PReD-Bench/PRed-Bench huggingface dataset:
Tumor promotion by depleting cells of protein kinase C delta
Authors: Y W Jiang
S Ohno
A Hornia
Q Zang
D A Foster
Z Lu
Journal: Molecular and cellular biology (1997)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Tumor-promoting; phorbol esters; protein kinase C (PKC); c-Src proto-oncogene; 12-O-tetradecanoylphorbol-13-acetate (TPA)
Affiliations: Department of Biological Sciences, Hunter College of The City University of New York, New York 10021, USA.

Abstract:  Tumor-promoting phorbol esters activate, but then deplete cells of, protein kinase C (PKC) with prolonged treatment. It is not known whether phorbol ester-induced tumor promotion is due to activation or depletion of PKC. In rat fibroblasts overexpressing the c-Src proto-oncogene, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced anchorage-independent growth and other transformation-related phenotypes. The appearance of transformed phenotypes induced by TPA in these cells correlated not with activation but rather with depletion of expressed PKC isoforms. Consistent with this observation, PKC inhibitors also induced transformed phenotypes in c-Src-overexpressing cells. Bryostatin 1, which inhibited the TPA-induced down-regulation of the PKCdelta isoform specifically, blocked the tumor-promoting effects of TPA, implicating PKCdelta as the target of the tumor-promoting phorbol esters. Consistent with this hypothesis, expression of a dominant negative PKCdelta mutant in cells expressing c-Src caused transformation of these cells, and rottlerin, a protein kinase inhibitor with specificity for PKCdelta, like TPA, caused transformation of c-Src-overexpressing cells. These data suggest that the tumor-promoting effect of phorbol esters is due to depletion of PKCdelta, which has an apparent tumor suppressor function. 

Retracted: No

PubPeer comments:
 Figure 2. Much more similar than expected. ![file] ,
Identification of histone deacetylase 3 as a biomarker for tumor recurrence following liver transplantation in HBV-associated hepatocellular carcinoma
Authors: Jian Wu
Xiao-Wen Feng
Zhe Yang
Shu-Sen Zheng
Hai-Yang Xie
Feng Zhang
Lin Zhou
Li-Ming Wu
Journal: PLoS ONE (2010)
Discipline: Multidisciplinary
Keywords: class I histone deacetylases; hepatocellular carcinoma; prognosis; immunohistochemistry; hepatitis B virus
Affiliations: Key Lab of Combined Multi-Organ Transplantation, Key Lab of Organ Transplantation, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Abstract:  Background: Recent studies have shown that high expression levels of class I histone deacetylases (HDACs) correlate with malignant phenotype and poor prognosis in some human tumors. However, the expression patterns and prognostic role of class I HDAC isoforms in hepatocellular carcinoma (HCC) remain unclear. Methodology/principal findings: The expression patterns and clinical significance of class I HDAC isoforms were assessed by immunohistochemistry in a cohort of 43 hepatitis B virus-associated HCC patients treated with liver transplantation. In addition, the effects of HDAC inhibition on HCC cell behavior were investigated by knockdown of the HDAC isoform with short interfering RNA. Class I HDACs were highly expressed in a subset of HCCs with positivity for HDAC1 in 51.2%, HDAC2 in 48.8%, and HDAC3 in 32.6% of cases. The expression levels of HDAC isoforms were significantly associated with the proliferation index of HCC. Kaplan-Meier curves showed that a high expression level of HDAC2 or HDAC3 implicated significantly reduced recurrence-free survival. Cox proportional hazards model analysis revealed HDAC3 overexpression was an unfavorable independent prognostic factor (P = 0.002; HR 3.907). In vitro, inhibition of HDAC2 and HDAC3, but not HDAC1, suppressed proliferation and the invasiveness of liver cancer cells. Conclusions/significance: Our findings demonstrate that HDAC3 plays a significant role in regulating tumor cell proliferation and invasion, and it could be served as a candidate biomarker for predicting the recurrence of hepatitis B virus-associated HCC following liver transplantation and a potential therapeutic target. 

Retracted: Yes

PubPeer comments:
 ![file] , 
 https: pubpeer.com publications 616A48B4001ED082802189C565A709 ,
Megalin mediates the transport of leptin across the blood-CSF barrier
Authors: José Antonio Molina
Izaskun Rodal
Eva Carro
Felix Bermejo
Marcelo O Dietrich
Carlos Spuch
Dessire Antequera
Justo G de Yébenes
Journal: Neurobiology of Aging (2008)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Leptin; blood-brain barrier; megalin; transport; obesity
Affiliations: Department of Biochemistry, ICBS, University Federal do Rio Grande de Sul, Porto Alegre, RS, Brazil. 

Abstract:  Leptin, a peptide hormone secreted by adipose tissue, exhibits a large range of central and peripheral actions. It has been proposed that the participation of leptin in diseases such as obesity is due to, at least in part, its impaired transport across the blood-brain barrier (BBB). Since, the mechanisms by which brain takes up leptin remain unclear, we set out to study how leptin may cross the BBB. We have used different immunoassays and lentiviral vectors to analyze the role of megalin in the transport of leptin in rodents and humans. We demonstrate that circulating leptin is transported into the brain by binding to megalin at the choroid plexus epithelium. Indeed, the downregulation of megalin expression in physiological and pathological situations such as aging and Alzheimer's disease was correlated with poor entry of leptin into the brain. Moreover, amyloid beta (Abeta) deposits of choroid plexus could be disturbing megalin function. The present data indicate that leptin represents a novel megalin ligand of importance in the levels and therapeutic actions of leptin into the brain. 

