PReD-Bench/PRed-Bench huggingface dataset:
Complexin in ivermectin resistance in body lice
Authors: Yassina Bechah
Nadia Amanzougaghene
Oleg Mediannikov
Florence Fenollar
Eric Chabrière
Said Azza
Didier Raoult
Philippe Decloquement
Amira Ben-Amara
Claude Nappez
Journal: PLoS Genetics (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ivermectin; pediculicide; resistance; mutations; GluCl
Affiliations: Aix Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France., Aix Marseille Univ, IRD, APHM, VITROME, IHU-Méditerranée Infection, Marseille, France.

Abstract:  Ivermectin has emerged as very promising pediculicide, particularly in cases of resistance to commonly used pediculicides. Recently, however, the first field-evolved ivermectin-resistance in lice was reported. To gain insight into the mechanisms underlying ivermectin-resistance, we both looked for mutations in the ivermectin-target site (GluCl) and searched the entire proteome for potential new loci involved in resistance from laboratory susceptible and ivermectin-selected resistant body lice. Polymorphism analysis of cDNA GluCl showed no non-silent mutations. Proteomic analysis identified 22 differentially regulated proteins, of which 13 were upregulated and 9 were downregulated in the resistant strain. We evaluated the correlation between mRNA and protein levels by qRT-PCR and found that the trend in transcriptional variation was consistent with the proteomic changes. Among differentially expressed proteins, a complexin i.e. a neuronal protein which plays a key role in regulating neurotransmitter release, was shown to be the most significantly down-expressed in the ivermectin-resistant lice. Moreover, DNA-mutation analysis revealed that some complexin transcripts from resistant lice gained a premature stop codon, suggesting that this down-expression might be due, in part, to secondary effects of a nonsense mutation inside the gene. We further confirmed the association between complexin and ivermectin-resistance by RNA-interfering and found that knocking down the complexin expression induces resistance to ivermectin in susceptible lice. Our results provide evidence that complexin plays a significant role in regulating ivermectin resistance in body lice and represents the first evidence that links complexin to insecticide resistance. 

Retracted: No

PubPeer comments:
 The authors declare no conflict of interest in the paper. However, we can note that one of author is the funder if a pharmaceutical company called Arthrobac Pharma. The scope of this pharmaceutical company is to treat lices with ivermectine as shown in this poster. Which is Also the scope of this paper. Can the author explain if he still had any interest in this pharmaceutical company when the manuscript was submitted? ![Image](HTTPS: pubpeer.com storage image-1617569003770.png) , 
 What conflict of interest ? Study provides evidence that complexin plays a significant role in regulating ivermectin resistance. It s only an evidence linking complexin to insecticide resistance. ,
Exosomal microRNA-16-5p from adipose mesenchymal stem cells promotes TLR4-mediated M2 macrophage polarization in septic lung injury
Authors: Jingxiao Zhang
Xiaoqian Cui
Jian Sun
Jiakun Tian
Journal: International Immunopharmacology (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Adipose mesenchymal stem cells; Exosomes; Inflammation; Lung injury; Macrophage
Affiliations: Department of Critical Care Medicine, The Second Hospital of Jilin University, Changchun 130021, Jilin Provence, China., Department of Critical Care Medicine, The Second Hospital of Jilin University, Changchun 130021, Jilin Provence, China. Electronic address: .

Abstract:  This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The authors have requested that this paper be retracted as they were unable to replicate the experimental data reported in Figure 1A. The authors posit that changes in reagents or experimental conditions might be the source of their inability to do so. Additional concerns were raised about the reliability of the Western blot results in Figure 1E, Figure 4B and F, Figure 5B, and Figure 6B, as regarding ‘morphology space’ similarities contained within a series of papers with distinctive eyebrow blots, tabulated here (https://docs.google.com/spreadsheets/d/149EjFXVxpwkBXYJOnOHb6RhAqT4a2llhj9LM60MBffM/edit#gid=0 [nam11.safelinks.protection.outlook.com] [nam11.safelinks.protection.outlook.com]). The journal requested the authors comment on these concerns and provide raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article. 

Retracted: No

PubPeer comments:
 Fig 1A,  Detection of ADSC surface antigens by flow cytometry . ![file] Overhangs marked in the CD44 panel. , 
 Figs 1E, 4B F, 5B, 6B. ![file] Is it possible for the authors to upload scans of the original gels for these eyebrow-like Western Blots? They sample the same confined region of morphology space as Figs 1b, 7a of Yang et al (2021)... ![] Figs 1b, 6d f, 7b from Li et al (2021)... ![] ... and Figs 5b,d and 7b from Tang Hu (2021). ![] A few dozen other examples are tabulated [here] . , 
 Retracted [8 August 2022] .  The authors have requested that this paper be retracted as they were unable to replicate the experimental data reported in Fig. 1A. The authors posit that changes in reagents or experimental conditions might be the source of their inability to do so. Additional concerns were raised about the reliability of the Western blot results in Fig. 1E, Fig. 4B and F, Fig. 5B, and Fig. 6B, as regarding u2018morphology spaceu2019 similarities contained within a series of papers with distinctive eyebrow blots, tabulated here . The journal requested the authors comment on these concerns and provide raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article. ,
Thymoquinone inhibits growth and augments 5-fluorouracil-induced apoptosis in gastric cancer cells both in vitro and in vivo
Authors: Xufeng Guo
Xiaofei Lei
Mengyao Ji
Xiaoguang Lv
Weiguo Dong
Zirong Yang
Meng Liu
Journal: Biochemical and Biophysical Research Communications (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Thymoquinone; 5-fluorouracil; gastric cancer; chemosensitizing effect; apoptosis
Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China.

