PReD-Bench/PRed-Bench huggingface dataset:
Community interactions and spatial structure shape selection on antibiotic resistant lineages
Authors: Sam P Brown
Sylvie Estrela
Journal: PLoS Computational Biology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Polymicrobial interactions; antibiotic treatment; multispecies communities; individual-based simulation model; microbial biofilms
Affiliations: Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut, United States of America., Microbial Sciences Institute, Yale University, West Haven, Connecticut, United States of America., School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, United States of America.

Abstract:  Polymicrobial interactions play an important role in shaping the outcome of antibiotic treatment, yet how multispecies communities respond to antibiotic assault is still little understood. Here we use an individual-based simulation model of microbial biofilms to investigate how competitive and mutualistic interactions between an antibiotic-resistant and a susceptible strain (or species) influence the two-lineage community response to antibiotic exposure. Our model predicts that while increasing competition and antibiotics leads to increasing competitive release of the antibiotic-resistant strain, hitting a mutualistic community of cross-feeding species with antibiotics leads to a mutualistic suppression effect where both susceptible and resistant species are harmed. We next show that the impact of antibiotics is further governed by emergent spatial feedbacks within communities. Mutualistic cross-feeding communities can rescue susceptible members by subsidizing their growth inside the biofilm despite lack of access to the nutrient-rich and high-antibiotic growing front. Moreover, we show that antibiotic detoxification by resistant cells can protect nearby susceptible cells, but such cross-protection is more effective in mutualistic communities because mutualism drives mixing of resistant and susceptible cells. In contrast, competition leads to segregation, which ultimately prevents susceptible cells to profit from detoxification. Understanding how the interplay between microbial metabolic interactions and community spatial structuring shapes the outcome of antibiotic treatment can be key to effectively leverage the power of antibiotics and promote microbiome health. 

Retracted: No

PubPeer comments:
 Recently we are interested in your work, and to repeat your conclusion in simulation module, would you like to share your Protocol file (used to initiate iDynoMiCS simulations) with us ? ,
Synbiotic food consumption reduces levels of triacylglycerols and VLDL, but not cholesterol, LDL, or HDL in plasma from pregnant women
Authors: Teibeh Hashemi
Sima-Sadat Sabihi
Sabihe-Alsadat Alizadeh
Mohsen Taghizadeh
Fatemeh Abedi
Zatolla Asemi
Hossein Shakeri
Journal: Lipids (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: synbiotic food; pregnant women; blood lipid profiles; oxidative stress; probiotic
Affiliations: Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.

Abstract:  To our knowledge, no reports are available indicating the effects of synbiotic food consumption on blood lipid profiles and biomarkers of oxidative stress among pregnant women. This study was conducted to evaluate the effects of daily consumption of a synbiotic food on blood lipid profiles and biomarkers of oxidative stress in pregnant women. This randomized, double-blind, controlled clinical trial was performed among 52 primigravida pregnant women, aged 18 to 35-year-old at their third trimester. After a 2-week run-in period, subjects were randomly assigned to consume either a synbiotic (n = 26) or control food (n = 26) for 9 weeks. The synbiotic food consisted of a probiotic viable and heat-resistant Lactobacillus sporogenes (1 × 10⁷ CFU) and 0.04 g inulin (HPX)/g as the prebiotic. Patients were asked to consume the synbiotic and control foods two times a day. Biochemical measurements including blood lipid profiles, plasma total antioxidant capacity (TAC) and total glutathione (GSH) were conducted before and after 9 weeks of intervention. Consumption of a synbiotic food for 9 weeks resulted in a significant reduction in serum TAG (P = 0.04), VLDL (P = 0.04) and a significant rise in plasma GSH levels (P = 0.004) compared to the control food. No significant effects of the synbiotic food consumption on serum TC, LDL, HDL and plasma TAC levels (P &gt; 0.05) were observed. Trial registry code: http://www.irct.ir . IRCT201212105623N3. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A21 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
circPIP5K1A serves as a competitive endogenous RNA contributing to ovarian cancer progression via regulation of miR‐661/IGFBP5 signaling
Authors: Ruhai Yi
Aozheng Chen
Lei Wang
Jin Qiu
Yi Sun
Weihui Shi
Xue Li
Journal: Journal of cellular biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: IGFBP5; circPIP5K1A; invasion; miR-661; ovarian cancer
Affiliations: Department of Obstetrics and Gynecology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China., Department of Interventional & Vascular Surgery, Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China., Department of Obstetrics and Gynecology, Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China., Department of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China., Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Diabetes Research Insititute of Fujian Province, Fuzhou, Fujian, China.

