PReD-Bench/PRed-Bench huggingface dataset:
Forced into an ecological corner: Round-the-clock deep foraging on small prey by elephant seals
Authors: Roxanne S Beltran
Patrick W Robinson
Luis A Hückstädt
Akinori Takahashi
Sarah H Peterson
Daniel P Costa
Theresa R Keates
Yasuhiko Naito
Rachel R Holser
Taiki Adachi
Journal: Science Advances (2021)
Discipline: Multidisciplinary
Keywords: mesopelagic fishes; ecological importance; prey; large marine animals; ecosystem dynamics
Affiliations: National Institute of Polar Research, Tachikawa, Tokyo, Japan., Department of Ecology and Evolutionary Biology, University of California Santa Cruz, Santa Cruz, CA, USA., Institute of Marine Sciences, University of California Santa Cruz, Santa Cruz, CA, USA., Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, NC, USA., Department of Ocean Sciences, University of California Santa Cruz, Santa Cruz, CA, USA.

Abstract:  Small mesopelagic fishes dominate the world's total fish biomass, yet their ecological importance as prey for large marine animals is poorly understood. To reveal the little-known ecosystem dynamics, we identified prey, measured feeding events, and quantified the daily energy balance of 48 deep-diving elephant seals throughout their oceanic migrations by leveraging innovative technologies: animal-borne smart accelerometers and video cameras. Seals only attained positive energy balance after feeding 1000 to 2000 times per day on small fishes, which required continuous deep diving (80 to 100% of each day). Interspecies allometry suggests that female elephant seals have exceptional diving abilities relative to their body size, enabling them to exploit a unique foraging niche on small but abundant mesopelagic fish. This unique foraging niche requires extreme round-the-clock deep diving, limiting the behavioral plasticity of elephant seals to a changing mesopelagic ecosystem. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than you would expect. https: imgur.com Jm9I80Y ,
Histone acetylation-mediated regulation of the Hippo pathway
Authors: Abdelhadi Rebbaa
Dipanjan Basu
Miguel Reyes-Múgica
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Hippo pathway; tumorigenesis; cancer treatment; nuclear regulation; chromatin-modifying agents
Affiliations: Department of Pathology, University of Pittsburgh and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America.

Abstract:  The Hippo pathway is a signaling cascade recently found to play a key role in tumorigenesis therefore understanding the mechanisms that regulate it should open new opportunities for cancer treatment. Available data indicate that this pathway is controlled by signals from cell-cell junctions however the potential role of nuclear regulation has not yet been described. Here we set out to verify this possibility and define putative mechanism(s) by which it might occur. By using a luciferase reporter of the Hippo pathway, we measured the effects of different nuclear targeting drugs and found that chromatin-modifying agents, and to a lesser extent certain DNA damaging drugs, strongly induced activity of the reporter. This effect was not mediated by upstream core components (i.e. Mst, Lats) of the Hippo pathway, but through enhanced levels of the Hippo transducer TAZ. Investigation of the underlying mechanism led to the finding that cancer cell exposure to histone deacetylase inhibitors induced secretion of growth factors and cytokines, which in turn activate Akt and inhibit the GSK3 beta associated protein degradation complex in drug-affected as well as in their neighboring cells. Consequently, expression of EMT genes, cell migration and resistance to therapy were induced. These processes were suppressed by using pyrvinium, a recently described small molecule activator of the GSK 3 beta associated degradation complex. Overall, these findings shed light on a previously unrecognized phenomenon by which certain anti-cancer agents may paradoxically promote tumor progression by facilitating stabilization of the Hippo transducer TAZ and inducing cancer cell migration and resistance to therapy. Pharmacological targeting of the GSK3 beta associated degradation complex may thus represent a unique approach to treat cancer. 

Retracted: No

PubPeer comments:
 Figure 6B. * Red boxes: In the Day 1 row, the Ctl-CM and Bel-CM+PYR panels appear to look identical. ![file] ,
ORF73 of herpesvirus saimiri, a viral homolog of Kaposi's sarcoma-associated herpesvirus, modulates the two cellular tumor suppressor proteins p53 and pRb
Authors: Erle S Robertson
Subhash C Verma
Sumit Borah
Journal: Journal of Virology (2004)
Discipline: MICROBIOLOGY
Keywords: DNA tumor viruses; cell cycle regulation; pRb; p53; Kaposi's sarcoma associated herpesvirus (KSHV)
Affiliations: Department of Microbiology and Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Abstract:  All known DNA tumor viruses are known to target and inactivate two main cell cycle regulatory proteins, retinoblastoma protein (pRb) and p53. Inactivation of pRb promotes host cell cycle progression into S phase, and inactivation of p53 promotes cell immortalization. The DNA tumor virus Kaposi's sarcoma associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) was shown to target and inactivate pRb as well as p53. In this report we provide evidence that these functions are conserved in the homologous protein encoded by the related gammaherpesvirus herpesvirus saimiri (HVS). ORF73, the HVS homologue of LANA, is shown to bind both p53 and pRb in vitro and in vivo, to colocalize with p53 in human T cells infected with HVS, and in cells overexpressing both ORF73 and p53, as well as to adversely influence pRB/E2F and p53 transcriptional regulation. The C terminus of LANA, the region most highly conserved in ORF73, is shown to be responsible for both pRb and p53 interactions, supporting the hypothesis that these functions are conserved in both homologues. Finally, the region of p53 targeted by LANA (and ORF73) maps to the domain required for tetramerization. However, preliminary cross-linking studies do not detect disruption of p53 tetramerization by either LANA or HVS-encoded ORF73, suggesting that p53 inactivation may be by a mechanism independent of tetramer disruption. 