Retracted: No

PubPeer comments:
 This paper presents several issues that need urgent clarification regarding Western Blotting experiments. 1) In Figure 1E vs Figura 3D, the loading calbindin is the same for both blots, although they are different conditions (e.g. control or APP PS1 mice vs HIV or HIV-siMeg rats)? ![file] 2) In Figure 2C, the loading for young vs old seems very similar. ![file] If you zoom it, it is suggestive that they are the same. ![file] 3) If you compare figure 2F with 3C the Megalin bands are exactly the same. However, the P85 loading is not, indicating that in one of them the loading is incorrect. ![file] Also, the band of young Megalin looks exactly the same of P85. 4) The bands for Leptin HIV (Figure 2D) and aged mice (Figure 2B) are very similar. ![file] If you zoom it, you get a better view of what I`m saying. ![file] Can the authors provide the unedited gel to clarify all these points? , 
 Fig. 4D: Mean and error bars are more similar than expected ![file] I also agree with Leptinella Altilitoralis that some blots are more similar than expected (Fig. 3D) ![file] , 
 Fig. 2D and 4B: More similar than expected ![file] Fig. 2C and 3D: More similar than expected ![file] ,
Abstract inference of unchosen option values
Authors: Julie A Fiez
Karin M Cox
Journal: European Journal of Neuroscience (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: decision making; inference; learning; reinforcement; reward.
Affiliations: University of Pittsburgh Pittsburgh PA USA

Abstract:  Reinforcement learning research has pursued a persistent question: Does reward feedback prompt inferences that transcend simple associations? Reversal learning data suggest an affirmative answer: When the positive stimulus (S+) becomes the negative stimulus (S-), trained humans rapidly switch to choosing the former S-. The operations supporting such inferences remain ambiguous. Do participants identify transitions between stimulus-specific contexts (i.e., A+B- and A-B+), or deduce values by learning the abstract contingency structure? Across two experiments, we probed humans' use of abstract rules to infer the values of unchosen alternatives. In Experiment 1, 37 participants attempted a task that originally demonstrated monkeys' difficulty with this form of inference. We presented modified discrimination problems in which the initially chosen stimulus (abstract inference group) or unchosen stimulus (control group) was replaced with a novel stimulus of identical status on Trial 2. In the abstract inference condition, accurate performance can be achieved by applying the consistent contingency structure (but not memory of stimulus-specific reward associations) to infer to the unchosen stimulus' value. The abstract inference group learned to make accurate choices, but only after committing substantially more errors than were observed among control participants-suggesting that unchosen value inferences are infrequently drawn in standard discrimination scenarios. In Experiment 2, 17 participants completed abstract inference problems that had been modified to be suitable for fMRI investigations. Behavioral results both corroborated the Experiment 1 trends and further revealed marked individual differences in explicit awareness of the novel stimulus values. 

Retracted: No

PubPeer comments:
 The open peer review reports are not available on the article s website or on the stated Publons page:  The peer review history for this article is available at https: publons.com publon 10.1111 EJN.14577 Edited by Christoph M. Michel.u201d ,
Acupressure and fatigue in patients with end-stage renal disease–a randomized controlled trial
Authors: Shiow-Luan Tsay
Journal: International journal of nursing studies (2004)
Discipline: CLINICAL MEDICINE
Keywords: acupressure; fatigue; end-stage renal disease; randomized control trial; Piper Fatigue Scale

Abstract:  The purpose of the study is to investigate the effectiveness of acupressure on fatigue in patients with end-stage renal-disease (ESRD). The study was a randomized control trial; qualified patients were randomly assigned into acupressure group, sham group or control group. A total of 106 participants were included in the study. The measures included the revised Piper Fatigue Scale (PFS), VAS of Fatigue, the Pittsburgh Sleep Quality Index and the Beck Depression Inventory. Data of fatigue measures were collected at pretreatment and a week following treatment. Sleep quality and depression were collected during post-test only. The statistical methods included the descriptive statistics, one-way ANOVA, ANCOVA, and repeated-measures ANOVA. ANCOVA that adjusted for differences in baseline fatigue scores (PFS), post-test of depression and sleep quality, result was significant, F(2,100)=3.99, p=0.02. Post-hoc tests revealed that patients in the acupressure group were significantly having lower scores of fatigue than patients in the control group. ANCOVA results also significant for VAS of Fatigue among groups, F(2,100)=5.63, p=0.003. Comparisons indicated that there were significant differences between the acupressure group and the control group (p=0.01) and between the sham group and control group (p=0.003). Predialysis fatigue was assessed routinely by using a rating of 0-10. Repeated-measures ANOVA results demonstrate the group main effect was significant in the perceived fatigue (F(2,88)=19.46, p&lt;0.001). Follow-up tests indicated there were significant differences between the acupressure group and the control group (p&lt;0.001) and between the sham group and control group (p&lt;0.001). The study provided an alternative method for health care providers to managing ESRD patients with fatigue. 

