PReD-Bench/PRed-Bench huggingface dataset:
C-Kit expression in the gallbladder of guinea pig with chronic calculous cholecystitis and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal
Authors: Fang Wang
Hua Feng
Changmiao Wang
Journal: Iranian journal of basic medical sciences (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Artemisia capillaries Thunb; C-Kit; Gallstone; Interstitial cells of Cajal.
Affiliations: Department of General Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116000, China., Department of Physical Examination, First Affiliated Hospital, Dalian Medical University, Dalian 116000, China.

Abstract:  Objectives: To study the c-Kit expression in the gallbladder of cholesterol lithogenic guinea pig model and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal (ICCs). Materials and methods: A total of 45 guinea pigs were randomly assigned into three groups: the control group (guinea pigs fed a standard diet, normal group); the model group (guinea pigs fed a cholesterol gallstone-inducing diet); and the Chinese medicine group (guinea pigs fed the cholesterol gallstone-inducing diet and treated with A. capillaris through intragastric administration, therapy group). Each group had 15 guinea pigs. The gallbladders of the guinea pigs were harvested after 8 weeks. C-Kit expression was detected using an immunohistochemistry staining, real-time PCR, and Western blot analyses. The effect of A. capillaris on ICCs was evaluated by muscle strip contraction experiments. Results: C-Kit expression significantly decreased in the gallbladder of model group, but increased in the Chinese medicine group. The Contractility of guinea pig gallbladder muscle strip significantly improved in the Chinese medicine group. Conclusion: Our results indicated that A. capillaris improves gallbladder impairment by up-regulating c-Kit expression, and it also can improve the contractile response of in vitro guinea pig gallbladder muscle strips. 

Retracted: No

PubPeer comments:
 Figure 1. * Red boxes: Panels B (ICCs model group) and C (ICCs therapy group) appear to show an area of overlap, if one of the panels is rotated slightly. ![file] ,
MicroRNA-125 modulates radioresistance through targeting p21 in cervical cancer
Authors: Ángel Herrera-Gómez
Oliver Millan-Catalan
Guadalupe Robelo-Romero
Horacio Zamudio-Meza
Abraham Pedroza-Torres
David Isla-Ortiz
David Cantú de León
Gonzalo Montalvo-Esquivel
Yahir A Loissell-Baltazar
Óscar Ángeles-Zaragoza
Luis A Herrera
Carlos Pérez-Plasencia
Alma D Campos-Parra
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: Cervical cancer; radioresistance; microRNAs; miR-125a; CDKN1A
Affiliations: Cancer Genomics Group, National Cancer Institute of Mexico, Mï¿½xico City 14080, Mexico, Gynecology Functional Department, National Cancer Institute of Mexico, Mï¿½xico City 14080, Mexico, Cancer Research Unit, National Cancer Institute of Mexico, Mï¿½xico City 14080, Mexico, Radiotherapy Department, National Cancer Institute of Mexico, Mï¿½xico City 14080, Mexico, Deputy Director, National Cancer Institute of Mexico, Mï¿½xico City 14080, Mexico

Abstract:  Cervical cancer (CC) is one of the most common cancers diagnosed in women worldwide, and it is estimated that ~500,000 new patients are diagnosed with cervical cancer annually and that ~270,000 deaths occur each year. Patients with cervical cancer are treated with different radiotherapy schedules, either alone or with adjuvant chemotherapy. Unfortunately, nearly 50% of all patients with cervical cancer do not respond to standard treatment due to tumor radioresistance. In this scenario, several microRNAs (miRNAs) have been associated with the acquisition of the radioresistance phenotype. The aim of the present study was to evaluate the possible role of miR‑125a in the acquisition of radioresistance in cervical cancer. The expression of miR‑125a was assessed by means of RT‑qPCR in 30 cervical cancer samples from patients receiving standard treatment and 3 induced radioresistant cervical cancer cell lines. In addition, we employed miR‑125a mimics and inhibitors to evaluate its function in the induction of radioresistance. We showed that miR‑125a was downregulated in patients with cervical cancer who did not respond to standard treatment. Concordantly, radioresistant SiHa, CaSki and HeLa cell lines had low levels of miR‑125a with respect to the sensitive cell lines. Finally, we demonstrated that overexpression of miR‑125a sensitized cervical cancer cells to radiation therapy through the downregulation of CDKN1A. Our data corroborate previously published studies in which it was demonstrated that miRNAs could play a role in the regulation of the process of radioresistance. Additionally, we showed that overexpression of miR‑125a could be used as a radioresistance biomarker in patients with cervical cancer. 

Retracted: No

PubPeer comments:
 Figure 6B appears to include a repeated image. *** ![file] ,
Critical role of miR-10b in transforming growth factor-β1-induced epithelial–mesenchymal transition in breast cancer
Authors: Wang Feng
Wang Liuxing
Li Mengquan
Zhang Weijie
Xu Han
Fan Qingxia
Sun Yan
Journal: Cancer Gene Therapy (2014)
Discipline: CLINICAL MEDICINE
Keywords: Epithelial-mesenchymal transition (EMT); microRNA-10b (miR-10b); breast cancer; aggressiveness; E-cadherin
Affiliations: Department of Breast Disease Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China., Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.

