PReD-Bench/PRed-Bench huggingface dataset:
MicroRNA‚Ä?95 suppresses rectal cancer growth and metastasis via regulation of the PI3K/AKT signaling pathway
Authors: Yeli Wang
Miaoling Huang
Linsong Mu
Journal: Molecular Medicine Reports (2019)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miR-195; rectal cancer; IGF1; tumor suppressor
Affiliations: Department of Anorectal, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, P.R. China, Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, P.R. China

Abstract:  MicroRNAs (miRNAs) play a vital role in the progression of cancer, however, only limited data on miRNAs in rectal cancer are available. The aim of the present study was to investigate whether miR‚Ä?95 could inhibit the progression of rectal cancer. The miR‚Ä?95 mimic was transfected into 2 types of human rectal cancer cells (SW837 and SW1463). Cell viability and apoptosis were analyzed by Cell Counting Kit‚Ä? (CCK‚Ä?) assay and flow cytometry, and cell migration and invasion were assessed by scratch test and Transwell assay. The results revealed that insulin‚Äëlike growth factor 1 (IGF1) was predicted as a potential target of miR‚Ä?95 by Targetscan7.2, and the result was verified by dual‚Äëluciferase reporter assay. The co‚Äëtransfection of IGF1 was performed to confirm the underlying mechanism of tumor suppressor of miR‚Ä?95 in rectal cancer. The activation of PI3K/AKT signaling was determined by western blotting. The levels of miR‚Ä?95 in SW837 and SW1463 cells were revealed to be lower than in human rectal mucosa epithelial cells. After the transfection with miR‚Ä?95, the cell viability was decreased, while the apoptosis was significantly increased (SW837: 5.21% vs. 20.96%; SW1463: 4.19% vs. 25.22%). Moreover, cell migration and invasion were significantly inhibited in the mimic group. miR‚Ä?95 specifically targeted IGF1, however, the co‚Äëtransfection of IGF1 could partially reverse the inhibitory effects of miR‚Ä?95 on rectal cancer cells. It was also determined that the phosphorylation of PI3K and AKT were significantly inhibited in the mimic group. The tumor suppressive ability of miR‚Ä?95 in rectal cancer cell proliferation and metastasis was mediated by blocking IGF1 expression and inhibiting the PI3K/AKT pathway. 

Retracted: No

PubPeer comments:
 Figure 2A. * Red boxes. In the 48h row, the  Blank and  mimic control panels appear to show an area of overlap.  , 
 Figure 2B. * Blue boxes: The SW837 Blank panel appears to show an overlap with the SW837 mimic control panel. * Green boxes: The SW837 mimic panel appears to show an overlap with the SW1463 mimic control panel. * Pink box: (see below): The SW1463 mimic panel appears to show an overlap with the SW837 mimic panel in Figure 7A.  , 
 Figure 7A. Several panels appear to overlap, including one pane that overlaps with Figure 2B above (pink box).  ,
Functional interactions within yeast mediator and evidence of differential subunit modifications
Authors: Magnus Hallberg
Darius Balciunas
Hans Ronne
Stefan Bj√∂rklund
Journal: Journal of Biological Chemistry (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: RNA polymerase II; Mediator subunits; transcription activation; lexA fusion; functional interactions
Affiliations: Department of Plant Biology, Swedish University of Agricultural Sciences, Uppsala Genetic Center, Box 7080, Sweden.

Abstract:  It is possible to recruit RNA polymerase II to a target promoter and, thus, activate transcription by fusing Mediator subunits to a DNA binding domain. To investigate functional interactions within Mediator, we have tested such fusions of the lexA DNA binding domain to Med1, Med2, Gal11, Srb7, and Srb10 in wild type, med1, med2, gal11, sin4, srb8, srb10, and srb11 strains. We found that lexA-Med2 and lexA-Gal11 are strong activators that are independent of all Mediator subunits tested. lexA-Srb10 is a weak activator that depends on Srb8 and Srb11. lexA-Med1 and lexA-Srb7 are both cryptic activators that become active in the absence of Srb8, Srb10, Srb11, or Sin4. An unexpected finding was that lexA-VP16 differs from Gal4-VP16 in that it is independent of the activator binding Mediator module. Both lexA-Med1 and lexA-Srb7 are stably associated with Med4 and Med8, which suggests that they are incorporated into Mediator. Med4 and Med8 exist in two mobility forms that differ in their association with lexA-Med1 and lexA-Srb7. Within purified Mediator, Med4 is present as a phosphorylated lower mobility form. Taken together, these results suggest that assembly of Mediator is a multistep process that involves conversion of both Med4 and Med8 to their low mobility forms. 

Retracted: No

PubPeer comments:
 Could the author re-check the spliting sits in Fig.3?  ,
TPX2 promotes glioma cell proliferation and invasion via activation of the AKT signaling pathway
Authors: Hong-Jie Chen
Jian-He Zhang
Shou-Sen Wang
Jian-Jun Gu
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: AKT; TPX2; glioma; invasion; proliferation.
Affiliations: Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, Fuzhou, Fujian 350025, P.R. China; Department of Neurosurgery, Taizhou People's Hospital Affiliated to Medical College of Nantong University, Taizhou, Jiangsu 225300, P.R. China., Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, Fuzhou, Fujian 350025, P.R. China.