Abstract:  Increasing evidence demonstrates the crucial regulatory functions of circular RNAs in different cancer types. The major aim of the current study was to establish functions of circPIP5K1A during ovarian cancer. Our results showed an increased expression of circPIP5K1A in both ovarian cancers and cell lines, which was associated with poor prognosis. In functional analyses, downregulation of circPIP5K1A suppressed ovarian cancer cell migration, proliferation, and invasion in vitro. The miR-661 was indicated as a target of circPIP5K1A and insulin-like growth factor-binding protein 5 (IGFBP5) as a target of miR-661. circPIP5K1A silencing triggered downregulation of IGFBP5 through inducing an increase in miR-66 levels, as determined by the luciferase reporter assay. Data from cell counting kit-8, colony formation, wound healing, and Transwell assays showed that overexpression of IGFBP5 effectively reversed the circPIP5K1A depletion effects. The results collectively indicated that circPIP5K1A contributed to ovarian cancer progression via targeting the miR-661/IGFBP5 axis, supporting its utility as a candidate target for therapy of the disease. 

Retracted: No

PubPeer comments:
 In Figure 2g, microscopy data has been duplicated and presented as something else. ![file] ,
Identification of C-terminal Hsp70-interacting protein as a mediator of tumour necrosis factor action in osteoblast differentiation by targeting osterix for degradation
Authors: Jianmin Xie
Jieruo Gu
Journal: Journal of Cellular and Molecular Medicine (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CHIP; TNF-α; osteoblast; osterix.
Affiliations: Department of Rheumatology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China., Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Abstract:  In patients with inflammatory arthritis, tumour necrosis factor (TNF)-α are overproduced in inflamed joints. This leads to local erosion of cartilage and bone, periarticular osteopenia, as well as osteoporosis. But less is known regarding the molecular mechanisms that mediate the effect of TNF-α on osteoblast function. The purpose of this study was to test that C terminus of Hsc70-interacting protein (CHIP) has a specific role in suppressing the osteogenic activity of osteoblasts under inflammatory conditions. C2C12, MC3T3-E1 and HEK293T cell lines were cultured and cotransfected with related plasmids. After transfection, the cells were cultured further in the presence or absence of murine TNF-α and subjected to real time RT-PCR, Western blot, Ubiquitination assay, Co-immunoprecipitation, Luciferase reporter assay, Small interfering RNAs and Mineralization assay. The expression levels of TNF-α-induced CHIP and Osx were examined by RT-PCR and Western blot analysis. Co-immunoprecipitation and ubiquitination assays revealed ubiquitinated Osx, confirmed that CHIP indeed interacted with Osx and identified K55 and K386 residues as the ubiquitination sites in Osx, Luciferase reporter assay and Small interfering RNAs examined whether TNF-α target the bone morphogenetic protein signalling through CHIP. We established stable cell lines with the overexpression of HA-CHIP, Mineralization assay and CHIP siRNA demonstrated the important roles of CHIP on osteoblast function in conditions in which TNF-α is overexpressed. We found that the K55 and K386 residues are ubiquitination site(s) in Osx, and that TNF-α inhibits osteoblast differentiation by promoting Osx degradation through up-regulation of E3 ubiquitin ligase CHIP in osteoblast. Thus, CHIP targets Osx for ubiquitination and degradation in osteoblasts after chronic exposure to TNF-α, and inhibition of CHIP expression in osteoblasts may be a new mechanism to limit inflammation-mediated osteoporosis by promoting their differentiation into osteoblasts. 

Retracted: No

PubPeer comments:
 Figure 6C. Panels b) and c) look more similar to each other than expected. Boxes of the same color focus attention to areas that appear to look similar. ![file] ,
Exemestane blocks mesothelioma growth through downregulation of cAMP, pCREB and CD44 implicating new treatment option in patients affected by this disease
Authors: Iole Cordone
Serena Masi
Carlotta Morosetti
Rossella Galati
Barbara Nuvoli
Sabrina Germoni
Giancarlo Cortese
Raffaela Santoro
Journal: Molecular Cancer (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: aromatase; exemestane; mesothelioma; cell proliferation; migration
Affiliations: Molecular Medicine Area, Regina Elena National Cancer Institute, Rome 00144, Italy. .

Abstract:  Background: Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. Here, we evaluated the effect of exemestane, an inhibitor of aromatase, in the treatment of mesothelioma using in vitro and in vivo preclinical models. Results: We show a significant reduction of cell proliferation, survival, migration and block of cells in S phase of cell cycle in mesothelioma cells upon exemestane treatment. Moreover, we find that CD44, which is involved in mesothelioma cells migration, was modulated by exemestane via cAMP and pCREB. Most importantly, in mice mesothelioma xenograft exemestane causes a significant decrease in tumor size and the association pemetrexed/exemestane is more effective than pemetrexed/cisplatin. Conclusion: The preclinical mesothelioma model suggests that exemestane might be beneficial in mesothelioma treatment. 