Abstract:  Epithelial-mesenchymal transition (EMT) is a key process in the tumor metastatic cascade that is characterized by the loss of cell-cell junctions and cell polarity, resulting in the acquisition of migratory and invasive properties. Recent evidence showed that altered microRNA-10b (miR-10b) expression was implicated in the occurrence of EMT of breast cancer. However, the exact role and underlying mechanisms of miR-10b in the EMT of breast cancer still remain unknown. In this study, miR-10b was found to be upregulated in breast cancer tissues and breast cancer cell lines and the expression of miR-10b was shown to be closely correlated with aggressiveness in breast cancer. Treating breast cancer cells with the miR-10b inhibitor increased E-cadherin expression while decreasing vimentin expression. At the same time, on inhibition of miR-10b, the invasion and proliferation ability of breast cancer cells also decreased. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that induces EMT in multiple cell types. Here, we identified miR-10b as a target gene of TGF-β1. The expression of miR-10b increased during TGF-β1-induced EMT of breast cancer cells. Further study showed that inhibition of miR-10b expression partially reversed the EMT, invasion and proliferation induced by TGF-β1 in breast cancer cells. Taken together, these results demonstrated a novel function for miR-10b in TGF-β1-induced EMT in breast cancer and increased their metastatic potential. MiR-10b might become a possible target for gene therapy in breast cancer. 

Retracted: No

PubPeer comments:
 All Figures with raw data in this article are tainted with serious problems. ![file] ,
Catabolite repression of phosphoenolpyruvate carboxykinase by a zinc finger protein under biotin- and pyruvate carboxylase-deficient conditions in Pichia pastoris
Authors: Nallani Vijay Kumar
Pundi N Rangarajan
Journal: Microbiology (2011)
Discipline: MICROBIOLOGY
Keywords: methanol; biotin; zinc finger protein; ROP; Pichia pastoris
Affiliations: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India

Abstract:  We have identified a methanol- and biotin-starvation-inducible zinc finger protein named ROP [repressor of phosphoenolpyruvate carboxykinase (PEPCK)] in the methylotrophic yeast Pichia pastoris. When P. pastoris strain GS115 (wild-type, WT) is cultured in biotin-deficient, glucose-ammonium (Bio(-)) medium, growth is suppressed due to the inhibition of anaplerotic synthesis of oxaloacetate, catalysed by the biotin-dependent enzyme pyruvate carboxylase (PC). Deletion of ROP results in a strain (ΔROP) that can grow under biotin-deficient conditions due to derepression of a biotin- and PC-independent pathway of anaplerotic synthesis of oxaloacetate. Northern analysis as well as microarray expression profiling of RNA isolated from WT and ΔROP strains cultured in Bio(-) medium indicate that expression of the phosphoenolpyruvate carboxykinase gene (PEPCK) is induced in ΔROP during biotin- or PC-deficiency even under glucose-abundant conditions. There is an excellent correlation between PEPCK expression and growth of ΔROP in Bio(-) medium, suggesting that ROP-mediated regulation of PEPCK may have a crucial role in the biotin- and PC-independent growth of the ΔROP strain. To our knowledge, ROP is the first example of a zinc finger transcription factor involved in the catabolite repression of PEPCK in yeast cells cultured under biotin- or PC-deficient and glucose-abundant conditions. 

Retracted: No

PubPeer comments:
 Concerns about proper assessment of gene expression. ![file] , 
 The fact that AOXI, FLDI, DHAS,. PEX8 and PEX14 levels are comparable in both lanes indicates that equal amount was RNA was loaded in both lanes. Therefore no other loading control was required and reviewers did not insist on it. ,
Estradiol‐17β inhibits homocysteine mediated damage by promoting H 2 S production via upregulating CBS and CSE expression in human umbilical vein endothelial cells
Authors: Ying Zhang
Xiaona Niu
Dandan Zhang
Jia Wang
Xiuqin Hong
Jian Chen
Yu Jiang
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cystathine γ-lyase; cystathionine β-synthase; endogenous hydrogen sulfide; estrogen; homocysteine.
Affiliations: People's Hospital of Hunan Province, First Affiliated Hospital of Hunan Normal University, Changsha, China., Mawangdui Hospital, University of South China, Hengyang, China., People's Hospital of Hunan Province Emergency Medicine Research Institute, Changsha, China.

Abstract:  Associated with reduced hydrogen sulfide (H2 S) production in Hcy metabolic disorders, Plasma Hcy accumulation can bring about vascular dysfunction. Nevertheless, recently proposed therapies for vascular damage by estrogen could contribute to promoting endogenous hydrogen sulfide production. This study explores whether estrogen can come into play in protection in hyperhomocysteinemia and hypertensive patients at a population level, and then analyses the specific mechanism of estrogen protection in homocysteine (Hcy)-treated human umbilical vein endothelial cells (HUVECs) at the foundational level. A case-control study, conducted on 1277 female hypertension and non-hypertensive patients from Hunan Provincial People's Hospital, showed that the Hcy concentration of hypertensive patients emerged higher than that of healthy controls (P &lt; .001), and that of estrogen was the reverse (P &lt; .001). Estrogen had a negative correlation with systolic blood pressure and plasma Hcy concentration. HUVECs were treated with estrogen and Hcy in the basic experimental part, and 17β-estradiol (E2β) stimulated proliferation and inhibited damage in Hcy-treated umbilical vein endothelial cells. Treatment with Hcy dampens the expression of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) then cuts down H2 S production in cultured HUVECs, however, E2β reverses this process. To sum up, we have demonstrated a significant correlation between estrogen, Hcy concentration and systolic blood pressure reduction, which is bound up with Hcy metabolism and endogenous hydrogen sulfide production. The role of E2β was further strengthened by CBS and the CSE inhibitor through overthrowing the change in hydrogen sulfide of Hcy-treated HUVECs. 