Retracted: No

PubPeer comments:
 Figures 5C and 5D. Much more similar than expected. https: imgur.com axdVna9 , 
 Here s that image. ![file] ,
Calcium phosphate: a substitute for aluminum adjuvants?
Authors: Jean-Daniel Masson
Michel Thibaudon
Guillemette Crépeaux
Laurent Bélec
Journal: Expert Review of Vaccines (2017)
Discipline: IMMUNOLOGY
Keywords: Vaccine; adjuvant; aluminum salts; calcium phosphate; immune response
Affiliations: Association E3M (Entraide aux Malades de Myofasciite à Macrophages), Monprimblanc, France, Pharmacien « Service des Allergènes », de l’Institut Pasteur, Paris, France, Laboratoire de Microbiologie, hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, &amp; Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France, École nationale vétérinaire d’Alfort, Maisons-Alfort, France, Inserm U955 E10, Université Paris Est Créteil, Créteil, France

Abstract:  Calcium phosphate was used as an adjuvant in France in diphtheria, tetanus, pertussis and poliomyelitis vaccines. It was later completely substituted by alum salts in the late 80's, but it still remains as an approved adjuvant for the World Health Organization for human vaccination. Area covered: Thus, calcium phosphate is now considered as one of the substances that could replace alum salts in vaccines. The aim of this paper is to draw a review of existing data on calcium phosphate as an adjuvant in order to bring out the strengths and weaknesses for its use on a large scale. Expert commentary: Calcium phosphate is a compound naturally present in the organism, safe and already used in human vaccination. Beyond comparisons with the other adjuvants, calcium phosphate represents a good candidate to replace or to complete alum salts as a vaccine adjuvant. 

Retracted: No

PubPeer comments:
 The authors claimed that aluminium is responsible for autoimmune or neurological diseases. It is clear that vaccination against hepatitis B is not associated with multiple sclerosis (see De Stefano et al. Expert Rev Vaccines 2012;1:461-466). I am surprised that the authors did not quote this reference that contradicts their message. This is also the case for vaccine against human papillomavirus (Mailand et al. J Neurol 2017;264:1035-1050). May I suggest that readers will look at the paper published by Gasparini et al.: ![file] Their conclusion is clearcut ![file] ,
The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity
Authors: Hiroshi Funakoshi
Kouichi Tanonaka
Satoshi Takeo
Reiko Mizutani
Keiko Takagi
Kunio Matsumoto
Makiko Niimura
Norio Takagi
Toshikazu Nakamura
Journal: Neuroscience letters (2006)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: oxidative DNA damage; neuronal apoptotic cell death; cerebral ischemia; HGF; APE/Ref-1
Affiliations: Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Abstract:  Early oxidative DNA damage is regarded to be an initiator of neuronal apoptotic cell death after cerebral ischemia. Although evidence suggests that HGF has the ability to protect cells from oxidative stress, it remains unclear as to how HGF suppresses oxidative DNA damage after cerebral ischemia. Apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) is a multifunctional protein in the DNA base repair pathway that is responsible for repairing apurinic/apyrimidinic sites in DNA after oxidation. We demonstrated that both the immunoreactivity and the number of APE/Ref-1-positive cells in the hippocampal CA1 region were decreased after transient forebrain ischemia and that treatment with HGF suppressed this reduction. The expression of Cu/ZnSOD and MnSOD in the hippocampal CA1 region did not change after ischemia, regardless of treatment with or not with HGF. The activity of NADPH oxidase was increased mainly in glia-like cells in the hippocampal CA1 region after ischemia, and this increase was attenuated by HGF treatment. These results suggest that the protective effects of HGF against cerebral ischemia-induced cell death in the hippocampal CA1 region are related to the improvement of neuronal APE/Ref-1 expression and the inhibition of NADPH oxidase activity in glia-like cells. 

Retracted: No

PubPeer comments:
 In Figure 2 D and E, the GAPDH western blot has been duplicated and presented as something else (different experimental setup). ![file] ,
Effect of hypoxia on the Twist1 in EMT of cervical cancer cells
Authors: X He
J-X Liang
H-Y Jin
N Li
X-H Wang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Hypoxia; Twist1 expression; epithelial-mesenchymal transition; cervical cancer cells; HeLa cells
Affiliations: Department of Invasive Technology, Huaihe Hospital of Henan University, Kaifeng, Henan, China. .

Abstract:  Objective: To explore the effect of hypoxia on the Twist1 expression in epithelial-mesenchymal transition of the cervical cancer cells. Materials and methods: In this study, we simulated the normoxia and hypoxia environment, where HeLa cells were cultured, respectively. Cell invasion ability was measured by the transwell assay, while the GLI-1 protein and mRNA expressions were measured by Real-time polymerase chain reaction (RT-PCR) and Western blot assays. After that, HeLa cells were transfected with the GLI-1-specific siRNA, followed by the measurement of mRNA and protein expressions using RT-PCR and Western blot assays, as well as the cell invasion ability by the transwell assay. Results: We found that in hypoxic environment, GLI-1 was up-regulated in HeLa cells, with enhanced invasion ability. However, silencing the expression of GLI-1 could reverse the up-regulation of GLI-1 compromising the invasion ability of HeLa cells. Conclusions: Hypoxia may account for the increased invasion of HeLa cells, which is realized by the up-regulated GLI-1. 