Abstract:  Glioblastoma multiforme (GBM) is the most common and most malignant type of primary adult brain cancer. The most common phenotype associated with GBM is cellular invasion; however, the molecular mechanisms governing this process are poorly understood. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a nuclear protein with roles in cellular proliferation and mitotic spindle assembly. TPX2 is overexpressed in various malignancies, including human malignant astrocytoma. Despite this finding, the exact role of TPX2 in human glioma is not well defined. The present study reports the elevated expression of TPX2 in a number of glioma cell lines. TPX2 overexpression promoted cellular proliferation, decreased the percentage of cells in G0/G1 phase, and increased invasion of both U251 and U87 cells. Overexpression of TPX2 also significantly enhanced the phosphorylation of AKT, decreased the expression of p21, and increased the expression of cyclin D1 and matrix metallopeptidase (MMP)-9. In both U251 and U87 cells, knockdown of TPX2 resulted in phenotypes that are in direct contrast to those observed following TPX2 overexpression. Specifically, TPX2 knockdown inhibited cell proliferation, increased the percentage of cells in G0/G1 phase, inhibited invasion, decreased AKT phosphorylation, decreased the expression of MMP-9 and cyclin D1, and increased p21 expression. The AKT inhibitor IV in large part phenocopied the effect of TPX2 knockdown. The present data suggest that TPX2 promotes glioma cell proliferation and invasion via AKT signaling. 

Retracted: No

PubPeer comments:
 Figs 3C, 6C. Panels overlap (sometimes with 180-deg flips).   The two panels marked with green rectangles are very similar, with local differences as if cells were added. Here dramatised by color-reversing one of the panels are superimposing it on the other panel so that identical areas cancel out.  ,
The Uracil Transporter Fur4p Associates with Lipid Rafts
Authors: John D Hearn
Robert L Lester
Robert C Dickson
Journal: Journal of Biological Chemistry (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Sphingolipids; Saccharomyces cerevisiae; lcb1-100 cells; sphingoid long chain base intermediates; complex sphingolipids

Abstract:  Sphingolipids are abundant components of eucaryotic membranes, where they perform essential functions. To uncover new roles for sphingolipids, we studied Saccharomyces cerevisiae lcb1-100 cells, which have a temperature-sensitive block in the first step in sphingolipid synthesis. We find that the level of all five species of the sphingoid long chain base intermediates is reduced 2-7-fold in cells grown at a permissive temperature, and the level of complex sphingolipids is reduced 50%. In addition, lcb1-100 cells make no detectable phosphorylated sphingoid bases. After transfer to a restrictive temperature (a heat shock), the level of the major sphingoid bases drops rather than transiently rising, as in wild type cells. These changes affect lcb1-100 cells in multiple ways. Basal uracil transport by Fur4p is reduced 25%, and when cells are heat-shocked, uracil transport activity falls rapidly and is not restored as it is in wild type cells. Restoration requires a functional secretory pathway and synthesis of complex sphingolipids, leading us to hypothesize that Fur4p associates with lipid rafts. The finding that Fur4p is insoluble in TritonX-100 at 4 degrees C and behaves like a raft-associated protein on a density gradient supports this hypothesis. Raft association may be essential for regulating breakdown of Fur4p in response to stresses and other factors that govern uracil transport activity. Our results show that long chain bases do not contribute to the inactivation of Fur4p transport activity after heat stress, but they are essential for some later, but unknown, process that leads to degradation of the protein. Further studies using lcb1-100 cells should reveal new roles of sphingolipids in nutrient uptake and other membrane-dependent processes. 

Retracted: No

PubPeer comments:
 Figure 3E: The kinase activity of CRCK1 was increased by adding different concentrations of CaM, but it decreased when the Ca2-chelator EGTA, or CaM antagonist chlorpromazine (CPZ), or the peptide corresponding to the CaM-binding region (amino acids 160u2013183) was added. Red Boxes: time zero of EGTA and CPZ treatments appear to be much more similar than expected. Were experiments maybe done simultaneosly? Could the authors please clarify?  , 
 Figure 5A: some18S RNA loading control bands look much more similar than expected (blue boxes). Could the authors please check?  ,
Highly expressed long non-coding RNA DUXAP10 promotes proliferation of ovarian cancer
Authors: Q Zhang
Z-F Xu
W-W Wang
T-H Xu
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Long non-coding RNA; DUXAP10; Ovarian cancer; Cell lines; Gene Expression Omnibus
Affiliations: Department of Prenatal Diagnosis, State Key Laboratory of Reproductive Medicine, Obstretrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China. .

Abstract:  Objective: To investigate the expression of long non-coding RNA DUXAP10 in ovarian cancer and its effect on ovarian cancer cell lines HO8910 and A2780 cells. Materials and methods: Search the microarray dataset from the Gene Expression Omnibus (GEO) database using the keywords "ovarian cancer" and "GPL570". The differentially expressed genes in ovarian cancer tissues and normal ovarian tissues were analyzed by bioinformatics. Normal ovarian epithelial cells IOSE386, ovarian cancer HEY, HO8910 and A2780 cell lines were cultured. Cell proliferation assay was detected by CCK8 method and cloning formation assay was done. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of RNA. Results: The results showed that the expression of DUXAP10 in ovarian cancer tissues was significantly higher than that in normal ovarian tissues, which was consistent with those of TCGA. Clinical data analysis showed that the expression level of DUXAP10 was correlated with tumor size and FIGO stage in clinical patients. Compared with the negative control group, the proliferation ability and cell cloning ability of HO8910 cells overexpressing DUXAP10 were significantly increased (p&lt;0.001), while the proliferation and cell cloning ability of A2780 cells interfering with DUXAP10 were significantly decreased (p&lt;0.001), indicating that DUXAP10 played a role in promoting the proliferation of ovarian cancer cells. Conclusions: DUXAP10 was significantly overexpressed in ovarian cancer tissues, and its expression was positively correlated with tumor size and FIGO stage in clinical patients. DUXAP10 promoted the proliferation of ovarian cancer cells and was expected to be a predictor and a potential therapeutic target of ovarian cancer. 