Retracted: No

PubPeer comments:
 Figure 1A. * Red boxes: the 2uM panel appears to look very similar to the 4uM panel. ![file] ,
Expression of Concern: HER2 signaling enhances 5′UTR‐mediated translation of c‐Myc mRNA
Authors: Barbara Casati
Patrizia Casalini
Sylvie Ménard
Clelia Olgiati
Marilena Valeria Iorio
Enrico Galmozzi
Journal: Journal of Cellular Physiology (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: c-Myc protein; HER2 pathway; heregulin beta1; 5' untranslated region; P2 promoter
Affiliations: Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy

Abstract:  The increased levels of c-Myc protein observed previously in an ovarian carcinoma cell line stably transfected to express HER2 has suggested a role for the HER2 pathway in c-Myc expression. Analysis of HER2-transfected cells stimulated with heregulin beta1 (HRG) revealed increased c-Myc protein levels but not a corresponding increase in c-Myc mRNA expression or any change in c-Myc protein half-life. Transfection of HER2-overexpressing cells with a construct containing the 5' untranslated region (5'UTR) of c-Myc mRNA originated from the P2 promoter and placed upstream of the Renilla luciferase gene, enhanced reporter expression upon stimulation with HRG. The HRG-mediated increase in reporter activity correlated with the HRG-mediated induction observed for c-Myc protein, identifying the P2-derived leader (P2L) of c-Myc mRNA as the cis-element involved in c-Myc translational induction. Both the increase in c-Myc protein levels and P2L-enhanced translational activity were inhibited by the PI3K inhibitor wortmannin. Together, these results demonstrate that HRG stimulation of HER2 overexpressing cells leads to enhanced c-Myc protein synthesis through activation of the PI3K/Akt/mTOR pathway and that the P2L of c-Myc mRNA is the element responsible for induction of c-Myc translation. 

Retracted: No

PubPeer comments:
 https: retractionwatch.com 2020 05 29 a-journal-publishes-a-critical-letter-then-says-it-was-a-mistake #comment-1797420 From this article, the journal editor said, u201dI have looked at the manuscript in question, blown up under high resolution, and compared the control lanes (actin in Figure 1A and 1C, 28S in Figure 1B, and actin in Figure 2A) that you mentioned. It does look like the control images were reused. I will be contacting the author.u201d , 
 Expression of Concern: [24 February 2021] . ----------------------------------------------------------- The editors of the Journal of Cellular Physiology and the Wiley Periodicals LLC agree to publish an Expression of Concern regarding the above article, published online on 23 January 2004, in Wiley Online Library . In Spring 2020, the journal was contacted regarding concerns about the data presented in Figures 1Au2013C and 2A because of high level of similarities by a reader. As this article was published more than 10 years ago, the original data is not available for an investigation. Coauthors Marilena V. Iorio and Enrico Galmozzi who were available to comment, disagree with the concerns raised. A detailed image integrity check of all images and figures revealed unusual similarities in Figure 1B (28S). As a result, the journal is issuing this Expression of Concern to readers. ,
LncRNA DLX6-AS1 Promotes Malignant Phenotype and Lymph Node Metastasis in Prostate Cancer by Inducing LARGE Methylation
Authors: Shuxia Liang
Fuguang Sun
Zhifeng Zhao
Journal: Frontiers in Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: CpG island methylation; DNA methyltransferase 1; LncRNA homeobox 6 antisense 1; like-acetylglucosaminyltransferase; prostate cancer.
Affiliations: Department of Urology, Linyi People's Hospital of Shandong Province, Linyi, China., Special Needs Ward, Linyi People's Hospital of Shandong Province, Linyi, China.

Abstract:  Long non-coding RNAs (lncRNAs) have recently become recognized as crucial players in cancer cellular events including proliferation, migration, and invasion. Herein, we investigated the potential role of lncRNA DLX6-AS1 in prostate cancer cell malignant behaviors and lymph node metastasis. A differentially expressed lncRNA DLX6-AS1 and its downstream regulatory gene (LARGE) were predicted by analysis in silico. RT-qPCR and western blot analysis results demonstrated that DLX6-AS1 was highly expressed, but LARGE was poorly expressed in prostate cancer tissues and cells. The online website indicated that DLX6-AS1 negatively targeted LARGE expression, which was validated by Pearson correlation analysis and MSP. ChIP, RIP, and RNA pull-down assays further suggested that DLX6-AS1 downregulated LARGE expression through recruitment of DNMT1 to its promoter. We induced DLX6-AS1/LARGE overexpression or knockdown to examine their effects through Edu and Transwell assays, which revealed that DLX6-AS1 overexpression accelerated proliferation, invasion, and migration of prostate cancer cells, and that overexpression of LARGE rescued these effects. Tumors xenografts studies confirmed that DLX6-AS1 promoted lymph node metastasis by regulating LARGE, as evidenced by enhanced expression of MMP-9, uPAR, and cathepsin B. In summary, DLX6-AS1 stimulated prostate cancer malignant progression and lymph node metastasis by inducing DNMT1-mediated LARGE methylation, highlighting a potential therapeutic target against prostate cancer. 