Retracted: No

PubPeer comments:
 Figure 4A. * Red boxes: Two panels appear to show an overlap. ![file] ,
5, 7-Dimethoxyflavone sensitizes TRAIL-induced apoptosis through DR5 upregulation in hepatocellular carcinoma cells
Authors: Jian-Guo Cao
Li Tian
Jian-Feng Yang
Fei Liu
Journal: Cancer Chemotherapy and Pharmacology (2012)
Discipline: CLINICAL MEDICINE
Keywords: 5, 7-dimethoxyflavone; apoptosis; hepatocellular carcinoma; TRAIL; sensitization
Affiliations: Medical College, Hunan Normal University, Changsha 410013, China.

Abstract:  Purpose: 5, 7-dimethoxyflavone (DMF) has been reported to induce apoptosis in various cancer cells. The aim of this study was to examine whether DMF sensitizes human hepatocellular carcinoma (HCC) cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis and its mechanism. Methods: Human hepatocellular carcinoma cell lines Hep3B, Huh-7, and Hep G2 and human embryo liver L-02 cells were cultured in vitro. The cytotoxic activities were determined using MTT assay. The apoptotic cell death was examined using Flow cytometry using PI staining and DNA agarose gel electrophoresis. The activities of caspase-3, caspase-8, and caspase-9 were measured using ELISA. Intracellular ROS was measured by FCM using the fluorescent probe DCHF-DA, and the expression of DR4, DR5, CHOP, GPR78, and ATF4 proteins was analyzed using Western blot. Results: Our results demonstrated subtoxic concentrations of DMF sensitize HCC cells to TRAIL-induced apoptosis and induce the death receptor 5 (DR5) expression level, accompanying the generation of reactive oxygen species (ROS) and the upregulation of CHOP, GPR78, and ATF4 protein expression. Pretreatment with N-acetylcysteine (NAC) inhibited DMF-induced upregulation of DR5, CHOP, GPR78, and ATF4 protein expression and blocked the cotreatment-induced apoptosis. Furthermore, DMF-mediated sensitization of HCC cells to TRAIL was reduced by administration of a blocking antibody or small interfering RNAs for DR5, salubrinal, an inhibitor of ER stress, and the small interfering RNAs for CHOP. However, DMF could not induce the upregulation of DR5 expression, generation of ROS, and sensitization of TRAIL-induced apoptotic cell death in human embryo liver L-02 cells or normal human peripheral blood mononuclear cells (PBMCs). Conclusion: The present study demonstrates that DMF selectively enhances TRAIL-induced apoptosis by ROS-stimulated ER-stress triggering CHOP-mediated DR5 upregulation in HCC. 

Retracted: No

PubPeer comments:
 Figure 5 * Red and blue boxes: the same Actin lanes appear to be visible in panels A, B, and D. Part of a set of 29 papers reported to the journal in the summer of 2015 with a friendly reminder in April 2017, but no answer. With the exception of one paper, the journal did not correct or retract a single paper from this set. ![file] ,
Ablation of key oncogenic pathways by RITA-reactivated p53 is required for efficient apoptosis
Authors: Alena Maljukova
Olle Sangfelt
Fedor Nikulenkov
Yao Shi
Galina Selivanova
Martin Enge
Wenjie Bao
Vera V Grinkevich
Alexander Kel
Angela Gluch
Journal: Cancer Cell (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: oncogene addiction; p53; RITA; transcriptional repression; antiapoptotic proteins
Affiliations: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177, Stockholm, Sweden.

Abstract:  Targeting "oncogene addiction" is a promising strategy for anticancer therapy. We report a potent inhibition of crucial oncogenes by p53 upon reactivation by small-molecule RITA in vitro and in vivo. RITA-activated p53 unleashes the transcriptional repression of antiapoptotic proteins Mcl-1, Bcl-2, MAP4, and survivin; blocks the Akt pathway on several levels; and downregulates c-Myc, cyclin E, and beta-catenin. p53 ablates c-Myc expression via several mechanisms at the transcriptional and posttranscriptional level. We show that the threshold for p53-mediated transrepression of survival genes is higher than for transactivation of proapoptotic targets. Inhibition of oncogenes by p53 reduces the cell's ability to buffer proapoptotic signals and elicits robust apoptosis. Our study highlights the role of transcriptional repression for p53-mediated tumor suppression. 