Retracted: No

PubPeer comments:
 The central most important document underlying this paper has a dead link (footnote 4): https: www.ciber-research.eu download ECR-questionnaire-for-website-20191129.pdf If the authors could kindly correct the link or indicate the new URLs for this document, please. , 
 #1 It seems that replacing the .eu domain with .com does the trick. , 
 #2 Yes, thank you. I guess it s a consequence of the Brexit. ,
Short-term resveratrol exposure causes in vitro and in vivo growth inhibition and apoptosis of bladder cancer cells
Authors: Xiao-Hong Shu
Qing-You Kong
Xue Song
Jia Liu
Mo-Li Wu
Hong Li
Xiao-Yan Chen
Li-Jun Yu
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Adjuvant chemotherapies; Bladder transitional cell carcinomas; Resveratrol; Safety; Efficacy
Affiliations: Liaoning Laboratory of Cancer Genetics and Epigenomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Abstract:  Conventional adjuvant chemotherapies for bladder transitional cell carcinomas (TCCs) may cause strong systemic toxicity and local irritation. Non-toxic resveratrol inhibits TCC cell growth but its feasibility in clinical management of TCCs remains obscure. This study aimed to evaluate the safety and anti-TCC efficacy of resveratrol, using the experimental models closer to the clinical treatment condition. Human TCC EJ cells were exposed to 100 ¬µM, 150 ¬µM and 200 ¬µM resveratrol respectively for 1 hour and 2 hours to mimic intravesical drug instillation and the cell responses were analyzed by multiple experimental approaches. An orthotopic TCC nude mouse model was established by injecting EJ cells into the sub-urothelial layer and used for short-term intravesical resveratrol instillation. The safety of resveratrol instillation was evaluated and compared with that of MCC. The results revealed that 2 h 150 ¬µM or 200 ¬µM resveratrol treatment leaded to remarkable S phase arrest and apoptosis at 72 h time-point, accompanied with attenuated phosphorylation, nuclear translocation and transcription of STAT3, down-regulation of STAT3 downstream genes (survivin, cyclinD1, c-Myc and VEGF) and nuclear translocations of Sirt1 and p53. The importance of STAT3 signaling in cell growth was confirmed by treating EJ cells with JAK2 inhibitor tyrphostin AG490. The efficacy and safety of resveratrol instillation were proved by the findings from nude mouse orthotopic xenograft models, because this treatment caused growth suppression, distinctive apoptosis and STAT3 inactivation of the transplanted tumors without affecting normal urothelium. Our results thus suggest for the first time the practical values of resveratrol as a safe and effective agent in the post-operative treatment of TCCs. 

Retracted: No

PubPeer comments:
 Figure 2C and 4D. * Red boxes: The same VEGF lane appears to be visible in two different panels. Reported to the journal in October 2015, but no action taken as of today.  ,
Retracted : Upregulation of microRNA‚Ä?40‚Ä?p inhibits epithelial‚Äêmesenchymal transition, invasion, and metastasis of hepatocellular carcinoma through inactivation of the MAPK signaling pathway by targeting GRN
Authors: Chang-Jun Men
Xue-Wei Ding
Qiu-Yin Zhang
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: epithelial-mesenchymal transition; granulin; hepatocellular carcinoma; invasion and metastasis; microRNA-140-3p
Affiliations: Department of Gastroenterology, Tianjin First Central Hospital, Tianjin, PR China., Department of Gastrointestinal Tumor Surgery, Tianjin Cancer Hospital, Tianjin, PR China.

Abstract:  Invasion and metastasis in hepatocellular carcinoma (HCC) results in poor prognosis. Human intervention in these pathological processes may benefit the treatment of HCC. The aim of the present study is to elucidate the mechanism of miR-140-3p affecting epithelial-mesenchymal transition (EMT), invasion, and metastasis in HCC. Microarray analysis was performed for differentially expressed genes screening. The target relationship between miR-140-3p and GRN was analyzed. Small interfering RNA (siRNA) against granulin (GRN) was synthesized. EMT markers were detected, and invasion and migration were evaluated in HCC cells introduced with a miR-140-3p inhibitor or mimic, or siRNA against GRN. A mechanistic investigation was conducted for the determination of mitogen-activated protein kinase (MAPK) signaling pathway-related genes and EMT markers (E-cadherin, N-cadherin, and Vimentin). GRN was highlighted as an upregulated gene in HCC. GRN was a target gene of miR-140-3p. Elevation of miR-140-3p or inhibition of GRN restrained the EMT process and suppressed the HCC cell migration and invasion. HCC cells treated with the miR-140-3p mimic or siRNA-GRN exhibited decreased GRN expression and downregulated the expressions of the MAPK signaling pathway-related genes, N-cadherin, and Vimentin but upregulated the expression of E-cadherin. GRN silencing can reverse the activation of the MAPK signaling pathway and induction of EMT mediated by miR-140-3p inhibition. Taken together, the results show that miR-140-3p confers suppression of the MAPK signaling pathway by targeting GRN, thus inhibiting EMT, invasion, and metastasis in HCC. 