Retracted: No

PubPeer comments:
 Figure 1D has two wells that contain multiple areas of similarity if the adjacent well is rotated 90 degrees (cyan arrow). However, I have also noted two areas in which the images differ (see red and orange ellipses). Could the authors review and comment? I recently posted similar concerns regarding a paper with shared authors: https: pubpeer.com publications 87DD1CDCFBDA900E8BB676582F9FF3#2 *** ![file] , 
 Figure 2B. * In the left yTub panel, lanes 1 and 6 look similar but in mirror image. ![file] , 
 Some of the images in Figure 1D seem to have also been published in another paper by these authors published around the same time. TAM. *** ![file] ,
Molecular and cellular mechanisms of cigarette smoke-induced myocardial injury: prevention by vitamin C
Authors: Arunava Ghosh
Shovanendu Das
Archita Das
Indu B Chatterjee
Neekkan Dey
Dhruba J Chattopadhyay
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: Cardiovascular disease; cigarette smoking; myocardial injury; vitamin C; guinea pig model
Affiliations: Department of Biotechnology, DrBC Guha Centre for Genetic Engineering and Biotechnology, Calcutta University College of Science, Kolkata, India.

Abstract:  Background: Cardiovascular disease (CVD) remains one of the major killers in modern society. One strong risk factor of CVD is cigarette smoking that causes myocardial injury and leads to the genesis of pathological cardiovascular events. However, the exact toxic component(s) of cigarette smoke (CS) and its molecular and cellular mechanisms for causing myocardial injury leading to heart damage and its prevention are largely unknown. Methodology/principal findings: Using a guinea pig model, here we show that chronic exposure to CS produces myocardial injury that is prevented by vitamin C. Male guinea pigs were fed either vitamin C-deficient (0.5 mg/day) or vitamin C-sufficient (15 mg/day) diet and subjected to CS exposure from 5 Kentucky Research cigarettes (3R4F)/day (6 days/week) in a smoke chamber up to 8 weeks. Pair-fed sham controls were subjected to air exposure instead of CS exposure under similar conditions. Myocardial injury was produced in CS-exposed marginal vitamin C-deficient guinea pigs as evidenced by release of cardiac Troponin-T and I in the serum, oxidative stress, inflammation, apoptosis, thrombosis and collagen deposition in the myocardium. Treatment of rat cardiomyocyte cells (H9c2) in vitro and guinea pigs in vivo with p-benzoquinone (p-BQ) in amounts derived from CS revealed that p-BQ was a major factor responsible for CS-induced myocardial damage. A moderately large dose of vitamin C (15 mg/day) prevented CS/p-BQ-induced myocardial injury. Population based studies indicated that plasma vitamin C levels of smokers without disease were significantly lower (p = 0,0000) than that of non-smokers. Vitamin C levels of CS-related cardiovascular patients were further lower (p = 0.0000) than that of smokers without disease. Conclusions/significance: The results indicate that dietary supplementation of vitamin C may be a novel and simple therapy for the prevention of pathological cardiovascular events in habitual smokers. 

Retracted: No

PubPeer comments:
 Fig 2 duplication (brightness increased) ![file] Fig 4 duplication (brightness increased) ![file] ,
Sustained oxidative stress causes late acute renal failure via duplex regulation on p38 MAPK and Akt phosphorylation in severely burned rats
Authors: Wei Lei
Yi Liu
Dexin Wang
Xiaoqing Cai
Yafei Feng
Hongli Chen
Kaimin Wu
Lin Wang
Jia Li
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: late acute renal failure; reactive oxygen species; severely burned patients; rat model; signaling mechanisms
Affiliations: Department of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Abstract:  Background: Clinical evidence indicates that late acute renal failure (ARF) predicts high mortality in severely burned patients but the pathophysiology of late ARF remains undefined. This study was designed to test the hypothesis that sustained reactive oxygen species (ROS) induced late ARF in a severely burned rat model and to investigate the signaling mechanisms involved. Materials and methods: Rats were exposed to 100°C bath for 15 s to induce severe burn injury (40% of total body surface area). Renal function, ROS generation, tubular necrosis and apoptosis, and phosphorylation of MAPK and Akt were measured during 72 hours after burn. Results: Renal function as assessed by serum creatinine and blood urea nitrogen deteriorated significantly at 3 h after burn, alleviated at 6 h but worsened at 48 h and 72 h, indicating a late ARF was induced. Apoptotic cells and cleavage caspase-3 in the kidney went up slowly and turned into significant at 48 h and 72 h. Tubular cell ROS production shot up at 6 h and continuously rose during the 72-h experiment. Scavenging ROS with tempol markedly attenuated tubular apoptosis and renal dysfunction at 72 h after burn. Interestingly, renal p38 MAPK phosphorylation elevated in a time dependent manner whereas Akt phosphorylation increased during the first 24 h but decreased at 48 h after burn. The p38 MAPK specific inhibitor SB203580 alleviated whereas Akt inhibitor exacerbated burn-induced tubular apoptosis and renal dysfunction. Furthermore, tempol treatment exerted a duplex regulation through inhibiting p38 MAPK phosphorylation but further increasing Akt phosphorylation at 72 h postburn. Conclusions: These results demonstrate that sustained renal ROS overproduction induces continuous tubular cell apoptosis and thus a late ARF at 72 h after burn in severely burned rats, which may result from ROS-mediated activation of p38 MAPK but a late inhibition of Akt phosphorylation. 

