PReD-Bench/PRed-Bench huggingface dataset:
Inhibition of Lung Tumor Development in ApoE Knockout Mice via Enhancement of TREM-1 Dependent NK Cell Cytotoxicity
Authors: In Jun Yeo
Sang-Bae Han
Jin Tae Hong
Yong Sun Lee
Ki Cheon Kim
Journal: Frontiers in Immunology (2019)
Discipline: IMMUNOLOGY
Keywords: NK cells; T-bet; TREM-1; apolipoprotein E; lung tumor development.
Affiliations: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, South Korea.

Abstract:  Apolipoprotein E (ApoE) is known to regulate lipid homeostasis and associated with atherosclerogenesis. Eventhough atherosclerogenesis is associated with tumor development, the role of ApoE in lung tumorigenesis and metastasis is not clear. Thus, the tumor growth and metastasis were compared in WT and ApoE knockout (KO) mice. Urethane-induced lung tumor incidence and B16F10 lung metastasis in ApoE knockout (KO) mice were significantly reduced in comparison to that in WT mice. Knockdown of ApoE expression in lung cancer cells and B16F10 cells also decreased cancer cell growth and metastasis. The inhibitory effect of ApoE KO on tumor development and metastasis was associated with increase of infiltration of NK cells. NK cells derived from ApoE KO mice showed much greater cytotoxicity than those from WT mice. These cytotoxic effect of NK cells derived from ApoE KO mice was associated with higher expression of Granzyme B, Fas Ligand, IFN-Œ≥, TNF-Œ±, NKG2D, NKp46, and DNAM-1 expression. Triggering receptor expressed on myeloid cell (TREM)-1 is a proinflammatory mediator expressed on NK cells, and is known to be associated with NK cell cytotoxicity. Thus, we investigated the role of TREM-1 on ApoE KO mice originated NK cell mediated cytotoxicity for cancer cells. Blockade of TREM-1 expression with a TREM-1 antagonist prevented NK cell-mediated cytotoxicity. TREM-1 antibody recovered cytotoxic effect of NK cells derived from KO mice of T-bet, which upregulating gene for TREM-1. These data indicate that ApoE KO suppressed lung tumor development and metastasis via increase of TREM-1-dependent anti-tumor activity of NK cells. 

Retracted: No

PubPeer comments:
 Figure 3C appears to have two overlapping images, although they have been rotated slightly relative to each other. ***  ***  ,
Interleukin-37 reduces inflammation and impairs phagocytosis of platelets in immune thrombocytopenia (ITP)
Authors: Jihua Qiu
Xiaofei Ni
Guosheng Li
Ming Hou
Panpan Han
Xinguang Liu
Yajing Zhao
Qiang Liu
Xuebin Ji
Ju Li
Pengcheng Xu
Shuang Wang
Tao Sun
Jun Peng
Journal: Cytokine (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Bleeding scale; Immune thrombocytopenia; Interleukin-37; Macrophage; Monocyte.
Affiliations: Department of Hematology, Qilu Hospital, Shandong University, Jinan, China., Department of Geriatric Medicine, Qilu Hospital, Shandong University, Jinan, China., Department of Hematology, Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China., Department of Hematology, Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China; Leading Research Group of Scientific Innovation, Department of Science and Technology of Shandong Province, Qilu Hospital, Shandong University, Jinan, China., Department of Hematology, Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China. Electronic address: .

Abstract:  Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet count with heterogeneous bleeding manifestations. Severe bleeding in ITP is not completely related with low platelet count. FcŒ≥ receptor (FcŒ≥R)-mediated platelet destruction is one of the major mechanisms of ITP. Interleukin-37 (IL-37) is a fundamental natural suppressor of innate immunity and inflammatory responses in several autoimmune diseases. However, the role of IL-37 in the pathogenesis of ITP is unknown. In the present study, we identified that IL-37 expression was elevated in ITP patients, which was correlated with platelet count and the severity of bleeding in ITP, indicating that IL-37 could be a candidate in evaluating disease severity of ITP. In the in vitro study, IL-37 initiated an anti-inflammatory effect on monocytes/macrophages from ITP patients by down-regulating the phosphorylation of MAPK, AKT, and NF-Œ∫B signaling pathways. Moreover, IL-37 restored the balance of activating and inhibitory FcŒ≥Rs and decreased antibody-mediated platelet phagocytosis by monocytes/macrophages. Our findings suggest that IL-37 may be a promising indicator of the disease severity and supplementation of IL-37 may be therapeutically beneficial for ITP patients. 

Retracted: No

PubPeer comments:
  ,
MicroRNA-24 upregulation inhibits proliferation, metastasis and induces apoptosis in bladder cancer cells by targeting CARMA3
Authors: Wenwen Zheng
Denggao Huang
Xi Liu
Yingai Zhang
Zhiming Bai
Wei Liu
Shunlan Wang
Chong Zhang
Shufang Zhang
Journal: International Journal of Oncology (2015)
Discipline: CLINICAL MEDICINE
Keywords: miR-24; bladder cancer; CARMA3; proliferation; cell cycle
Affiliations: Central Laboratory, Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou 570208, P.R. China., Department of Urology, Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou 570208, P.R. China., Clinical Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, P.R. China.

