PReD-Bench/PRed-Bench huggingface dataset:
MicroRNA-381 enhances radiosensitivity in esophageal squamous cell carcinoma by targeting X-linked inhibitor of apoptosis protein
Authors: Dequan Yu
Mingxin Zhang
Jun Liang
Wenguang Ye
Suna Zhou
Yaoyou Cui
Journal: OncoTargets and therapy (2017)
Discipline: CLINICAL MEDICINE
Keywords: XIAP; apoptosis; esophageal squamous cell carcinoma; growth; miR-381.
Affiliations: Department of Radiotherapy., Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Abstract:  Background: Increasing evidence indicates that radioresistance remains a major problem in the treatment of patients with esophageal squamous cell carcinoma (ESCC). This study was designed to investigate the expression of microRNA-381 (miR-381) and its function in the radioresistance of ESCC. Methods: In this study, miR-381 expression was first detected in ESCC cell lines and tissue samples by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the effects of miR-381 expression on growth, apoptosis, and radiosensitivity of ESCC cells were analyzed by MTT, colony formation, and flow cytometry, respectively. Dual-luciferase reporter assays were performed to validate the regulation of a putative target of miR-381, in corroboration with qRT-PCR and Western blotting assays. Results: ESCC cell lines or tissues were found to express significantly lower miR-381 than normal esophageal epithelial cells or adjacent normal tissues, respectively. Ectopic expression of miR-381 in ESCC cell lines blocked proliferation, reduced colony formation, enhanced apoptosis, and increased radiosensitivity by enhancing irradiation-induced apoptosis. In addition, dual-luciferase reporter assays showed that miR-381 binds to the 3'-untranslated region of X-linked inhibitor of apoptosis protein (XIAP), suggesting that XIAP should be a direct target of miR-381. Re-expression of miR-381 suppressed XIAP protein expression in ESCC cells, and the effects of miR-381 upregulation on ESCC cells were found to be similar with silencing of XIAP. In addition, XIAP mRNA expression significantly increased in ESCC tissues and was inversely correlated with miR-381 expression. Conclusion: The results of this study suggest that miR-381/XIAP pathway contributed to the growth inhibition, increase in apoptosis, and enhancement of radiosensitivity in ESCC cells Therefore, miR-381 may be a potential therapeutic target in human ESCC. 

Retracted: No

PubPeer comments:
 Figure 3D. * Red boxes: The left and right c-PARP panels appear to look similar. ![file] , 
 Figure 6C. * Blue boxes: Lane 4 in the left c-PARP panel looks similar to lane 1 in the right Total caspase-3 panel. ![file] , 
 An update on Figure 3D. * Green boxes: Two lanes appear to look similar. ![file] , 
 ![file] ,
Comparative Evaluation of Glutamate-Sensitive Radiopharmaceuticals: Technetium-99m–Glutamic Acid and Technetium-99m–Diethylenetriaminepentaacetic Acid–bis(Glutamate) Conjugate for Tumor Imaging
Authors: Anil K Mishra
Anjani K Tiwari
Dipti Kakkar
Krishna Chuttani
Ankur Kaul
Harpal Singh
Journal: Cancer Biotherapy and Radiopharmaceuticals (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Single-photon emission computed tomography; radiopharmaceuticals; tumor scintigraphy; technetium-99m; glutamate conjugates
Affiliations: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India., Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi, India.