Retracted: No

PubPeer comments:
 See related comment here... https: pubpeer.com publications 65F469A5ABFE858D0CEF2375479647 , 
 And, also, is the author able to comment about the identity between some of the data in this paper and that of a third paper... 10.1046 j.1365-2648.2003.02725.x Tsay SL. Self-efficacy training for patients with end-stage renal disease. J Adv Nurs. 2003 Aug;43(4):370-5. PMID: 12887355 ![file] ![file] ,
Downregulation of microRNA‐367 promotes osteoblasts growth and proliferation of mice during fracture by activating the PANX3‐mediated Wnt/β‐catenin pathway
Authors: Hong-Lei Jia
Dong-Sheng Zhou
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PANX3 gene; Wnt/β-catenin pathway; fracture; microRNA-367; osteoblast.
Affiliations: Department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong University Jinan China

Abstract:  A majority of people suffering from bone fractures fail to heal and develop a nonunion, which is a challenging orthopedic complication requiring complex and expensive treatment. Previous data showed the inhibition of some microRNAs (miRNAs or miRs) can enhance fracture healing. The objective of the present study is to explore effects of miR-367 on the osteoblasts growth and proliferation of mouse during fracture via the Wnt/β-catenin pathway by targeting PANX3. Primarily, the femur fracture model was successfully established in 66 (C57BL/6) 6-week-old male mice. To verify whether miR-367 target PANX3, we used the target prediction program and performed luciferase activity determination. Subsequently, to figure out the underlying regulatory roles of miR-367 in fracture, osteoblasts were elucidated by treatment with miR-367 mimic, miR-367 inhibitor, or siRNA against PANX3 to determine the expression of miR-367, siPANX3, β-catenin, and Wnt5b as well as cell proliferation and apoptosis. The results demonstrated that PANX3 was verified as a target gene of miR-367. MiR-367 was found to highly expressed but PANX3, β-catenin, and Wnt5b were observed poorly expressed in fracture mice. downregulated miR-367 increased the mRNA and protein expression of PANX3, β-catenin, and Wnt5b, increased cell growth, proliferation, and migration, while decreased cell apoptosis in osteoblasts. Altogether, our study demonstrates that the downregulation of miR-367 may promote osteoblasts growth and proliferation in fracture through the activation of the PANX3-dependent Wnt/β-catenin pathway. 

Retracted: Yes

PubPeer comments:
 A small inconsistency: in the Suppl., this is referred to as Malat1, but in the Fig1f, as mascRNA and not Malat1. It is however, understood that mascRNA is part of Malat1 locus. ![file] , 
 Indeed we looked at mascRNA (uncapped) as control. The raw data in the table are labelled Malat1 because, as Prionotus indicated, mascRNA originates in Malat1. Detailed information can be found in the methods section. The following primers were used: MascRACE-f GACGCTGGTGGCTGGCACT MascRACE-r ACACCGCAGGGACTTGAACC . We thank Prionotus for the comment. ,
Reduction in ATP levels triggers immunoproteasome activation by the 11S (PA28) regulator during early antiviral response mediated by IFNβ in mouse pancreatic β-cells
Authors: Dorota Skowyra
John A Corbett
Alison S Salvatori
R Mark L Buller
Wieke Freudenburg
Jill Schriewer
Pradipta Chakraborty
Jennifer Richards
Madhav Gautam
Aaron Baldwin
Jared James
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Autoimmune destruction; insulin producing; pancreatic β-cells; immunoproteasome; MHC class I molecules
Affiliations: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America.

Abstract:  Autoimmune destruction of insulin producing pancreatic β-cells is the hallmark of type I diabetes. One of the key molecules implicated in the disease onset is the immunoproteasome, a protease with multiple proteolytic sites that collaborates with the constitutive 19S and the inducible 11S (PA28) activators to produce immunogenic peptides for presentation by MHC class I molecules. Despite its importance, little is known about the function and regulation of the immunoproteasome in pancreatic β-cells. Of special interest to immunoproteasome activation in β-cells are the effects of IFNβ, a type I IFN secreted by virus-infected cells and implicated in type I diabetes onset, compared to IFNγ, the classic immunoproteasome inducer secreted by cells of the immune system. By qPCR analysis, we show that mouse insulinoma MIN6 cells and mouse islets accumulate the immune proteolytic β1(i), β2(i) and β5(i), and 11S mRNAs upon exposure to IFNβ or IFNγ. Higher concentrations of IFNβ than IFNγ are needed for similar expression, but in each case the expression is transient, with maximal mRNA accumulation in 12 hours, and depends primarily on Interferon Regulatory Factor 1. IFNs do not alter expression of regular proteasome genes, and in the time frame of IFNβ-mediated response, the immune and regular proteolytic subunits co-exist in the 20S particles. In cell extracts with ATP, these particles have normal peptidase activities and degrade polyubiquitinated proteins with rates typical of the regular proteasome, implicating normal regulation by the 19S activator. However, ATP depletion rapidly stimulates the catalytic rates in a manner consistent with levels of the 11S activator. These findings suggest that stochastic combination of regular and immune proteolytic subunits may increase the probability with which unique immunogenic peptides are produced in pancreatic β-cells exposed to IFNβ, but primarily in cells with reduced ATP levels that stimulate the 11S participation in immunoproteasome function. 

