have implications for meeting the DHA requirements of vegetarian populations. 

Retracted: No

PubPeer comments:
 Figure 1 purports to show curcumin suspended in three different oils, but the images appear to show overlapping fields of view at different magnification. Could the authors please comment? *** ![file] ,
MicroRNA-675-3p regulates IL-1β-stimulated human chondrocyte apoptosis and cartilage degradation by targeting GNG5
Authors: Min-Qian Zheng
Qi-Rong Dong
Xiao-Fei Shen
Yi Cheng
Journal: Biochemical and Biophysical Research Communications (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: GNC5; Long noncoding RNA XIST; Osteoarthritis; miR-675-3p.
Affiliations: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, PR China., Department of Orthopedics, Yan Cheng City No.1 People's Hospital, Yan Cheng, 224005, PR China., Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, PR China. Electronic address: .

Abstract:  Growing evidence has indicated that microRNAs (miRNAs) are modulators of osteoarthritis (OA) development and progression. In this study, we first evaluated the anti-apoptosis and chondroprotective effects of microRNA-675-3p (miR-675-3p) on interleukin-1β (IL-1β)-stimulated human chondrocytes. The overexpression of miR-675-3p inhibited apoptosis and cartilage matrix degradation and promoted cell proliferation in human chondrocytes. Target gene prediction and luciferase reporter assays suggested that G-protein subunit γ 5 (GNG5) may be the target gene of miR-675-3p. The overexpression of miR-675-3p inhibited IL-1β-stimulated chondrocyte apoptosis, and this effect was reversed by the overexpression of GNG5. Finally, we used bioinformatic tools and biological methods to show that the long noncoding RNA X-inactive specific transcript (lncRNA XIST) could bind to miR-675-3p, which affects the expression of GNG5 mRNA. Our findings may substantiate miR-675-3p as a new treatment for OA. 

Retracted: No

PubPeer comments:
 **In figure 1A and 1B, MicroRNA-675-3p was incorrectly marked as miR-874-3p and miR-146. ** ![file] **In figure 2 A, they used qRT-PCR to detect changes in cleaved cas-3 mRNA levels. This is ridiculousuff01uff01uff01** ![file] ,
Herpes simplex virus thymidine kinase/ganciclovir–induced cell death is enhanced by co-expression of caspase-3 in ovarian carcinoma cells
Authors: I A McNeish
N Lemoine
T Tenev
M Marani
S Bell
G Vassaux
Journal: Cancer Gene Therapy (2001)
Discipline: CLINICAL MEDICINE
Keywords: genetic prodrug activation therapy; herpes simplex virus thymidine kinase; ganciclovir; caspase-3; apoptosis
Affiliations: ICRF Molecular Oncology Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK. 

Abstract:  There is a need to enhance the efficacy of genetic prodrug activation therapy using herpes simplex virus thymidine kinase (tk) and ganciclovir (GCV) following disappointing results in early clinical trials. tk/GCV has been shown to lead to the activation of caspase-3, a potent executor of apoptosis. We demonstrate that co-expression of pro-caspase-3 with tk/GCV leads to enhanced cell death in ovarian carcinoma cells in vitro. Following transfection with recombinant adenoviral vectors encoding tk, GCV treatment leads to greater cell death in pro-caspase-3-expressing clones of SKOV3 and IGROV1 than control cells, as well as more rapid activation of caspase-3 and more rapid cleavage of PARP. Flow cytometry suggests that there is a greater degree of S-phase block in the pro-caspase-3-expressing clones than in control cells following treatment with tk/GCV. None of these effects is seen following transfection with a control adenovirus that does not encode tk. The increased cell death, early caspase-3 activation and PARP cleavage, and flow cytometric changes seen in pro-caspase-3-expressing cells can be partially inhibited by treatment with benzyloxycarbonyl-val-ala-asp fluoromethylketone, a synthetic caspase inhibitor. Our data suggest that co-expression of pro-caspase-3 may lead to a significant enhancement of the efficacy of tk/GCV therapy. 