Retracted: No

PubPeer comments:
 Images in Figure 6 appear to overlap (red boxes). u201cThe authors acknowledge financial support from the National Institute of Health grant 1R01CA193880-01A1, and U54CA210181 (MF), U.S. Department of Defense grant W81XWH-12-1-0414 (MF), the Ernest Cockrell Jr. Distinguished Endowed Chair fund (MF), and Dottie and Jimmy C. Adair Myelodysplastic Syndrome Treatment and Research Funding.u201d *** ![file] ,
Oral ulcer healing and anti-Candida efficacy of an alcohol-free chitosan-curcumin mouthwash
Authors: S Kuadkaew
S Pattharachayakul
K Sawanyawisuth
S Mahattanadul
M W Mustafa
S Ungphaiboon
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: oral ulcer healing; anti-Candida efficacy; alcohol-free; chitosan-curcumin mouthwash; buccal mucosal ulcer
Affiliations: Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand. .

Abstract:  Objective: The purpose of this study was to investigate oral ulcer healing and anti-Candida efficacy of an alcohol-free 0.1% chitosan-curcumin mouthwash. Materials and methods: A buccal mucosal ulcer was induced in hamster by topical application of acetic acid. The test mouthwash was applied to the ulcer twice a day for 7 consecutive days beginning on the fourth day after the ulcer induction. The anti-Candida efficacy of the mouthwash was determined against both free floating and biofilm forms of Candida albicans. Results: The mouthwash significantly decreased the ulcer severity with a better ulcer healing efficacy than that of a standard benzydamine mouthwash. The mouthwash also exerted a comparable anti-Candida efficacy to a standard chlorhexidine mouthwash. Conclusions: An alcohol-free 0.1% chitosan-curcumin mouthwash may serve as a safe and potential topical alternative agent in the management of oral inflammatory ulcer and of candidiasis. 

Retracted: No

PubPeer comments:
 Figure 1. The bottom right panel (0.15% benzydamine mouthwash) appears to contain the same area twice. First, here is an overview of the whole figure: ![file] Here is a detail of that panel, with the repetitive area highlighted in red boxes. Could the authors please explain what happened here? ![file] ,
Bradykinin Promotes Cell Proliferation, Migration, Invasion, and Tumor Growth of Gastric Cancer Through ERK Signaling Pathway
Authors: Xiefu Zhang
Yang Fu
Junfeng Sun
Guanghui Liu
Guojun Wang
Journal: Journal of Cellular Biochemistry (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: B1R; B2R; BRADYKININ; ERK; GASTRIC CANCER.
Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China.

Abstract:  Bradykinin (BK) has been reported to be involved in the progression of diverse types of cancer. In the present study, we investigated the possible role of BK in cell proliferation, migration, invasion, and tumor growth of gastric cancer (GC). Cell proliferation was evaluated by MTT assays. Cell migration and invasion were assessed by Transwell assays. Tumor growth of nude mice was detected by establishing subcutaneous xenograft tumor model. Silencing of bradykinin B1 receptor (B1R) and the bradykinin B2 receptor (B2R) was performed by transfecting cells with si-B1R and si-B2R, respectively. The protein expression levels of phospho-ERK1/2 (p-ERK1/2), matrix metalloproteinase (MMP)-2, MMP-9, and E-Cadherin were examined by Western blot. Data revealed that BK promoted cell proliferation, migration, invasion, and the in vivo tumor growth of GC cells SGC-7901 and HGC-27. Furthermore, BK elevated the protein levels of p-ERK1/2, MMP-2, and MMP-9, but reduced E-Cadherin. In addition, by repressing B2R using si-B2R or inhibiting ERK signaling pathway using PD98059, BK-mediated promotion of cell proliferation, migration, and invasion and upregulation of p-ERK1/2, MMP-2/9, as well as downregulation of E-Cadherin were attenuated. Taken together, the present study demonstrated that BK promoted cell proliferation, migration, invasion, and tumor growth by binding to B2R via ERK signaling pathway. Our findings may provide promising options for the further treatment of GC. J. Cell. Biochem. 118: 4444-4453, 2017. © 2017 Wiley Periodicals, Inc. 

Retracted: No

PubPeer comments:
 Figures 2, 4, and 7. Several panels representing different cell lines and experiments appear to show overlapping areas, as highlighted by boxes of the same color. Similarities found with the help of ImageTwin.io by Markus Zlabinger. ![file] , 
 Thanks for pointing the mistakes. We are really sorry . We may place the wrong figures. We will contact the Editor for the correction. ,
Cellular senescence in knee osteoarthritis: molecular mechanisms and therapeutic implications
Authors: Fuxing Pei
Lingyun Lu
Xijie Yu
Lu Liu
Yan Wang
Jinwei Xie
Journal: Ageing Research Reviews (2021)
Discipline: CLINICAL MEDICINE
Keywords: Cellular senescence; Chondrocyte; Osteoarthritis; Senescence associated secretory phenotype.

Abstract:  Cellular senescence is the inability of cells to proliferate, which has both beneficial and detrimental effects on tissue development and homeostasis. Chronic accumulation of senescent cells is associated with age-related disease, including osteoarthritis, a common joint disease responsible for joint pain and disability in older adults. The pathology of this disease includes loss of cartilage, synovium inflammation, and subchondral bone remodeling. Senescent cells are present in the cartilage of people with advanced osteoarthritis, but the link between cellular senescence and this disease is unclear. In this review, we summarize current evidence for the role of cellular senescence of different cell types in the onset and progression of osteoarthritis. We focus on the underlying mechanisms of senescence in chondrocytes, which maintain the cartilage in joints, and review the role of the Forkhead family of transcription factors, which are involved in cartilage maintenance and osteoarthritis. Finally, we discuss the potential therapeutic value and implications of targeting senescent cells using senolytic agents or immune therapies, targeting the senescence-associated secretory phenotype of these cells using senomorphic agents, and renewing the plasticity of stem cells and chondrocytes. Our review highlights current gaps in understanding of the mechanism of senescence that may, when addressed, provided new options for modifying and treating disease in osteoarthritis. 