Abstract:  Increasing evidence has confirmed that dysregulation of microRNAs (miRNAs) can contribute to the progression and metastasis of human tumors. Previous studied have shown dysregulation of miR-24 in a variety of tumors. However, the roles of miR-24 in human bladder cancer have not been well clarified. Therefore, we investigated the biological functions and molecular mechanisms of miR-24 in human bladder cancer cell lines, evaluating whether it could be a therapeutic biomarker of bladder cancer in the future. In our study, we found that miR-24 is downregulated in human bladder cancer cell lines. Moreover, the low level of miR-24 was associated with increased expression of CARMA3 in bladder cancer cells. Upregulation of miR-24 significantly inhibited proliferation, arrested cell cycle and induced apoptosis in bladder cancer cells. In addition, invasion and epithelial to mesenchymal transition (EMT) of bladder cancer cells was suppressed by overexpressing miR-24. Bioinformatics analysis predicted that the CARMA3 was a potential target gene of miR-24. Further study by luciferase reporter assay demonstrated that miR-24 could directly target CARMA3. Overexpression of CARMA3 in bladder cancer cells transfected with miR-24 mimic partially reversed the inhibitory effect of miR-24. In conclusion, miR-24 inhibited cell proliferation, invasion and EMT in bladder cancer cells by downregulation of CARMA3, and that downregulation of CARMA3 was essential for the miR-24-inhibited cell proliferation, invasion and EMT in bladder cancer cells. 

Retracted: No

PubPeer comments:
 Fig 4:  TEM images of (a) bare FeO-gelatin nanoparticles and (b)FeO-gelatin nanoparticles after Cr(VI)l adsorption .  There is some uncertainty whether the NPs are  TEM images of bare (a) **FeO-gelatin nanoparticles**, and (b) TEM images of FeO-gelatin nanoparticles after Cr(VI)l adsorption , as in Fig 4 of [Agrawal Bajpai (2010)] ...  ...or  TEM images of (a) starch nanoparticles and (b) iron oxide impregnated starch nanoparticles , as in Fig 4 of [Likhitkar Bajpai (2014)] .  ,
LINC00511/miRNA-143-3p Modulates Apoptosis and Malignant Phenotype of Bladder Carcinoma Cells via PCMT1
Authors: Yan-Pei Li
Yi-Li Liu
Dong-Wei Xue
Li-Ming Dong
Ming-Huan Mao
Xi-Ling Zhang
Xi-Yan Zhang
Journal: Frontiers in Cell and Developmental Biology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LINC00511; PCMT1; apoptosis; bladder cancer; invasion.
Affiliations: Department of Urologic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China., Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

Abstract:  Bladder cancer has easy recurrence characteristics, but its occurrence and development mechanism are still unclear. Non-coding RNA is a kind of RNA that exists widely and cannot be translated into proteins, which has played a key role in the regulation of biological functions of tumor cells. However, the regulation mechanism of non-coding RNA on bladder tumors is not fully understood. By microarray analysis and database analysis, we found that LINC00511 was significantly highly expressed in bladder cancer. The expressions of LINC00511, miR-143-3p, and PCMT in bladder cancer tissues and cells were detected by quantitative reverse transcription-polymerase chain reaction. The relationship between the expressions of miR-143-3p and PCMT1 and the clinicopathological parameters of the tumor was analyzed. The proliferation and invasion of bladder cancer cells were detected by MTT assay and Transwell assay. The expression levels of E-cadherin and vimentin in bladder cancer cells were detected by Western blot. Cell apoptosis was detected by flow cytometry. In vivo, TCCSUP or SW780 cells were inoculated into BALB/c nude mice to detect tumor volume and weight. Bioinformatics and dual luciferase reporter gene were used to analyze the relationship between LINC00511 and miR-143-3p and its downstream target gene PCMT1. The results showed that LINC00511 could target miR-143-3p/PCMT1 to regulate the proliferation, migration, and apoptosis of bladder cancer TCCSUP or SW780 cells and promote the occurrence and development of bladder cancer. 

Retracted: No

PubPeer comments:
 Western Blots in Fig.1 and Fig.4 showed similar features. Those bands were drawn on a featureless flat gray background with high-contrast and sharp-edge (blue arrow). I would be very grateful if authors could provide the original image to solve this problem.  , 
 #1 The blots were scanned from X-ray films without any improper manipulation. The contrast might have been set a little bit high. ,
Identification of the miRNA-3185/CYP4A11 axis in cardiac tissue as a biomarker for mechanical asphyxia
Authors: Heng Zhang
Bi Xiao
Yan Zeng
Li Tao
Kaijun Ma
Long Chen
Qun Shi
Hongmei Xu
Jianlong Ma
Yehui Lv
Liujun Han
Journal: Forensic Science International (2020)
Discipline: CLINICAL MEDICINE
Keywords: Biomarker; CYP4A11; Cardiac tissue; Mechanical asphyxia; MiRNA-3185.
Affiliations: Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Children's Hospital of Fudan University, Shanghai 201102, China., Shanghai University of Medicine & Health Sciences, Shanghai 201318, China., Criminal Investigation Department of Shenzhen Public Security Bureau, Shenzhen Institute of Criminal Science and Technology, Shenzhen 518000, China., Forensic Lab, Criminal Science and Technology Institute, Shanghai Public Security Bureau, Shanghai 200082, China., Forensic Lab, Criminal Science and Technology Institute, Shanghai Public Security Bureau, Shanghai 200082, China. Electronic address: ., Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: .