Retracted: No

PubPeer comments:
 This article provides a dual-process theory of suicide. The problem with this is that there are no reliable empirical facts about implicit processes that may influence suicide attempts. Instead, the article relies on questionable results from studies that relied on selective reporting of significant results with inflated effect size estimates. They cite an article that shows very little incremental predictive validity, r .1. Moreover, implicit measures have low construct validity and depression and suicide Implicit Association Tests have not been properly validated. https: replicationindex.com 2021 04 11 implicit-suicide ,
One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering
Authors: Hui Yang
Haoyi Wang
Chikdu S Shivalila
Rudolf Jaenisch
Linyu Shi
Albert W Cheng
Journal: Cell (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CRISPR/Cas system; genome-engineering technology; gene targeting; reporter mice; conditional mutant mice
Affiliations: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Abstract:  The type II bacterial CRISPR/Cas system is a novel genome-engineering technology with the ease of multiplexed gene targeting. Here, we created reporter and conditional mutant mice by coinjection of zygotes with Cas9 mRNA and different guide RNAs (sgRNAs) as well as DNA vectors of different sizes. Using this one-step procedure we generated mice carrying a tag or a fluorescent reporter construct in the Nanog, the Sox2, and the Oct4 gene as well as Mecp2 conditional mutant mice. In addition, using sgRNAs targeting two separate sites in the Mecp2 gene, we produced mice harboring the predicted deletions of about 700 bps. Finally, we analyzed potential off-targets of five sgRNAs in gene-modified mice and ESC lines and identified off-target mutations in only rare instances. 

Retracted: No

PubPeer comments:
 Retracted [March 2017](http: www.kjpp.net journal view.html?volume=21 number=2 spage=277). Subsequently, retracting [Zhao et al (2014)] , the editors of PLoS documented further overlaps. --------------------------------- It was brought to the Editors-in-Chiefu2019s attention that there were significant similarities between this paper and previously published articles. Upon further investigation by Editorial team of *Korean J Physiol Pharmacol*, this paper might be liable for defamatory publication as substantial overlapped data were found with previously published articles [1,2]. Bo Liu, the corresponding author, has admitted that the authors asked an agency for writing and submitting the article to *Korean J Physiol Pharmacol*. Bo Liu has admitted this scientific misbehavior and apologized to the Editors and readership of *Korean J Physiol Pharmacol*. However, Min Hu, another corresponding author has not yet given any clarification. In accordance with this Journalu2019s policy, the entire article has been retracted at the request of the Editors. We apologize to all affected parties for the inconveniences caused. REFERENCES 1. Zhao Z, Hu J, Gao X, Liang H, Liu Z. Activation of AMPK attenuates lipopolysaccharide-impaired integrity and function of blood-brain barrier in human brain microvascular endothelial cells. Exp Mol Pathol. 2014;97(3):386-392. doi: 10.1016 j.yexmp.2014.09.006. 2. Yu HY, Cai YB, Liu Z. Activation of AMPK improves lipopolysaccharide-induced dysfunction of the blood-brain barrier in mice. Brain Inj. 2015;29(6):777-784. doi: 10.3109 02699052.2015.1004746. ,
BRIP1 overexpression is correlated with clinical features and survival outcome of luminal breast cancer subtypes
Authors: Allal Ouhtit
Marwa Al-Riyami
Hamad Al-Riyami
Syed Gauhar A Rizvi
Adil Al-Ajmi
Ishita Gupta
Yahya Tamimi
Journal: Endocrine Connections (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: BRIP1; biomarkers; breast cancer; oncogene; overexpression.
Affiliations: Department of GeneticsCollege of Medicine and Health Sciences, Sultan Qaboos University, Alkoudh, Sultanate of Oman., Department of Biological and Environmental SciencesCollege of Arts and Sciences, Qatar University, Doha, Qatar., Department of SurgeryCollege of Medicine and Health Sciences, Sultan Qaboos University, Alkoudh, Sultanate of Oman., Department of Family Medicine and Public HealthCollege of Medicine and Health Sciences, Sultan Qaboos University, Alkoudh, Sultanate of Oman., Department of PathologyCollege of Medicine and Health Sciences, Sultan Qaboos University, Alkoudh, Sultanate of Oman., Department of BiochemistryCollege of Medicine and Health Sciences, Sultan Qaboos University, Alkoudh, Sultanate of Oman .

