PReD-Bench/PRed-Bench huggingface dataset:
Dual regulation by pairs of cyclin-dependent protein kinases and histone deacetylases controls G1 transcription in budding yeast
Authors: Jason Moffat
Wei Ye
Holly Sassi
Helena Friesen
Dewald van Dyk
Supipi Kaluarachchi
Nazareth Bastajian
Richelle Sopko
Brenda J Andrews
Dongqing Huang
Michael Costanzo
Journal: PLoS Biology (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: transcription; Saccharomyces cerevisiae; SBF; MBF; Whi5
Affiliations: Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.

Abstract:  START-dependent transcription in Saccharomyces cerevisiae is regulated by two transcription factors SBF and MBF, whose activity is controlled by the binding of the repressor Whi5. Phosphorylation and removal of Whi5 by the cyclin-dependent kinase (CDK) Cln3-Cdc28 alleviates the Whi5-dependent repression on SBF and MBF, initiating entry into a new cell cycle. This Whi5-SBF/MBF transcriptional circuit is analogous to the regulatory pathway in mammalian cells that features the E2F family of G1 transcription factors and the retinoblastoma tumor suppressor protein (Rb). Here we describe genetic and biochemical evidence for the involvement of another CDK, Pcl-Pho85, in regulating G1 transcription, via phosphorylation and inhibition of Whi5. We show that a strain deleted for both PHO85 and CLN3 has a slow growth phenotype, a G1 delay, and is severely compromised for SBF-dependent reporter gene expression, yet all of these defects are alleviated by deletion of WHI5. Our biochemical and genetic tests suggest Whi5 mediates repression in part through interaction with two histone deacetylases (HDACs), Hos3 and Rpd3. In a manner analogous to cyclin D/CDK4/6, which phosphorylates Rb in mammalian cells disrupting its association with HDACs, phosphorylation by the early G1 CDKs Cln3-Cdc28 and Pcl9-Pho85 inhibits association of Whi5 with the HDACs. Contributions from multiple CDKs may provide the precision and accuracy necessary to activate G1 transcription when both internal and external cues are optimal. 

Retracted: No

PubPeer comments:
null, 
 for bands around 56kDa, lane 1 and lane 7 appear to have the same bubbles. for lane 3 and lane 9 , they also share lots same pattern. , 
 Illustrating what comment #1 was refering to ![file] ,
Study to elucidate molecular mechanism behind zinc chemo-preventive role during lung carcinogenesis
Authors: Y-J Lu
J-D Wang
Z-Y Shen
S-Y Zhu
Journal: European review for medical and pharmacological sciences (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: zinc supplementation; p53 acetylation; COX-2 activity; lung carcinogenesis; mice
Affiliations: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Su Zhou, China. .

Abstract:  Objective: The present planned to elucidate the mechanistic role zinc supplementation in the modulation of p53 post-translational acetylation, the activity of cyclooxygenase-2 (COX-2) along with other biophysical parameters during benzo(a)pyrene (BP) induced lung carcinogenesis in mice. Materials and methods: The mice were segregated into four groups viz., normal control, BP treated, BP + zinc and zinc alone treated. Lung carcinogenesis was induced by a single intra-peritoneal (IP) injection of BP (100 mg/kg body weight). Zinc was supplemented to mice at dose levels of 227 mg/kg body weight in drinking water. All the treatments were continued for 20 weeks. Results: The BP caused a significant rise in the expression of p53. On the other hand, protein expressions of acetylated (lys382)-p53 were significantly decreased, following BP treatment. Also, a significant decrease was observed in the enzyme activities of caspase 3 and caspase 9. Moreover, BP treatment brought about a significant increase in the activity of COX-2. Supplementation of zinc to BP treated mice stimulated acetylation of p53 as observed by an increase in the protein expression of acetylated (lys382)-p53. Also, the enzyme activities of caspase 3 and caspase 9 showed a significant elevation upon zinc supplementation. On the other hand, the zinc supplementation brought about moderation in the expression of enzymatic activity of COX-2 which was restored within the normal limits. Further, BP treatment recorded increased 3H-thymidine uptake as well as enhanced 14C-glucose uptake and its turnover which were reduced significantly following simultaneous treatment with zinc. Conclusions: The treatment with zinc has the potential to modulate p53 acetylation to stimulate apoptosis against experimentally induced lung carcinogenesis. 

Retracted: No

PubPeer comments:
 Figure 1. * Red arrows: Lane  C in the Acetyl-p53 looks similar to lane  BP in the b-Actin panel. ![file] ,
The 25 kDa subunit of cleavage factor Im Is a RNA-binding protein that interacts with the poly(A) polymerase in Entamoeba histolytica
Authors: Laurence A Marchat
Guillermo Mendoza-Hernández
Jorge Fernández-Retana
Socorro Charcas-López
César López-Camarillo
Marisol Pezet-Valdez
María Esther Ramírez-Moreno
Esther Orozco
Mavil López-Casamicha
Juan David Ospina-Villa
Jacqueline Soto-Sánchez
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: polyadenylation; mRNA export; mRNA stability; mRNA translation; Entamoeba histolytica
Affiliations: Programa Institucional de Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía del IPN, Guillermo Massieu Helguera #239, Fracc La Escalera, Ticomán, México DF, Mexico.