Retracted: No

PubPeer comments:
 Dear Dr. Pei and Editors from Ageing Research Reviews and Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi: We read this very interesting review regarding cellular senescence in knee osteoarthritis. However, we found that this review is translated (word by word, except the FOXO section) from one review (Review in Chinese), with the same group of the authors, published in April 2021 . We believe this is a typical behavior of redundant publication, which should draw attention from both editorial boards of Ageing Research Review and Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. Thanks! Diplodia Tsugae ,
Upregulated expression of ROCK1 promotes cell proliferation by functioning as a target of miR‐335‐5p in non‐small cell lung cancer
Authors: Yongqian Jiang
Hongjian Bo
Haicheng Tang
Hongmiao Li
Wenwen Du
Shu Song
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ROCK1; cell proliferation; miR-335-5p; non-small cell lung cancer.
Affiliations: Department of Respiratory Medicine, The First People's Hospital of Yancheng, Yancheng, China., The Fourth Affiliated Hospital of Nantong University, Yancheng, China., Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China., Department of Respiratory Medicine, Jianhu Hospital Affiliated to Nantong University, Yancheng, China., Department of Pathology, The First People's Hospital of Yancheng, Yancheng, China.

Abstract:  Lung cancer is regarded as one of the dominant causes in cancer patients among men and women all over the world. Rho-associated coiled-coil forming protein kinase l (ROCK1) is characterized as pivotal downstream effectors of the small GTPase RhoA and reported to participate in tumor metastasis. miR-335-5p acts as tumor suppressor microRNA and is identified to be downregulated in tumor tissues. miR-335-5p/ROCK1 axis has been demonstrated to promote cell proliferation and metastasis in gastric cancer, hepatocellular carcinoma and so on. However, the role it plays in promoting cell proliferation in non-small cell lung cancer (NSCLC) is poorly understood. Here, we demonstrated that the upregulated expression of ROCK1 was highly correlated with downregulated expression of miR-335-5p in NSCLC tissues and cell lines. Mechanistically, Knockdown of ROCK1 inhibited cell proliferation in vitro, accompanied by cell cycle change confirmed by flow analysis. Furthermore, miR-335-5p can downregulate the ROCK1 expression by directly binding to the 3'-untranslated region in posttranscriptional level. In vivo animal model showed similar results. Our findings highlighted the crucial role that miR-335-5p acted as a tumor suppressor to modulate cell proliferation and cell cycle progression via downregulating ROCK1 expression. And this miR-335-5p/ROCK1 axis contributed to NSCLC pathogenesis and might be promising targets for NSCLC therapy. 

Retracted: Yes

PubPeer comments:
 Retraction, December 2021: https: onlinelibrary.wiley.com doi 10.1002 jcp.30674  The above article, published online in Journal of Cellular Physiology on 29 May 2019 in Wiley Online Library has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The authors asked for a retraction and stated that unintentional errors occurred during the research process, so that the experimental results cannot be verified. Thus, the conclusions are considered to be invalid. The authors were not available to approve the retraction text after the investigation was concluded. ,
Methanolic extract of Ruta graveolens L. inhibits inflammation and oxidative stress in adjuvant induced model of arthritis in rats
Authors: A Helen
M Ratheesh
G L Shyni
Journal: Inflammopharmacology (2009)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Ruta graveolens L.; anti-inflammatory; antioxidant effects; methanolic extract; adjuvant induced arthritis
Affiliations: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram 695581, India.

Abstract:  Ruta graveolens L. (Rutaceae) are traditionally used for the treatment of rheumatism, arthritis and other inflammatory conditions in the traditional medicine of India. The purpose of this study was to investigate anti-inflammatory and anti-oxidant effects of methanolic extract of Ruta graveolens L. in adjuvant induced arthritis in rats. Methanolic extract of Ruta graveolens (MER) exhibited maximum percentage of oedema inhibition at a dose of 20 mg/kg on 21st day of adjuvant arthritis. The effect was higher than that of standard drug indomethacin. The activities of cycloxygenase-2 and myeloperoxidase and concentration of thiobarbituric acid reactive substance (TBARS) were decreased and the activities of antioxidant enzymes, vitamins C &amp; E and reduced glutathione level were increased on treatment with MER. The increment in ESR and total WBC, reduction in RBC count and haemoglobin and aberrant changes to the C-reactive protein (CRP) and ceruloplasmin levels observed in the arthritic animals were also found to be significantly restored in MER treated rats. Histopathology of paw tissue showed decreased oedema formation and cellular infiltration on supplementation with MER. Thus the results demonstrated the potential beneficiary effect of methanolic extract of Ruta graveolens on adjuvant induced arthritis in rats. 