Abstract:  Death by mechanical asphyxia is one of the most difficult conclusions to make in forensic science, especially in corpses displaying slight or no trauma to the surface of the body. Therefore, death by mechanical asphyxia is difficult to prove in medico-legal practice. MicroRNAs (miRNAs) are a class of small, non-coding RNAs involved in the regulation of numerous physiological and pathological cellular processes. In the present study, we demonstrate that significantly increased expression of miR-3185 in cardiac tissues was detected among cases of mechanical asphyxia compared to case of craniocerebral injury, hemorrhagic shock, sudden cardiac death and poisoning. We observed no correlation between the expression of miR-3185 and postmortem interval, age or temperature. Further work indicated that CYP4A11 is a putative target gene of miR-3185 and expressed at a relatively low level in cardiac tissue specimens from cases of mechanical asphyxia compared with specimens from cases of craniocerebral injury, hemorrhagic shock, sudden cardiac death and poisoning. Our results suggest that the miRNA-3185/CYP4A11 axis is associated with mechanical asphyxia-induced death and may provide new insight into asphyxial death investigations. 

Retracted: No

PubPeer comments:
  The authors might have missed that these type of converging diagrams are called **Venn **diagrams, not Venny. Venny is a [tool ] that can create them. ,
Human LACC1 increases innate receptor-induced responses and a LACC1 disease-risk variant modulates these outcomes
Authors: Jie Yan
Clara Abraham
Matija Hedl
Amit Lahiri
Journal: Nature Communications (2017)
Discipline: Multidisciplinary
Keywords: inflammatory disease; LACC1; NOD2; macrophages; mtROS
Affiliations: Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut 06510, USA.

Abstract:  Functional consequences for most inflammatory disease-associated loci are incompletely defined, including in the LACC1 (C13orf31) region. Here we show that human peripheral and intestinal myeloid-derived cells express laccase domain-containing 1 (LACC1); LACC1 is expressed in both the cytoplasm and mitochondria. Upon NOD2 stimulation of human macrophages, LACC1 associates with the NOD2-signalling complex, and is critical for optimal NOD2-induced signalling, mitochondrial ROS (mtROS) production, cytokine secretion and bacterial clearance. LACC1 constitutively associates with succinate dehydrogenase (SDH) subunit A, and amplifies pattern recognition receptor (PRR)-induced SDH activity, an important contributor to mtROS production. Relative to LACC1 Ile254, cells transfected with Crohn's disease-risk LACC1 Val254 or LACC1 with mutations of the nearby histidines (249,250) have reduced PRR-induced outcomes. Relative to LACC1 Ile254 carriers, Val254 disease-risk carrier macrophages demonstrate decreased PRR-induced mtROS, signalling, cytokine secretion and bacterial clearance. Therefore, LACC1 is critical for amplifying PRR-induced outcomes, an effect that is attenuated by the LACC1 disease-risk variant. 

Retracted: No

PubPeer comments:
   ,
Suppressor of cytokine signaling-3 Provides a novel interface in the cross-talk between angiotensin II and insulin signaling systems
Authors: L√≠cio A Velloso
Paty Karoll Picardi
Kleber G Franchini
Vivian C Calegari
M√°rio J A Saad
M√¥nica Alves
Rosana Y Inoue
Journal: Endocrinology (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Angiotensin II; insulin signaling; SOCS-3; phosphorylation; insulin receptor
Affiliations: Department of Internal Medicine, State University of Campinas, 13081-970 Campinas S√£o Paulo, Brazil., Department of Internal Medicine, State University of Campinas, 13081-970 Campinas SaÃÉo Paulo, Brazil

Abstract:  Angiotensin II inhibits insulin-induced activation of phosphatidylinositol 3-kinase through a mechanism, at least in part, dependent on serine phosphorylation of the insulin receptor and insulin receptor substrates (IRS)-1/2. Recent evidence shows that suppressor of cytokine signaling-3 (SOCS-3) is induced by insulin and angiotensin II and participates in the negative control of further stimulation of each of these signaling systems independently. In the present study, we evaluated the interaction of angiotensin II-induced SOCS-3 with the insulin signaling pathway in the heart of living rats. A single iv dose of angiotensin II promotes a significant increase of SOCS-3 in heart, an effect that lasts up to 180 min. Once induced, SOCS-3 interacts with the insulin receptor, JAK-2, IRS-1, and IRS-2. The inhibition of SOCS-3 expression by a phosphorthioate-modified antisense oligonucleotide partially restores angiotensin II-induced inhibition of insulin-induced insulin receptor, IRS-1 and IRS-2 tyrosine phosphorylation, and IRS-1 and IRS-2 association with p85-phosphatidylinositol 3-kinase and [Ser473] phosphorylation of Akt. Moreover, the inhibition of SOCS-3 expression partially reverses angiotensin II-induced inhibition of insulin-stimulated glucose transporter-4 translocation to the cell membrane. These results are reproduced in isolated cardiomyocytes. Thus, SOCS-3 participates, as a late event, in the negative cross-talk between angiotensin II and insulin, producing an inhibitory effect on insulin-induced glucose transporter-4 translocation. 