Retracted: No

PubPeer comments:
null, 
 https: www.the-scientist.com news-opinion italian-institute-revokes-appointment-of-cancer-researcher-67709 ,
A novel mitochondrial ATP6 frameshift mutation causing isolated complex V deficiency, ataxia and encephalomyopathy
Authors: Christopher B Jackson
Brendan J Battersby
Jean-Marc Nuoffer
Barbara Schröter
André Schaller
Dagmar Hahn
Thomas Schmitt-Mechelke
Paula Marttinen
Uwe Richter
Journal: European Journal of Medical Genetics (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ATP synthase; Complex V deficiency; MT-ATP6; Mitochondrial DNA (mtDNA); Mitochondrial disease.
Affiliations: Institute of Clinical Chemistry, University Hospital Bern, Switzerland; Research Programs for Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Finland. Electronic address: ., Institute of Clinical Chemistry, University Hospital Bern, Switzerland., Department of Neuropaediatrics, Children's Hospital, Cantonal Hospital Lucerne, Switzerland. Electronic address: ., Institute of Biotechnology, University of Helsinki, Finland. Electronic address: ., Institute of Clinical Chemistry, University Hospital Bern, Switzerland. Electronic address: ., Division of Human Genetics, Bern, University Hospital Bern, Switzerland. Electronic address: .

Abstract:  We describe a novel frameshift mutation in the mitochondrial ATP6 gene in a 4-year-old girl associated with ataxia, microcephaly, developmental delay and intellectual disability. A heteroplasmic frameshift mutation in the MT-ATP6 gene was confirmed in the patient's skeletal muscle and blood. The mutation was not detectable in the mother's DNA extracted from blood or buccal cells. Enzymatic and oxymetric analysis of the mitochondrial respiratory system in the patients' skeletal muscle and skin fibroblasts demonstrated an isolated complex V deficiency. Native PAGE with subsequent immunoblotting for complex V revealed impaired complex V assembly and accumulation of ATPase subcomplexes. Whilst northern blotting confirmed equal presence of ATP8/6 mRNA, metabolic 35S-labelling of mitochondrial translation products showed a severe depletion of the ATP6 protein together with aberrant translation product accumulation. In conclusion, this novel isolated complex V defect expands the clinical and genetic spectrum of mitochondrial defects of complex V deficiency. Furthermore, this work confirms the benefit of native PAGE as an additional diagnostic method for the identification of OXPHOS defects, as the presence of complex V subcomplexes is associated with pathogenic mutations of mtDNA. 

Retracted: No

PubPeer comments:
 ![file] ,
Effect of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione, isolated from Averrhoa carambola L. (Oxalidaceae) roots, on advanced glycation end-product-mediated renal injury in type 2 diabetic KKAy mice
Authors: Jianchun Huang
Xing Lin
Shijun Zhang
Kintoko
Xiaohui Xu
Ni Zheng
Renbin Huang
Qingwei Wen
Journal: Toxicology Letters (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Averrhoa carambola L.; DMDD; diabetic nephropathy; KKAy mice; advanced glycation end-products
Affiliations: Department of Pharmacology, Guangxi Medical University, Nanning 530021, PR China.

Abstract:  The roots of Averrhoa carambola L. (Oxalidaceae) have a long history of medical use in traditional Chinese medicine for treating diabetes and diabetic nephropathy. 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) was isolated from the tuberous roots of A. carambola L. The purpose of this study was to investigate the beneficial effect of DMDD on the advanced glycation end-product-mediated renal injury in type 2 diabetic KKAy mice with regard to prove its efficacy by local traditional practitioners in the treatment of kidney frailties in diabetics. KKAy mice were orally administrated DMDD (12.5, 25, 50mg/kg body weight/d) or aminoguanidine (200mg/kg body weight/d) for 8 weeks. Hyperglycemia, renal AGE formation, and the expression of related proteins, such as the AGE receptor, nuclear factor-κB, transforming growth factor-β1, and N(ε)-(carboxymethyl)lysine, were markedly decreased by DMDD. Diabetes-dependent alterations in proteinuria, serum creatinine, creatinine clearance, and serum urea-N and glomerular mesangial matrix expansion were attenuated after treatment with DMDD for 8 weeks. The activities of superoxide dismutase and glutathione peroxidase, which are reduced in the kidneys of KKAy mice, were enhanced by DMDD. These findings suggest that DMDD may inhibit the progression of diabetic nephropathy and may be a therapeutic agent for regulating several pharmacological targets to treat or prevent of diabetic nephropathy. 

Retracted: No

PubPeer comments:
 Fig 2J.  cell cycle and cell cycle ratio detected by flow cytometry . Raw cell-count histogram in NC panel has somehow developed an overhang. ![file] Figs 2K, 7L. The spacing of points in the upper right quadrants of these flow-cytometry plots is neater and more regular than one would expect for cells being sampled randomly from an underlying distribution. ![file] ,
Effective protection of rabbits’ explosive brain injury through blocking gap junction communication
Authors: S Wen-Jiang
Y Yan-Yan
Z Liang-Chao
Z Yong-Ming
L Bing-Cang
T Hong
L Jia-Chuan
Journal: African health sciences (2013)
Discipline: CLINICAL MEDICINE
Keywords: caspase-3; connexin-43 (Cx43); explosive brain injury.
Affiliations: Department of Neurosurgery, 105th Hospital of PLA, Hefei City, 230031, P.R. China.