Retracted: No

PubPeer comments:
 The mean and SEM in the experimental data of tables 1 and 2 were as same in another publication. For Table 1, only one value was found to be different. For table 2, the first two group shows exactly the same experimental data. Could the authors show their raw data obtained from the ELISA reader for the two papers separately to clarify this? ![file] ![file] , 
 #1 These concerns are well founded given the problems in another paper by this group, [Ratheesh et al. 2017](http: pubpeer.com publications 04967355EED1938046187F153D5A39). Could the authors please comment? ,
The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer
Authors: Leigh C Murphy
Yulian Niu
Sanat K Mandal
Ethan D Emberley
Jeffery N Myers
Spencer B Gibson
Peter H Watson
Sandra Troup
Linda Curtis
Journal: Cancer Research (2005)
Discipline: CLINICAL MEDICINE
Keywords: S100A7; breast cancer; survival; nuclear factor-kappaB; phospho-Akt
Affiliations: Department of Biochemistry and Medical Genetics, University of Manitoba, Canada.

Abstract:  S100A7 is among the most highly expressed genes in preinvasive breast cancer, is a marker of poor survival when expressed in invasive disease, and promotes breast tumor progression in experimental models. To explore the mechanism of action, we examined the role of S100A7 in cell survival and found that overexpression of S100A7 in MDA-MB-231 cell lines promotes survival under conditions of anchorage-independent growth. This effect is paralleled by increased activity of nuclear factor-kappaB (3-fold) and phospho-Akt (4-fold), which are known to mediate prosurvival pathways. S100A7 and phospho-Akt are also correlated in breast tumors examined by immunohistochemistry (n = 142; P &lt; 0.0001; r = 0.34). To explore the underlying mechanism, we examined the role of a putative c-Jun activation domain-binding protein 1 (Jab1)-binding domain within S100A7 using a panel of MDA-MB-231 breast cell lines stably transfected with either S100A7 or S100A7 mutated at the Jab1 domain. Structural analysis by three-dimensional protein modeling, immunoprecipitation, and yeast two-hybrid assay and functional analysis using transfected reporter gene and Western blot assays revealed that the in vitro effects of S100A7 on phospho-Akt and the nuclear factor-kappaB pathway are dependent on the Jab1-binding site and the interaction with Jab1. Enhanced epidermal growth factor receptor signaling was also found to correlate with the increased phospho-Akt. Furthermore, the Jab1-binding domain is also necessary for the enhanced tumorigenicity conferred by S100A7 expression in murine xenograft tumors in vivo. We conclude that the S100A7-Jab1 pathway acts to enhance survival under conditions of cellular stress, such as anoikis, which may promote progression of breast cancer. 

Retracted: No

PubPeer comments:
 Figure 6C appears to have two images which overlap. Green box shows approximate area of overlap. *** ![file] , 
 #1 Overlap between Figs 2C, 6C, displaying MDA-MD-231 cells either plain or transfected with Akt-1 cDNA respectively (with 0 Casticin). ![file] , 
 Although the journal acknowledged being victimized by a paper mill, this particular paper does not yet show an editorial expression of concern or retraction, despite the clear evidence above. , 
 March 31, 2021 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. ,
Long noncoding RNA HOTAIR silencing inhibits invasion and proliferation of human colon cancer LoVo cells via regulating IGF2BP2
Authors: Dong-Dong Yang
Yuan-Yuan Wang
Yong-Jun Dai
Xue-Liang Wu
Li-Kun Wang
Yong-Jiang Yang
Jun Xue
Rui-Yun Lu
Chen-Yu Wang
Fei Guo
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: colon cancer; epithelial-mesenchymal transition (EMT); human colon cancer lovo cell; insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2); invasion
Affiliations: Department of General SurgeryThe First Affiliated Hospital of Hebei North UniversityZhangjiakou China, Department of Gastrointestinal SurgeryThe First Hospital of Hebei Medical UniversityShijiazhuang China, Department of UltrasoundThe First Affiliated Hospital of Hebei North UniversityZhangjiakou China

Abstract:  Colon cancer is one of the most life-threatening malignancies worldwide. Long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) is a cancer-associated biomarker involved in the metastasis and prognosis of several cancers. However, whether and how HOTAIR affects colon cancer progression is still unclear. Consequently, we used RNA interference to knock down HOTAIR to explore its effects on human colon cancer cells. The dual luciferase reporter gene assay was initially used for testify the regulating relationship between lncRNA HOTAIR and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). We determined the expressions of HOTAIR, IGF2BP2, E-cadherin, and vimentin. Meanwhile, cell growth, cycle and apoptosis, migration, and invasion were assayed. LoVo cells were transplanted into nude mice, and tumor formation and microvessel density were evaluated. LncRNA HOTAIR positively regulated IGF2BP2. Besides, the expressions of HOTAIR and E-cadherin and the apoptosis were increased, while the expressions of IGF2BP2 and vimentin, the growth, invasion and migration of LoVo cells, the average tumor weight, and microvessel density value were decreased. Of importance, overexpressed IGF2BP2 could reverse the above impacts. Taken together, the current study indicates that silencing of HOTAIR could inhibit the invasion, proliferation, and migration, and promote apoptosis of colon cancer LoVo cells through suppressing IGF2BP2 and the epithelial-mesenchymal transition. 