Abstract:  In eukaryotes, polyadenylation of pre-mRNA 3' end is essential for mRNA export, stability and translation. Taking advantage of the knowledge of genomic sequences of Entamoeba histolytica, the protozoan responsible for human amoebiasis, we previously reported the putative polyadenylation machinery of this parasite. Here, we focused on the predicted protein that has the molecular features of the 25 kDa subunit of the Cleavage Factor Im (CFIm25) from other organisms, including the Nudix (nucleoside diphosphate linked to another moiety X) domain, as well as the RNA binding domain and the PAP/PAB interacting region. The recombinant EhCFIm25 protein (rEhCFIm25) was expressed in bacteria and used to generate specific antibodies in rabbit. Subcellular localization assays showed the presence of the endogenous protein in nuclear and cytoplasmic fractions. In RNA electrophoretic mobility shift assays, rEhCFIm25 was able to form specific RNA-protein complexes with the EhPgp5 mRNA 3´ UTR used as probe. In addition, Pull-Down and LC/ESI-MS/MS tandem mass spectrometry assays evidenced that the putative EhCFIm25 was able to interact with the poly(A) polymerase (EhPAP) that is responsible for the synthesis of the poly(A) tail in other eukaryotic cells. By Far-Western experiments, we confirmed the interaction between the putative EhCFIm25 and EhPAP in E. histolytica. Taken altogether, our results showed that the putative EhCFIm25 is a conserved RNA binding protein that interacts with the poly(A) polymerase, another member of the pre-mRNA 3' end processing machinery in this protozoan parasite. 

Retracted: No

PubPeer comments:
 Concerns about Figures 2, 4, and 5. These have been reported to the journal over four years ago, but have not been addressed so far. Figure 2E. * In pink: lanes 3 and 4 look very similar. ![file] , 
 Figure 4A. * Blue arrow: lane 7 is surrounded by sharp horizontal lines and has a very different background than the surrounding lanes. ![file] , 
 Figure 5B. * In green: lanes 2 and 6 look very similar. ![file] , 
 An additional finding for Figure 4A. * Blue boxes: Lanes 1 and 6 appear to look like mirror images of each other. ![file] ,
MicroRNA let-7i induced autophagy to protect T cell from apoptosis by targeting IGF1R
Authors: Chunfeng Hou
Min Sun
Yanliang Lin
Mengzhu Zhu
Journal: Biochemical and Biophysical Research Communications (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ankylosing Spondylitis; Apoptosis; Autophagy; IGF1R; MicroRNA let-7i.
Affiliations: Department of Rheumatology, Jining First People's Hospital, Jining, Shandong 272111, PR China., Department of Rheumatology, Chinese Medicine Hospital in Linyi City, Linyi, Shandong 276000, PR China. Electronic address: ., Clinic Institute, Jining Medical University, Jining, Shandong 272013, PR China., Department of Center Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, PR China.

Abstract:  MicroRNA let-7i is up-regulated in T cells from patients with Ankylosing Spondylitis (AS). In this study, we investigated the role of let-7i in T cells survival. Our results demonstrated down-regulation of insulin-like growth factor-1 receptor (IGF1R) in T cells from patients with AS. Luciferase reporter assay suggested IGF1R as direct target of let-7i. Overexpression of let-7i in Jurkat cells significantly suppressed IGF1R expression, which mimicked the action of IGF1R siRNA. IGF1R inhibition led to a strinking decrease in phosphorylation of mTOR and Akt, down-regulation of Bcl-2, up-regulation of Bax and cleavage of caspase 3 and PARP. Meanwhile, IGF1R inhibition induced autophagy. Autophagy induced by let-7i overexpression contributed to protect cells from apoptosis. Our data indicated that let-7i might control T cells fates in AS by targeting IGF1R. 

Retracted: No

PubPeer comments:
 The results in this paper are based on some invalid results previously published and hence invalid as well. See also https: pubpeer.com publications 88C56A5FE591B00AA85810604F1BCB https: pubpeer.com publications 74A552E8948BB32792497B07D2ECC8 https: pubpeer.com publications 90A78462D5A764BC10AE9A70F9C87D https: pubpeer.com publications 7803CF906784F287F8261176A52D9E https: pubpeer.com publications 88C56A5FE591B00AA85810604F1BCB https: pubpeer.com publications 451C6DD8CE75F4D063319A0F980A4F ![file] , 
 **Dear** **Rhipidura Albiventris**, **Thank you very much** **for your interests in our work!** **And we are so sorry for the late reply.** **Please see** **the following** **responses:** **C.** The results in this paper are based on some invalid results previously published and hence invalid as well. **A.** Thank you for your comments! Our work still makes sense. And these results previously published are also valid. Please refer to the responses in [](http: ) https: pubpeer.com publications 763257B958790969FC1AF53012DD5B#2 [](http: ) https: pubpeer.com publications 451C6DD8CE75F4D063319A0F980A4F#1 [](http: ) https: pubpeer.com publications 7803CF906784F287F8261176A52D9E#1 **Thanks again** **for your** **interests!** **Best Regards,** **Qian Lei** , 
 #2 Dear Qian Lei, Thank you very much for your reply. Once again, I must admit that you are right according to your understanding of integrals and suppose that you are serious on this issue, on which I do not doubt. ,
The role of activated NLRP3 inflammatory body in acute kidney injury in rats caused by sepsis and NLRP3-TXNIP signaling pathway
Authors: Huanghao Deng
Hongyi Jiang
Biao Yuan
Fangzhi Chen
Zhitao Dong
Xiaokun Zhao
Yinhuai Wang
Journal: Saudi Journal of Biological Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Abdominal resection by surgical suture; Acute kidney injury; NLRP3 inflammatory corpuscles; NLRP3-TXNIP signaling pathway.
Affiliations: Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