Abstract:  Thymoquinone (TQ), a component derived from the bioactive constituent of black seed (Nigella sativa), has been shown to exert biological activity on various types of human cancers. However, there are few studies addressing its effects on gastric cancer. Here, we present the first report describing the chemosensitizing effect of thymoquinone and 5-fluorouracil (5-FU) on gastric cancer cells both in vitro and in vivo. Studies have shown that pretreatment with TQ significantly increased the apoptotic effects induced by 5-FU in gastric cancer cell lines in vitro. Moreover, we found that TQ enhanced the 5-FU-induced killing of gastric cancer cells by mediating the downregulation of the anti-apoptotic protein bcl-2, the upregulation of the pro-apoptotic protein bax, and the activation of both caspase-3 and caspase-9. In addition to the in vitro results, it has been shown that the combined treatment of TQ with 5-FU represents a significantly more effective antitumor agent than either agent alone in a xenograft tumor mouse model. These data suggest that the TQ/5-FU combined treatment induces apoptosis by enhancing the activation of both caspase-3 and caspase-9 in gastric cancer cells. These results, which provide molecular evidence both in vitro and in vivo, support our conclusion that thymoquinone can activate caspase-3 and caspase-9 and thus result in the chemosensitisation of gastric cancer cells to 5-FU-induced cell death. 

Retracted: No

PubPeer comments:
 Figure 4C. * Red boxes: The TQ and 5-FU treatment group panels look more similar than expected. ![file] , 
 #1 Dear Elisabeth M Bik Thank you for your kind comment. After receiving the comment information, we immediately checked the original documents carefully. We found that the two pictures you mentioned are actually the same picture by a mistakenly picture selecting. We are very sorry for our carelessness. It is a mistake to pick a wrong picture for preparing of this figure that did not affect on conclusion. We have contacted the editor immediately to make corrections. Thank you for your attention. Sincerely yours Xiaofei Lei , 
 #2 I thank the author for replying. Given the propensity of what appears to be the same research group to carelessly commingle images (see thread below), I would think it is difficult to trust the research results from this lab. https: pubpeer.com publications A22019AA1BEF68FCD1657F33C54116 ,
MicroRNA-365 inhibits proliferation, migration and invasion of glioma by targeting PIK3R3
Authors: Min Rao
Yonggang Zhu
Hongguang Zhao
Songbai Xu
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: microRNA-365; cancer; glioma; proliferation; migration

Abstract:  A growing body of evidence suggests that microRNA-365 (miR-365) played crucial role in the initiation and development of many types of cancers. However, the biological role of miR-365 in human glioma remains unclear. Herein, the aims of this study were to investigate the role and underlying mechanisms of miR-365 in glioma by a series of in vitro and in vivo experiments. We found that miR-365 was strongly downregulated in malignant glioma tissues and cell lines. Restoration of the expression of miR-365 in glioma cells significantly inhibited cell proliferation, migration and invasion in vitro and tumor growth in vivo. Notably, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was proved to be a direct target of miR-365 in glioma cells, and its mRNA expression was inversely correlated with miR-365 expression in clinical glioma tissues. PIK3R3 overexpression in miR-365 expressing cells could rescue proliferation, migration and invasion inhibition of miR-365. In addition, miR-365 was able to inhibit the phosphorylation of AKT and mTOR in vitro and in vivo, which are key participants in the AKT/mTOR pathway. These results suggest that miR-365 functioned as a tumor suppressor in glioma by targeting PIK3R3, suggesting that miR-365 has potential as therapeutic targets for glioma. 

Retracted: No

PubPeer comments:
 *[left]* Fig 3D.  The PIK3R3 ... protein expression levels were determined in U87 cells transfected with miR-365 mimic or miR-NC by ... western blotting . *[right]* Fig 5B from [Zhu et al (2016)] .  Runx22 expression on ... protein level were measured in U87 cells transfected with si-Runx2 or si-NC by ... western blot . ![file] The only difference seems to be in focus. , 
 Fig 6D.  PIK3R3 protein level was determined in tumor tissues from different groups by western blotting. ![file] Fig 7 from [Cao et al (2017)] . ![file] ,
<p>MiR-4766-5p Inhibits The Development And Progression Of Gastric Cancer By Targeting NKAP</p>
Authors: Dan Hong
Zhiyu Wang
Guotao Fang
Yanan Wang
Aimin Zang
Yaning Wei
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: NKAP; gastric cancer; miR-4766-5p; progression.
Affiliations: Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding City, Hebei Province 071000, People's Republic of China., Department of Medical Pathology, Affiliated Hospital of Hebei University, Baoding City, Hebei Province 071000, People's Republic of China.