Retracted: No

PubPeer comments:
 Figure 5. Much more similar than expected.  , 
 Penultimate author [calling for] new research integrity office at Unicamp. ,
Mechanistic insights into the contribution of epithelial damage to airway remodeling. Novel therapeutic targets for asthma
Authors: Andrew S Giraud
Stephanie Tortorella
Simon G Royce
Mimi L K Tang
Xuelei Li
Liana Goodings
Chrishan S Samuel
Bryna S M Chow
Journal: American Journal of Respiratory Cell and Molecular Biology (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: airway epithelial repair defect; airway remodeling; airway hyperresponsiveness (AHR); naphthalene (NA)-induced murine model; trefoil factor 2 (TFF2)
Affiliations: 1 Department of Allergy and Immune Disorders, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Abstract:  It has been suggested that an inherent airway epithelial repair defect is the root cause of airway remodeling in asthma. However, the relationship between airway epithelial injury and repair, airway remodeling, and airway hyperresponsiveness (AHR) has not been directly examined. We investigated the contribution of epithelial damage and repair to the development of airway remodeling and AHR using a validated naphthalene (NA)-induced murine model of airway injury. In addition, we examined the endogenous versus exogenous role of the epithelial repair peptide trefoil factor 2 (TFF2) in disease pathogenesis. A single dose of NA (200 mg/kg in 10 ml/kg body weight corn oil [CO] vehicle, intraperitoneally) was administered to mice. Control mice were treated with CO (10 ml/kg body weight, intraperitoneally). At 12, 24, 48, and 72 hours after NA or CO injection, AHR and various measures of airway remodeling were examined by invasive plethysmography and morphometric analyses, respectively. TFF2-deficient mice and intranasal treatment were used to examine the role of the epithelial repair peptide. NA treatment induced denudation and apoptosis of airway epithelial cells, goblet cell metaplasia, elevated AHR, and increased levels of endogenous TFF2. Airway epithelial changes peaked at 12 hours after NA treatment, whereas airway remodeling changes were observed from 48 hours. TFF2 was protective against epithelial damage and induced remodeling and was found to mediate organ protection via a platelet-derived growth factor-associated mechanism. Our findings directly demonstrate the contribution of epithelial damage to airway remodeling and AHR and suggest that preventing airway epithelial damage and promoting epithelial repair may have therapeutic implications for asthma treatment. 

Retracted: No

PubPeer comments:
 In Fig 6D, Coomassie blueu2013stained bands in lanes 2-5 look unexpectedly similar to a mirror image of lanes 8-11.  ,
miR-490-3p modulates the progression of prostate cancer through regulating histone deacetylase 2
Authors: Y-S Zhang
H Fan
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miRNAs; prostate cancer; miR-490-3p; HDAC2; tumor-suppressive
Affiliations: Urology Department, Peking Union Medical College Hospital, No. 1 ShuaiFuYuan, DongCheng District, Beijing, P. R. China. .

Abstract:  Objective: microRNAs (miRNAs) were regarded as critical participators for human cancers progression including prostate cancer (PCa) and have the potential to be used as treatment targets for cancers. Herein, we validated a tumor-suppressive miRNA, miR-490-3p, which may suppress PCa progression. Histone deacetylase 2 (HDAC2) is a protein that aberrantly expressed in several cancers. However, the role of HDAC2 in the progression of PCa has not been fully elucidated. Materials and methods: Expression of miR-490-3p and HDAC2 in PCa was investigated. The effects of miR-490-3p or HDAC2 expression on PCa cell behaviors were analyzed. Association between miR-490-3p and HDAC2 was analyzed by luciferase activity reporter assay and Western blot assay. Results: We demonstrated that miR-490-3p functioned as a tumor-suppressive role in PCa progression. We found miR-490-3p expression was decreased in PCa cell lines. Down-regulation of miR-490-3p promoted the growth, migration, invasion but inhibited apoptosis of PCa cells. HDAC2 was validated as a direct target of miR-490-3p and promoted the progression of PCa cells. Further studies showed that HDAC2 could reverse the effects of miR-490-3p on growth, migration, invasion and apoptosis of PCa cells. Conclusions: Our data highlighted the key role of miR-490-3p in the progression of PCa. Thus, miR-490-3p may be a novel cancer-specific therapeutic. 

Retracted: No

PubPeer comments:
 Figure 3A.  miR-490-3p overexpression inhibits PCa cell migration and invasion. (A) Cell migration ... in DU145 and LNCaP cell lines with miRNAs transfection. I wish to report a glitch in the Matrix.  Fig 4D.  Overexpression of HDAC2 reversed the effects of miR-490-3p ... (D) Cell migration . More glitching.  ,
Proteasome inhibitor PS-341 (bortezomib) induces calpain-dependent IkappaB(alpha) degradation
Authors: Xingming Deng
Ping Yue
Sagar Lonial
Shuzhen Chen
Shi-Yong Sun
Chunyang Li
Fadlo R Khuri
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: proteasome; PS-341; NF-kappaB; IkappaB(alpha); cancer cells
Affiliations: Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, Georgia 30322, USA.

Abstract:  The proteasome, a key component of the ubiquitin-proteasome pathway, has emerged as an important cancer therapeutic target. PS-341 (also called Bortezomib or Velcade) is the first proteasome inhibitor approved for newly diagnosed and relapsed multiple myeloma and is currently being tested in many clinical trials against other types of cancers. One proposed mechanism by which PS-341 exerts its anticancer effect is inactivation of nuclear factor-kappaB (NF-kappaB) through prevention of IkappaB(alpha) degradation. In this study, we show that PS-341 at concentrations that effectively inhibited the growth of human cancer cells, instead of increasing IkappaB(alpha) stability, paradoxically induced IkappaB(alpha) degradation. As a result, PS-341 facilitated p65 nuclear translocation and increased NF-kappaB activity. Moreover, IkappaB(alpha) degradation by PS-341 occurred early before induction of apoptosis and could not be inhibited by a pan-caspase inhibitor or caspase-8 silencing; however, it could be prevented with calpain inhibitors, calcium-chelating agents, calpain knockdown, or calpastatin overexpression. In agreement, PS-341 increased calpain activity. These data together indicate that PS-341 induces a calpain-mediated IkappaB(alpha) degradation independent of caspases. In the presence of a calpain inhibitor, the apoptosis-inducing activity of PS-341 was dramatically enhanced. Collectively, these unexpected findings suggest not only a novel paradigm regarding the relationship between proteasome inhibition and NF-kappaB activity but also a strategy to enhance the anticancer efficacy of PS-341. 