Abstract:  Objective: The model of acute renal injury (AKI) induced by sepsis in rats was established by abdominal resection through surgical suture. The activation mechanism of nod-like receptor with pyrin domain containing 3 (NLRP3) inflammatory corpuscle in AKI induced by sepsis was analyzed. Methods: Here, 60 male rats were selected and divided into two groups, including sham-operated group (NO-OPs group, n = 15) and sepsis group (CELP group, n = 45). In order to examine each index of CELP group, four time points (10, 20, 30, and 40 h) were set as control. In NO-OPs group, only abdominal resection through surgical suture was carried out. The expression levels of NLRP3, apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), caspase-1, and the expression level of NLRP3-TXNIP signaling pathway were measured by immunohistochemistry, Western blotting, immunoprecipitation, and mito-TEMPO (a mitochondria-targeted antioxidant) 40 h after operation and 10, 20, 30, and 40 h post-operation in CELP group. Herein, 40 h post-operation in NO-OPs group and 10, 20, 30, and 40 h post-operation in CELP group, peripheral blood samples were collected. Results: Compared with NO-OPs group, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in CELP group were increased (P &lt; 0.05). Compared with NO-OPs group, the expression levels of interleukin-1β (IL-1β), NLRP3, ASC, and caspase-1 in CELP group were increased (P &lt; 0.05). The expression level of TXNIP in renal tubular epithelial cells in rats was up-regulated. There was a positive correlation between TXNIP and NLRP3. The binding of NLRP3-TXNIP signaling pathway could be inhibited by siRNA transfection or mito-TMPO, and the activity of NLRP3 inflammatory bodies could be inhibited as well. Conclusion: Activation of NLRP3 inflammatory corpuscles could promote AKI induced by sepsis. Simultaneously, renal injury may lead to the production of mitochondrial reactive oxygen species (mROS), which may induce the binding of TXNIP to NLRP3. 

Retracted: No

PubPeer comments:
 An image in Figure 2D and 2E appear to overlap (green boxes), although contrast appears changed. *** ![file] , 
 An image in Figure 1B and 1C appear to overlap (red boxes), although dimensions appear different despite similar scale bars. *** ![file] ,
Effect of ozone on intestinal recovery following intestinal ischemia–reperfusion injury in a rat
Authors: Arnold G Coran
Ibrahim Matter
Ron Shaoul
Arie Bitterman
Igor Sukhotnik
Bassel Haj
Yulia Pollak
Journal: Pediatric Surgery International (2014)
Discipline: CLINICAL MEDICINE
Keywords: Ozone; Intestinal recovery; Enterocyte turnover; Ischemia-reperfusion injury; Antioxidant enzymes
Affiliations: Laboratory of Intestinal Adaptation and Recovery, Department of Pediatric Surgery and Surgery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, 31048, Haifa, Israel.

Abstract:  Background: Growing evidence suggests that ozone (O3) protects the host against pathological conditions mediated by reactive oxygen species by increasing the activity of antioxidant enzymes. The purpose of the present study was to examine the effect of O3 on intestinal recovery and enterocyte turnover after intestinal ischemia-reperfusion (IR) injury in rats. Methods: Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy; (2) sham-O3 rats underwent laparotomy and were treated with an ozone/oxygen mixture intraperitoneally and intraluminally (50 %/50 %); (3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 20 min followed by 48 h of reperfusion, and (4) IR-O3 rats underwent IR and were treated with an ozone/oxygen mixture similar to group 2. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 48 h following IR. Western blot was used to determine ERK and Bax protein levels. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with p &lt; 0.05 considered statistically significant. Results: Treatment of IR rats with O3 resulted in a significant increase in mucosal weight in jejunum (70 %) and ileum (32 %), mucosal DNA (twofold increase) and protein (35 %) in ileum, villus height and crypt depth in jejunum (61 and 16 %, correspondingly) and ileum (31 and 43 %, correspondingly) compared to IR animals. IR-O3 rats also had a significantly lower intestinal injury score as well as a lower apoptotic index in jejunum and ileum compared and IR animals. A significant increase in cell proliferation rates in IR-O3 animals was accompanied by increased levels of p-ERK protein. Conclusions: Treatment with ozone prevents intestinal mucosal damage, stimulates cell proliferation and inhibits programmed cell death following intestinal IR in a rat. 

Retracted: No

PubPeer comments:
 Figure 5. * Panels here look similar to panels in a 2005 paper by a shared researcher, i.e. Igor Sukhotnik et al., Digestive Diseases and Sciences (2005), DOI: 110.1007 s10620-005-3067-x - https: pubpeer.com publications CE47ED34ECDDF7DE045CF2A4F54CAD * Blue boxes: The 2005 Sham panel looks similar to the 2014 IR panel * Red boxes: The 2005 SBS panel looks similar to the 2014 IR-O3 panel. ![file] ,
Interferon-γ affects leukemia cell apoptosis through regulating Fas/FasL signaling pathway
Authors: J Wang
Z-H Wu
H Zhang
H-L Xia
X-F Hou
C-J Li
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: hematopoietic cell proliferation; apoptosis; leukemia; interferon γ; Fas/FasL signaling pathway
Affiliations: Department of Hematology, The Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Anhui, China. .