Abstract:  In Oman, breast cancer is most common, representing approximately more than 25% of all cancers in women. Relatively younger populations of patients (25-40 years) present surprisingly with an aggressive phenotype and advanced tumor stages. In this study, we investigated differential gene expressions in Luminal A, Luminal B, triple-negative and Her2+ breast cancer subtypes and compared data to benign tumor samples. We identified a potential candidate gene BRIP1, showing differential expression in the four breast cancer subtypes examined, suggesting that BRIP1 has the profile of a useful diagnostic marker, suitable for targeted therapeutic intervention. RT-qPCR and Western blotting analysis showed higher BRIP1 expression in luminal samples as compared to triple-negative subtype patient's samples. We further screened BRIP1 for eventual mutations/SNPs/deletions by sequencing the entire coding region. Four previously identified polymorphisms were detected, one within the 5'-UTR region (c.141-64G &gt; A) and three in the BRCA-binding domain (c.2755T &gt; C, c.2647G &gt; A and c.3411T &gt; C). Kaplan-Meier analysis revealed that patients with overexpression of BRIP1 displayed a poor survival rate (P &lt; 0.05). BRIP1 has a dual function of an oncogene and a tumor suppressor gene in addition to its role as a potential biomarker to predict survival and prognosis. Data obtained in this study suggest that BRIP1 can plausibly have an oncogenic role in sporadic cancers. 

Retracted: No

PubPeer comments:
 Figure 5A shows protein expression in different types of breast cancers. * Boxes of the same color highlight b-actin bands that look more similar than expected. Some bands appear to be visible multiple times within the same photo (bands marked with red or blue boxes), while other bands are shown in a different order, depending on the breast cancer type they represent. ![file] ,
Long Noncoding RNA DRAIC Inhibits Prostate Cancer Progression by Interacting with IKK to Inhibit NF-κB Activation
Authors: David Wotton
Shekhar Saha
Canan Kuscu
Manjari Kiran
Anindya Dutta
Ajay Chatrath
Marty W Mayo
Journal: Cancer Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: DRAIC; long noncoding RNA; prostate cancer; NF-κB; IKK complex
Affiliations: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia., Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia. .

Abstract:  DRAIC is a 1.7 kb spliced long noncoding RNA downregulated in castration-resistant advanced prostate cancer. Decreased DRAIC expression predicts poor patient outcome in prostate and seven other cancers, while increased DRAIC represses growth of xenografted tumors. Here, we show that cancers with decreased DRAIC expression have increased NF-κB target gene expression. DRAIC downregulation increased cell invasion and soft agar colony formation; this was dependent on NF-κB activation. DRAIC interacted with subunits of the IκB kinase (IKK) complex to inhibit their interaction with each other, the phosphorylation of IκBα, and the activation of NF-κB. These functions of DRAIC mapped to the same fragment containing bases 701-905. Thus, DRAIC lncRNA inhibits prostate cancer progression through suppression of NF-κB activation by interfering with IKK activity. SIGNIFICANCE: A cytoplasmic tumor-suppressive lncRNA interacts with and inhibits a major kinase that activates an oncogenic transcription factor in prostate cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/5/950/F1.large.jpg. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. The Western blots in Figure 6C appear to be of low resolution, with compression artifacts, showing very black, saturated bands, and almost no background in most panels. Do the authors have any higher resolution versions of these blot panels, please? ![file] , 
 Another concern about Figure 5. * Red boxes: The WT panel in Figure 5N appears to overlap with the WT+Bav11 panel in Figure 5R. * Blue boxes: The WT panel in Figure 5R appears to look similar to the KO1+Bav11 panel in Figure 5R. Are these sets of panels showing the same experiments? ![file] , 
 Authors response: Thank you for pointing out the error in Fig. 5N,5R. When assembling the composites, wrong panels were used. Below is the correct assembly. The quantitation of colonies remains unchanged. Regarding Fig. 6C, below is another blot of the same experiment. This too is at low resolution, but the result seems very clear and remains unchanged.![file] , 
 #3 Thank you for your reply. The new u201cduplicateu201d 6C appears intended to be a replacement image representing a different experiment. Iu2019d like to inquire as to why a high resolution scan of the first version of 6C isnu2019t available. This paper appears to be only a few months old. *** ![file] ,
A human chondrogenic cell line retains multi-potency that differentiates into osteoblasts and adipocytes
Authors: Yasumasa Yoshizawa
Masao Nagumo
Yohei Uyama
Akira Yamaguchi
Kimitoshi Yagami
Saburo Kakuta
Journal: Bone (2004)
Discipline: CLINICAL MEDICINE
Keywords: Retraction; Author; RT-PCR experiments; Figure preparation; Duplicated bands
Affiliations: Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan. 