Retracted: No

PubPeer comments:
 2020 correction. https: www.jbc.org content 295 26 8869.short In Fig. 2A, results from two different immunoblots were spliced together without declaration. This figure was corrected by adding a line between the two immunoblots. In Fig. 6B and Fig. S4, some cells from the same field were rearranged. These errors have now been corrected. Finally, the treatment time for PS-341 in Fig. S4 should be 8 h, not 4 h as indicated in the original figure legend. This error was corrected as well. These corrections do not affect the results or conclusions of this work. ,
Signaling pathways leading to the activation of IKK and MAPK by thymosin alpha1
Authors: Cynthia Tuthill
Xiao Peng
Mingwei Zhu
Xin Wang
Justin Chan
Yinsheng Wan
Wen-Ming Chu
Ana Maria Dragoi
Ping Zhang
Meisheng Jiang
Journal: Annals of the New York Academy of Sciences (2007)
Discipline: Multidisciplinary
Keywords: Thymosin alpha 1; interleukin-6; interleukin-10; interleukin-12; molecular pathways
Affiliations: Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.

Abstract:  Thymosin alpha 1 (Talpha1) has therapeutic potential in the treatment of infectious diseases and cancer. However, the exact molecular pathways for Talpha1 action are not fully understood. We found that Talpha1 induces the production of interleukin-6 (IL-6), IL-10, and IL-12 in murine bone marrow-derived macrophages (BMDMs) through IKK and MAPK pathways. Talpha1 triggers the activation of AP-1 and the phosphorylation of JNK and p38. Inhibition of p38 impairs IL-6 production in response to Talpha1. Further, TRAF6 is involved in the activation of JNK and IRAK4 is involved for the activation of IKK and PKCzeta in a Talpha1-induced system. Loss of IRAK4 largely blocked induction of IL-6. Thus, our studies define early signal events that are critical for the Talpha1-induced immune responses. 

Retracted: No

PubPeer comments:
 Identified by another reader. ***  ,
Cytokine expression in placenta-derived mesenchymal stem cells in patients with pre-eclampsia and normal pregnancies
Authors: Min Jeong Oh
Jong Ha Hwang
Oye Sun Seok
Jae Kwan Lee
Mi Jung Lee
Geum Joon Cho
Yu Chin Paek
Hyun Joo Seol
Journal: Cytokine (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cytokines; Placenta-derived mesenchymal stem cells; Pre-eclampsia; Normal pregnancies; sICAM-1
Affiliations: Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Republic of Korea.

Abstract:  Objectives: The aim of this study was to investigate the levels of cytokines in placenta-derived mesenchymal stem cells (MSCs) in normal pregnancies and those with pre-eclampsia. Materials and methods: C5a, CD40 Ligand, G-CSF, GM-CSF, GROalpha, I-309, sICAM-1, IFN-gamma, IL-1alpha, IL-1beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-16, IL-17, IL-17E, IL-23, IL-27, IL-32alpha, IP-10, I-TAC, MCP-1, MIF, MIP-1alpha, MIP-1beta, Serpin E1, RANTES, SDF-1, TNFalpha, and sTREM-1 were measured in mesenchymal stem cells using the human cytokine array panel A. The soluble intracellular adhesion molecule-1 (sICAM-1), stromal-derived factor-1 (SDF-1) and monocyte chemotactic protein-1 (MCP-1) were measured by real-time PCR and confirmed by Western blot analysis. Results: MSCs derived from the deciduas of normal pregnancies had significantly elevated levels of sICAM (p=0.000) and SDF-1 (p=0.011), compared to the pregnancies with pre-eclampsia. The level of MCP-1 in the decidua-derived MSCs was not significantly different. No significant difference was observed between normal and pre-eclamptic pregnancies for the amnion-derived MSCs. Conclusions: The decreased levels of sICAM and SDF-1 found in the decidua-derived MSCs from pre-eclamptic pregnancies might be associated with some of the immunological alterations in pre-eclampsia. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: The right-most sICAM band looks remarkably similar to the right-most MCP-1 band. Reported to the journal in October 2015, but no action taken as of today.  ,
Selective PP2A Enhancement through Biased Heterotrimer Stabilization
Authors: Stefan Sch√ºchner
David L Brautigan
Abbey L Perl
Nilesh Zaware
Derek J Taylor
Egon Ogris
Sudeh Izadmehr
Daniel Leonard
Matthew D Galsky
Danica D Wiredja
Yinghua Chen
Daniela M Schlatzer
Wenqing Xu
Janna Kiselar
Caitlin M O&#x27;Connor
Goutham Narla
Zhizhi Wang
Nikhil Vasireddi
Wei Huang
Journal: Cell (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: B56Œ±; PP2A; SMAP; c-Myc; cancer

Abstract:  Impairment of protein phosphatases, including the family of serine/threonine phosphatases designated PP2A, is essential for the pathogenesis of many diseases, including cancer. The ability of PP2A to dephosphorylate hundreds of proteins is regulated by over 40 specificity-determining regulatory "B" subunits that compete for assembly and activation of heterogeneous PP2A heterotrimers. Here, we reveal how a small molecule, DT-061, specifically stabilizes the B56Œ±-PP2A holoenzyme in a fully assembled, active state to dephosphorylate selective substrates, such as its well-known oncogenic target, c-Myc. Our 3.6 √Ö structure identifies molecular interactions between DT-061 and all three PP2A subunits that prevent dissociation of the active enzyme and highlight inherent mechanisms of PP2A complex assembly. Thus, our findings provide fundamental insights into PP2A complex assembly and regulation, identify a unique interfacial stabilizing mode of action for therapeutic targeting, and aid in the development of phosphatase-based therapeutics tailored against disease specific phospho-protein targets. 