Retracted: Yes

PubPeer comments:
 Retracted [19 July 2021] . ---------------------------------------------- The above article, published online on 01 May 2019 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. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid. --------------------------------------- The paper contains Western Blots of the distinctive stylised  string-of-sausages form, and had been listed in [a spreadsheet dedicated to products of the  Contractor papermill] . It had not previously been flagged in Pubpeer.  ,
Nanog safeguards early embryogenesis against global activation of maternal Œ≤-catenin activity by interfering with TCF factors
Authors: Mudan He
Shengbo Jiao
Yonghua Sun
Ding Ye
Fenghua Zhang
Ru Zhang
Houpeng Wang
Journal: PLoS Biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Maternal Œ≤-catenin activity; Nanog; dorsal induction; pluripotency; maternal-zygotic transition
Affiliations: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Wuhan, China., College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China.

Abstract:  Maternal Œ≤-catenin activity is essential and critical for dorsal induction and its dorsal activation has been thoroughly studied. However, how the maternal Œ≤-catenin activity is suppressed in the nondorsal cells remains poorly understood. Nanog is known to play a central role for maintenance of the pluripotency and maternal -zygotic transition (MZT). Here, we reveal a novel role of Nanog as a strong repressor of maternal Œ≤-catenin signaling to safeguard the embryo against hyperactivation of maternal Œ≤-catenin activity and hyperdorsalization. In zebrafish, knockdown of nanog at different levels led to either posteriorization or dorsalization, mimicking zygotic or maternal activation of Wnt/Œ≤-catenin activities, and the maternal zygotic mutant of nanog (MZnanog) showed strong activation of maternal Œ≤-catenin activity and hyperdorsalization. Although a constitutive activator-type Nanog (Vp16-Nanog, lacking the N terminal) perfectly rescued the MZT defects of MZnanog, it did not rescue the phenotypes resulting from Œ≤-catenin signaling activation. Mechanistically, the N terminal of Nanog directly interacts with T-cell factor (TCF) and interferes with the binding of Œ≤-catenin to TCF, thereby attenuating the transcriptional activity of Œ≤-catenin. Therefore, our study establishes a novel role for Nanog in repressing maternal Œ≤-catenin activity and demonstrates a transcriptional switch between Œ≤-catenin/TCF and Nanog/TCF complexes, which safeguards the embryo from global activation of maternal Œ≤-catenin activity. 

Retracted: No

PubPeer comments:
  We have screened the Xenopus database but could not find any ortholog of Nanog in Xenopus. Really sad to see that our old work about this very question remains invisible to most researchers... 10.1371 journal.pone.0085104 10.1371 journal.pone.0036855 Good to know that the subject still rises interest. I recommend looking up P. Scerbo s great follow up work, great reads indeed. Cheers to all. ,
DCA increases the antitumor effects of capecitabine in a mouse B16 melanoma allograft and a human non-small cell lung cancer A549 xenograft
Authors: Wei-da Huang
Mao-Fa Zheng
Si-yu Shen
Journal: Cancer Chemotherapy and Pharmacology (2013)
Discipline: CLINICAL MEDICINE
Keywords: Capecitabine; Sodium dichloroacetate (DCA); Anticancer agent; TP expression; Apoptosis
Affiliations: Department of Biochemistry, School of Life Science, Fudan University, Handan Road 220, Shanghai, 200433, China.

Abstract:  Purpose: Capecitabine is one of the few chemotherapy drugs with high oral availability. Recently, sodium dichloroacetate (DCA) has shown great potential as an anticancer agent. In the present study, we assessed the anticancer effect of DCA in combination with capecitabine for cancers that modestly expressed TP. Methods: A mouse B16 melanoma allograft and a human non-small cell lung cancer A549 xenograft were used to assess the effect of DCA and capecitabine combined treatment. Histology and immunohistochemistry were used to detect the apoptosis and proliferation of cancer cells. Real-time PCR and Western blot were carried out to detect the expression of TP and caspases, respectively. Results: For the first time, we report that DCA increased the antitumor effects of capecitabine in a mouse B16 allograft and a human A549 xenograft by promoting apoptosis of tumor cells. DCA has little effect on the expression of TP. Conclusions: Our finding suggests that DCA in combination with capecitabine might be potential as a new therapeutic regimen against some cancers. 

Retracted: No

PubPeer comments:
 Figure 4b * Red boxes: The CAP and DCA + CAP panels appear to show an overlap.  Reported to the journal together with 28 other papers in the summer of 2015, with a friendly reminder in April 2017, but no answer. With the exception of one paper, the journal did not correct or retract a single paper from this set. Could the authors please clarify if the journal contacted them back in 2015? , 
 Figure 5A. * Blue boxes: Here, as well, the CAP and DCA+CAP panels appear to show an overlap.  ,
Tanshinone IIA Affects Autophagy and Apoptosis of Glioma Cells by Inhibiting Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway
Authors: Shudong Wang
Feier Chen
Weiyao Wang
Tianjiao Meng
Lijuan Ding
Ling Qi
Donghai Zhao
Peng Lv
Lihua Dong
Journal: Pharmacology (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Tanshinone IIA; cell viability; apoptosis; autophagy; human glioma
Affiliations: Department of Radiation Oncology, First Hospital of Jilin University, Changchun, China.