Abstract:  Objective: Imbalance of hematopoietic cell proliferation and apoptosis is one of the major causes of leukemia. Enhanced cell proliferation and reduced apoptosis lead to hemocytes accumulation. Fas/FasL signaling pathway promotes cell apoptosis. This study investigated the impact of interferon γ (IFN-γ) on chronic myelogenous leukemia cell proliferation and apoptosis to elucidate its interaction with Fas/FasL signaling pathway. Patients and methods: Leukemia K562 cells were routinely cultivated and treated with 10 U/ml, 100 U/ml, and 1000 U/ml interferon for 12 h, 24 h, and 48 h, respectively. MTT assay was applied to test cell proliferation. TUNEL assay was adopted to determine cell apoptosis. Western blot was selected to detect Fas/FasL expression. Results: Different concentrations of IFN-γ inhibited cell proliferation at various time points. IFN-γ at 1000 U/ml treatment for 48 h exhibited the strongest suppressive effect on cell proliferation (p &lt; 0.05). IFN-γ intervention enhanced K562 cell apoptosis with concentration and time dependence (p &lt; 0.05). Fas and FasL proteins expressions upregulated after treated by IFN-γ following dose elevation and time extension (p &lt; 0.05). Conclusions: IFN-γ inhibits leukemia K562 cell proliferation and promotes cell apoptosis via facilitating Fas and FasL proteins expressions. 

Retracted: No

PubPeer comments:
 Figure 1. * Red boxes: The 100 and 1000 U ml panels appear to show an overlap, albeit with a different zoom stretch factor. ![file] ,
MiR 3180-5p promotes proliferation in human bladder smooth muscle cell by targeting PODN under hydrodynamic pressure
Authors: De-Yi Luo
Liang Zhou
Tong-Xin Yang
Cai Tang
Yu-Chun Zhu
Hong Shen
Yi Sun
Kun-Jie Wang
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Human bladder smooth muscle cells; pressure cycles; microarray analysis; miR-3180-5p; PCR
Affiliations: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China., Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.

Abstract:  Human bladder smooth muscle cells (HBSMCs) were subjected to pressure cycles of up to 200 cm H2O to a pressure of 0 cm H2O for 24 hours. The total RNA extracted from each group was subjected to microarray analysis. miR-3180-5p emerged as the most overexpressed of all the differentially expressed microRNAs, and this finding was validated by PCR. We then used CCK-8 to quantify cell proliferation after liposome-mediated transfection. Subsequently, we investigated the change in PODN and its downstream signaling proteins, including cyclin-dependent kinase 2 (cdk2) and p21. In addition, flow cytometry was performed to quantify cell-cycle distribution. The results show that miR-3180-5p, the microRNA that was most overexpressed in response to HP, reduced the expression of PODN and podocan (p = 0.004 and p = 0.041, respectively). Silencing of PODN via miR-3180-5p overexpression revealed a significant promotion of cell proliferation increased in the CCK-8 experiment, p = 0.00077). This cell proliferation was accompanied by an increase in cdk2 expression (p = 0.00193) and a decrease in p21 expression (p = 0.0095). The percentage of cells in (S + G2/M) improved after transfection (p = 0.002). It was apparent that HP upregulates miR-3180-5p, which inhibits the expression of PODN and promotes HBSMC proliferation via the cdk2 signaling pathway. 

Retracted: No

PubPeer comments:
 Some bands in Figure 6 show areas of sharp transition that could indicate unexpected splicing. Could the authors provide an uncropped original scan? 6C is shown as an example. *** Enhanced contrast ![file] *** Original ![file] , 
 ![file] , 
 #2 Thank you. Could you indicate which lanes were selected for 6C? ,
Systematic identification of Celastrol-binding proteins reveals that Shoc2 is inhibited by Celastrol
Authors: Yi-Fan Dong
Lang Yan
Zhang Xiao-Fang
Wei Xue
Chen Ji-Kuai
Zhu Jiang-Bo
Chang Wen-Jun
Huang Xiao-Pei
Pan Ya-Min
Journal: Bioscience reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Celastrol; Colorectal cancer; ERK; Human proteome microarray; Shoc2.
Affiliations: Department of Health Toxicology, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, P.R. China, Department of Health Toxicology, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, P.R. China., The First Department of Endoscopy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China, Department of Environmental Hygiene, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, P.R. China

Abstract:  Colorectal cancer (CRC) is the third most commonly diagnosed cancer. Celastrol exhibits anti-tumor activities in a variety of cancers. However, the effect of Celastrol on human CRC and the underlying mechanisms still need to be elucidated. The present study aimed to use in vitro and in vivo methods to clarify the anti-tumor effect of Celastrol and use protein microarrays to explore its mechanisms. We demonstrated that Celastrol effectively inhibited SW480 CRC cell proliferation. Two weeks of Celastrol gavage significantly inhibited the growth of xenografts in nude mice. A total of 69 candidate proteins were identified in the protein microarray experiment, including the most highly enriched protein Shoc2, which is a scaffold protein that modulates cell motility and metastasis through the ERK pathway. Celastrol significantly inhibited ERK1/2 phosphorylation in cell lines and xenograft tumors. Down-regulation of Shoc2 expression using Shoc2 siRNA also inhibited ERK1/2 phosphorylation. Furthermore, down-regulation of Shoc2 expression also significantly inhibited proliferation, colony formation, and migration functions of tumor cells. In addition, the LD0 of Celastrol by gavage is equal or more than 80 mg/kg in C57 male mice. In summary, we unraveled the anti-CRC function of Celastrol and confirmed for the first time that it inhibited the ERK1/2 pathway through binding to Shoc2. 