Retracted: No

PubPeer comments:
 Fig 5 C,D.  HOTAIR silencing induced the cell cycle arrest of LoVo cells in the G0 G1 phase and promoted cell apoptosis. (A,B) LoVo cell cycle after transfection. (C,D) LoVo cell apoptosis after transfection . The Figure has confused cell-cycle and apoptosis flow cytometry, but that could have been the fault of the journal. ![file] I cannot help wondering about the software and hardware used to plot these peculiar diagrams. ,
An atlas of genetic correlations across human diseases and traits
Authors: Mark J Daly
Verneri Anttila
Po-Ru Loh
Elise B Robinson
Alkes L Price
Brendan Bulik-Sullivan
Hilary K Finucane
ReproGen Consortium
Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3
Benjamin M Neale
Laramie Duncan
John R B Perry
Felix R Day
Alexander Gusev
Psychiatric Genomics Consortium
Nick Patterson
Journal: Nature Genetics (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Genetic correlation; GWAS; LD Score regression; Traits; Diseases
Affiliations: Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.

Abstract:  Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual-level genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique-cross-trait LD Score regression-for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity, and educational attainment and several diseases. These results highlight the power of genome-wide analyses, as there currently are no significantly associated SNPs for anorexia nervosa and only three for educational attainment. 

Retracted: No

PubPeer comments:
 On page 7, found **u201cdear reader we admire your perseverance in making it this faru201d** in the 26-page long u2018Supplementary Text and Figuresu2019 document: ![file] Thanks for the engaging your readership! ,
Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants
Authors: Richard B van Breemen
Ruth N Muchiri
Scotland Farley
Timothy A Bates
Jules B Weinstein
Fikadu G Tafesse
Hans C Leier
Journal: Journal of Natural Products (2022)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: vaccines; small-molecule therapeutic agents; severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); COVID-19; Affinity selection-mass spectrometry
Affiliations: Linus Pauling Institute, Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2900 SW Campus Way, Corvallis, Oregon 97331, United States, Molecular Microbiology & Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, United States

Abstract:  As a complement to vaccines, small-molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, which cause COVID-19. Affinity selection-mass spectrometry was used for the discovery of botanical ligands to the SARS-CoV-2 spike protein. Cannabinoid acids from hemp (Cannabis sativa) were found to be allosteric as well as orthosteric ligands with micromolar affinity for the spike protein. In follow-up virus neutralization assays, cannabigerolic acid and cannabidiolic acid prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein and prevented entry of live SARS-CoV-2 into cells. Importantly, cannabigerolic acid and cannabidiolic acid were equally effective against the SARS-CoV-2 alpha variant B.1.1.7 and the beta variant B.1.351. Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2. 

Retracted: No

PubPeer comments:
 I find this article speculative and misinformative. The experiments are performed in vitro in an artificial model with kidney monkey cells. Concentrations needed to block infection by 50% of viruses is extremely high and far from clinical relevant. Elimination rate of CBD CBG in plasma is high. ![file] ,
A novel interaction of PAK4 with PPARγ to regulate Nox1 and radiation-induced epithelial-to-mesenchymal transition in glioma
Authors: Y K Banasavadi-Siddegowda
T-H Lai
B Kaur
D Kesanakurti
S Mohanam
V K Puduvalli
N K Jacob
Z Qamri
D Sampath
D Maddirela
Journal: Oncogene (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Tumor recurrence; Glioblastoma; Epithelial-to-mesenchymal transition; Ionizing radiation; PAK4

Abstract:  Tumor recurrence in glioblastoma (GBM) is, in part, attributed to increased epithelial-to-mesenchymal transition (EMT) and enhanced tumor cell dissemination in adjacent brain parenchyma after ionizing radiation (IR). EMT is associated with aggressive behavior, increased stem-like characteristics and treatment resistance in malignancies; however, the underlying signaling mechanisms that regulate EMT are poorly understood. We identified grade-dependent p21-activated kinases 4 (PAK4) upregulation in gliomas and further determined its role in mesenchymal transition and radioresistance. IR treatment significantly elevated expression and nuclear localization of PAK4 in correlation with induction of reactive oxygen species (ROS) and mesenchymal transition in GBM cells. Stable PAK4 overexpression promoted mesenchymal transition by elevating EMT marker expression in these cells. Of note, transcription factor-DNA-binding arrays and chromatin immunoprecipitation experiments identified the formation of a novel nuclear PAK4/PPARγ complex which was recruited to the promoter of Nox1, a peroxisome proliferator-activated receptor gamma (PPARγ) target gene. In addition, IR further elevated PAK4/PPARγ complex co-recruitment to Nox1 promoter, and increased Nox1 expression and ROS levels associated with mesenchymal transition in these cells. Conversely, specific PAK4 downregulation decreased PPARγ-mediated Nox1 expression and suppressed EMT in IR-treated cells. In vivo orthotopic tumor experiments showed inhibition of growth and suppression of IR-induced PPARγ and Nox1 expression by PAK4 downregulation in tumors. Our results provide the first evidence of a novel role for PAK4 in IR-induced EMT and suggest potential therapeutic efficacy of targeting PAK4 to overcome radioresistance in gliomas. 