Abstract:  Purpose: It is widely known that some specific microRNAs can regulate the expressions of genes in gastric cancer cells at the post-transcriptional level. Previous studies have identified that miRNA-4766-5p was involved in tumor cell proliferation and can be an independent prognostic indicator for malignant pleural mesothelioma. However, the mechanism underlying gastric cancer via the miRNA-4766-5p pathway remains to be blank. Methods: We investigated the expression of miR-4766-5p in gastric cancer tissues and cells through qRT-PCR. We used RNAi to change the expressions of miR-4766-5p in gastric cancer cell lines, AGS and MKN45. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the mRNA expression of miR-4766-5p. We identified cell proliferation by CCK8 and clone formation assays. We analyzed the cell apoptosis and cycle through flow cytometry. At last, we used a dual-luciferase reporter assay to illustrate the interaction between miR-4766-5p and NKAP and used Western blot to determine the protein expression of signaling pathways. Results: We found that 1) miR-4766-5p was down-regulated in gastric cancer tissues and cells lines; 2) miR-4766-5p inhibited cell proliferation of gastric cancer cell lines significantly; 3) miR-4766-5p significantly inhibited cell migration and invasion of gastric cancer cells; 4) miR-4766-5p induced gastric cancer cell apoptosis. 5) NKAP was a direct target gene of miR-4766-5p; and 6) miR-4766-5p induced inactivation of AKT/mTOR pathway. Conclusion: The above results indicate that miR-4766-5p suppressed the proliferation and metastasis of gastric cancer cells through targeting NKAP. Our findings could probably contribute to the diagnostics and prognostics of gastric cancer through new methodologies. 

Retracted: No

PubPeer comments:
 Figure 3E. * Red boxes: In the MKN45 row, the  Con and  pNC panels appear to show an overlap. ![file] , 
 Figure 6A. The bands in the Western blot panels look very similar to those in a potential papermill with more than 400 papers as described here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The bands have the unnatural shapes and regular spacing in common, but do not appear to have the characteristic background of the 400 other papers. Could the authors take away any concern about these panels by showing the uncropped blots, please? ![file] ,
Effect of explant source, perlite nanoparticles and TiO/perlite nanocomposites on phytochemical composition of metabolites in callus cultures of Hypericum perforatum
Authors: S Jafarirad
S Mahjouri
M Kosari-Nasab
R Ebadollahi
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: biologically-synthesized nanoparticles; secondary metabolites; perlite NPs; TiO2/perlite nanocomposites; growth characteristics
Affiliations: Research institute for Fundamental sciences (RIFS), University of Tabriz, Tabriz, Iran., Research institute for Fundamental sciences (RIFS), University of Tabriz, Tabriz, Iran. ., Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ., Department of Plant Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. ., Department of Plant Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Abstract:  It appears that the biologically-synthesized nanoparticles (NPs) have potential to perform as effective elicitors for the production of valuable secondary metabolites in plants. Besides, it has been reported that the toxicity of the biologically-synthesized NP is not as much as that of the chemically-synthesized NPs. Therefore, it is necessary to test their advantages aspects. In this study, the physical synthesis of perlite NPs and biologically-synthesis of TiO2/perlite nanocomposites (NCs) were conducted. Subsequently, their effects and explant source influence on the growth characteristics and secondary metabolite profiles of Hypericum perforatum callus cultures were evaluated. According to the obtained results, morphology of the synthesized perlite NPs and TiO2/perlite NCs were mesoporous and spherical with sizes ranging about 14.51-23.34 and 15.50-24.61 nm, respectively. Addition of perlite NPs and TiO2/perlite NCs to the culture medium at the concentration range of 25-200 mg/L showed no adverse impacts on the growth characteristics of H. perforatum calli. According to the GC-MS analysis, the stress caused by perlite NPs and TiO2/perlite NCs led to an increase in the variety, amount and number of volatile compounds. The calli obtained from in vitro grown plants produced more volatile compounds relative to the calli obtained from field grown plants under the nanomaterial stress conditions. The production of hypericin and pseudohypericin were also determined in the callus cultures under desired nanomaterials elicitation. Accordingly, our results suggest that perlite NPs and TiO2/perlite NCs can possibly be considered as effective elicitors for the production of volatile compounds, hypericin, and pseudohypericin in callus cultures of H. perforatum. 