Retracted: No

PubPeer comments:
 Figure 1C appears to have a repeated image. *** ![file] ,
Purification and characterization of anti-tubercular and anticancer protein from Staphylococcus hominis strain MANF2: In silico structural and functional insight of peptide
Authors: B Mahizhaveni
Abdul-Kareem Mohammed Ghilan
Paul Agastian
Naif Abdullah Al-Dhabi
Mariadhas Valan Arasu
Ameer Khusro
Azger Dusthackeer
Chirom Aarti
Galal Ali Esmail
Journal: Saudi Journal of Biological Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Anti-tubercular; Anticancer; In silico tools; MALDI-TOF MS/MS; Protein
Affiliations: Research Department of Plant Biology and Biotechnology, Loyola College (Autonomous), University of Madras, Chennai 34, Tamil Nadu, India., Department of Bacteriology, National Institute for Research in Tuberculosis, ICMR, Sathyamoorty Road, Chetpet, Chennai 31, Tamil Nadu, India., Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

Abstract:  The present context was investigated to purify and characterize anti-tubercular as well as anticancer protein from fermented food associated Staphylococcus hominis strain MANF2. Initially, the anti-tubercular potency of strain MANF2 was assessed against Mycobacterium tuberculosis H37Rv using luciferase reporter phase assay which revealed pronounced relative light unit (RLU) reduction of 92.5 ± 1.2%. The anticancer property of strain MANF2 was demonstrated against lung cancer (A549) and colon cancer (HT-29) cell lines using MTT assay which showed reduced viabilities. Anti-tubercular activities of the purified protein were observed to be increased significantly (P &lt; 0.05) ranging from 34.6 ± 0.3 to 71.4 ± 0.4% of RLU reduction. Likewise, the purified protein showed significantly (P &lt; 0.05) reduced viabilities of A549 and HT-29 cancer cells with IC50 values of 46.6 and 48.9 µg/mL, respectively. The nominal mass of the purified protein was found to be 7712.3 Da as obtained from MALDI-TOF MS/MS spectrum. The protein showed the sequence homology with 1-336 amino acids of Glyceraldehyde-3-phosphate dehydrogenase from Staphylococcus sp., thus, categorizing as a new class of Glyceraldehyde-3-phosphate dehydrogenase-like protein. The amino acid sequence of the most abundant peptide (m/z = 1922.12) in the purified protein was obtained as 'KAIGLVIPEIDGKLDGGAQRV' and it was identified as peptide NMANF2. In silico tools predicted significant stereo-chemical, physiochemical, and functional characteristics of peptide NMANF2. In a nutshell, protein purified from strain MANF2 can certainly be used as an ideal therapeutic agent against tuberculosis and cancer (lung and colon). 

Retracted: No

PubPeer comments:
 Figure 5: There is a duplicated image, I ve added the red rectangles to show where I mean. Would the authors please comment? ![file] , 
 Figure 6 appears to contain a duplication as well, with some aspect ratio shenanigans. ![file] ,
Requirement of the mymA Operon for Appropriate Cell Wall Ultrastructure and Persistence of Mycobacterium tuberculosis in the Spleens of Guinea Pigs
Authors: Radhika Gupta
V D Ramanathan
Anil K Tyagi
Amit Singh
P R Narayanan
R A Vishwakarma
C N Paramasivan
Journal: Journal of Bacteriology (2005)
Discipline: MICROBIOLOGY
Keywords: mymA operon; VirS; Mycobacterium tuberculosis; mycolic acids; fatty acids
Affiliations: Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021, India.

Abstract:  We had recently reported that the mymA operon (Rv3083 to Rv3089) of Mycobacterium tuberculosis is regulated by AraC/XylS transcriptional regulator VirS (Rv3082c) and is important for the cell envelope of M. tuberculosis. In this study, we further show that a virS mutant (MtbdeltavirS) and a mymA mutant (Mtbmym::hyg) of M. tuberculosis exhibit reduced contents and altered composition of mycolic acids along with the accumulation of saturated C24 and C26 fatty acids compared to the parental strain. These mutants were markedly more susceptible to major antitubercular drugs at acidic pH and also showed increased sensitivity to detergent (sodium dodecyl sulfate) and to acidic stress than the parental strain. We show that disruption of virS and mymA genes impairs the ability of M. tuberculosis to survive in activated macrophages, but not in resting macrophages, suggesting the importance of the mymA operon in protecting the bacterium against harsher conditions. Infection of guinea pigs with MtbdeltavirS, Mtbmym::hyg, and the parental strain resulted in an approximately 800-fold-reduced bacillary load of the mutant strains compared with the parental strain in spleens, but not in the lungs, of animals at 20 weeks postinfection. Phenotypic traits were fully complemented upon reintroduction of the virS gene into MtbdeltavirS. These observations show the important role of the mymA operon in the pathogenesis of M. tuberculosis at later stages of the disease. 