Retracted: No

PubPeer comments:
 Figure 7B appears to show two overlapping panels - shown in pink. Puzzlingly, there are some discrepancies between the paywalled final paper and the free PubMedCentral version, with respect to the included authors and some of the figures. Figure 7B in particular is different in the paywalled paper and does not appear to show the overlap that is visible in the PMC version. Still, this is of note, since one of the authors has been involved in several of the Jasti S Rao papers flagged here on PubPeer. This paper was published after Rao left the University of Illinois at Peoria. ![file] ,
Metabolic reprogramming of Kaposi's sarcoma associated herpes virus infected B-cells in hypoxia
Authors: Hem Chandra Jha
Yonggang Pei
Rajnish Kumar Singh
Erle S Robertson
Fengchao Lang
Journal: PLoS pathogens (2018)
Discipline: MICROBIOLOGY
Keywords: Kaposi's sarcoma associated herpesvirus (KSHV); hypoxia inducible factors (HIFs); metabolic reprogramming; RNA sequencing analysis; glucose dependency
Affiliations: Departments of Otorhinolaryngology-Head and Neck Surgery and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America., Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, Madhya Pradesh, India.

Abstract:  Kaposi's sarcoma associated herpesvirus (KSHV) infection stabilizes hypoxia inducible factors (HIFs). The interaction between KSHV encoded factors and HIFs plays a critical role in KSHV latency, reactivation and associated disease phenotypes. Besides modulation of large-scale signaling, KSHV infection also reprograms the metabolic activity of infected cells. However, the mechanism and cellular pathways modulated during these changes are poorly understood. We performed comparative RNA sequencing analysis on cells with stabilized hypoxia inducible factor 1 alpha (HIF1α) of KSHV negative or positive background to identify changes in global and metabolic gene expression. Our results show that hypoxia induces glucose dependency of KSHV positive cells with high glucose uptake and high lactate release. We identified the KSHV-encoded vGPCR, as a novel target of HIF1α and one of the main viral antigens of this metabolic reprogramming. Bioinformatics analysis of vGPCR promoter identified 9 distinct hypoxia responsive elements which were activated by HIF1α in-vitro. Expression of vGPCR alone was sufficient for induction of changes in the metabolic phenotype similar to those induced by KSHV under hypoxic conditions. Silencing of HIF1α rescued the hypoxia associated phenotype of KSHV positive cells. Analysis of the host transcriptome identified several common targets of hypoxia as well as KSHV encoded factors and other synergistically activated genes belonging to cellular pathways. These include those involved in carbohydrate, lipid and amino acids metabolism. Further DNA methyltranferases, DNMT3A and DNMT3B were found to be regulated by either KSHV, hypoxia, or both synergistically at the transcript and protein levels. This study showed distinct and common, as well as synergistic effects of HIF1α and KSHV-encoded proteins on metabolic reprogramming of KSHV-infected cells in the hypoxia. 

Retracted: No

PubPeer comments:
 Figure 3G. Much more similar than you would expect. https: imgur.com aaNYnUF , 
 Last author appears to be on the editorial board of this journal: https: journals.plos.org plospathogens s editorial-board ,
Induction of matrix metalloproteinase-9 and -3 in nonsteroidal anti-inflammatory drug-induced acute gastric ulcers in mice: regulation by melatonin
Authors: Snehasikta Swarnakar
Krishnendu Ganguly
Journal: Journal of Pineal Research (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: gastric ulcer; extracellular matrix; matrix metalloproteinases; NSAIDs; inflammation
Affiliations: Department of Physiology, Drug Development Diagnostic Division, Indian Institute of Chemical Biology, Kolkata, India.

Abstract:  The pathogenesis of gastric ulcer is associated with remodeling of extracellular matrix (ECM) by various matrix metalloproteinases (MMPs). However, how MMPs are regulated during nonsteroidal anti-inflammatory drug (NSAID)-induced acute gastric ulceration is not well studied. In this study, different NSAIDs (80 mg/kg b.w.) were applied to generate acute gastric ulcer in the BALB/c mouse and the regulation of MMPs were investigated. NSAIDs caused dose-dependent induction in MMP-9 and -3 activities and expressions in ulcerated gastric tissues along with significant infiltration of inflammatory cells and disruption of gastric mucosal layer. In addition, an increase in tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 expression, excessive generation of hydroxyl radical ((*)OH), and protein oxidation and lipid peroxidation were observed in acute ulcerated gastric tissues. In this study, the efficacy of melatonin on activities of MMP-9 and -3 during prevention of gastric ulcers was tested. Melatonin at a dose of 60 mg/kg b.w. downregulated MMP-9 and -3 both at the enzyme and protein levels in mouse gastric tissues during prevention as well as healing of acute gastric ulcers. It also blocked oxidative stress via inhibition of protein oxidation, lipid peroxidation, (*)OH generation and SOD-2 expression. Moreover, it suppressed myeloperoxidase activity and expressions of TNF-alpha, IL-1beta and IL-8. This study documents for the first time that induction of MMP-9 and -3 activities accompany NSAID-induced inflammation and oxidative stress in gastric tissues and indicates that, melatonin may be a preventive or therapeutic remedy for gastric ulcers. 

Retracted: No

PubPeer comments:
 A sharp boundary between lanes (red arrows) in fig 3A ![file] , 
 Unexpected similarity between some bands in Fig 4B ![file] , 
 Unexpected similarity between some bands in Fig 5A ![file] , 
 Unexpected similarity between some bands in Fig 6A ![file] ,