Retracted: No

PubPeer comments:
 Readers should become aware of a recent preprint entitled Cellular toxicity of iHAP1 and DT-061 does not occur through PP2A-B56 targeting that calls into question part of the conclusions obtained by Leonard et al., 2020 study. https: www.biorxiv.org content 10.1101 2021.07.08.451586v1 From the paper: We acknowledge the extensive studies conducted by Leonard et al. (2020) to analyse the interaction between DT-061 and PP2A-B56a complexes. Our analysis of the published cryo-EM structure of DT-061 bound to PP2A-B56a argues that the flexible C-terminal tail of the catalytic subunit could also be modelled into the density ascribed to DT-061. It is important to point out that the cryo-EM structure is the most compelling evidence for direct binding of DT-061 to PP2AB56a. The biochemical experiments in Leonard et al. (2020) focused on the stabilization of PP2A complexes by DT-061 which could be unrelated to direct binding. We were unable to recapitulate a stabilizing effect on the PP2A-B56a holoenzyme as observed by Leonard et al. (2020) either in vitro or in vivo. Our extensive analysis of DT-061 reveals that its cellular toxicity is related to disruption of Golgi and ER function ,
The endocytic pathways of carbon dots in human adenoid cystic carcinoma cells
Authors: Tingting Kong
Wenqing Zhang
Yuanyuan Wei
Bofeng Zhu
Xiaoye Jin
Journal: Cell Proliferation (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ACC-2 cell; carbon dots; endocytic inhibitor; endocytic pathway.
Affiliations: Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China., Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an Jiaotong University, Xi'an, China., Department of Forensic Genetics, School of Forensic Medicine, Southern Medical University, Guangzhou, China.

Abstract:  Objectives: This study aimed at investigating cellular uptake pathways of carbon dots (CDs) in human adenoid cystic carcinoma cell line ACC-2. Materials and methods: We synthesized CDs using a hydrothermal method with citric acid and polyethylenimine (PEI, Mw = 25 000). The CDs incubated with the ACC-2 cells showed their bioimaging capabilities using a confocal microscopy test. Flow cytometry was used to analyse cellular uptake pathways of CDs in ACC-2 cells. Results: Our findings indicated that CDs possessed good biocompatibility in ACC-2 cells. CDs were endocytosed mainly via micropinocytosis and energy-dependent pathways. Conclusions: In general, these findings suggested that CDs had excellent biomedical imaging properties for ACC-2 cells and there was a potential opportunity to develop biomedical applications. 

Retracted: No

PubPeer comments:
 The cell line used in this papert is ACC-2. It is used as a model of salivary adenoid cystic carcinoma (ACC). But it is widely known since 2009 that it is a HeLa contaminated cell line. Thus all conclusions of this paper has applied to adenoid cystic carcinoma are irrelevant. See: * [The relevant Cellosaurus entry] * The article showing that the cell line is contaminated: [PMID:19557180] ,
MicroRNA-613 attenuates the proliferation, migration and invasion of Wilms' tumor via targeting FRS2
Authors: Y-Y Zhang
H-F Wang
M Xu
H-W Zhuang
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Wilms' tumor; microRNA-613; cell proliferation; metastasis; therapeutic targets
Affiliations: Department of Pediatric Surgery, Linyi Central Hospital, Linyi, China. .

Abstract:  Objective: Wilms' tumor is the most common malignant tumor in children worldwide. Considering the poor therapeutic effect on Wilms' tumor, we determined the effects of microRNA-613 on cell proliferation and metastasis in vitro, providing therapeutic targets for the treatment of Wilms' tumor. Patients and methods: Quantitative real-time PCR (qRT-PCR) was employed to identify the expression level of miR-613. CCK8 and colony formation assays were incorporated to assess cell viability and proliferation capacity. Cell migration and invasion assays were performed to investigate the metastasis capacity of Wilms' tumor cells. Flow cytometry was used to detect cell cycle distribution and cell apoptosis. Protein levels were assessed by western blotting assay. The target gene was predicted and verified by bioinformatics analysis and luciferase assay. Results: The expression of miR-613 was downregulated in Wilms' tumor tissues compared with adjacent normal tissues (n=32). Overexpression of miR-613 could attenuate Wilms' tumor cell viability, proliferation, invasion, and migration capacity, as well as induce cell cycle arrest at the G0/G1 phase. FRS2 was chosen as the target of miR-613 by bioinformatics analysis and a luciferase reporter assay. MiR-613 expression was inversely correlated with FRS2 in Wilms' tumor tissues. Moreover, restoration of FRS2 rescued the tumor suppressive role of miR-613 in Wilms' tumor cell growth and metastasis. Conclusions: MiR-613 had a tumor-suppressive effect on Wilms' tumor progression and metastasis via targeting FRS2 in vitro, which provided an innovative and candidate target for the diagnosis and treatment of Wilms' tumor. 