Retracted: No

PubPeer comments:
 Figure 2. * Aqua boxes: Two panels, Tempol and SB203580, appear to show an overlap. ![file] , 
 Figure 3B. * Green arrows focus attention to an unexpected  patch or discontinuity in the background around the left-most lane in the Cleaved caspase-3 panel. ![file] , 
 Figure 4F. * A green arrow draws attention to an unexpected background intensity shift. Contrast enhanced. ![file] ,
Melatonin promotes angiogenesis during protection and healing of indomethacin-induced gastric ulcer: role of matrix metaloproteinase-2
Authors: Snehasikta Swarnakar
Anamika Vivek Sharma
Krishnendu Ganguly
Russel J Reiter
Journal: Journal of Pineal Research (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Matrix metalloproteinase (MMP)-2; angiogenesis; melatonin; indomethacin-induced gastric ulcers; rat corneal micropocket assay
Affiliations: Department of Physiology, Drug Development Diagnostics and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata, India.

Abstract:  Matrix metalloproteinase (MMP)-2 is considered as a crucial regulator of angiogenesis, a process of new blood vessel formation. We reported previously that melatonin (N-acetyl-5-methoxy tryptamine), an antioxidant and anti-inflammatory agent, prevents indomethacin-induced gastric ulcers. Herein, we investigated the effect of melatonin on MMP-2-mediated angiogenesis during gastroprotection. Angiogenic properties of melatonin were tested in both rat corneal micropocket assay and in mouse model of indomethacin-induced gastric lesions. Melatonin augmented angiogenesis that was associated with amelioration of MMP-2 expression and activity and, upregulation of vascular endothelial growth factor (VEGF) in rat cornea. Melatonin prevented gastric lesions by promoting angiogenesis via upregulation of VEGF followed by over-expression of MMP-2. Similarly, healing of gastric lesions was associated with early expression of VEGF followed by MMP-2. In addition, upregulation of MMP-2 was parallel to MMP-14 and inverse to tissue inhibitor of metalloprotease (TIMP)-2 expression during gastroprotection. Our data demonstrated that melatonin exerts angiogenesis through MMP-2 and VEGF over-expression during protection and healing of gastric ulcers. This study highlights for the first time a phase-associated regulation of MMP-2 activity in gastric mucosa and an angiogenic action of melatonin to rescue indomethacin-induced gastropathy. 

Retracted: No

PubPeer comments:
 Unexpected similarity in fig 4A ![file] ,
Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes
Authors: Cem Z Görgün
Masato Furuhashi
Lale Ozcan
Eric Vaillancourt
Umut Ozcan
Erkan Yilmaz
Ross O Smith
Gökhan S Hotamisligil
Journal: Science (2006)
Discipline: Multidisciplinary
Keywords: Endoplasmic reticulum stress; obesity; insulin resistance; type 2 diabetes; chemical chaperones
Affiliations: Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA.

Abstract:  Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes. 

Retracted: No

PubPeer comments:
 The number of lanes doesnu2019t match in Figure 2A. Could authors check please? ![file] ,
Role of miR-16-5p in the proliferation and metastasis of hepatocellular carcinoma
Authors: F-Y Fei
F Ding
H Xiao
C-Y Huang
J Li
B Cheng
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-16-5p; hepatocellular carcinoma; IGF1R; invasion; migration
Affiliations: Department of Clinical Laboratory, Shanghai Pudong New Area People's Hospital, Shanghai, China. .