Retracted: No

PubPeer comments:
 ![file] , 
 ![file] , 
 Figure 3. Much more similar than you would expect. https: imgur.com r9oaYz9 ,
LncRNA BC200 regulates the cell proliferation and cisplatin resistance in non-small cell lung cancer via PI3K/AKT pathway
Authors: S-X Wang
B-B Gao
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; BC200; lung cancer; NSCLC; tumor development
Affiliations: Cancer Treatment Center, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, China. .

Abstract:  Objective: Long non-coding RNA (lncRNA) exerts tissue specificity and regulates the occurrence and progression of tumors. Previous bioinformatics showed that lncRNA BC200 is served as an oncogene. However, the specific role of BC200 in lung cancer (LC) is rarely reported. The aim of this study is to elucidate the regulatory effects of BC200 on tumor development and cisplatin resistance in non-small cell lung cancer (NSCLC). Patients and methods: The expression level of BC200 in 76 pairs of NSCLC tissues and adjacent normal tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation analyses were conducted to investigate the relation between BC200 expression and prognosis of NSCLC patients. Subsequently, BC200 expression in LC cell lines was detected. After construction of si-BC200 and si-NC, the cellular functions of LC cells were detected through colony formation, flow cytometry and transwell assay, respectively. Western blot was performed to detect the protein expressions of key genes in the PI3K/AKT pathway in LC cells. Finally, cell counting kit-8 (CCK-8) assay was carried out to explore the effect of BC200 on cisplatin resistance of LC cells via calculating IC50. Results: Higher expression of BC200 was found in NSCLC tissues than that of adjacent normal tissues. BC200 expression was positively correlated with tumor stage, lymph node metastasis and distant metastasis of NSCLC patients, whereas not correlated to age and sex. Knockdown of BC200 inhibited proliferation, invasion and migration of LC cells. Western blot results showed that protein expressions of PI3K, AKT and STAT3 were downregulated after BC200 knockdown in LC cells. Additionally, the IC50 in H1299/DDP cells transfected with si-BC200 was lower than in those transfected with si-NC. The apoptotic rate in H1299 cells transfected with si-BC200 was remarkably lower than those transfected with si-NC. Conclusions: BC200 is highly expressed in NSCLC, which is positively correlated with tumor stage and metastasis of NSCLC patients. BC200 promotes the malignant progression of NSCLC via regulating cisplatin-induced apoptosis of H1299/DDP cells. 

Retracted: No

PubPeer comments:
 Fig 1D.  Kaplan-Meier survival curves of NSCLC patients based on BC200 expression. Patients in the high-level BC200 group had a significantly more unfavorable prognosis than those in the low-level BC200 group . ![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. ,
Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer
Authors: Y-Y Park
X Sastre-Garau
P-A Defossez
K Kim
S-O Lee
D Yamada
J-S Lee
G Chadalapaka
S Safe
Journal: Oncogene (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: POK family members; transcription factors; oncogenesis; ZBTB4; breast cancer
Affiliations: Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77843, USA.

Abstract:  The human POK family members are transcription factors with a POZ domain and zinc-fingers that act primarily as transcriptional repressors. Several members of this family are involved in oncogenesis and this prompted us to assess whether expression levels of individual POK family members are associated with clinical outcomes in cancer. We have observed that ZBTB4 (zinc-finger and BTB domain containing 4) is downregulated in breast cancer patients, and that its expression is significantly correlated with relapse-free survival. Further integrative analysis of mRNA and microRNA (miR) expression data from the NCI-60 cell lines revealed an inverse correlation between ZBTB4 and oncogenic miRs derived from the miR-17-92 cluster and its paralogs. The experimental results using MDA-MB-231 and MCF-7 human breast cancer cells confirm that miRNAs derived from these clusters, containing miR-17-5p, miR-20a, miR-106a, miR-106b and miR-93, negatively regulate ZBTB4 expression. Overexpression of ZBTB4 or restoration of ZBTB4 by using an antagomir inhibit growth and invasion of breast cancer cells, and this effect is due, in part, to ZBTB4-dependent repression of the specificity protein 1 (Sp1), Sp3 and Sp4 genes, and subsequent downregulation of several Sp-dependent oncogenes, in part, through competition between ZBTB4 and Sp transcription factors for GC-rich promoter sequences. These results confirm that ZBTB4 functions as a novel tumor-suppressor gene with prognostic significance for breast cancer survival, and the oncogenic miR-17-92/ZBTB4/Sp axis may be a potential therapeutic target. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 #1 I agree with the findings in Figure 7C noted above, and would also suggest that the two other images seem identical. *** ![file] ,
Long noncoding RNA LINC00052 suppressed the proliferation, migration and invasion of glioma cells by upregulating KLF6
Authors: C-F Xu
P Liu
D-F Hu
J Tan
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; LINC00052; glioma; tumorigenesis; qRT-PCR
Affiliations: Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, .