Abstract:  Objective: To test the effects of Tanshinone IIA (Tan IIA) on cell viability, cycle, apoptosis, and autophagy of human glioma cell U251 by regulating phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signal pathway. Methods: Tan IIA and PI3K agonist (740 Y-P) were used to treat glioma cells U251. MTT assay was used to assess cell viability and flow cytometry was used to detect cell apoptosis and cell cycle. The expressions of apoptosis-related proteins (Bcl-2 and Bax), autophagy-related proteins (LC3B and Beclin 1) and PI3K/Akt/mTOR signal pathway-associated proteins (p-PI3K, p-Akt and p-mTOR) were evaluated by Western blotting. Results: Tan IIA decreased the expression of p-PI3K and p-Akt proteins, inhibited cell viability and promoted apoptosis. Meanwhile, the expression of Bax increased, while the expression of Bcl-2 decreased. In addition, Tan IIA promoted autophagy in U251 glioma cells and raised the expression of LC3B and Beclin 1. However, 740 Y-P played a reversed role of Tan IIA in cell viability, cycle, apoptosis, and autophagy of U251 cells. Conclusion: Tan IIA could suppress the viability of U251 cells and induce cell apoptosis and autophagy, which might be related to the inhibition of the PI3K/Akt/mTOR signal pathway. 

Retracted: No

PubPeer comments:
 Fig 3(b)  Distribution of apoptotic cells in the 4 groups repeats some features between two panels.  ,
Design and development of molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles as potential multifunctional agents to treat Alzheimer's disease
Authors: Santosh Kumar Prajapati
Sushant Kumar Shrivastava
Avanish Tripathi
Ankit Seth
Piyoosh Sharma
Sairam Krishnamurthy
Manish Kumar Tripathi
Priyanka Kumari Choubey
Prabhash Nath Tripathi
Journal: European Journal of Medicinal Chemistry (2019)
Discipline: CHEMISTRY
Keywords: Acetylcholinesterase (AChE); Alzheimer's disease; AŒ≤ aggregation; Molecular hybridization; Multi-functional agents
Affiliations: Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India., Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India. Electronic address: .

Abstract:  The diverse nature of Alzheimer's disease (AD) has prompted researchers to develop multi-functional agents. Herein, we have designed and synthesized molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles. Biological activities of synthesized compounds suggested significant and balanced inhibitory potential against target enzymes. In particular, compound 49 containing 2,4-difluoro substitution at terminal phenyl ring considered as most potential lead with inhibition of acetylcholinesterase (hAChE, IC50 = 0.054 ŒºM), butyrylcholinesterase (hBChE, IC50 = 0.787 ŒºM) and beta-secretase-1 (hBACE-1, IC50 = 0.098 ŒºM). The enzyme kinetics study of 49 against hAChE suggested a mixed type of inhibition (Ki = 0.030 ŒºM). Also, 48 and 49 showed significant displacement of propidium iodide from the peripheral anionic site (PAS) of hAChE, excellent blood-brain barrier (BBB) permeability in parallel artificial membrane permeation assay (PAMPA), and neuroprotective ability against SH-SY5Y neuroblastoma cell lines. Further, 49 also exhibited anti-AŒ≤ aggregation activity in self- and AChE-induced thioflavin T assay, which was ascertained by morphological characterization by atomic force microscopy (AFM). Moreover, in vivo behavioral studies signified learning and memory improvement by compound 49 in scopolamine- and AŒ≤-induced cognitive dysfunctions performed on Y-maze and Morris water maze. The ex vivo studies suggested decreased AChE activity and antioxidant potential of compound 49, with good oral absorption characteristics ascertained by pharmacokinetic studies. 

Retracted: No

PubPeer comments:
 More similar than one would expect when considering two images from as many papers. Requesting authors to post unedited source file images for these two panels.  , 
 #1 @Pitcairnia Hirtzii The panel presented in both the papers are different and do not bear any resemblance whatsoever with each other except being both belong to aggregates of amyloid beta. The images are the outcomes of different raw data and are not duplication by altering magnification. I therefore do not accept your opinion on the same. Sushant ,
miR‚Ä?78a‚Ä?p inhibits cellular proliferation and migration in glioblastoma multiforme by targeting tetraspanin 17
Authors: Zhi-Qiang Shen
Li-Mei Ma
Xiao-Bing Guo
Xiao-Chao Zhang
Peng Chen
Journal: Oncology reports (2019)
Discipline: CLINICAL MEDICINE
Keywords: Glioblastoma multiforme; MicroRNAs; miR‚Ä?78; Tetraspanin 17; TSPAN17
Affiliations: Department of Anatomy and Histology/Embryology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China., School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.

Abstract:  Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor and patients with this disease tend to have poor clinical outcome. MicroRNAs (miRs) are important regulators of a number of key pathways implicated in tumor pathogenesis. Recently, the expression of miR‚Ä?78 was shown to be dysregulated in several different types of cancer, including gastric cancer, colorectal cancer and oral carcinoma. Additional studies have demonstrated that miR‚Ä?78 may serve as a potential therapeutic target against human breast cancer. However, the underlying mechanisms and potential targets of miR‚Ä?78a‚Ä?p involved in GBM remain unknown. The aim of the present of was to determine the effects of miR‚Ä?78a‚Ä?p and its potential targets. Tetraspanin 17 (TSPAN17) is involved in the neoplastic events in GBM and is a member of the tetraspanin family of proteins. The tetraspanins are involved in the regulation of cell growth, migration and invasion of several different types of cancer cell lines, and may potentially act as an oncogene associated with GBM pathology. The results of the present study showed that high miR‚Ä?78a‚Ä?p and low TSPAN17 expression levels were associated with improved survival in patients with GBM. Additionally, high levels of TSPAN17 were linked to the poor prognosis of patients with GBM aged 50‚Ä?0, larger tumor sizes (‚â? cm) and an advanced World Health Organization stage. TSPAN17 was identified and confirmed as a direct target of miR‚Ä?78a‚Ä?p using a luciferase reporter assay in human glioma cell lines. Overexpression of miR‚Ä?78a‚Ä?p in either of U87MG or MT‚Ä?30 cells decreased the expression of TSPAN17, promoted apoptosis and decreased proliferation, migration and invasion. Overexpression of TSPAN17 attenuated the aforementioned effects induced by miR‚Ä?78a‚Ä?p overexpression. The present study indicated that miR‚Ä?78a‚Ä?p suppresses the progression of GBM by reducing TSPAN17 expression, and may thus serve as a potential therapeutic target for treating patients with GBM. 