Retracted: No

PubPeer comments:
 Figure 2A. Three of the SK-NEP-1 panels look very similar to their corresponding G401 panels, albeit in mirror image. Boxes and arrows of the same color indicate panels that have a mirrored doppelgu00e4nger, while arrows indicate orientation.  , 
 Figure 2B. The SK-NEP-1 miRNA-613 panel looks very similar to the G401 miRNA-613 panel, albeit rotated 180 degrees. Shown with orange boxes and arrows to indicate orientation.  ,
Circular RNA hsa_circ_0004277 contributes to malignant phenotype of colorectal cancer by sponging miR‚Ä?12‚Ä?p to upregulate the expression of PTMA
Authors: Jinxin Chen
Xing Liu
Jia Xu
Bowen Xiang
Hongwei Sun
Lu Yang
Zhimin Tian
Baoli Qin
Journal: Journal of Cellular Physiology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: circ-0004277; colorectal cancer; miR-512-5p.
Affiliations: Medical Oncology Department of Gastrointestinal Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China., Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China., Scientific Research and Education Department, The People's Hospital of Liaoning Province, Shenyang, China., Cardiovascular Department, The People's Hospital of Liaoning Province, Shenyang, China.

Abstract:  In recent years, extensive reports have been published concerning the molecular mechanism underlying the occurrence and progression of colorectal cancer. Circular RNAs (circRNAs) have been identified as important modulators in the biological processes of colorectal cancer. Microarray analysis unveiled that differential circ-0004277 expression was identified in tissue samples of colorectal cancer. High circ-0004277 expression was then verified in tissue samples and cell lines of colorectal cancer via qRT-PCR. Kaplan-Meier analysis was used for identifying the association between circ-0004277 expression and the overall survival rate of colorectal cancer patients. A relationship existed between higher circ-0004277 expression and decreased overall survival rate of colorectal cancer patients. From a functional perspective, circ-0004277 knockdown accelerated cell apoptosis and restrained cell proliferation of colorectal cancer. From mechanistic perspective, circ-0004277 upregulated PTMA by sponging miR-512-5p. Rescue assay was used for verifying the roles of the circ-0004277-miR-512-5p-PTMA axis. Both miR-512-5p and PTMA participated in circ-0004277-mediated colorectal cancer cell proliferation based on experiments. In summary, our study showed that circ-0004277 promoted the proliferation of colorectal cancer cells as a miR-512-5p sponge to upregulate the PTMA expression. 

Retracted: No

PubPeer comments:
 In Figure 2, 3 and 7, several flow cytometry dot plots have been duplicated and presented as something else. No trust left in this paper and the peer-reviewing at Journal of Cellular Physiology.   ,
Src-dependent phosphorylation of the epidermal growth factor receptor on tyrosine 845 is required for zinc-induced Ras activation
Authors: Sarah J Parsons
Lee M Graves
James M Samet
Weidong Wu
Gordon N Gill
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Zn2+ ions; Ras activation; EGFR; Src kinase; phosphorylation
Affiliations: Center for Environmental Medicine and Lung Biology, the Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

Abstract:  Previous studies have shown that exposure of cells to Zn2+ ions induces Ras and MAPK activation through the EGF receptor (EGFR). To further determine the role of EGFR in Zn2+-induced signaling, mouse B82L fibroblasts expressing no detectable EGFR protein (B82L-par), wild type EGFR (B82L-wt), kinase-deficient EGFR (B82L-K721M), or COOH-truncated EGFR (B82L-c'958) were tested. Exposure to Zn2+ induced Ras activity in B82L-wt, B82L-K721M, and B82L-c'958 but not in B82L-par cells, indicating that the tyrosine kinase domain and the auto-phosphorylation sites of the EGFR were not required for Zn2+-induced Ras activation. Zn2+ induced Src activation in all B82L cell lines, including B82L-par, indicating that Src activation is independent of the presence of the EGFR. A Src kinase inhibitor blocked Zn2+-induced Ras activation in all the B82L cell lines capable of this response, suggesting the involvement of Src kinase in Zn2+-induced Ras activation via the EGFR. Zn2+ induced the association of the EGFR with Src and specifically increased the phosphorylation of EGFR at tyrosine 845 (Tyr-845), a known Src phosphorylation site. Stably transfected B82L cells with a point mutation of the EGFR at Tyr-845 (B82L-Y845F) exhibited only basal Ras activity following exposure to Zn2+. These data demonstrate that Src-dependent phosphorylation of the EGFR at Tyr-845 is required for EGFR transactivation and Zn2+-induced Ras activation. 

Retracted: No

PubPeer comments:
 **The EGFR bands in FIG.5B (Red box) and the EGFR bands in FIG.6B (Red box) were similar.**  ,
Lethal and nonlethal murine malarial infections differentially affect apoptosis, proliferation, and CD8 expression on thymic T cells
Authors: S Sharma
S Khanam
S Pathak
Journal: Parasite Immunology (2015)
Discipline: IMMUNOLOGY
Keywords: 17XL; 17XNL; Plasmodium yoelii; T-cell development; apoptosis
Affiliations: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India.