Abstract:  Objective: Recent studies have discovered a class of dysregulated long noncoding RNAs (lncRNAs) related to carcinogenesis. This study aims to uncover the molecular functions of lncRNA LINC00052 in the tumorigenesis of glioma. Patients and methods: Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect LINC00052 expression in 40 glioma samples and 4 glioma cell lines. Besides, regulatory effects of LINC00052 on the in vitro behaviors of glioma cells were evaluated by the proliferation assay, transwell assay and wound healing assay. Furthermore, the interaction between LINC00052 and kruppel-like factor 6 (KLF6) in mediating the progression of glioma was studied by performing qRT-PCR and Western blot. Results: LINC00052 expression was remarkably downregulated in glioma samples compared with that in adjacent samples. Moreover, cell proliferation, invasion, and migration of glioma were inhibited after overexpression of LINC00052 in vitro. Besides, LINC00052 overexpression upregulated mRNA and protein level of KLF6. Besides, the expression of KLF6 in tumor tissues was positively correlated to the expression of LINC00052. Conclusions: These results suggested that LINC00052 could repress cell migration, invasion and proliferation in glioma through upregulating KLF6, which may offer a new therapeutic intervention for glioma patients. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. ,
Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease
Authors: Lin Jiang
Min-Hyun Kim
Liangyou Rui
Haoran Su
Chung Owyang
Xiaoyin Wu
Martin G Myers Jr
Hong Shen
Yuan Li
Journal: Nature Communications (2020)
Discipline: Multidisciplinary
Keywords: Leptin; sympathetic nervous system; energy expenditure; weight loss; Sh2b1
Affiliations: Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Division of Metabolism and Endocrinology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. ., Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. .

Abstract:  Leptin stimulates the sympathetic nervous system (SNS), energy expenditure, and weight loss; however, the underlying molecular mechanism remains elusive. Here, we uncover Sh2b1 in leptin receptor (LepR) neurons as a critical component of a SNS/brown adipose tissue (BAT)/thermogenesis axis. LepR neuron-specific deletion of Sh2b1 abrogates leptin-stimulated sympathetic nerve activation and impairs BAT thermogenic programs, leading to reduced core body temperature and cold intolerance. The adipose SNS degenerates progressively in mutant mice after 8 weeks of age. Adult-onset ablation of Sh2b1 in the mediobasal hypothalamus also impairs the SNS/BAT/thermogenesis axis; conversely, hypothalamic overexpression of human SH2B1 has the opposite effects. Mice with either LepR neuron-specific or adult-onset, hypothalamus-specific ablation of Sh2b1 develop obesity, insulin resistance, and liver steatosis. In contrast, hypothalamic overexpression of SH2B1 protects against high fat diet-induced obesity and metabolic syndromes. Our results unravel an unrecognized LepR neuron Sh2b1/SNS/BAT/thermogenesis axis that combats obesity and metabolic disease. 

Retracted: No

PubPeer comments:
 Does the food intake of the animals change in the experiments done in Figure 4? If overexpression is the opposite of the KO (Figure 3) then it will be expected that food intake would be reduced. Which suggests that it is not protective to HFD but simply reduces the amount of food taken in. ,
Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1
Authors: David M Sabatini
William C Comb
Liron Bar-Peled
Lawrence D Schweitzer
Journal: Cell reports (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mTORC1; mRNA translation; ribosome biogenesis; autophagy; amino acids
Affiliations: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, MIT, Cambridge, MA 02139, USA; Broad Institute, Cambridge, MA 02142, USA; The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA., Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, MIT, Cambridge, MA 02139, USA; Broad Institute, Cambridge, MA 02142, USA; The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA. Electronic address: .

Abstract:  mTORC1 controls key processes that regulate cell growth, including mRNA translation, ribosome biogenesis, and autophagy. Environmental amino acids activate mTORC1 by promoting its recruitment to the cytosolic surface of the lysosome, where its kinase is activated downstream of growth factor signaling. mTORC1 is brought to the lysosome by the Rag GTPases, which are tethered to the lysosomal membrane by Ragulator, a lysosome-bound scaffold. Here, we identify c17orf59 as a Ragulator-interacting protein that regulates mTORC1 activity through its interaction with Ragulator at the lysosome. The binding of c17orf59 to Ragulator prevents Ragulator interaction with the Rag GTPases, both in cells and in vitro, and decreases Rag GTPase lysosomal localization. Disruption of the Rag-Ragulator interaction by c17orf59 impairs mTORC1 activation by amino acids by preventing mTOR from reaching the lysosome. By disrupting the Rag-Ragulator interaction to inhibit mTORC1, c17orf59 expression may represent another mechanism to modulate nutrient sensing by mTORC1. 