Retracted: Yes

PubPeer comments:
 This is one of three papers by the same authors which widely duplicated the content. ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ,
An E. coli cell-free expression toolbox: application to synthetic gene circuits and artificial cells
Authors: Jonghyeon Shin
Vincent Noireaux
Journal: ACS Synthetic Biology (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell-free protein synthesis; synthetic gene circuits; E. coli sigma factors; transcription machinery; circuit motifs
Affiliations: School of Physics and Astronomy, University of Minnesota, 116 Church Street SE, Minneapolis, Minnesota
55455, United States

Abstract:  Cell-free protein synthesis is becoming a powerful technique to construct and to study complex informational processes in vitro. Engineering synthetic gene circuits in a test tube, however, is seriously limited by the transcription repertoire of modern cell-free systems, composed of only a few bacteriophage regulatory elements. Here, we report the construction and the phenomenological characterization of synthetic gene circuits engineered with a cell-free expression toolbox that works with the seven E. coli sigma factors. The E. coli endogenous holoenzyme E(70) is used as the primary transcription machinery. Elementary circuit motifs, such as multiple stage cascades, AND gate and negative feedback loops are constructed with the six other sigma factors, two bacteriophage RNA polymerases, and a set of repressors. The circuit dynamics reveal the importance of the global mRNA turnover rate and of passive competition-induced transcriptional regulation. Cell-free reactions can be carried out over long periods of time with a small-scale dialysis reactor or in phospholipid vesicles, an artificial cell system. This toolbox is a unique platform to study complex transcription/translation-based biochemical systems in vitro. 

Retracted: No

PubPeer comments:
 The conclusion is not supported by the results or I am missing something. The result section of the abstract reads  44 women (40%) reached an ongoing pregnancy. In the placebo group, 52 women (46%) reached an ongoing pregnancy. No benefit of metformin over the placebo. ![file] The authors tried to find something in favor of metformin, nothing significant pos up for women older than 28 and or having WHR u2265 0.85. Table 2 3 shows no significant effect showing the benefit of metformin for whatever obesity or age groups the authors have shown. Age (years) u2265 28, WHR u2265 0.85: RR=1.6 (0.98u20133.8). Also a selctive p-value reporting in Table 3. ![file] Still, the conclusion reads  Metformin may be an effective addition to clomifene citrate in infertile women with PCOS, especially in older and viscerally obese patients. The metformin and placebo tablets were provided by Merck France. Funding Merck Sante France provided the metformin and placebo tablets. ,
Puerarin suppresses production of nitric oxide and inducible nitric oxide synthase in lipopolysaccharide-induced N9 microglial cells through regulating MAPK phosphorylation, O-GlcNAcylation and NF-κB translocation
Authors: Chao Yu
Zhu Yang
Gao-Ming Zheng
Journal: International Journal of Oncology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Microglial cells; inflammation; neurodegenerative diseases; Puerarin; neuroprotection
Affiliations: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, PR China.

Abstract:  Microglial cells play a critical role in mediating central nervous system inﬂammatory processes. Activated microglial cells induced by proinflammatory factor, such as lipopolysaccharide (LPS), release many kinds of neurotoxic cytokines including reactive oxygen species (ROS) which contributes to the pathogenesis of neurodegenerative diseases. Puerarin, extracted from kudzu root, possesses the characteristic of neuroprotection, antioxidation and anticancer. In the present study, we observed that LPS induced over-production of nitric oxide (NO) and increased the level of intracellular ROS in N9 microglial cells, but it was inhibited by puerarin. Furthermore, treatment with puerarin on N9 cells suppressed the over-expression of inducible nitric oxide synthase (iNOS) induced by LPS which is implicated in intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) level, phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathway. We also observed that the enhanced phosphorylation of p38, JNK and ERK1/2 in N9 cells induced by LPS were inhibited by puerarin, otherwise the down-regulation of O-GlcNAcylation level of protein in N9 cell induced by LPS was up-regulated by pretreatment with puerarin. These results indicate that puerarin effectively inhibits microglia activation induced by LPS through inhibiting expression of iNOS, production of NO and ROS which was mediated via regulating O-GlcNAcylation, phosphorylation of MAPK and NF-κB translocation. 