Abstract:  Background: The gap junction plays an important role in spreading of apoptotic and necrotic signals from injured and stressed cells to the neighboring viable cells. The present study was performed to investigate the important role of gap junction communication on rabbits' explosive brain injury. Methods: Explosion of paper detonators was used to create explosive brain injury model in 60 rabbits, which was randomly divided into control group and experimental group. Octanol, an efficient blocker of gap junction, was injected in the left ventricle to block gap junction communication in the experimental group 2 hours before injury, while the same volume of saline was utilized in the control group. Results: Penumbra volume around the brain contusion in the experimental group was significantly less than that in the control group at 1d and 3d after brain damage. RT-PCR and Western blotting analysis indicated that the expression of connexin-43 (Cx43) and caspase-3 was significantly lower in the experimental group than that in the control group at all time points. Conclusion: Rabbits' explosive brain injury can be efficiently attenuated through blocking the gap junction communication, which benefit for deeper understanding the mechanism of brain injury. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have a differential splice. Could the authors please post the original uncropped scan? *** Inverse ![file] *** Original ![file] ,
Stereoscopic 3D geometric distortions analyzed from the viewer’s point of view
Authors: Guangtao Zhai
Xiaokang Yang
Zhongpai Gao
Journal: PLoS ONE (2020)
Discipline: Multidisciplinary
Keywords: Stereoscopic 3D; geometric distortions; binocular depth cue; monocular depth cues; retinal disparity models
Affiliations: Artificial intelligence institute, Shanghai Jiao Tong University, Shanghai, China.

Abstract:  Stereoscopic 3D (S3D) geometric distortions can be introduced by mismatches among image capture, display, and viewing configurations. In previous work of S3D geometric models, geometric distortions have been analyzed from a third-person perspective based on the binocular depth cue (i.e., binocular disparity). A third-person perspective is different from what the viewer sees since monocular depth cues (e.g., linear perspective, occlusion, and shadows) from different perspectives are different. However, depth perception in a 3D space involves both monocular and binocular depth cues. Geometric distortions that are solely predicted by the binocular depth cue cannot describe what a viewer really perceives. In this paper, we combine geometric models and retinal disparity models to analyze geometric distortions from the viewer's perspective where both monocular and binocular depth cues are considered. Results show that binocular and monocular depth-cue conflicts in a geometrically distorted S3D space. Moreover, user-initiated head translations averting from the optimal viewing position in conventional S3D displays can also introduce geometric distortions, which are inconsistent with our natural 3D viewing condition. The inconsistency of depth cues in a dynamic scene may be a source of visually induced motions sickness. 

Retracted: No

PubPeer comments:
  Pictorial depth cues include...accommodation... I don t think this can be true - accommodation - the adjustment of the shape of the lens to bring objects at different distances into focus - can t be an aid to perceiving the *illusion* of depth created in pictures. ,
PD-1 Deficiency Promotes Macrophage Activation and T-Helper Cell Type 1/T-Helper Cell Type 17 Response in Pneumocystis Pneumonia
Authors: Zhao-Hui Tong
Chao Zhang
Heng-Mo Rong
Kan Zhai
Ting Li
Journal: American Journal of Respiratory Cell and Molecular Biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PD-1; Pneumocystis; T cell; macrophage; pneumonia.
Affiliations: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Abstract:  Pneumocystis is an unusual, opportunistic fungal pathogen capable of causing Pneumocystis pneumonia (PCP) in immunocompromised hosts. Although PCP was discovered &gt;100 years ago, its pathogenesis remains unclear. The inhibitory receptor PD-1 (programmed death 1), a negative regulator of activated T cells, has been reported to take part in tumor escape, immune tolerance, and infection immunity. In this study, we examined the role of the PD-1/PD-L1 (programmed death-ligand 1) pathway in patients with PCP and in mice. The expression levels of PD-1/PD-L1 in patients with PCP and in mice were measured by real-time PCR and flow cytometry. The effects of PD-1 deficiency are demonstrated using wild-type and PD-1-/- mice. Our data show that Pneumocystis infection promotes PD-1/PD-L1 expression; PD-1 deficiency enhances the phagocytic function of macrophages and the pulmonary T-helper cell type 1 (Th1)/Th17 response, which might contribute to Pneumocystis clearance; and PD-1 deficiency affects the polarization of macrophages. PCP mice treated with anti-PD-1 antibody showed improved pulmonary clearance of Pneumocystis. Collectively, our results demonstrate that the PD-1/PD-L1 pathway plays a role in regulating the innate and adaptive immune responses, suggesting that manipulation of this pathway may constitute an immunotherapeutic strategy for PCP. 

Retracted: No

PubPeer comments:
 truncation of diagrams at different thresholds ![file] duplication between Fig 7 and Suppl Fig 5 ![file] ,
Effects of blocking urokinase receptor signaling by antisense oligonucleotides in a mouse model of experimental prostate cancer bone metastases
Authors: B Monia
S Serratí
N Rucci
S D&#x27;Alessio
G L Gravina
F Margheri
M Del Rosso
M Bologna
F Annunziato
A Angelucci
G Fibbi
F Liotta
R Angeli
A Teti
M Pucci
L Cosmi
Journal: Gene therapy (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: tumor cell; invasion; metastasis; urokinase plasminogen activator receptor; uPAR
Affiliations: Department of Experimental Pathology and Oncology, University of Florence, Italy.