Retracted: No

PubPeer comments:
 It may be a simple formatting error, but portions of Figures 5 6 are duplicated in panel A ,
MicroRNA-374a Governs Aggressive Cell Behaviors of Glioma by Targeting Prokineticin 2
Authors: Haozhe Piao
Ji Shi
Ye Zhang
Haiyang Liang
Yi Chen
Rui Zhang
Rui Sui
Journal: Technology in Cancer Research & Treatment (2019)
Discipline: CLINICAL MEDICINE
Keywords: Prok2; glioma; invasion; miR-374a; tumor suppressor.
Affiliations: 1 Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Dadong District, Shenyang, PR China., 2 Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Dadong District, Shenyang, PR China.

Abstract:  MicroRNA-374a has been abnormally expressed in several cancer types; however, its role in glioma remains unclear. Therefore, we aimed to investigate whether microR-374a participated in the progression of glioma. Expression of microR-374a in glioma cell lines and normal cell line was measured by quantitative real-time polymerase chain reaction. Luciferase reporter assay and Western blot were used to detect the targets of microR-374a. In vitro functional experiments were conducted to investigate the biological role of microR-374a. Low expression of microR-374a was found in glioma cell lines. Prokineticin 2 was identified as a direct target of microR-374a in glioma. Investigations on the mechanisms related to glioma progression showed that microR-374a inhibited glioma cell proliferation, cell cycle progression, and cell invasion through targeting Prokineticin 2. Taken together, these results revealed that microR-374a functions as tumor suppressor by targeting Prokineticin 2, suggesting it might be a novel therapeutic target for glioma. 

Retracted: No

PubPeer comments:
 Figure 2D appears to have an image overlap, after rotation. ***  , 
 Retracted [24 August 2021] . H t [RetractionWatch] . -------------------------------------------- At the request of the Journal Editor the following article has been retracted. Zhang Y, Zhang R, Sui R, et al. MicroRNA-374a Governs Aggressive Cell Behaviors of Glioma by Targeting Prokineticin 2. Technology in Cancer Research Treatment, DOI:10.1177 1533033818821401 Significant similarities between this paper and a number of other papers have been identified, as well as indication of image and data manipulation suggestive of the use of a u201cpaper millu201d. These papers share common structures and wording yet do not share any common authors. The authors did not provide a sufficient response or evidence to refute these claims. As a result, the scientific accuracy of this paper is not reliable. Adhering to the international guidelines established by the Committee on Publication Ethics, the Journal has determined these are grounds for retraction. ,
The B cell receptor promotes B cell activation and proliferation through a non-ITAM tyrosine in the Igalpha cytoplasmic domain
Authors: Heide Christine K Patterson
Manfred Kraus
You-Me Kim
Hidde Ploegh
Klaus Rajewsky
Journal: Immunity (2006)
Discipline: IMMUNOLOGY
Keywords: Igalpha; ITAM; tyrosine; phosphorylation; B cell receptor
Affiliations: The CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA.

Abstract:  In addition to the tyrosines of the Igalpha and beta immunoreceptor tyrosine-based activation motifs (ITAMs), the evolutionarily conserved Igalpha non-ITAM tyrosine 204 becomes phosphorylated upon antigen recognition by the B cell receptor (BCR). Here we demonstrate that splenic B cells from mice with a targeted mutation of Igalpha Y204 exhibited an isolated defect in T cell-independent B cell activation, proliferation, and antibody response upon BCR engagement, yet normal BCR capping, antigen internalization, antigen presentation, and T cell-dependent antibody production. Mutant B cells, present in normal numbers, exhibited unimpaired BCR-induced spleen tyrosine kinase (Syk) phosphorylation but reduced B cell linker protein (BLNK) phosphorylation, calcium flux, and nuclear factor kappaB (NFkappaB), c-jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) activation. These results suggest that Igalpha non-ITAM tyrosine 204 promotes a distinct cellular response, namely T-independent B cell proliferation and differentiation via phosphorylation of the adaptor BLNK. 

Retracted: No

PubPeer comments:
 https: twitter.com dgurdasani1 status 1410175550702997507 , 
 https: twitter.com globalhlthtwit status 1411704237042634757 , 
 https: twitter.com apsmunro status 1396858104290156549 , 
 https: twitter.com globalhlthtwit status 1411795147243900928 , 
 https: twitter.com petertomasi1 status 1411876011071971328 ,
Involvement of NF-kappaB and glutathione in cytotoxic effects of nitric oxide and taxol on human leukemia cells
Authors: Maria Cl√°udia Santos-Silva
Jamil Assreuy
Marta Sampaio de Freitas
Journal: Leukemia Research (2006)
Discipline: CLINICAL MEDICINE
Keywords: Nitric oxide; glutathione; cytotoxicity; gamma-glutamylcysteine synthetase; NF-kappaB
Affiliations: Department of Clinical Analysis, Center of Health Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florian√≥polis, SC 88049-900, Brazil. 