Retracted: No

PubPeer comments:
 ![file] The nuclear form of NF-KB is 65KD, why is two bands? and the figure legend is NF-KB(HE) is wrong.It should be corrected. , 
 ![file] The p-ERK and t-ERK are two bands, however,in this figure, western blot results only detected one band.It should be corrected. ,
Cell atavistic transition: Paired box 2 re-expression occurs in mature tubular epithelial cells during acute kidney injury and is regulated by Angiotensin II
Authors: Yushen Jiang
Bin Huang
Yingpeng Cui
Tang Jiang
Juan Ouyang
Qingsong Zhou
Yanlan Liang
Peisong Chen
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Tubular epithelial cells; acute kidney injury; Pax2; kidney injury molecule-1; Angiotensin II
Affiliations: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China., Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Abstract:  The regeneration of tubular epithelial cells (TECs) after acute kidney injury (AKI) is crucial for the recovery of renal structure and function. The mechanism by which quiescent TECs re-obtain a potential to regenerate remains unknown. In this study, we observed a transient re-expression of embryonic gene Paired box 2 (Pax2) in adult rat TECs in vivo during ischemia-reperfusion induced AKI and most Pax2 positive TECs co-expressed kidney injury molecule-1 (KIM-1), a tubular injury marker. The re-expression of Pax2 was accompanied by increased levels of intrarenal Angiotensin II, which is a crucial injury factor of AKI. Furthermore, we also found a temporary re-expression of Pax2 in NRK-52E cells under the stimulation of Angiotensin II. This stimulatory effect could be blocked by PD123319 (Angiotensin II type 2 receptor (AT2R) inhibitor) and AG490 (Janus Kinase 2 (JAK2) inhibitor). As Pax2 is essential for the phenotypic conversion from mesenchymal stem cells to TECs during kidney development, we proposed that the re-expression of Pax2 in mature TECs may be an indicator of "atavistic" transition which mimics but reverses the processes of development of TECs. This could be proved by that a progenitor marker, CD24, was also found to be transiently expressed shortly after the expression of Pax2 in NRK-52E cells stimulated with Angiotensin II. The expression of CD24 was also suppressed by PD123319 and AG490. Moreover, knockdown of Pax2 by RNA interference could significantly reduce the expression of CD24 in NRK-52E cells stimulated with Angiotension II. Those findings suggest that mature TECs can trans-differentiate into progenitor-like cells by "atavistic transition", which may participate in the recovery of tissue structure and Pax2 may play a pivotal role in this process. That might have important implications for further understanding of tubular regeneration after injury. 

Retracted: No

PubPeer comments:
 May 2015 correction found here: https: journals.plos.org plosone article?id=10.1371 journal.pone.0127718 It reads:  *In Fig 3A of the original published article the panels for beta-actin mRNA were duplicated for the Sham and IRI treatment. The authors apologize for this error and have provided the correct figure here. * Here is the original problem with Figure 3A, reported to the journal in April 2014. I thank the authors for correcting this duplication. ![file] ,
Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1
Authors: O Bachs
D Talaya
E Rius
N Agell
M Taulés
A López-Girona
Journal: Journal of Biological Chemistry (1998)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: calmodulin; G1 progression; cyclin-dependent kinase 4; Cdk4; cyclin D1
Affiliations: Department of Cell Biology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Faculty of Medicine, University of Barcelona, Casanova 143, 08036 Barcelona, Spain.

Abstract:  Although it is known that calmodulin is involved in G1 progression, the calmodulin-dependent G1 events are not well understood. We have analyzed here the role of calmodulin in the activity, the expression, and the intracellular location of proteins involved in G1 progression. The addition of anti-calmodulin drugs to normal rat kidney cells in early G1 inhibited cyclin-dependent kinase 4 (Cdk4) and Cdk2 activities, as well as retinoblastoma protein phosphorylation. Protein levels of cdk4, cyclin D1, cyclin D2, cyclin E, p21, and p27 were not affected after CaM inhibition, whereas decreases in the amount of cyclin A and Cdc2 were observed. The decrease of Cdk4 activity was due neither to changes in its association to cyclin D1 nor to changes in the amount of p21 or p27 bound to cyclin D1-Cdk4 complexes. Calmodulin inhibition also produced a translocation of nuclear cyclin D1 and Cdk4 to the cytoplasm. This translocation could be responsible for the decreased Cdk4 activity upon calmodulin inhibition. Immunoprecipitation, calmodulin affinity chromatography, and direct binding experiments indicated that calmodulin associates with Cdk4 and cyclin D1 through a calmodulin-binding protein. The facts that Hsp90 interacts with Cdk4 and that its inhibition induced Cdk4 and cyclin D1 translocation to the cytoplasm point to Hsp90 as a good candidate for being the calmodulin-binding protein involved in the nuclear accumulation of Cdk4 and cyclin D1. 

Retracted: No

PubPeer comments:
 ![file] ,
Induced pluripotent stem cells reveal functional differences between drugs currently investigated in patients with hutchinson-gilford progeria syndrome
Authors: Marc Peschanski
Karima Djabali
Annachiara de Sandre-Giovannoli
Cécile Martinat
Nicolas Levy
Véronique Cordette
Anne-Laure Egesipe
Amelie Le Corf
Anne-Laure Jaskowiak
Yacine Laabi
Xavier Nissan
Claire Navarro
Sophie Blondel
Journal: Stem Cells Translational Medicine (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Aging; Drug development; Mesenchymal stem cells; Pluripotent stem cells; Progeria.
Affiliations: INSERM/Université Evry Val d'Essonne 861, and Centre d'Etude des Cellules Souches, Institut for Stem Cell Therapy and Exploration of Monogenic Diseases, Association Française Contre les Myopathies, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Evry, France; INSERM-Aix-Marseille Université Unité Mixte de Recherche S 910 Génétique Médicale et Génomique Fonctionnelle, Faculté de Médecine Timone, Marseille, France; Department of Dermatology and IMETUM, Technische Universitat Munchen, Munich, Germany; AP-HM Département de Génétique Médicale, Hôpital d'Enfants, Timone, Marseille, France.