Retracted: No

PubPeer comments:
 ![file] , 
 AUTHOR CORRECTION Volume 187, no. 12, p. 4173u20134186, 2005, https: doi.org 10.1128 JB.187.12.4173-4186.2005. Page 4176, Fig. 2 legend: The following sentence should be added to the end: u201cPanel A is reprinted with permission from reference 58.u201d The reuse of this panel does not affect the conclusions of this work. u2022tCopyright u00a9 2021 American Society for Microbiology. All Rights Reserved. The problem in this article is on Page 4177 in Figure 4, and not on Page 4176 and in Figure 2 as mentioned in Author Correction. Appreciate if the authors clarify it? , 
 ![file] , 
 ![file] ,
mTORC1 controls fasting-induced ketogenesis and its modulation by ageing
Authors: David M Sabatini
Timothy R Peterson
Shomit Sengupta
Stephanie Oh
Mathieu Laplante
Journal: Nature (2010)
Discipline: Multidisciplinary
Keywords: mTORC1; liver physiology; ketogenesis; fasting; TSC1
Affiliations: Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.

Abstract:  The multi-component mechanistic target of rapamycin complex 1 (mTORC1) kinase is the central node of a mammalian pathway that coordinates cell growth with the availability of nutrients, energy and growth factors. Progress has been made in the identification of mTORC1 pathway components and in understanding their functions in cells, but there is relatively little known about the role of the pathway in vivo. Specifically, we have little knowledge regarding the role mTOCR1 has in liver physiology. In fasted animals, the liver performs numerous functions that maintain whole-body homeostasis, including the production of ketone bodies for peripheral tissues to use as energy sources. Here we show that mTORC1 controls ketogenesis in mice in response to fasting. We find that liver-specific loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor, leads to a fasting-resistant increase in liver size, and to a pronounced defect in ketone body production and ketogenic gene expression on fasting. The loss of raptor (regulatory associated protein of mTOR, complex 1) an essential mTORC1 component, has the opposite effects. In addition, we find that the inhibition of mTORC1 is required for the fasting-induced activation of PPARα (peroxisome proliferator activated receptor α), the master transcriptional activator of ketogenic genes, and that suppression of NCoR1 (nuclear receptor co-repressor 1), a co-repressor of PPARα, reactivates ketogenesis in cells and livers with hyperactive mTORC1 signalling. Like livers with activated mTORC1, livers from aged mice have a defect in ketogenesis, which correlates with an increase in mTORC1 signalling. Moreover, we show that the suppressive effects of mTORC1 activation and ageing on PPARα activity and ketone production are not additive, and that mTORC1 inhibition is sufficient to prevent the ageing-induced defect in ketogenesis. Thus, our findings reveal that mTORC1 is a key regulator of PPARα function and hepatic ketogenesis and suggest a role for mTORC1 activity in promoting the ageing of the liver. 

Retracted: No

PubPeer comments:
 Could authors please share the raw values of the qPCR experiments to shed light on why control groups seems to present same mean and SEM values in different graphs? Examples below: ![file] ![file] Same issue observed in some ChIP-Seq results. The exact same error bars in so many different conditions is unexpected, but this could be easily clarified by checking the raw data if the authors are willing to provide it. ![file] ,
DNA profiling and in vitro cytotoxicity studies of tetrazolo[1,5-a]pyrimidine-based copper(II) complexes
Authors: Dharmasivam Mahendiran
Aziz Kalilur Rahiman
Vijaykumar Veena
Ummer Muhammed Rafi
Liviu Mitu
Azees Khan Haleel
Journal: BioMetals (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Apoptosis; Copper(II) complexes; DNA interaction; Molecular docking; Tetrazolo[1,5-a]pyrimidines.
Affiliations: Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai, 600 014, India., Molecular Pharmacology and Pathology Program, Department of Pathology, Bosch Institute, University of Sydney, Sydney, NSW, 2006, Australia., Department of Chemistry, Faculty of Science, University of Pitesti, 110 040, Pitesti, Romania., Department of Biotechnology, School of Chemical and Biological Sciences, REVA University, Bangalore, 560 064, India., Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai, 600 014, India. .

Abstract:  A series of N-benzoylated mononuclear copper(II) complexes of the type [Cu(L1-6)Cl2] (1-6), where L1= ethyl 4-benzoyl-5-methyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate, L2= ethyl 4-(4-nitrobenzoyl)-5-methyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate, L3 = ethyl 4-benzoyl-5-methyl-7-(4-methoxyphenyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate, L4 = ethyl 4-(4-nitrobenzoyl)-5-methyl-7-(4-methoxyphenyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate, L5 = ethyl 4-benzoyl-5-methyl-7-(4-chlorophenyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate and L6 = ethyl 4-(4-nitrobenzoyl)-5-methyl-7-(4-chlorophenyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate have been synthesized and characterized by spectral methods. Electron paramagnetic resonance spectra of complexes show four lines, characteristic of square planar geometry. The binding studies of the complexes with calf thymus DNA (CT-DNA) revealed groove mode of binding, which were further supported by molecular docking studies. Gel electrophoresis experiments demonstrated the ability of the complexes to cleave plasmid DNA in the absence of activators. Further, the cytotoxicity activity of the complexes were examined on three cancerous cell lines (lung (A549), cervical (HeLa) and colon (HCT-15)), and on two normal cells (human embryonic kidney (HEK) and peripheral blood mononuclear cells (PBMC)) by MTT assay. 

Retracted: No

PubPeer comments:
 Could the authors comment on what appear to be several repeated features in Figure 4a? ![file] , 
 Could the authors comment on what appear to be several repeated features in Figure 4 a b? ![file] , 
 Could the authors comment on what appear to be some repeated features in Figure 5b? ![file] ,
Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway
Authors: Jin-Taek Hwang
Seong-Kyu Lee
Young Min Kim
Ock Jin Park
Haing Woon Baik
In-Ja Park
Joohun Ha
Journal: Cancer Letters (2007)
Discipline: CLINICAL MEDICINE
Keywords: EGCG; cancer cell proliferation; signaling pathways; apoptosis; chemotherapy
Affiliations: Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species, Kyung Hee University College of Medicine, Seoul, South Korea.