Abstract:  An important factor implicated in tumor cell predisposition for invasion and metastasis is the malignancy-related upregulation of urokinase plasminogen activator receptor (uPAR). uPAR signals by activating different tyrosine kinases in different cells. We examined the effects of inhibiting uPAR signaling by inhibition of uPAR expression with antisense oligonucleotides (aODNs) in PC3 human prostate cancer cells and evaluated aODN effect in a mouse model of prostate cancer bone metastasis. Following uPAR aODN treatment, PC3 cells exhibited a strong decrease in uPAR expression, evaluated by flow cytometry and by polymerase chain reaction, and of FAK/JNK/Jun phosphorylation. The synthesis of cyclins A, B, D1 and D3 was inhibited, as shown by Western blotting, flow cytometry and polymerase chain reaction, and PC3 cells accumulated in the G2 phase of the cell cycle. PC3 cells' adhesion was unaffected, while proliferation and invasion of Matrigel were impaired. A total of 60 mice were subjected to intracardiac injection of PC3 cells and were randomly assigned to three groups: aODN (treated with 0.5 mg intraperitoneum/mouse/day), dODN (treated with the same amounts of a degenerated ODN) and control (injected with a saline solution). At 28 days after heart injection, mice were subjected to a digital scan of total body radiography, which revealed 80% reduction in mice affected by bone metastasis. The use of uPAR aODNs produced a substantial prophylactic effect against prostate cancer bone metastasis, which has to be ascribed to downregulation of uPAR expression. 

Retracted: No

PubPeer comments:
 Figures 6a and c lack general background. How can any of the bands be anchored? , 
null, 
 Figure 5a. Much more similar than you would expect. https: imgur.com ndLOeWq , 
 Figure 5a continued. Much more similar than you would expect. https: imgur.com xOGyY6b , 
 Much more similar than you would expect. https: imgur.com vuJd7PY ,
Oral feeding of pomegranate fruit extract inhibits early biomarkers of UVB radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis
Authors: Naghma Khan
Deeba N Syed
Farrukh Afaq
Hasan Mukhtar
Journal: Photochemistry and Photobiology (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Pomegranate; antioxidant; anti-inflammatory; UVB; photocarcinogenesis
Affiliations: Department of Dermatology, University of Wisconsin, Madison, WI, USA. 

Abstract:  Pomegranate from the plant Punica granatum L. possesses strong antioxidant and anti-inflammatory properties. Recently, we have demonstrated that treatment of normal human epidermal keratinocytes with pomegranate fruit extract (PFE) inhibited UVB-mediated activation of nuclear factor kappa B (NF-κB) and mitogen activated protein kinases pathways. Here, we evaluated the effect of PFE on early biomarkers of photocarcinogenesis employing SKH-1 hairless mice. PFE was provided in drinking water (0.2%, wt/vol) to SKH-1 hairless mice for 14 days before a single UVB (180 mJ cm(-2)) irradiation. We found that oral feeding of PFE inhibited UVB-induced: (1) skin edema; (2) hyperplasia; (3) infiltration of leukocytes; (4) lipid peroxidation; (5) hydrogen peroxide generation; (6) ornithine decarboxylase (ODC) activity; and (7) ODC, cyclooxygenase-2 and proliferating cell nuclear antigen protein expression. Oral feeding of PFE enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Importantly, PFE treatment further enhanced UVB-mediated increase in tumor suppressor p53 and cyclin kinase inhibitor p21. Furthermore, oral feeding of PFE inhibited UVB-mediated: (1) nuclear translocation of NF-κB; (2) activation of IKKα; and (3) phosphorylation and degradation of IκBα. Taken together, we provide evidence that oral feeding of PFE to mice affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar than expected. https: imgur.com cvlNxHC ,
PU.1 directly regulates cdk6 gene expression, linking the cell proliferation and differentiation programs in erythroid cells
Authors: Arthur I Skoultchi
Olga Ujhelly
Kevin S Choe
Sandeep N Wontakal
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell proliferation; differentiation; leukemia cells; transcription factor PU.1; erythroid differentiation
Affiliations: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Abstract:  Cell proliferation and differentiation are highly coordinated processes during normal development. Most leukemia cells are blocked from undergoing terminal differentiation and also exhibit uncontrolled proliferation. Dysregulated expression of transcription factor PU.1 is strongly associated with Friend virus-induced erythroleukemia. PU.1 inhibits erythroid differentiation by binding to and inhibiting GATA-1. PU.1 also may be involved in controlling proliferation of erythroid cells. We reported previously that the G(1) phase-specific cyclin-dependent kinase 6 (CDK6) also blocks erythroid differentiation. We now report that PU.1 directly stimulates transcription of the cdk6 gene in both normal erythroid progenitors and erythroleukemia cells, as well as in macrophages. We propose that PU.1 coordinates proliferation and differentiation in immature erythroid cells by inhibiting the GATA-1-mediated gene expression program and also by regulating expression of genes that control progression through the G(1) phase of the cell cycle, the period during which the decision to differentiate is made. 