Abstract:  Hutchinson-Gilford progeria syndrome is a rare congenital disease characterized by premature aging in children. Identification of the mutation and related molecular mechanisms has rapidly led to independent clinical trials testing different marketed drugs with a preclinically documented impact on those mechanisms. However, the extensive functional effects of those drugs remain essentially unexplored. We have undertaken a systematic comparative study of the three main treatments currently administered or proposed to progeria-affected children, namely, a farnesyltransferase inhibitor, the combination of an aminobisphosphonate and a statin (zoledronate and pravastatin), and the macrolide antibiotic rapamycin. This work was based on the assumption that mesodermal stem cells, which are derived from Hutchinson-Gilford progeria syndrome-induced pluripotent stem cells expressing major defects associated with the disease, may be instrumental to revealing such effects. Whereas all three treatments significantly improved misshapen cell nuclei typically associated with progeria, differences were observed in terms of functional improvement in prelamin A farnesylation, progerin expression, defective cell proliferation, premature osteogenic differentiation, and ATP production. Finally, we have evaluated the effect of the different drug combinations on this cellular model. This study revealed no additional benefit compared with single-drug treatments, whereas a cytostatic effect equivalent to that of a farnesyltransferase inhibitor alone was systematically observed. Altogether, these results reveal the complexity of the modes of action of different drugs, even when they have been selected on the basis of a similar mechanistic hypothesis, and underscore the use of induced pluripotent stem cell derivatives as a critical and powerful tool for standardized, comparative pharmacological studies. 

Retracted: No

PubPeer comments:
 image duplication ![file] ,
MiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2
Authors: Bin Wang
Xing Sun
Biao Deng
Qi Lin
Jiaqing Fang
Lisheng Zhou
Xuchao Zhu
Zhongwei Cao
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: miR-203; colorectal cancer; tumor suppressor gene; downregulated; EIF5A2
Affiliations: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China., Department of Gastroenterology, Tianyou Hospital, TongJi University, 500 Zhennan Road, Shanghai, 200331, China., Department of Nuclear Medicine, Shanghai Tenth People's Hospital, TongJi University, 301 Yanchang Road, Shanghai, 200072, China., Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China., Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Xietu Road, Shanghai, 200032, China.

Abstract:  While it is known that miR-203 is frequently downregulated in many types of human cancer, little is known regarding its expression and functional role in colorectal cancer (CRC). In this study, we aimed to investigate the expression and the potential mechanisms of miR-203 in colorectal cancer. MiR-203 was significantly downregulated in CRC tissues compared with matched normal adjacent tissues. Our clinical data show that decreased miR-203 was associated with an advanced clinical tumor-node-metastasis stage, lymph node metastasis, and poor survival in CRC patients. Furthermore, externally induced expression of miR-203 significantly inhibited CRC cell proliferation and invasion in vitro and in vivo. Mechanistically, we identified EIF5A2 as a direct and functional target of miR-203. The levels of miR-203 were inversely correlated with levels of the EIF5A2 in the CRC tissues. Restoration of EIF5A2 in the miR-203-overexpressing CRC cells reversed the suppressive effects of miR-203. Our results demonstrate that miR-203 serves as a tumor suppressor gene and may be useful as a new potential therapeutic target in CRC. 

Retracted: No

PubPeer comments:
 Figure 4 appears to have a duplicated image, with the colors adjusted. The only difference is that there is a smudge in one and not the other. Note also that this is for a different cell line. ![file] , 
 We made a big mistake. In the results, we regarded LOVO cells as SW620 cells. From our results, we can see the inconsistency of the cell morphology before and after SW 620 cells. We uploaded the original data to the magazine. We admitted that we have adjusted the grey of the images, but all the results have not been repaired. It will promote us to treat all results with a more cautious attitude in future scientific research.![file] , 
 - *[left]* Fic 4c from  Silencing GTSE-1 expression inhibits proliferation and invasion of hepatocellular carcinoma cells ([Guo et al 2016] ). - *[right]* **Fig 6D**. ![file] ,
Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells
Authors: Sanjay Gupta
Farrukh Afaq
Hasan Mukhtar
Journal: Oncogene (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Apigenin; prostate cancer; cell growth inhibition; AR protein expression; PSA
Affiliations: Department of Dermatology, Case Western Reserve University & The Research Institute of University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA. 

Abstract:  Apigenin, a common dietary flavonoid abundantly present in fruits and vegetables, may have the potential for prevention and therapy for prostate cancer. Here, we report for the first time that apigenin inhibits the growth of androgen-responsive human prostate carcinoma LNCaP cells and provide molecular understanding of this effect. The cell growth inhibition achieved by apigenin treatment resulted in a significant decrease in AR protein expression along with a decrease in intracellular and secreted forms of PSA. These effects were also observed in DHT-stimulated cells. Further, apigenin treatment of LNCaP cells resulted in G1 arrest in cell cycle progression which was associated with a marked decrease in the protein expression of cyclin D1, D2 and E and their activating partner cdk2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. The induction of WAF1/p21 appears to be transcriptionally upregulated and is p53 dependent. In addition, apigenin inhibited the hyperphosphorylation of the pRb protein in these cells. Apigenin treatment also resulted in induction of apoptosis as determined by DNA fragmentation, PARP cleavage, fluorescence microscopy and flow cytometry. These effects were found to correlate with a shift in Bax/Bcl-2 ratio more towards apoptosis. Apigenin treatment also resulted in down-modulation of the constitutive expression of NF-kappaB/p65. Taken together, these findings suggest that apigenin has strong potential for development as an agent for prevention against prostate cancer. 