Abstract:  EGCG [(-)epigallocatechin-3-gallate], a green tea-derived polyphenol, has been shown to suppress cancer cell proliferation, and interfere with the several signaling pathways and induce apoptosis. Practically, there is emerging evidence that EGCG has a potential to increase the efficacy of chemotherapy in patients. We hypothesized that EGCG may exert cell cytotoxicity through modulating AMPK (AMP-activated protein kinase) followed by the decrease in COX-2 expression. EGCG treatment to colon cancer cells resulted in a strong activation of AMPK and an inhibition of COX-2 expression. The decreased COX-2 expression as well as prostaglandin E(2) secretion by EGCG was completely abolished by inhibiting AMPK by an AMPK inhibitor, Compound C. Also, the activation of AMPK was accompanied with the reduction of VEGF (vascular endothelial growth factor) and glucose transporter, Glut-1 in EGCG-treated cancer cells. These findings support the regulatory role of AMPK in COX-2 expression in EGCG-treated cancer cells. Furthermore, we have found that reactive oxygen species (ROS) is an upstream signal of AMPK, and the combined treatment of EGCG and chemotherapeutic agents, 5-FU or Etoposide, exert a novel therapeutic effect on chemo-resistant colon cancer cells. AMPK, a molecule of newly defined cancer target, was shown to control COX-2 in EGCG-treated colon cancer cells. 

Retracted: No

PubPeer comments:
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Inhibition of macroautophagy triggers apoptosis
Authors: Philippe Dessen
Nathanael Larochette
Daniel Meley
Rosa-Ana González-Polo
Tamotsu Yoshimori
Didier Métivier
Jean-Luc Perfettini
Patricia Boya
Guido Kroemer
Patrice Codogno
Gérard Pierron
Noelia Casares
Sylvie Souquere
Journal: Molecular and cellular biology (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Mammalian cells; cell death; apoptosis; autophagy; nutrient depletion
Affiliations: CNRS-UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille-Desmoulins, F-94805 Villejuif, France. ., CNRS-UMR8125, Institut Gustave Roussy, Institut André Lwoff, Villejuif, France, Laboratoire Replication de l'ADN et Ultrastructure du Noyau, UPR-1983, and INSERM U504, National Institute of Genetics, Mishima, Japan

Abstract:  Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-methyladenine, hydroxychloroquine, bafilomycin A1, or monensin). Cell death occurred through apoptosis (type 1 cell death), since it was reduced by stabilization of mitochondrial membranes (with Bcl-2 or vMIA, a cytomegalovirus-derived gene) or by caspase inhibition. Under conditions in which the fusion between lysosomes and autophagosomes was inhibited, the formation of autophagic vacuoles was enhanced at a preapoptotic stage, as indicated by accumulation of LC3-II protein, ultrastructural studies, and an increase in the acidic vacuolar compartment. Cells exhibiting a morphology reminiscent of (autophagic) type 2 cell death, however, recovered, and only cells with a disrupted mitochondrial transmembrane potential were beyond the point of no return and inexorably died even under optimal culture conditions. All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways. 

Retracted: No

PubPeer comments:
 Figure 4 u2013 more similar than expected ![file] ,
Thyroid hormone stimulates protein synthesis in the cardiomyocyte by activating the Akt-mTOR and p70S6K pathways
Authors: Agnes Kenessey
Kaie Ojamaa
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Thyroid hormones; cardiomyocyte hypertrophy; Tri-iodo-L-thyronine (T3); PI3K; Akt
Affiliations: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030., The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030; Departments of Cell Biology and Medicine, New York University School of Medicine, New York, New York 10016. Electronic address: .

Abstract:  Thyroid hormones affect cardiac growth and phenotype; however, the mechanisms by which the hormones induce cardiomyocyte hypertrophy remain uncharacterized. Tri-iodo-L-thyronine (T3) treatment of cultured cardiomyocytes for 24 h resulted in a 41 +/- 5% (p &lt; 0.001) increase in [(3)H]leucine incorporation into total cellular protein. This response was abrogated by the phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin. Co-immunoprecipitation studies showed a direct interaction of cytosol-localized thyroid hormone receptor TRalpha1 and the p85alpha subunit of PI3K. T3 treatment rapidly increased PI3K activity by 52 +/- 3% (p &lt; 0.005), which resulted in increased phosphorylation of downstream kinases Akt and mammalian target of rapamycin (mTOR). This effect was abrogated by pretreatment with wortmannin or LY294002. Phosphorylation of p70(S6K), a known target of mTOR, occurred rapidly following T3 treatment and was inhibited by rapamycin and wortmannin. In contrast, phosphorylation of the p85 variant of S6K in response to T3 was not blocked by LY294002, wortmannin, or rapamycin, thus supporting a T3-activated pathway independent of PI3K and mTOR. 40 S ribosomal protein S6, a target of p70(S6K), and 4E-BP1, a target of mTOR, were both phosphorylated within 15-25 min of T3 treatment and could be inhibited by wortmannin and rapamycin. Thus, rapid T3-mediated activation of PI3K by cytosolic TRalpha1 and subsequent activation of the Akt-mTOR-S6K signaling pathway may underlie one of the mechanisms by which thyroid hormone regulates physiological cardiac growth. 