Retracted: No

PubPeer comments:
 ![file] ,
Effect on Multipotency and Phenotypic Transition of Unrestricted Somatic Stem Cells from Human Umbilical Cord Blood after Treatment with Epigenetic Agents
Authors: Foued Ghanjati
Simeon Santourlidis
Journal: Stem Cells International (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DNA methylation; epigenetic mechanism; somatic stem cells; USSCs; differentiation potential
Affiliations: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University, 40225 Düsseldorf, Germany.

Abstract:  The epigenetic mechanism of DNA methylation is of central importance for cellular differentiation processes. Unrestricted somatic stem cells (USSCs) from human umbilical cord blood, which have a broad differentiation spectrum, reside in an uncommitted epigenetic state with partial methylation of the regulatory region of the gene coding for the pluripotency master regulator OCT4. Thus we hypothesized that further opening of this "poised" epigenetic state could broaden the differentiation potential of USSCs. Here we document that USSCs drastically change their phenotype after treatment by a new elaborated cultivation protocol which utilizes the DNA hypomethylating compound 5'-aza-2-deoxycytidine (5-Aza-CdR) and the histone deacetylase inhibitor trichostatin A (TSA). This treatment leads to a new stable, spheroid-forming cell type which we have named SpheUSSC. These cells can be stably propagated over at least 150 cell divisions, express OCT4, retain the potential to undergo osteogenic differentiation, and have additionally acquired the ability to uniformly differentiate into adipocytes, unlike the source USSC population. Here we describe our treatment protocol and provide evidence that it induces a dedifferentiation step and concomitantly the acquisition of an extended differentiation capability of the new SpheUSSC type. 

Retracted: No

PubPeer comments:
 This study caught my eye, as it appears in a chapter of the Aronson et al. Social Psychology textbook. I m not sure how much to believe it. The sample sizes are very small, with between 10 and 12 participants per cell of the 2x2 experiment. What s more, the means and SDs in Table 1 don t seem to make sense. If the measure is on a 1-12 scale, then the SDs are much too large for what is possible on this scale. I tried taking the square root in case they had confused sigma and sigma^2, but SPRITE was still incapable of finding a valid solution for most cells. ,
Mesenchymal stem cell graft improves recovery after spinal cord injury in adult rats through neurotrophic and pro-angiogenic actions
Authors: Dorothée Cantinieaux
Selim Sid
Olivier Botman
Jean Schoenen
Rachelle Franzen
Renaud Quertainmont
Journal: PloS one (2012)
Discipline: Multidisciplinary
Keywords: spinal cord injury; functional recovery; mesenchymal stem cells; tissue protection; axonal regrowth
Affiliations: GIGA Neurosciences, Axonal Regeneration and Cephalic Pain Unit, University of Liege, Liege, Belgium.

Abstract:  Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord pathophysiology that begets the multifactorial approaches assessed to favour tissue protection, axonal regrowth and functional recovery. In this context, it appears that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to graft MSCs after a spinal cord compression injury in adult rat to assess their effect on functional recovery and to highlight their mechanisms of action. We found that in intravenously grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their open field and grid navigation scores compared to control animals. At the histological analysis of their dissected spinal cord, no MSCs were found within the host despite their BrdU labelling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a significant increase of NGF expression in the injured tissue. Also, a significant tissue sparing effect of MSC graft was observed. Finally, we also show that MSCs promote vascularisation, as the density of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring here some new evidences that MSCs most likely act throughout their secretions and not via their own integration/differentiation within the host tissue. 

Retracted: No

PubPeer comments:
 Figure 1B![file] seems to show the same sample as figure 3C ![file] even though the experimental conditions are different (P4 5 vs P12). Could the authors please check? , 
 Figure 1C![file] seems to show the same sample as figure 3D ![file] even though the experimental conditions are different. Could the authors please check? , 
 #2 I agree with these concerns and have added additional author emails in hopes that one will respond. ,
Retracted : Effects of long non‐coding RNA HOST2 on cell migration and invasion by regulating MicroRNA let‐7b in breast cancer
Authors: Fang Wang
Peng-Wei Lu
Yuan-Ting Gu
Lin Li
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HOST2; breast cancer; invasion; let-7b; lncRNA
Affiliations: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.

Abstract:  The study intends to investigate the effects of long non-coding RNA HOST2 (lncRNA HOST2) on cell migration and invasion by regulating microRNA let-7b (let-7b) in breast cancer. Breast cancer and adjacent normal tissues were collected from 98 patients with breast cancer. Breast cancer MCF-7 cells were divided into the blank, negative control (NC), pcDNA3-Mock, siHOST2, let-7b inhibitor, pcDNA3-HOST2, let-7b mimic, pcDNA3-HOST2 + let-7b mimic, and siHOST2 + let-7b inhibitor groups. RT-qPCR was used to detect the mRNA expressions of HOST2, let-7b, and c-Myc. Western blotting was conducted to measure the c-Myc expression. Scratch test and Transwell assay were applied to detect the cell motility, migration, and invasion. Xenograft tumor in nude mice was performed to evaluate the effect of different transfection on the tumor growth. Compared with adjacent normal tissues, HOST2 expression was higher but let-7b expression lower in breast cancer tissues. HOST2 expression in breast cancer cells was remarkably increased compared with that in the normal breast epithelial MCF-10A cells. In MCF-7 cells, in comparison with the blank and NC groups, expressions of HOST2 and c-Myc were reduced, but let-7b expression was remarkably elevated in the siHOST2 and let-7b mimic groups; the let-7b inhibitor group exhibited higher expressions of HOST2 and c-Myc but lower let-7b expression. Overexpression of HOST2 could promote cell motility, migration and invasion, thus enhancing the growth of breast cancer tumor. By inhibiting HOST2, opposite trends were found. LncRNA HOST2 promotes cell migration and invasion by inhibiting let-7b in breast cancer patients. 