Retracted: No

PubPeer comments:
 Figure 5. Profiles more similar than expected, yet percentages different. https: imgur.com WpTXhPk ,
<p>LncRNA MAGI2-AS3 Affects Cell Invasion and Migration of Cervical Squamous Cell Carcinoma (CSCC) via Sponging miRNA-233/EPB41L3 Axis</p>
Authors: Yi Zheng
Anli Hou
Yali Zhang
Huilan Liu
Yujuan Fan
Xiuying Zhou
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: EPB41L3; cervical squamous cell carcinoma; lncRNA MAGI2-AS3; miR-223.
Affiliations: Department of Gynaecology, University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen City, Guangdong Province 518106, People's Republic of China., Department of Gynaecology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 067000, People's Republic of China., Department of Central Lab, University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen City, Guangdong Province 518106, People's Republic of China.

Abstract:  Introduction: The incidence of cervical squamous cell carcinoma (CSCC) has expanded in recent years. However, the function of long non-coding RNA (lncRNA) MAGI2-AS3 in the occurrence and progression of CSCC remains unclear. Therefore, the role of lncRNA MAGI2-AS3 in cervical squamous cell carcinoma (CSCC) was investigated in our study. Methods: We used qRT-PCR analysis to identify the level of MAGI2-AS3 mRNA expression in CSCC clinical samples and cell lines. We investigated cell migration and invasion of CSCC cells transfected with MAGI2-AS3, miR-233 mimic, or EPB41L3 with transwell assays. Bioinformatics analysis and a luciferase reporter assay were employed to predict the interaction between MAGI2-AS3 and miR-233. Results: We found that MAGI2-AS3 and EPB41L3 were both downregulated in CSCC and the expression of this two was positively correlated. Bioinformatics analysis showed that MAGI2-AS3 might bind to miR-233, which could directly target EPB41L3. In CSCC cells, overexpression of MAGI2-AS3 led to upregulated, while overexpression of miRNA-233 led to downregulated expression of EPB41L3. However, MAGI2-AS3 and miR-233 did not affect the expression of each other. In addition, overexpression of MAGI2-AS3 and EPB41L3 led to inhibited cancer cell invasion and migration, while overexpression of miR-233 played an opposite role and attenuated the effects of overexpressing MAGI2-AS3. Conclusion: MAGI2-AS3 may sponge miR-233 to upregulate EPB41L3, thereby inhibiting CSCC cell invasion and migration. 

Retracted: No

PubPeer comments:
 Two images in figure 4 appear to overlap. The authors may want to check the other images carefully as there may be more. *** ![file] *** ![file] ,
RBBP6 aggravates the progression of ovarian cancer by targeting PIK3R6
Authors: Y-J Liu
L-L Cui
R-Y Jia
Y-X Ding
L-Z Xu
Z-S Liu
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: RBBP6; ovarian cancer; proliferation; metastasis; PIK3R6
Affiliations: Department of Clinical Laboratory, Heze Center for Disease Control and Prevention, Heze, China. .

Abstract:  Objective: RBBP6 is identified to be a cancer-associated gene by bioinformatics analysis. This study aims to explore the role of RBBP6 in regulating proliferation and metastasis in ovarian cancer, thus providing theoretical references for ovarian cancer treatment. Patients and methods: Differential expressions of RBBP6 in ovarian cancer and normal ones were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between RBBP6 and prognosis in ovarian cancer patients was analyzed. The interaction between RBBP6 and PIK3R6 was detected by bioinformatics analysis and Dual-Luciferase reporter assay. Moreover, regulatory effects of RBBP6 and PIK3R6 on proliferative and migratory potentials in A2780 and CAOV3 cells were examined by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Finally, tumorigenicity assay was conducted in nude mice to illustrate the in vivo regulations of PBBP6 and PIK3R6 on ovarian cancer growth. Results: RBBP6 was upregulated in ovarian cancer tissues than normal ones. RBBP6 was irrelevant to age, tumor size and tumor node metastasis (TNM) staging in ovarian cancer patients, but correlated to lymphatic metastasis and distant metastasis. RBBP6 was abundantly expressed in ovarian cancer cells, and among the tested cell lines, CAOV3 and A2780 expressed the highest level of RBBP6. Knockdown of RBBP6 attenuated in vitro proliferative and migratory potentials in CAOV3 and A2780 cells. PIK3R6 was the target gene binding RBBP6, which was positively regulated by RBBP6. Overexpression of PIK3R6 could abolish the inhibited proliferative and migratory potentials in ovarian cancer cells with RBBP6 knockdown. In addition, the knockdown of RBBP6 slowed the in vivo growth of ovarian cancer in nude mice, and the alleviated cancer progression was reversed by overexpression of PIK3R6. Conclusions: RBBP6 is highly expressed in ovarian cancer cases, which stimulates proliferative and migratory potentials by targeting PIK3R6. RBBP6 may be a novel therapeutic target for ovarian cancer. 