Retracted: No

PubPeer comments:
 In figure 6, cluster 7 is characterized as a putative  stem cells cluster, due it s expression of  EMT markers but they strongly resemble non-epithelial cells. These cells must have been sorted and sequenced due to the impurity of the sort. The data is accessible in GEO (GSE111429) and can be rapidly processed to verify the claims. There may be Zeb1+ basal cells (figure 6g), but these are certainly not the ones present in cluster 7, which are clearly non-epithelial. ,
Inducible miR-145 expression by HIF-1a protects cardiomyocytes against apoptosis via regulating SGK1 in simulated myocardial infarction hypoxic microenvironment
Authors: Ning Xue
Nianzi Sun
Fanyan Meng
Qingxin Wang
Hongliang Ma
Guanghui Pang
Journal: Cardiology journal (2018)
Discipline: CLINICAL MEDICINE
Keywords: HIF-1a; PI3K/AKT; SGK1; hypoxia; miR-145
Affiliations: Linyi People's Hospital. .

Abstract:  Background: Myocardial infarction (MI) is partly due to myocardial cell damage caused by hypoxia. MicroRNAs (miRNAs) have been proved to be closely related to the development and progression of many cardiovascular diseases. This study investigated the role of miR-145 in cardiomyocytes under hypoxic condition. Methods: The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to test miR-145 expression in H9c2 cells with hypoxia-inducible factor (HIF)-a abnormal expression under hypoxic condition. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide (MTT), Tran-swell assay and flow cytometry were used to investigate the effects of miR-145 on cell viability, migration and apoptosis under normoxic or hypoxic condition, respectively. Meanwhile, reactive oxygen species (ROS) content in hypoxic H9c2 cells was analyzed. Western blotting was used to explore the potential mechanism of miR-145 protective effects on cardiomyocytes. Expression levels of miR-145 and SGK1 in rat MI model were also assessed. Results: Results showed that miR-145 was upregulated in H9c2 and HL-1 cells under hypoxic condi-tion, which was promoted by HIF-1a. MiR-145 overexpression enhanced cell viability and migration under normoxic condition. Under hypoxic condition, miR-145 overexpression promoted cell viability, inhibited apoptosis and ROS activity. Western blotting results proved that miR-145 overexpression inhibited the activation of apoptotic related factors, and promoted activation of PI3K/AKT signaling pathway via SGK1 upregulation. Expression levels of miR-145 and SGK1 were both upregulated in rat MI models. Conclusions: HIF-1a could induce miR-145 upregulation in hypoxic H9c2 and HL-1 cells. MiR-145 protected H9c2 cells against hypoxic damage. SGK1 upregulation and activated PI3K/AKT may have participated in the protective effects of miR-145 on cardiomyocytes. 

Retracted: No

PubPeer comments:
 ![file] ,
Long non-coding RNA H19 promotes the proliferation and invasion of breast cancer through upregulating DNMT1 expression by sponging miR-152
Authors: Yan Li
Xin Li
Xinwei Han
Jiaxiang Wang
Zhen Li
Ya Li
Kewei Ren
Journal: Journal of Biochemical and Molecular Toxicology (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: DNMT1; LncRNA H19; breast cancer; miR-152.
Affiliations: Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China., Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China., Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China., Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

Abstract:  Long non-coding RNA (lncRNA) H19 in tumors played important roles in various biological processes. However, the biological role and molecular mechanism of H19 in breast cancer are unclear. Here, we found that H19 was aberrantly upregulated in human breast tumor tissues and cells. A negative correlation between H19 and miR-152 and positive correlation between H19 and DNMT1 mRNA were observed. Downregulation of H19 and DNMT1 significantly retarded breast cancer cell proliferation and invasion. H19 act as an endogenous sponge by directly binding to miR-152. miR-152 directly targeted DNMT1 and was regulated by H19. Besides, H19 overexpression dramatically relieved the inhibition of miR-152 on DNMT1 expression. miR-152 inhibition and DNMT1 overexpression obviously reversed the inhibitory effects of H19 downregulation on cell proliferation and invasion. In conclusion, H19 promoted proliferation and invasion of breast cancer through the miR-152/DNMT1 axis, providing a novel mechanism about the occurrence and development of breast cancer. 

Retracted: No

PubPeer comments:
 Figure 2D appears to have some partial overlaps, when the si-control image is rotated. You would need to rotate two different ways to get all of the overlaps. ![file] , 
 There is a generic quality to the Western Blot images. Here, FIg 4  (G and H) Western blot were used to detect the expression of DNMT1 in breast cancer cells transfected with si-H19, miR-152 mimics, pcDNA 3.1-H19, miR-152 mimics + pcDNA 3.1-H19, or matched controls. ![file] Unexpected similarity between parts of the DNMT1 bands from MCF-7 and MDA-MB-231 samples (after vertical stretch). ,
The role of gut microbiota in the pathogenesis and management of allergic diseases
Authors: D. Compare
G. Nardone
Journal: European review for medical and pharmacological sciences (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: gut microbiota; pathogenesis; allergic diseases; management; withdrawn

Abstract:  The article “The role of gut microbiota in the pathogenesis and management of allergic diseases” by D. Compare, G. Nardone, published in Eur Rev Med Pharmacol Sci 2014; 17 (2 Suppl): 11-17 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,