Retracted: Yes

PubPeer comments:
 Fig 3B.  Expression of Host2, Let-7b and c-Myc in each group ... (B) western blotting bands of c-Myc protein expression in each group . ![file] The resolution is not ideal, but the similarity can still be seen between the present loading control and those in Fig 9A from [Wu et al (2018a)] , or 5C of [Wu et al (2018b)] . More appearances are listed in those threads. ![] , 
 Retracted [30 June 2021] . ---------------------- The above article, published online on 13 December 2017 in Wiley Online Library has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid. ,
mA mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
Authors: Qi Wu
Nan Huang
Zhongqi Cui
Fenyong Sun
Qiuhui Pan
Liang Deng
Guohui Li
Ji Ma
Journal: Genes (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AMPK; HCC; LKB1; WTAP; autophagy.
Affiliations: School of Life Sciences, Jiangsu University, Zhenjiang 212013, China., Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China., Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200072, China., Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics, Shanghai 200072, China.

Abstract:  The N6-methyladenosine (m6A) RNA modification can regulate autophagy to modulate the growth and development of tumors, but the mechanism of m6A modification for the regulation of autophagy in hepatocellular carcinoma cells (HCC) remains unclear. In the study, the knockdown of the Wilms' tumor 1-associating protein (WTAP) was made in HCC to study the correlation between m6A modification and autophagy. A fluorescent confocal microscopy analysis showed that the knockdown of WTAP could facilitate the autophagy of HCC. A Western blot analysis showed that the level of p-AMPK was decreased in WTAP-knockdown HCC cells. Additionally, LKB1, the upstream kinase of AMPK, was regulated by WTAP and it could mediate the phosphorylation of AMPK in an m6A-dependent manner. Further studies revealed that the knockdown of WTAP could reduce the level of LKB1 mRNA with m6A. This could result in the increased stability of LKB1 mRNA to promote its expression. The knockdown of WTAP could upregulate the level of autophagy and inhibit HCC proliferation. However, the overexpression of WTAP could resist autophagic cell death. 

Retracted: No

PubPeer comments:
 sharp transition in the first lane of figure 1C , 
 The images in Fig. 1G could not merge ![file] ,
Curcumin prevents experimental autoimmune encephalomyelitis by inhibiting proliferation and effector CD4+ T cell activation
Authors: Y-R Wang
J-T Liu
J-Q Liu
Y-Q Yan
X Wang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Multiple sclerosis; CD4+ T cells; Curcumin; Apoptosis; Proliferation
Affiliations: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China. .

Abstract:  Objective: Multiple sclerosis (MS) has affected over 2 million people worldwide and it is thought to be initiated by the activated central nervous system (CNS). Reactive CD4+ T cells (TH1, TH17, and Treg phenotypes) are crucial to MS. The TH1 phenotype can promote major histocompatibility complex-II expression and TH17 can induce inflammatory gene expression. Curcumin, a yellow pigment, is found in turmeric rhizomes and has been reported to have various activities, such as anti-proliferative and anti-inflammatory activity. Curcumin has great potential in MS treatment. Little is known about the effect of curcumin on MS. Therefore, we investigated the effect of curcumin on MS, especially on CD4+ T cells. Materials and methods: CD4+ T cells (TH1, TH17, and Treg cells) were cultured in Iscove's Modified Dulbecco's Medium (IMDM) medium. Cell proliferation was evaluated by MTT assay. The ability of individual CD4+ T cells to aggregate into viable colony clusters was assessed by clonogenic survival assay. Apoptosis of CD4+ T cells was determined by flow cytometry. The expression of Bcl-2, Bax, and active caspase-3 was detected by Western blotting. The effect of curcumin on the activation molecule was also evaluated by flow cytometry. Results: MTT assay showed that curcumin significantly inhibited CD4+ T cell viability. Furthermore, TH1, TH17, and Treg all showed a dose-dependent but not time-dependent. The results of clonogenic survival assay revealed that curcumin markedly decreased the colony formation ability of CD4+ T cells. Flow cytometry results indicated that curcumin-induced remarkable apoptosis in TH1, TH17, and Treg cells. After treatment with curcumin, the expression of Bcl-2 was decreased and that of Bax and active caspase-3 was increased. Western blotting results also showed that curcumin-induced apoptosis in CD4+ T cells. Hence, our results demonstrated that curcumin inhibited CD4+ T cell proliferation via inducing apoptosis in CD4+ T cells. Meanwhile, flow cytometry results also showed that curcumin directly inhibited CD4+ T cell activation. Conclusions: Curcumin could inhibit CD4+ T cell proliferation and effector cell activation. 

Retracted: No

PubPeer comments:
 Figure 3A. Several panels appear to look unexpectedly similar to each other, with some small variations. In fact, among the 12 panels, I seem to see only three different panels (marked in red, blue, and green). Could the authors maybe checked what happened here, please? ![file] , 
 Figure 5 appears to show some panels that look similar, too. Marked here with pink boxes. ![file] ,