Retracted: No

PubPeer comments:
 Fig 1C.  Kaplan-Meier curves depicted based on RBBP6 levels in ovarian cancer patients ![file] It is another manifestation of  Hoya s Law for J.BUOn ERMPS :  When 40 or 50 cases of any given cancer are dichotomised into half-groups of high- or low-expression of any given noncoding RNA, survival rate for one half-group or both always drops to 0% at 75 months. ,
Leucine Supplementation Has No Further Effect on Training-induced Muscle Adaptations
Authors: Guilherme Giannini Artioli
Felipe Jardim
Hamilton Roschel
Isabel Thomazi DE Andrade
Victoria Hevia-Larraín
Stuart M Phillips
Rodrigo Leite Gomes
Monique Cajueiro
Patrícia Campos-Ferraz
Bruno Gualano
Juarez Neves-Junior
Journal: Medicine and science in sports and exercise (2020)
Discipline: CLINICAL MEDICINE
Keywords: leucine; muscle protein synthesis; resistance training; muscle mass; muscle strength
Affiliations: Applied Physiology and Nutrition Research Group, University of São Paulo, São Paulo, BRAZIL., Department of Kinesiology, McMaster University, Hamilton, CANADA., Faculty of Applied Sciences, University of Campinas, Limeira, São Paulo, BRAZIL.

Abstract:  Introduction: Several acute studies have suggested that leucine is a key amino acid to drive muscle protein synthesis. However, there are very few studies on the long-term effects of leucine supplementation on resistance training (RT)-induced gains in muscle mass and strength. We sought to determine the impact of 10 g of leucine on muscle mass and strength in response to RT in healthy young men. Methods: Twenty-five, resistance-trained men (27 ± 5 yr; 78.4 ± 11.6 kg; 24.8 ± 3.0 kg·m) consuming 1.8 ± 0.4 g protein·kg·d, were randomly assigned to receive 2 × 5 g·d supplementation of either free leucine (LEU n = 12) or alanine (PLA n = 13) while undergoing a supervised 12-wk, twice-weekly lower-limb RT program. One-repetition maximum (leg-press 1RM) and muscle cross-sectional area (mCSA) of the vastus lateralis were determined before (PRE) and after (POST) the intervention. Additionally, three 24-h dietary recalls were also performed at PRE and POST. Results: Protein intake was roughly double that of the RDA in both groups and remained unchanged across time with no differences detected between groups. Similar increases were observed between groups in leg-press 1RM (LEU, 19.0% ± 9.4% and PLA, 21.0% ± 10.4%, P = 0.31) and mCSA (LEU, 8.0% ± 5.6% and PLA, 8.4% ± 5.1%, P = 0.77). Conclusions: High-dose leucine supplementation did not enhance gains in muscle strength and mass after a 12-wk RT program in young resistance-trained males consuming adequate amounts of dietary protein. 

Retracted: No

PubPeer comments:
 Copy pasted from https: journals.lww.com acsm-msse Citation 2021 01000 Corrigendum.33.aspx (Medicine Science in Sports Exercise. 53(1):247, January 2021):  The authors of articles (1)u2013(4) below amend their conflict-of-interest statements to include the following: Dr. Stuart M. Phillips is listed as an inventor on patent (Canadian) 3052324 issued to Exerkine, and a patent (US) 16 182891 pending to Exerkine (but reports no financial gains). Dr. Phillips reports personal fees from Enhanced Recovery (donated to charity), equity from Exerkine (all proceeds donated to charity), outside the submitted work. See https: retractionwatch.com 2021 02 12 eleven-papers-corrected-after-nutrition-prof-fails-to-disclose-patent-company-ties for backgrounds. ,
miR-370 and miR-373 regulate the pathogenesis of osteoarthritis by modulating one-carbon metabolism via SHMT-2 and MECP-2, respectively
Authors: Eun-Jung Jin
Jinsoo Song
Dongkyun Kim
Churl-Hong Chun
Journal: Aging Cell (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: SHMT-2/MECP-2; human articular chondrocyte; miR-370/373; one-carbon metabolism; osteoarthritis
Affiliations: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Korea., Department of Orthopedic Surgery, Wonkwang University School of Medicine, Iksan, Chunbuk, 570-749, Korea.

Abstract:  The aim of this study was to determine the mechanism underlying the association between one-carbon metabolism and DNA methylation during chronic degenerative joint disorder, osteoarthritis (OA). Articular chondrocytes were isolated from human OA cartilage and normal cartilage biopsied, and the degree of cartilage degradation was determined by safranin O staining. We found that the expression levels of SHMT-2 and MECP-2 were increased in OA chondrocytes, and 3'UTR reporter assays showed that SHMT-2 and MECP-2 are the direct targets of miR-370 and miR-373, respectively, in human articular chondrocytes. Our experiments showed that miR-370 and miR-373 levels were significantly lower in OA chondrocytes compared to normal chondrocytes. Overexpression of miR-370 or miR-373, or knockdown of SHMT-2 or MECP-2 reduced both MMP-13 expression and apoptotic cell death in cultured OA chondrocytes. In vivo, we found that introduction of miR-370 or miR-373 into the cartilage of mice that had undergone destabilization of the medial meniscus (DMM) surgery significantly reduced the cartilage destruction in this model, whereas introduction of SHMT-2 or MECP-2 increased the severity of cartilage destruction. Together, these results show that miR-370 and miR-373 contribute to the pathogenesis of OA and act as negative regulators of SHMT-2 and MECP-2, respectively. 

Retracted: No

PubPeer comments:
 Duplication: Same image from an independent experiment. It was assumed that the same sample was used. ![file] , 
 Thank you for your comment on our paper. we had checked the original images and original data. It was a totally different images..However, we just found that the magnified images of last two images has been misplaced and we asked the erratum. , 
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