Abstract:  Single-photon emission computed tomography has become a significant imaging modality with huge potential to visualize and provide information of anatomic dysfunctions that are predictive of future diseases. This imaging tool is complimented by radiopharmaceuticals/radiosubstrates that help in imaging specific physiological aspects of the human body. The present study was undertaken to explore the utility of technetium-99m (⁹⁹(m)Tc)-labeled glutamate conjugates for tumor scintigraphy. As part of our efforts to further utilize the application of chelating agents, glutamic acid was conjugated with a multidentate ligand, diethylenetriaminepentaacetic acid (DTPA). The DTPA-glutamate conjugate [DTPA-bis(Glu)] was well characterized by IR, NMR, and mass spectroscopy. The biological activity of glutamic acid was compared with its DTPA conjugate by radiocomplexation with ⁹⁹(m)Tc (labeling efficiency ≥98%). In vivo studies of both the radiolabeled complexes ⁹⁹(m)Tc-Glu and ⁹⁹(m)Tc-DTPA-bis(Glu) were then carried out, followed by gamma scintigraphy in New Zealand albino rabbits. Improved serum stability of ⁹⁹(m)Tc-labeled DTPA conjugate indicated that ⁹⁹(m)Tc remained bound to the conjugate up to 24 hours. Blood clearance showed a relatively slow washout of the DTPA conjugate when compared with the labeled glutamate. Biodistribution characteristics of the conjugate in Balb/c mice revealed that DTPA conjugation of glutamic acid favors less accumulation in the liver and bone and rapid renal clearance. Tumor scintigraphy in mice showed increasing tumor accumulation, stable up to 4 hours. These preliminary studies show that ⁹⁹(m)Tc-DTPA-bis(Glu) can be a useful radiopharmaceutical for diagnostic applications in single-photon emission computed tomography imaging. 

Retracted: No

PubPeer comments:
 Figure-3: NMR spectrum of (A) DTPA-bis(anhydride) shows a strange mirror image similarity between two peaks ![file] , 
 Figure-10a of this paper is also repurposed for another study published by same author in MedChemComm (2015) doi: 10.1039 c5md00104h. The issue is open in pubpeer. It seems , the author is habitual of such practice. ,
Retinoblastoma tumor suppressor protein signals through inhibition of cyclin-dependent kinase 2 activity to disrupt PCNA function in S phase
Authors: H Wan
E S Knudsen
I Todorov
S P Angus
A F Fribourg
Z Sever-Chroneos
K E Knudsen
Journal: Molecular and Cellular Biology (2001)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RB; cell cycle; S-phase inhibition; DNA replication; chromatin binding
Affiliations: Department of Cell Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267-0521, USA., Department of Cell Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267-0521,
1
 and, Dumont Transplant Center, University of California—Los Angeles School of Medicine, Los Angeles, California 90095-70542

Abstract:  The retinoblastoma tumor suppressor protein (RB) is a negative regulator of the cell cycle that inhibits both G(1) and S-phase progression. While RB-mediated G(1) inhibition has been extensively studied, the mechanism utilized for S-phase inhibition is unknown. To delineate the mechanism through which RB inhibits DNA replication, we generated cells which inducibly express a constitutively active allele of RB (PSM-RB). We show that RB-mediated S-phase inhibition does not inhibit the chromatin binding function of MCM2 or RPA, suggesting that RB does not regulate the prereplication complex or disrupt early initiation events. However, activation of RB in S-phase cells disrupts the chromatin tethering of PCNA, a requisite component of the DNA replication machinery. The action of RB was S phase specific and did not inhibit the DNA damage-mediated association of PCNA with chromatin. We also show that RB-mediated PCNA inhibition was dependent on downregulation of CDK2 activity, which was achieved through the downregulation of cyclin A. Importantly, restoration of cyclin-dependent kinase 2 (CDK2)-cyclin A and thus PCNA activity partially restored S-phase progression in the presence of active RB. Therefore, the data presented identify RB-mediated regulation of PCNA activity via CDK2 attenuation as a mechanism through which RB regulates S-phase progression. Together, these findings identify a novel pathway of RB-mediated replication inhibition. 

Retracted: No

PubPeer comments:
 Figure 5F. Much more similar than expected. https: imgur.com bw2e033 , 
 Thank you for bringing this up. I do not disagree that bands look surprisingly similar. However, with image amplification over-saturation (even in the published paper images) you will see that they are not identical. ,
miRNA 206 and miRNA 574-5p are highly expression in coronary artery disease
Authors: Xiaoliang Chen
Jianqing Zhou
Lin Zhang
Shizhong Bu
Guofeng Shao
Ningsheng Liu
Tashina Jehangir
Xiaoyan Huang
Jiangfang Lian
Ping Peng
Yanna Ba
Xi Yang
Journal: Bioscience reports (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: biomarker; coronary artery disease; miRNA; plasma.
Affiliations: Ningbo Medical Center, Lihuili Hospital, Ningbo University, Ningbo, Zhejiang 315041, P.R. China., Ningbo Medical Center, Lihuili Hospital, Ningbo University, Ningbo, Zhejiang 315041, P.R. China Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China., Diabetes Research Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China., Department of Pathology, Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, P.R. China  ., Ningbo Medical Center, Lihuili Hospital, Ningbo University, Ningbo, Zhejiang 315041, P.R. China  .