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the author, Dr. Kimihito Yagami. Dr. Yagami's collaborators Yohei Uyama, Yasumasa Yoshizawa, Saburo Kakuta, Akira Yamaguchi, Masao Nagumo were not involved in the RT-PCR experiments and figure preparation The editor, Sundeep Khosla, was notified by an independent group that specific bands in Figure 3 of the paper appear to be duplicated. This was brought to the attention of the authors. Due to the long interval from the original publication of the paper, the raw data was not available; however, the authors subsequently chose to retract the entire manuscript, and the editor agreed. 

Retracted: Yes

PubPeer comments:
 Figure 3, some bands look more similar than expected (boxes of same color). GAPDH controls look also strange. Although this article is 18-year-old, could the authors please comment and post the original scan of the gels at high resolution? ![file] , 
 RETRACTED, on April 2022: https: www.sciencedirect.com science article pii S8756328203004575?via%3Dihub This article has been retracted: please see Elsevier Policy on Article Withdrawal . This article has been retracted at the request of the author, Dr. Kimihito Yagami. Dr. Yagami s collaborators Yohei Uyama, Yasumasa Yoshizawa, Saburo Kakuta, Akira Yamaguchi, Masao Nagumo were not involved in the RT-PCR experiments and figure preparation. The editor, Sundeep Khosla, was notified by an independent group that specific bands in Figure 3 of the paper appear to be duplicated. This was brought to the attention of the authors. Due to the long interval from the original publication of the paper, the raw data was not available; however, the authors subsequently chose to retract the entire manuscript, and the editor agreed. ,
Sarm1 induction and accompanying inflammatory response mediates age-dependent susceptibility to rotenone-induced neurotoxicity
Authors: Piyali Mukherjee
Sudipta Bar
Dipanjana Banerjee
Ankita Sarkar
Malinki Sur
Swati Bhat
Puja Dey
Journal: Cell Death Discovery (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Aging; Environmental risk factors; Pesticide exposure; Neurodegenerative diseases; Parkinson's disease
Affiliations: 1Department of Life Sciences, Presidency University, 86/1, College Street, Kolkata, 700073 West Bengal India., 2Department of Biological Sciences, IISER Kolkata, Mohanpur, 741246 West Bengal India.

Abstract:  Aging is a complex biological process and environmental risk factors like pesticide exposure have been implicated in the increased incidence of age-related neurodegenerative diseases like Parkinson's disease (PD) but the etiology remains unknown. There is also lack of a proper animal model system to study the progressive effect of these environmental toxins on age-associated neurodegeneration. In this study, we established a drosophila model of aging to study the age-dependent vulnerability to the environmental toxin rotenone that has been implicated in sporadic cases of PD. We demonstrate that age plays a determining role in the increased susceptibility to chronic rotenone exposure that is accompanied by severe locomotor deficits, decreased lifespan and loss of dopaminergic (DA) neurons. Chronic low dose exposure to rotenone results in the rapid induction of the neurodegenerative molecule SARM1/dSarm. Further, the age-dependent dSarm induction is accompanied by a heightened inflammatory response (increased expression of Eiger and Relish) that is independent of reactive oxygen species (ROS) generation in the observed rotenone-induced neurotoxicity. dSarm induction and subsequent locomotor deficits is reversed in the presence of the anti-inflammatory molecule resveratrol. Thus, dSarm and heightened inflammatory responses may play a crucial role in age-dependent vulnerability to the pesticide rotenone thus making it an attractive target to help develop cost-effective therapeutic strategies to prevent ongoing dopaminergic neuronal loss as seen in PD. 