Abstract:  Nitric oxide (NO) has been shown to be cytotoxic for normal and transformed cell lines. One of the intracellular targets for NO action is glutathione (GSH). GSH determinates cellular redox potential and modulates several biological events. During oxidative and nitrosative stress, glutathione system imbalance is associated with the upregulation of gamma-glutamylcysteine synthetase (gamma-GCS) expression, which is mediated by nuclear factor kappaB (NF-kappaB). Our previous studies demonstrated a cytotoxic effect of NO and taxol on human lymphoblastic leukemia cells triggered by inhibition of NF-kappaB activity. In this study, we have demonstrated the involvement of GSH in taxol- and NO-induced cytotoxic effects on human CEM leukemia cells. NO- and taxol-induced a depletion of GSH levels in CEM cells, which was potentialized by l-buthionine-S,R-sulfoximine (BSO), an inhibitor of gamma-GCS. BSO induced an increase in nuclear translocation of NF-kappaB. However, when cells were treated with NO or taxol in association with BSO, these compounds inhibited the constitutive activity of NF-kappaB. These results suggest that oxidative and nitrosative damage in lymphoblastic leukemia cells shall be mediated by NO- and taxol-induced GSH depletion as a consequence of preventing GSH synthesis. 

Retracted: No

PubPeer comments:
 Figure 5B - some bands look quite similar to bands found in Figures 2-5 of Marta Sampaio De Freitas et al., Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (2003) - doi: 10.1016 s0925-4439(03)00096-6 - https: pubpeer.com publications B7E253C7712EA443A96BD248B5C95D Can the authors please clarify if all bands represent the same experiments in both papers?  Here is a collage of blots in the 2003 paper:  These bands are also visible in different constellations in Santos-Silva et al. Cancer Letters (2001) doi: 10.1016 s0304-3835(01)00664-4 - https: pubpeer.com publications 655036839E4DA1B840CA1C40F002BA and in MC Santos-Silva s PhD thesis found here: https: repositorio.ufsc.br bitstream handle 123456789 84103 183506.pdf ,
Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole
Authors: Patricia T W Cohen
Tam√°s Zeke
Nick Morrice
Cristina V√°zquez-Martin
Journal: Biochemical Journal (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ppp5; protein phosphatase; Hsp70; Hsp90; arachidonic acid
Affiliations: Medical Research Council Protein Phosphorylation Unit, Division of Cell Signalling, School of Life Sciences, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.

Abstract:  Ppp5 (protein phosphatase 5) is a serine/threonine protein phosphatase that has been conserved throughout eukaryotic evolution. In mammalian cells, FLAG-tagged Ppp5 and endogenous Ppp5 are found to interact with endogenous Hsp (heat-shock protein) 70, as well as Hsp90. Incubation of cells with arachidonic acid or the microtubule-depolymerizing agent, nocodazole, causes loss of interaction of Hsp70 and Hsp90 with FLAG-tagged Ppp5 and increase of Ppp5 activity. In response to the same treatments, endogenous Ppp5 undergoes proteolytic cleavage of the N- and C-termini, with the subsequent appearance of high-molecular-mass species. The results indicate that Ppp5 is activated by proteolysis on dissociation from Hsps, and is destroyed via the proteasome after ubiquitination. Cleavage at the C-terminus removes a nuclear localization sequence, allowing these active cleaved forms of Ppp5 to translocate to the cytoplasm. The response of Ppp5 to arachidonic acid and nocodazole suggests that Ppp5 may be required for stress-related processes that can sometimes cause cell-cycle arrest, and leads to the first description for in vivo regulation of Ppp5 activity. 

Retracted: No

PubPeer comments:
 Figure 4. Much more similar and different than expected.  , 
 Figure 2B. Vertical changes in signal in different places in different panels.  , 
 2021 Expression of Concern. https: portlandpress.com biochemj article 478 22 4025 230282 Human-protein-phosphatase-5-dissociates-from-heat A reader has contacted the Biochemical Journal Editorial Board to draw attention to a potential concern regarding some of the data Figures in this article. The concerns raised are regarding band similarities in Figure 2B and evidence of gel splicing in this figure, Figure 4, and others. Due to the time elapsed between publication of the article and the concerns being raised, as well as the recent passing of the senior author, Lady Tricia Cohen, it will not be possible to conduct an investigation and source the original data to verify or allay the concerns raised. Following COPE guidance, the Editorial Board has therefore decided to issue an Expression of Concern to alert readers to this issue. The authors have been informed of this notification. ,
Evidence for a dominant-negative effect in ACTA1 nemaline myopathy caused by abnormal folding, aggregation and altered polymerization of mutant actin isoforms
Authors: Kay E Davies
Sandra T Cooper
Sophie Clement
Adam L Maxwell
Kathryn N North
Nigel G Laing
Ana Domazetovska
Kristen J Nowak
Biljana Ilkovski
Journal: Human Molecular Genetics (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: nemaline myopathy; ACTA1 gene; muscle alpha-skeletal actin; gamma-filamin; myotilin