Retracted: No

PubPeer comments:
 I observed that the HA-Metap2 bands of Figure 4A and 4B are very similar. ![file] After ultra-zoom them, I got more confident that they are very similar indeed. Could the authors check it please? ![file] , 
 Thank you for your comment I am the first author of the paper and prepared these figures. Indeed I inadvertently mis-cropped the HA-Metap2 bands in the lysate samples that were used for Figure 4b. The samples for Figures 4a and 4b were run and immunoblotted at the same time and HA-Metap2 looks nearly identical in the two experiments. I have attached the updated Figure 4b as well as annotated versions of the original scans of the blots probed with the anti-HA antibody. Thank you for catching this mistake, Lawrence Schweitzer ![file] ![file] , 
 #2 Are the authors intending to publish a correction? ,
Long noncoding RNA ILF3-AS1 regulates myocardial infarction via the miR-212-3p/SIRT1 axis and PI3K/Akt signaling pathway
Authors: K Fang
D-H Ren
Z-L Shi
Z Yang
J-Y Zhang
J Sun
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Myocardial infarction; Long noncoding RNAs; ILF3-AS1; Hypoxia-induced apoptosis; H9c2 cells
Affiliations: Department of Critical Care Medicine, Hang Zhou Red Cross Hospital, Hangzhou, Zhejiang, China. .

Abstract:  Objective: Myocardial infarction (MI) is a serious cardiac disease due to its high incidence and mortality worldwide. Long noncoding RNAs (lncRNAs) have been found to play an essential role in the pathological progress of various cardiovascular diseases. ILF3-AS1 is a newly identified lncRNA, and many studies have demonstrated that ILF3-AS1 affects the development of various malignancies. However, the biological function of ILF3-AS1 and its underlying mechanism in MI are still unknown. In the present study, the function of ILF3-AS1 and the possible mechanisms against hypoxia-induced apoptosis in H9c2 cells were investigated. Materials and methods: H9c2 cells were exposed to hypoxia (1% O2) to mimic the in vitro model of MI. The levels of lncRNA ILF3-AS1 and microRNA miR-212-3p were measured by real-time PCR (RT-PCR). Transfection was performed to upregulate the levels of ILF3-AS1 and miR-212-3p. Western blot assays were carried out to measure protein expression. The relationship between ILF3-AS1 and miR-212-3p was verified by Dual-Luciferase reporter assay. Results: We found that ILF3-AS1 was downregulated by hypoxia. Overexpression of ILF3-AS1 resulted in the relief of hypoxia-induced damage to H9c2 cells by rescuing cell viability, migration, and invasion and suppressing apoptosis, while downregulation of ILF3-AS1 had the opposite effects. Moreover, ILF3-AS1 could negatively regulate miR-212-3p expression, and upregulation of ILF3-AS1 could alleviate hypoxic injury via downregulation of miR-212-3p. Moreover, miR-212-3p negatively regulated SIRT1 expression. Further investigations revealed that ILF3-AS1 activated PI3K/Akt signaling and that application of the PI3K inhibitor LY294002 could abrogate the protective effects of ILF3-AS1 against hypoxia. Conclusions: In summary, we concluded that ILF3-AS1 provides protection against hypoxia-induced injury via the PI3K/Akt pathway, which may provide clues for the treatment of patients with MI. 

Retracted: No

PubPeer comments:
 ![file] , 
 Figure 4, I ![file] ,
miR29a and miR378b Influence CpG-Stimulated Dendritic Cells and Regulate cGAS/STING Pathway
Authors: Jian Lin
Abid Ullah Shah
Naila Siddique
Qian Yang
Yanan Cao
Journal: Vaccines (2019)
Discipline: IMMUNOLOGY
Keywords: CpG; Dendritic Cells; cGAS/STING; miR-29a; miR-378b.
Affiliations: College of Veterinary medicine, Nanjing Agricultural University, Wei gang 1, Nanjing 210095, China., National Reference Laboratory for Poultry Diseases, Animal Sciences Institute, National Agricultural Research Center, Islamabad 44000, Pakistan., College of Life Sciences, Nanjing Agricultural University, Wei gang 1, Nanjing 210095, China.

Abstract:  The Cytosine-phosphate-guanosine (CpG) motif, which is specifically recognized intracellularly by dendritic cells (DCs), plays a crucial role in regulating the innate immune response. MicroRNAs (miRNAs) can strongly influence the antigen-presenting ability of DCs. In this study, we examine the action of miRNAs on CpG-stimulated and control DCs, as well as their effect on cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase (cGAS) and the stimulator of interferon genes (STING) signal pathway. Firstly, we selected miRNAs (miR-29a and miR-378b) based on expression in CpG-stimulated mouse bone marrow-derived dendritic cells (BMDCs). Secondly, we investigated the functions of miR-29a and miR-378b on CpG-stimulated and unstimulated BMDCs. The results showed that miR-29a and miR-378b increased expression of both the immunoregulatory DC surface markers (CD86 and CD40) and the immunosuppressive molecule CD273 by DCs. Thirdly, cytokine detection revealed that both miR-29a and miR-378b enhanced interferon-β (IFN-β) expression while suppressing tumor necrosis factor-α (TNF-α) production. Finally, our results suggest that miR-378b can bind TANK-binding kinase binding protein 1 (TBKBP1) to activate the cGAS/STING signaling pathway. By contrast, miR-29a targeted interferon regulatory factor 7 (IRF7) and promoted the expression of STING. Together, our results provide insight into the molecular mechanism of miRNA induction by CpG to regulate DC function. 