Abstract:  Objective: The aim of this study was to investigate the role of miR-16-5p in hepatocellular carcinoma (HCC), and to explore the possible underlying mechanism. Patients and methods: 100 pairs of cancerous and para-cancerous tissues surgically removed in our hospital were collected. Real Time quantitative-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression level of miR-16-5p in tissues. Bioinformatics and Dual-Luciferase reporter gene assay were used to screen and verify the potential target genes of miR-16-5p, respectively. Human HCC SMMC-7721 cells were used for functional experiments. Cell proliferation was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Cell invasion and migration were evaluated by transwell and scratch wound-healing assay, respectively. The protein expression levels of epithelial-mesenchymal transition (EMT) associated markers were measured by Western blot (WB) assay. Results: QRT-PCR showed that miR-16-5p expression in HCC tissues was significantly lower than that of adjacent normal liver tissues. At the cellular level, miR-16-5p was lowly expressed in HCC cells (SMMC-7721). Bioinformatics websites (including Targetscan, PicTar, miRanda) predicted that insulin-like growth factor 1 receptor (IGF1R) was a potential target gene of miR-16-5p. Meanwhile, IGF1R was selected for further investigation due to its metastatic function. The results showed that no significant difference was found in the mRNA expression level of IGF1R in HCC tissues. However, the protein level of IGF1R was significantly up-regulated, which was negatively correlated with miR-16-5p. Combined with Dual-Luciferase reporter gene assay, it was confirmed that miR-16-5p could regulate the expression of IGF1R in a targeted manner. Furthermore, down-regulation of IGF1R significantly reduced the inhibitory effect of miR-16-5p on the proliferation and metastasis of SMMC-7721 cells. Conclusions: We showed that miR-16-5p suppressed invasion and migration of HCC cells, mechanically by directly targeting and inhibiting IGF1R protein expression. The newly identified miR-16-5p/IGF1R axis might provide new insights into the pathogenesis of HCC and novel potential therapeutic targets for the treatment of HCC. 

Retracted: No

PubPeer comments:
 Figure 4.  MiR-16-5p IGF1R axis inhibited the invasion and migration of HCC cells. A, The migration and invasion of HCC cells were detected by wound-healing assay and transwell assay, respectively (**p 0.01, ***p 0.001 vs. NC group; ##p 0.01 vs. miR-16-5p Mimics group). I have a concern. ![file] ,
Cloning and characterization of a novel WD-40 repeat protein that dramatically accelerates osteoblastic differentiation
Authors: P Divieti
F Gori
M B Demay
Journal: Journal of Biological Chemistry (2001)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: bone morphogenetic proteins; BIG-3; osteoblastic differentiation; WD-40 protein; MC3T3E1 cells
Affiliations: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.

Abstract:  The bone morphogenetic proteins (BMPs) play a pivotal role in endochondral bone formation. Using differential display polymerase chain reaction, we have identified a novel gene, named BIG-3 (BMP-2-induced gene 3 kb), that is induced as a murine prechondroblastic cell line, MLB13MYC clone 17, acquires osteoblastic features in response to BMP-2 treatment. The 3-kilobase mRNA encodes a 34-kDa protein containing seven WD-40 repeats. Northern and Western analyses demonstrated that BIG-3 mRNA and protein were induced after 24 h of BMP-2 treatment. BIG-3 mRNA was expressed in conditionally immortalized murine bone marrow stromal cells, osteoblasts, osteocytes, and growth plate chondrocytes, as well as in primary calvarial osteoblasts. Immunohistochemistry demonstrated that BIG-3 was expressed in the osteoblasts of calvariae isolated from mouse embryos. To identify a role for BIG-3 in osteoblast differentiation, MC3T3-E1 cells were stably transfected with the full-length coding region of BIG-3 (MC3T3E1-BIG-3) cloned downstream of a cytomegalovirus promoter in pcDNA3.1. Pooled MC3T3E1-BIG-3 clones expressed alkaline phosphatase activity earlier and achieved a peak level of activity 10-fold higher than cells transfected with the empty vector (MC3T3E1-EV) at 14 days. Cyclic AMP production in response to parathyroid hormone was increased 10- and 14-fold at 7 and 14 days, respectively, in MC3T3E1-BIG-3 clones, relative to MC3T3E1-EV clones. This increase in cAMP production was associated with an increase in PTH binding. Expression of BIG-3 increased mRNA levels encoding Cbfa1, type I collagen, and osteocalcin and accelerated formation of mineralized nodules. In conclusion, we have identified a novel WD-40 protein, induced by BMP-2 treatment, that dramatically accelerates the program of osteoblastic differentiation in stably transfected MC3T3E1 cells. 

Retracted: No

PubPeer comments:
 ![file] ![file] ,
Selenium Supplementation Affects Insulin Resistance and Serum hs-CRP in Patients with Type 2 Diabetes and Coronary Heart Disease
Authors: E Aghadavod
F Bahmani
S M Mirhashemi
A Farrokhian
Z Asemi
M Taghizadeh
F Raygan
M H Aarabi
Journal: Hormone and Metabolic Research (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: selenium supplementation; metabolic status; type 2 diabetes mellitus; coronary heart disease; inflammation
Affiliations: Department of Cardiology, School of Medicine, Kashan University of Medical Sciences, Kashan, I. R. Iran, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I. R. Iran