Abstract:  We have studied a cohort of nemaline myopathy (NM) patients with mutations in the muscle alpha-skeletal actin gene (ACTA1). Immunoblot analysis of patient muscle demonstrates increased gamma-filamin, myotilin, desmin and alpha-actinin in many NM patients, consistent with accumulation of Z line-derived nemaline bodies. We demonstrate that nebulin can appear abnormal secondary to a primary defect in actin, and show by isoelectric focusing that mutant actin isoforms are present within insoluble actin filaments isolated from muscle from two ACTA1 NM patients. Transfection of C2C12 myoblasts with mutant actin(EGFP) constructs resulted in abnormal cytoplasmic and intranuclear actin aggregates. Intranuclear aggregates were observed with V163L-, V163M- and R183G-actin(EGFP) constructs, and modeling shows these residues to be adjacent to the nuclear export signal of actin. V163L and V163M actin mutants are known to cause intranuclear rod myopathy, however, intranuclear bodies were not reported in patient R183G. Transfection studies in C2C12 myoblasts showed significant alterations in the ability of V136L and R183G actin mutants to polymerize and contribute to insoluble actin filaments. Thus, we provide direct evidence for a dominant-negative effect of mutant actin in NM. In vitro studies suggest that abnormal folding, altered polymerization and aggregation of mutant actin isoforms are common properties of NM ACTA1 mutants. Some of these effects are mutation-specific, and likely result in variations in the severity of muscle weakness seen in individual patients. A combination of these effects contributes to the common pathological hallmarks of NM, namely intranuclear and cytoplasmic rod formation, accumulation of thin filaments and myofibrillar disorganization. 

Retracted: No

PubPeer comments:
  , 
 #1 That s pretty weak. I would not be willing to place a wager in support of your claim. Here s another view of the same region, after adjusting the gradient map:  , 
 #2 Lane 11 is the lane under question. There are quite a lot of similarities between the upper and lower lanes. , 
  ,
Mitogen-activated protein kinases regulate susceptibility to ventilator-induced lung injury
Authors: Emeka Ifedigbo
Augustine M K Choi
A Murat Kaynar
Alexander Hoetzel
Simon C Watkins
Wei Wu
M√°ria Szilasi
Naftali Kaminski
Stefan W Ryter
Tam√°s Dolinay
Journal: PLoS ONE (2008)
Discipline: Multidisciplinary
Keywords: Mechanical ventilation; ventilator-induced lung injury; mitogen-activated protein kinases; p38; mitogen activated protein kinase kinase-3
Affiliations: Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Abstract:  Background: Mechanical ventilation causes ventilator-induced lung injury in animals and humans. Mitogen-activated protein kinases have been implicated in ventilator-induced lung injury though their functional significance remains incomplete. We characterize the role of p38 mitogen-activated protein kinase/mitogen activated protein kinase kinase-3 and c-Jun-NH(2)-terminal kinase-1 in ventilator-induced lung injury and investigate novel independent mechanisms contributing to lung injury during mechanical ventilation. Methodology and principle findings: C57/BL6 wild-type mice and mice genetically deleted for mitogen-activated protein kinase kinase-3 (mkk-3(-/-)) or c-Jun-NH(2)-terminal kinase-1 (jnk1(-/-)) were ventilated, and lung injury parameters were assessed. We demonstrate that mkk3(-/-) or jnk1(-/-) mice displayed significantly reduced inflammatory lung injury and apoptosis relative to wild-type mice. Since jnk1(-/-) mice were highly resistant to ventilator-induced lung injury, we performed comprehensive gene expression profiling of ventilated wild-type or jnk1(-/-) mice to identify novel candidate genes which may play critical roles in the pathogenesis of ventilator-induced lung injury. Microarray analysis revealed many novel genes differentially expressed by ventilation including matrix metalloproteinase-8 (MMP8) and GADD45alpha. Functional characterization of MMP8 revealed that mmp8(-/-) mice were sensitized to ventilator-induced lung injury with increased lung vascular permeability. Conclusions: We demonstrate that mitogen-activated protein kinase pathways mediate inflammatory lung injury during ventilator-induced lung injury. C-Jun-NH(2)-terminal kinase was also involved in alveolo-capillary leakage and edema formation, whereas MMP8 inhibited alveolo-capillary protein leakage. 

Retracted: No

PubPeer comments:
 Figures 2B and 7C. Much more similar and different than expected.  ,
Stabilization of Ribosomal RNA of the Small Subunit by Spermidine in Staphylococcus aureus
Authors: Stefano Marzi
Iskander Khusainov
Margarita Belinite
Marat Yusupov
Heddy Soufari
Yaser Hashem
Pascale Romby
Journal: Frontiers in Molecular Biosciences (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: RNA stability; Staphylococcus aureus; ribosomal RNA; ribosome 70¬†S; translation.
Affiliations: Institut de G√©n√©tique et de Biologie Mol√©culaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Universit√© de Strasbourg, Illkirch, France., Institut Europ√©en de Chimie et Biologie (IECB), ARNA U1212, Universit√© de Bordeaux, Pessac, France., Architecture et R√©activit√© de l'ARN, CNRS 9002, Universit√© de Strasbourg, Strasbourg, France.

Abstract:  Cryo-electron microscopy is now used as a method of choice in structural biology for studying protein synthesis, a process mediated by the ribosome machinery. In order to achieve high-resolution structures using this approach, one needs to obtain homogeneous and stable samples, which requires optimization of ribosome purification in a species-dependent manner. This is especially critical for the bacterial small ribosomal subunit that tends to be unstable in the absence of ligands. Here, we report a protocol for purification of stable 30 S from the Gram-positive bacterium Staphylococcus aureus and its cryo-EM structures: in presence of spermidine at a resolution ranging between 3.4 and 3.6 √Ö and in its absence at 5.3 √Ö. Using biochemical characterization and cryo-EM, we demonstrate the importance of spermidine for stabilization of the 30 S via preserving favorable conformation of the helix 44. 

Retracted: No

PubPeer comments:
 Figure1 A fourth; How come in such low magnesium you are getting 70S. also without mentioning the density of spermidine, how can we conclude that good resolution is because of it . It can be due to biasness in collecting datasets? ,