Retracted: No

PubPeer comments:
 ![file] , 
 #1 The problem has been solved, a Correction was published. https: www.mdpi.com 2076-393X 8 2 305 htm ,
The TORC1-activated Proteins, p70S6K and GRB10, Regulate IL-4 Signaling and M2 Macrophage Polarization by Modulating Phosphorylation of Insulin Receptor Substrate-2
Authors: Nagaraj M Gowda
Kristi J Warren
Nicola M Heller
Joshua J Thompson
Xi Fang
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: GRB10; IL-4; IRS-2; S6 kinase; allergy
Affiliations: From Johns Hopkins University, School of Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, Maryland 21205., From Johns Hopkins University, School of Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, Maryland 21205 .

Abstract:  Lung M2 macrophages are regulators of airway inflammation, associated with poor lung function in allergic asthma. Previously, we demonstrated that IL-4-induced M2 gene expression correlated with tyrosine phosphorylation of the insulin receptor substrate-2 (IRS-2) in macrophages. We hypothesized that negative regulation of IRS-2 activity after IL-4 stimulation is dependent upon serine phosphorylation of IRS-2. Herein, we describe an inverse relationship between tyrosine phosphorylation (Tyr(P)) and serine phosphorylation (Ser(P)) of IRS-2 after IL-4 stimulation. Inhibiting serine phosphatase activity increased Ser(P)-IRS-2 and decreased Tyr(P)-IRS-2 leading to reduced M2 gene expression (CD200R, CCL22, MMP12, and TGM2). We found that inhibition of p70S6K, downstream of TORC1, resulted in diminished Ser(P)-IRS-2 and prolonged Tyr(P)-IRS-2 as well. Inhibition of p70S6K increased expression of CD200R and CCL22 indicating that p70S6K negatively regulates some, but not all, human M2 genes. Knocking down GRB10, another negative regulatory protein downstream of TORC1, enhanced both Tyr(P)-IRS-2 and increased expression of all four M2 genes. Furthermore, GRB10 associated with IRS-2, NEDD4.2 (an E3-ubiquitin ligase), IL-4Rα, and γC after IL-4 stimulation. Both IL-4Rα and γC were ubiquitinated after 30 min of IL-4 treatment, suggesting that GRB10 may regulate degradation of the IL-4 receptor-signaling complex through interactions with NEDD4.2. Taken together, these data highlight two novel regulatory proteins that could be therapeutically manipulated to limit IL-4-induced IRS-2 signaling and polarization of M2 macrophages in allergic inflammation. 

Retracted: No

PubPeer comments:
 Although the authors present several statistically significant results, most of these results are only marginally or just statistically significant. This undermines the credibility of the published results. Large replication studies and bias-adjusted meta-analysis suggest that incidental anchoring is not a robust phenomenon, has at best a small effect size, and may only occur under conditions that are not well understood. https: doi.org 10.1525 collabra.310 https: replicationindex.com 2021 06 04 incidental-anchoring-audit ,
Katanin localization requires triplet microtubules in Chlamydomonas reinhardtii
Authors: Eileen O&#x27;Toole
Jessica M Esparza
Susan K Dutcher
Benjamin Kozak
Linya Li
Alison J Albee
Thomas H Giddings Jr
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Centrioles; basal bodies; cellular processes; recruitment; proteins
Affiliations: Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America.

Abstract:  Centrioles and basal bodies are essential for a variety of cellular processes that include the recruitment of proteins to these structures for both centrosomal and ciliary function. This recruitment is compromised when centriole/basal body assembly is defective. Mutations that cause basal body assembly defects confer supersensitivity to Taxol. These include bld2, bld10, bld12, uni3, vfl1, vfl2, and vfl3. Flagellar motility mutants do not confer sensitivity with the exception of mutations in the p60 (pf19) and p80 (pf15) subunits of the microtubule severing protein katanin. We have identified additional pf15 and bld2 (ε-tubulin) alleles in screens for Taxol sensitivity. Null pf15 and bld2 alleles are viable and are not essential genes in Chlamydomonas. Analysis of double mutant strains with the pf15-3 and bld2-6 null alleles suggests that basal bodies in Chlamydomonas may recruit additional proteins beyond katanin that affect spindle microtubule stability. The bld2-5 allele is a hypomorphic allele and its phenotype is modulated by nutritional cues. Basal bodies in bld2-5 cells are missing proximal ends. The basal body mutants show aberrant localization of an epitope-tagged p80 subunit of katanin. Unlike IFT proteins, katanin p80 does not localize to the transition fibers of the basal bodies based on an analysis of the uni1 mutant as well as the lack of colocalization of katanin p80 with IFT74. We suggest that the triplet microtubules are likely to play a key role in katanin p80 recruitment to the basal body of Chlamydomonas rather than the transition fibers that are needed for IFT localization. 