Abstract:  To our knowledge, this study is the first indicating the effects of selenium supplementation on metabolic status of patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). This study was conducted to evaluate the effects of selenium supplementation on metabolic profiles, biomarkers of inflammation, and oxidative stress of patients with T2DM and CHD. This randomized, double-blind, placebo-controlled trial was performed among 60 patients with T2DM and CHD aged 40-85 years. Participants were randomly divided into 2 groups. Group A received 200 μg selenium supplements (n=30) and group B received placebo per day (n=30) for 8 weeks. Fasting blood samples were taken at the beginning of the study and after 8-week intervention to quantify metabolic profiles. After 8 weeks, compared with the placebo, selenium supplementation resulted in a significant decrease in serum insulin levels (- 2.2±4.6 vs. + 3.6±8.4 μIU/ml, p=0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (- 0.7±1.3 vs. + 0.9±2.4, p=0.004), homeostatic model assessment-beta cell function (HOMA-B) (- 7.5±17.2 vs. + 15.1±34.5, p=0.002) and a significant increase in quantitative insulin sensitivity check index (QUICKI) (+0.01±0.03 vs. - 0.01±0.03, p=0.02). In addition, patients who received selenium supplements had a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) (- 1 372.3±2 318.8 vs. - 99.8±1 453.6 ng/ml, p=0.01) and a significant rise in plasma total antioxidant capacity (TAC) concentrations (+ 301.3±400.6 vs. - 127.2±428.0 mmol/l, p&lt;0.001) compared with the placebo. A 200 μg/day selenium supplementation among patients with T2DM and CHD resulted in a significant decrease in insulin, HOMA-IR, HOMA-B, serum hs-CRP, and a significant increase in QUICKI score and TAC concentrations. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A55 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,
Trends in Autism Research in the Field of Education in Web of Science: A Bibliometric Study
Authors: Jesús López-Belmonte
Noemí Carmona-Serrano
Juan-Antonio López-Núñez
Antonio-José Moreno-Guerrero
Journal: Brain Sciences (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: SciMAT; Web of Science; autism; bibliometric analysis; scientific mapping.
Affiliations: Ceuta Autism Association, University of Granada, 51001 Ceuta, Spain., Department of Didactics and School Organization, University of Granada, 51001 Ceuta, Spain., Department of Didactics and School Organization, University of Granada, 18071 Granada, Spain.

Abstract:  Autism spectrum disorder (ASD) is conceived as a neurodevelopmental disorder. The scientific literature welcomes studies that reflect the possible singularities that people with ASD may present both in their daily lives and at an educational level. The main objective of this study is to analyze the scientific production on the term autism in Web of Science, focused on the educational field, in order to identify the research trends in this field of study. The intention is to offer researchers who study autism in the educational field some clear research directions. A bibliometric-type methodology was developed using the scientific mapping technique. For this purpose, a performance analysis and a co-word analysis were carried out. Work was conducted with an analysis unit of 5512 documents. The results show that the volume of production has been irregular from the beginning to the present. The collection of documents on the subject began to be relevant, in terms of the volume of production, from 2007, and this has persisted to the present. It is concluded that there are two lines of research. The first is the line focused on mothers of children with ASD and the second is the line of research focused on young people with ASD. In addition, since 2012, new lines of research have been generated, focused on the diagnosis and inclusion of these students in educational centers. 

Retracted: No

PubPeer comments:
 This analysis of unusual editorial behaviour is relevant, given that two of the prolific authors, Matson and Sigafoos, are both featured: http: deevybee.blogspot.com 2016 06 editorial-integrity-publishers-on-front.html. ,
Schizophrenia risk from complex variation of complement component 4
Authors: Mark J Daly
Katherine Tooley
Matthew Baum
Michael C Carroll
Steven A McCarroll
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Heather de Rivera
Beth Stevens
Giulio Genovese
Samuel A Rose
Vanessa Van Doren
Nolan Kamitaki
Avery Davis
Aswin Sekar
Jessy Presumey
Allison R Bialas
Robert E Handsaker
Timothy R Hammond
Journal: Nature (2016)
Discipline: Multidisciplinary
Keywords: Schizophrenia; heritable brain illness; pathogenic mechanisms; major histocompatibility complex (MHC) locus; complement component 4 (C4) genes
Affiliations: Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA., Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA., MD-PhD Program, Harvard Medical School, Boston, Massachusetts 02115, USA., Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA., Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA., Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Abstract:  Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia. 

Retracted: No

PubPeer comments:
 The WT DLGN image in Figure 7D looks quite similar to an image from a paper published a few years before. Could the authors please check this? ![file] ,
ITGA3 interacts with VASP to regulate stemness and epithelial-mesenchymal transition of breast cancer cells
Authors: Xinglong Li
Lianhong Li
Xinye Cui
An&#x27;na Cao
Han Zhang
Journal: Gene (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Breast cancer; EMT; ITGA3; Stemness; VASP.
Affiliations: Department of Pathology, Dalian Medical University, Dalian 116044, China., Department of General Surgery, The First Affiliated Hospital, Dalian Medical University, Dalian 116011, China., Department of Pathology, Dalian Medical University, Dalian 116044, China. Electronic address: .