Abstract:  Although thymic atrophy and apoptosis of the double-positive (DP) T cells have been reported in murine malaria, comparative studies investigating the effect of lethal and nonlethal Plasmodium infections on the thymus are lacking. We assessed the effects of P. yoelii lethal (17XL) and nonlethal (17XNL) infections on thymic T cells. Both strains affected the thymus. 17XL infection induced DP T-cell apoptosis and a selective decrease in surface CD8 expression on developing thymocytes. By contrast, more severe but reversible effects were observed during 17XNL infection. DP T cells underwent apoptosis, and proliferation of both DN and DP cells was affected around peak parasitemia. A transient increase in surface CD8 expression on thymic T cells was also observed. Adult thymic organ culture revealed that soluble serum factors, but not IFN-Œ≥ or TNF-Œ±, contributed to the observed effects. Thus, lethal and nonlethal malarial infections led to multiple disparate effects on thymus. These parasite-induced thymic changes are expected to impact the na√Øve T-cell repertoire and the subsequent control of the immune response against the parasite. Further investigations are required to elucidate the mechanism responsible for these disparate effects, especially the reversible involution of the thymus in case of nonlethal infection. 

Retracted: No

PubPeer comments:
 Figure 5A. It is very strange that two images appear to have unexpectedly similar regions, but not identical.  ,
Hispidulin potentiates the antitumor effect of sunitinib against human renal cell carcinoma in laboratory models
Authors: Jianjun Peng
Hui Gao
Chunbo Wang
Qixiao Jiang
Yantao Han
Journal: Cell biochemistry and biophysics (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: hispidulin; sunitinib; renal cell carcinoma; cell proliferation; apoptosis
Affiliations: Department of pharmacology, Medical College, Qingdao University, Qingdao, 266021, Shandong, China.

Abstract:  The aim of the study was to evaluate the effect of the hispidulin, a naturally occurring flavonoid, in combination with a new multi-targeted oral medication, sunitinib on renal cell carcinoma (RCC) cell proliferation in vitro and on tumor growth in vivo. After treatment with hispidulin or sunitinib, either alone or in combination, MTT assay was used to examine cell viability and flow cytometry analysis was employed to examine cell cycle distribution and apoptosis of the RCC cell lines 786-0 and Caki-1. Western blotting was employed to examine the expression of proteins related to pStat3 signaling pathway. Furthermore, a xenograft mouse model was applied to study the antitumor efficacy of sunitinib or hispidulin alone or in combination, with immunohistochemistry to detect expression of proteins related to xenograft growth and angiogenesis. Hispidulin dose-dependently inhibited proliferation and induced apoptosis in both of the tested RCC cell lines when used alone; when combined with sunitinib, relatively low concentration of hispidulin enhanced the antitumor activity of the latter. The antitumor activity of hispidulin and its enhancement of the antitumor activity of sunitinib correlated with the suppression of pStat3 signaling and the consequent downregulation of Bcl-2 and survivin. Moreover, combination of hispidulin and sunitinib inhibited the growth and angiogenesis of xenografts generated from Caki-1 significantly. Immunohistochemistry indicated decreased expression of proteins promoting xenograft growth and angiogenesis after combination treatment of hispidulin and sunitinib. Our results showed that hispidulin, by inhibiting pStat3 signaling, exhibited antitumor activity and the joint use of hispidulin and sunitinib could provide greater antitumor efficacy compared to either drug alone. Therefore, combination treatment with hispidulin and sunitinib might offer a novel therapeutic option for patients with RCC. 

Retracted: No

PubPeer comments:
  Fig. 3 Hispidulin enhanced sunitinib-induced apoptosis in 786-0 and Caki-1 cells. Cytometric graphs shown were of representatives of three experiments (a). Cells were treated with 25 lM hispidulin or 4 lM sunitinib or in combination for 48 h. Cell apoptosis was measured by flow cytometry Two pairs of panels have surprisingly many cells in common within 3 or 4 quadrants.  ,
Long-lasting effects of chronic rTMS to treat chronic rodent model of depression
Authors: Shu-fang Feng
Tian-yao Shi
Fan-Yang
Wua-ning Wang
Yun-chun Chen
Qing-rong Tan
Journal: Behavioural Brain Research (2012)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: rTMS; antidepressant effect; long-lasting effect; CUMS rat model; depression

Abstract:  Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated in the pre-clinical and clinical settings to have an antidepressant effect. However, studies on the long-lasting effect of rTMS, especially when the effect is measured after treatment has ceased for a few weeks is lacking. We examined this question in a chronic unpredicted mild stress (CUMS) rat model of depression. We gave 3 weeks of high frequency (15 Hz) rTMS, venlafaxine, or these two treatments combined to a modified CUMS paradigm, and then investigated the prolonged effect of treatments. Behavioral testing (sucrose preference test, open field test, forced swimming test, novelty suppressed feeding test), plasma hormone level, hippocampal BrdU labeling, and amount of related neurotropic factors were used to assess the effects of stress and treatments. Long-term chronic rTMS significantly reversed andehonic-like behavior, increased hippocampus cell proliferation, BDNF protein level, phosphorylation of ERK1/2 compared with CUMS rats two weeks after the cessation of rTMS treatment. However, the changes in plasma hormone level were not sustained for that amount of time. Venlafaxine had no interaction with the physical stimulation. Our results suggest that high frequency rTMS has long-lasting effects, which may have some relationship with neuroplasticity. 

Retracted: No

PubPeer comments:
 There appears to be a duplication in the western blots in Figure 7. Could the authors look into this and perhaps upload uncropped blots?  I am also not quite sure how the same loading controls could be used for the set of samples from two different weeks? Should there not be two rows of loading controls as well..? ,