Retracted: No

PubPeer comments:
 This article has a 2016 correction: https: journals.plos.org plosone article?id=10.1371 journal.pone.0145569 The text of the correction reads: *The authors would like to correct Fig 1, as errors were introduced in the preparation of this figure for publication. In Fig 1B, the bld2-6; BLD2 panel and the pf15-1; PF15HA panel are duplicates. The authors regrew the cell cultures in these panels, as well as the parental strains shown in the same panels of Fig 1A, and they have provided a corrected version of Fig 1 here. The authors confirm that these changes do not alter their findings. The authors have provided the underlying images as Supporting Information.* Here is the original Figure 1, marked with red boxes for image duplication software training purposes: ![file] Thank you to the authors for correcting this error. ,
The effect of leptin on intestinal recovery following ischemia-reperfusion injury in a rat
Authors: Arnold G Coran
Habib Helou
Kamal Khateeb
Eitan Shiloni
Michael Lurie
Jorge G Mogilner
Jacoob Bejar
Igor Sukhotnik
Journal: Pediatric surgery international (2007)
Discipline: CLINICAL MEDICINE
Keywords: leptin; enterocyte turnover; intestinal recovery; ischemia-reperfusion injury; rat
Affiliations: Deparment of Pediatric Surgery and Pathology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 47 Golomb St., P.O.B. 4940, Haifa 31048, Israel. 

Abstract:  Recent evidence suggests that the adipose tissue derived cytokine leptin (LEP) is involved in the modulation of growth and differentiation of normal small intestine. The purpose of the present study was to examine the effect of leptin on enterocyte turnover and intestinal recovery after ischemia-reperfusion (IR) injury in a rat. Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy, (2) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 24 h of reperfusion, and (3) IR-LEP rats underwent IR and were treated with leptin given subcutaneously at a dose of 50 microg/kg once a day for 48 h before and 24 h following IR. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P &lt; 0.05 considered statistically significant. Treatment with leptin resulted in a significant increase in bowel weight in ileum, mucosal weight in jejunum and ileum, mucosal DNA content in ileum, mucosal protein content in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in jejunum compared to IR-animals. IR-LEP rats also had a significantly lower intestinal injury score as well as lower apoptotic index and higher cell proliferation index in jejunum and ileum compared to the IR-animals. In conclusion, pre-treatment with leptin prevents gut mucosal damage and improves intestinal rehabilitation following intestinal IR in a rat. 

Retracted: No

PubPeer comments:
 This paper is part of a set of at least 3 papers that appear to share microscopy images. All papers list Igor Sukhotnik as an author. Boxes of the same color highlight areas in microscopy panels that look similar. Could the authors please clarify if these are all representing the same experiments, over a period of 12 years? * Sukhotnik I et al., Pediatr Surg Int (2007) 23:473u2013478, DOI: 10.1007 s00383-006-1863-9 * Sukhotnik I et al., Dig Dis Sci (2007) 52:1497u20131504, DOI: 10.1007 s10620-006-9629-8 * Benu2010Shahar Y et al., Pediatric Surgery International (2019), DOI: 10.1007 s00383-018-4406-2 ![file] ,
Anti-proliferative and anti-neuroinflammatory eudesmanolides from Wedelia (Sphagneticola trilobata (L.) Pruski)
Authors: Jingwen Xu
Lianlian Sun
Zhe Wang
Yihai Wang
Xiangjiu He
Journal: Fitoterapia (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Anti-neuroinflammatory; Anti-proliferation; Eudesmanolides; Sphagneticola trilobata (L.) Pruski; Wedelia.
Affiliations: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China., School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou 510006, China. Electronic address: ., School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou 510006, China.

Abstract:  Wedelia (Sphagneticola trilobata, Syn. Wedelia trilobata), a notoriously invasive agricultural weed, can inhibit the growth and development of crops in the field. Eight new eudesmanolides (1-8), along with twelve known congeners (9-20), were isolated and identified from the flowers of Wedelia. Their chemical structures were elucidated through various spectroscopic techniques. The isolates were tested for anti-proliferative activities against HeLa, HepG2, and SGC-7901 tumor cell lines. Most eudesmanolides exhibited significant anti-proliferative activities with good selectivity. Meanwhile, the cells morphology and clonogenic survival assays were observed for compounds 1-3. Moreover, compound 6 displayed obvious anti-neuroinflammatory effect by inhibition of NO production in LPS-induced microglia BV-2 cells with the IC50 value of 11.77 ± 0.83 μM. Hence, this study demonstrated that the eudesmanolides from Wedelia possessed significant antitumor and anti-inflammatory activity, which provided some guides for the further development and a new thinking for its control. 

Retracted: No

PubPeer comments:
 There is an obvious overlap in Fig. 3A with stretching. ![file] ,