Abstract:  Background: The interaction of integrin and extracellular matrix (ECM) has a profound implication on pathological conditions such as tumor growth and infiltration. Related reports have confirmed that integrin α3 (ITGA3) influences the development of bladder cancer, head and neck cancer, colorectal cancer and other cancers. However, the mechanism of ITGA3 in breast cancer is unknown. Methods: The impact of ITGA3 on the biological features of breast cancer cells was explored using the Transwell and wound healing assays. In addition, its influence on stemness of breast cancer cells was examined with the sphere formation assay. The possible mechanism by which ITGA3 regulates breast cancer was explored using Western blot. The interaction between ITGA3 and VASP was determined by co-immunoprecipitation and immunofluorescence staining assays. Results: Results show that downregulation of ITGA3 promotes breast cancer cell proliferation, apoptosis, invasion and migration. Indeed, suppression of ITGA3 negatively regulates the stemness of breast cancer cells and EMT process. Our findings indicate that ITGA3 interacts with VASP and regulates its expression, and knockdown of ITGA3 inhibits the activity of the PI3K-AKT axis. Conclusion: Our results show that ITGA3-VASP modulates breast cancer cell stemness, EMT and PI3K-AKT pathways. Therefore, ITGA3 might be a druggable target for clinical breast cancer management. 

Retracted: No

PubPeer comments:
 Figure 1G potential overlap ![file] ,
miR-302 cluster inhibits angiogenesis and growth of K562 leukemia cells by targeting VEGFA
Authors: Chong Chen
Qingyun Wu
Xiao Han
Kailin Xu
Kunming Qi
Wei Chen
Lingyu Zeng
Mingshan Niu
Jiang Cao
Hai Cheng
Li Li
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: VEGFA; angiogenesis; chronic myeloid leukemia; miR-302.
Affiliations: Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China, ., Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.

Abstract:  Background: miR-302 cluster has been reported as a tumor suppressor in many human cancers; yet, its function in chronic myeloid leukemia (CML) tumorigenesis remains largely unclear. The study was aimed to explore the functional roles of miR-302 cluster in CML progression. Materials and methods: Quantitative reverse transcriptase PCR and Western blot were performed to evaluate miR-302 cluster and vascular endothelial growth factor A (VEGFA) expression levels. Cell Counting Kit-8 assay, colony formation assay and human umbilical vein endothelial cell line capillary tube formation were used to determine the influence of miR-302 cluster on the growth and angiogenesis of K562 cells, respectively. Luciferase reporter assay was employed to confirm the direct target interaction between miR-302 cluster and VEGFA. Results: This study demonstrated that miR-302 cluster was frequently downregulated in CML samples and cell lines and high level of miR-302 cluster was significantly associated with good prognosis of CML patients. Compared with miRNA negative control, miR-302 cluster mimics obviously suppressed cell growth, colony formation and angiogenesis. Further studies revealed that VEGFA was a direct target gene of miR-302 cluster. Moreover, overexpression of VEGFA dramatically abated the inhibition of miR-302 cluster on cell growth and angiogenesis. Conclusion: The present study, for the first time, identified miR-302 cluster as a tumor suppressor, and overexpression of miR-302 cluster inhibited growth and angiogenesis in K562 cells. miR-302 cluster may be a potential therapeutic target in CML to develop the adjuvant antiangiogenic therapy based on VEGFA. 

Retracted: No

PubPeer comments:
 Something appears to have gone wrong with the quality of the western blot images in the paper. Could the authors perhaps provide the original uncropped blots? ![file] ,
Rudhira/BCAS3 is a cytoskeletal protein that controls Cdc42 activation and directional cell migration during angiogenesis
Authors: Ganesh P Bhat
K Vijayraghavan
Mamta Jain
Maneesha S Inamdar
Journal: Experimental Cell Research (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cell migration; Rudhira; directional; endothelial cells; Cdc42 activation
Affiliations: Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.

Abstract:  Cell migration is a common cellular process in angiogenesis and tumor metastasis. Rudhira/BCAS3 (Breast Cancer Amplified Sequence 3) is a conserved protein expressed in the embryonic vasculature and malignant tumors. Here, we show for the first time that Rudhira plays an active role in directional cell migration. Rudhira depletion in endothelial cells inhibits Matrigel-induced tube formation and retards healing of wounded cell monolayers. We demonstrate that during wound healing, Rudhira rapidly re-localizes and promotes Cdc42 activation and recruitment to the leading edge of migrating cells. Rudhira deficient cells show impaired downstream signaling of Cdc42 leading to dramatic changes in actin organization and classic cell polarity defects such as loss of microtubule organizing center (MTOC) and Golgi re-orientation. Biochemical assays and co-localization studies show that Rudhira interacts with microtubules as well as intermediate filaments. Thus, Rudhira could control directional cell migration and angiogenesis by facilitating crosstalk between cytoskeletal elements. 