Retracted: No

PubPeer comments:
 Figure 2D seems to compare TH and Elav staining among control and rotenone-treated flies. The ideal way to do this experiment would be to costain for TH and Elav in the same brain in each set and take a multichannel confocal image. However, the brains in all the four images seem to be different. Moreover, the details of the Elav antibody are not mentioned in the paper. Could the authors please provide details of the how the experiment was done and provide the details of the Elav antibody? ,
Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities
Authors: Astar Winoto
Wei-Jen Tang
Stephanie L Osborn
Martin Samuels
Christine Feig
Andrea E Murmann
Vincent J Kidd
Marcus E Peter
Andrew Thorburn
Jörg Volkland
Elizabeth C Alappat
Benjamin Boyerinas
Clive A Slaughter
Journal: Molecular cell (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FADD; apoptosis; cell cycle progression; proliferation; phosphorylation
Affiliations: The Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois 60637, USA.

Abstract:  FADD is essential for death receptor (DR)-induced apoptosis. However, it is also critical for cell cycle progression and proliferation, activities that are regulated by phosphorylation of its C-terminal Ser194, which has also been implicated in sensitizing cancer cells to chemotherapeutic drugs and in regulating FADD's intracellular localization. We now demonstrate that casein kinase Ialpha (CKIalpha) phosphorylates FADD at Ser194 both in vitro and in vivo. FADD-CKIalpha association regulates the subcellular localization of FADD, and phosphorylated FADD was found to colocalize with CKIalpha on the spindle poles in metaphase. Inhibition of CKIalpha diminished FADD phosphorylation, prevented the ability of Taxol to arrest cells in mitosis, and blocked mitogen-induced proliferation of mouse splenocytes. In contrast, a low level of cycling splenocytes from mice expressing FADD with a mutated phosphorylation site was insensitive to CKI inhibition. These data suggest that phosphorylation of FADD by CKI is a crucial event during mitosis. 

Retracted: No

PubPeer comments:
 **Figure 1A and 1E purporting to show two different treatment conditions are the same image. Figure 1E has been squashed slightly. Could the authors please comment?** ![file] ,
[6]-Gingerol-induced cell cycle arrest, reactive oxygen species generation, and disruption of mitochondrial membrane potential are associated with apoptosis in human gastric cancer (AGS) cells
Authors: Veeresh Kumar Sali
Debjani P Mansingh
Sunanda O J
Hannah R Vasanthi
Journal: Journal of Biochemical and Molecular Toxicology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: [6]-gingerol; apoptosis; gastric cancer; mitochondrial membrane potential (MMP); reactive oxygen species (ROS).
Affiliations: Natural Products Research Laboratory, Department of Biotechnology; Pondicherry University; Puducherry India

Abstract:  Ginger (Zingiber officinale Roscoe), a monocotyledonous herb, is widely used as an herbal medicine owing to the phytoconstituents it possesses. In the current study, the quantity of [6]-gingerol, the major phenolic ketone, in the fresh ginger and dried ginger rhizome was found to be 6.11 µg/mg and 0.407 µg/mg. Furthermore, [6]-gingerol was assessed for its antiapoptotic effects in human gastric adenocarcinoma (AGS) cells evidenced by acridine orange/ethidium bromide staining technique and Annexin-V assay. An increase in reactive oxygen species (ROS) generation led to a decrease in mitochondrial membrane potential (MMP) and subsequent induction of apoptosis. Results disclose that perturbations in MMP are associated with deregulation of Bax/Bcl-2 ratio at protein level, which leads to upregulation of cytochrome-c triggering the caspase cascade. These enduringly suggest that [6]-gingerol can be effectively used for targeting the mitochondrial energy metabolism to manage gastric cancer cells. 

Retracted: No

PubPeer comments:
 April 2021 Expression of Concern found here: https: onlinelibrary.wiley.com doi 10.1002 jbt.22793 It reads:  This Expression of Concern is for the above article, published online on 8 August 2018 in Wiley Online Library (wileyonlinelibrary.com), and has been published by agreement between the journal Editoru2010inu2010Chief Hari Bhat and Wiley Periodicals, LLC. The expression of concern has been agreed upon due to concerns regarding the data presented in the study and the authors inability to furnish all sets of raw data and images upon request. ,