Retracted: No

PubPeer comments:
 ![file] , 
 Thanks for the post. We are re-examining all the data and will follow up on this shortly. , 
 Thank you for the important observation and your interest in our work. We apologize that the wrong GAPDH panel was inadvertently inserted into Fig 6F. We have found the right GAPDH blot and it also shows equal loading. Hence there is no change in our results and conclusions. Further the same conclusion has been reached using other approaches too. Hence the inferences we make from this work hold true. We are contacting the journal to submit an erratum with the correct GAPDH panel for Figure 6F. Regards Maneesha Inamdar , 
 This is called a healthy scientific discussion...this will benefit scientist community in general and student in particular. I salute both the reviwer and the author for sporting spirits to keep the science above. Thanks PS: This subject is not related to me but i am happy with the discussion ,
Interleukin-4 induces up-regulation of endothelial cell claudin-5 through activation of FoxO1: role in protection from complement-mediated injury
Authors: Barbara A Benson
Gregory M Vercellotti
Karen R Wasiluk
Daniel Goldish
Alexander K Tsai
Agustin P Dalmasso
Journal: Journal of Biological Chemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell Junctions; Claudin-5; Complement; Endothelium; Foxo
Affiliations: From the Departments of Surgery.

Abstract:  Injury to endothelial cells (ECs) often results in cell retraction and gap formation. When caused by antigen aggregation or complement, this injury can be prevented by pretreatment of the ECs with IL-4, suggesting that IL-4 modifies the intercellular junction. Therefore, we investigated the effects of IL-4 on expression of intercellular junction proteins and whether such effects are required for IL-4-induced resistance of ECs against complement-mediated injury. We found that IL-4 induces upregulation of the junction protein claudin-5 in porcine ECs through activation of Jak/STAT6 and phosphorylation and translocation of FoxO1 from the nucleus to the cytoplasm. Increased claudin-5 expression resulted in increased transmembrane electrical resistance of the endothelial monolayer and participated in IL-4-induced protection of the ECs from complement injury. Down-regulation of FoxO1 using siRNA by itself caused up-regulation of claudin-5 expression and partial protection from cytotoxicity. This protection was enhanced by stimulation with IL-4. We previously reported that increased phospholipid synthesis and mitochondrial protection were required for IL-4-induced resistance of ECs against complement injury and now we demonstrate a contribution of claudin-5 expression in IL-4-induced protection. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is Axxx 2. Account Res 2020; 28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable , 
 #1 This paper is A4 ,
Phosphatidylinositol 3-kinase and mTOR signaling pathways regulate RNA polymerase I transcription in response to IGF-1 and nutrients
Authors: Martyn J James
Joost C B M Zomerdijk
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ribosomal RNA gene transcription; RNA polymerase I; Insulin-like growth factor-1; Phosphatidylinositol 3-kinase; PI3K
Affiliations: Division of Gene Regulation and Expression, Wellcome Trust Biocentre, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.

Abstract:  Regulation of ribosomal RNA gene transcription by RNA polymerase I (Pol I) is fundamental to ribosome biogenesis and therefore protein translation capacity and cell growth, yet little is known of the key signaling cascades involved. We show here that insulin-like growth factor-1 (IGF-1)-induced Pol I transcription in HEK293 cells is entirely dependent on phosphatidylinositol 3-kinase (PI3K) activity and, additionally, is modulated by the mammalian target of rapamycin (mTOR), which coordinates Pol I transcription with the availability of amino acids. The mitogen-activated protein kinase (MAPK) pathway is weakly stimulated by IGF-1 in these cells and partly contributes to Pol I transcription regulation. Activation of Pol I transcription by IGF-1 results from enhancement of the activity of the Pol I transcription machinery and increased occupancy by SL1 of the endogenous tandemly repeated ribosomal promoters in vivo. The inputs from PI3K, mTOR, and MAPK pathways converge to direct appropriate rRNA gene expression by Pol I in the nucleolus of mammalian cells in response to environmental cues, such as growth factors and nutrients. 

Retracted: No

PubPeer comments:
 Fig. 1B u2013 more similar than expected ![file] , 
 #1 Thank you for pointing out this mistake; the pre-rRNA was inadvertently duplicated for the S6K Western blot. The Editors of the Journal of Biological Chemistry have approved to publish a correction, which typically takes 3-4 weeks to appear. The University of Dundee fully supports this decision and thanks the author of the comment for their diligence. , 
 2020 correction. https: www.jbc.org content 295 20 7178.short There was an error in Fig 1B. The pre-rRNA was inadvertently duplicated for S6K. This error has now been corrected and does not affect the results or conclusions of this work. , 
 The scientific record has been corrected with the publication of an erratum to the satisfaction of the School of Life Sciences Research Integrity Group. ,