Abstract:  Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide. Innovative diagnostic biomarkers are a pressing need for this disease. miRNAs profiling is an innovative method of identifying biomarkers for many diseases and could be proven as a powerful tool in the diagnosis and treatment of CAD. We performed miRNA microarray analysis from the plasma of three CAD patients and three healthy controls. Subsequently, we performed quantitative real-time PCR (qRT-PCR) analysis of miRNA expression in plasma of another 67 CAD patients and 67 healthy controls. We identified two miRNAs (miR-206 and miR-574-5p) that were significantly up-regulated in CAD patients as compared with healthy controls (P&lt;0.05). The receiver operating characteristic (ROC) curves indicated these two miRNAs had great potential to provide sensitive and specific diagnostic value for CAD. 

Retracted: No

PubPeer comments:
 The plots in Figure 4A and 4B appear unexpectedly similar. Could the authors review and comment? *** ![file] ,
Long non-coding RNA CRNDE promotes the proliferation, migration and invasion of hepatocellular carcinoma cells through miR-217/MAPK1 axis
Authors: Ke Ma
Ji Ke
Kan-Paatib Barnabo Nampoukime
Haihao Wang
Qiannan Guo
Peiwen Yang
Journal: Journal of Cellular and Molecular Medicine (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CRNDE; LncRNA; MAPK1; MiR-217; hepatocellular carcinoma.
Affiliations: Division of Cardiothoracic and vascular surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China., Department of Forensic Science and Criminal Intelligence, Hubei University of Police, Wuhan, Hubei, China., Reproductive Medicine Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China., Division of Infectious Disease, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Abstract:  Hepatocellular carcinoma (HCC) is an invasive malignant tumour and the second major cause of cancer-related deaths over the world. CRNDE and miR-217 are non-coding RNAs which play critical roles in cell growth, proliferation, migration. Mitogen-activated protein kinase 1 (MAPK1) also participates in cancer cell process. Hence, this study aimed at investigating the effect of CRNDE on migration and invasion of HCC and figuring out the role of miR-217 and MAPK1 in this process. The overexpression of CRNDE was demonstrated by a microarray-based lncRNA profiling study. CRNDE expression in HCC was verified by qRT-PCR. MTT assay and BrdU staining were applied to detect cell proliferation level. Transwell assay was utilized to examine cell migration and invasiveness abilities. Wound healing assay was performed for further exploration of cell migration capacity. MiR-217 was predicted by bioinformatics. The dual luciferase reporter assay was performed to corroborate the targeting relationship between CRNDE, miR-217 and MAPK1. MAPK1, the downstream target of miR-217, was predicted using bioinformatics and was further confirmed by qRT-PCR and Western blot. The interaction between CRNDE, miR-217 and MAPK1 was studied by qRT-PCR, Western blot, MTT, BrdU, transwell assay and wound healing assay. CRNDE was up-regulated in HCC tissues and HCC cell lines. The high expression of CRNDE facilitated cell proliferation, migration and invasion, while the inhibited one affected on the contrary. MiR-217, negatively correlated with CRNDE expression, was the target of CRNDE and was more lowly expressed in HCC. With the high expression of miR-217, HCC cell proliferation, migration and invasion were suppressed. MAPK1, the possible target of miR-217, was negatively correlated with miR-217 but positively correlated with CRNDE and had the same effect in HCC formation process as CRNDE. Long non-coding RNA CRNDE promotes the proliferation, migration and invasion of HCC cells through miR-217/MAPK1 axis. 

Retracted: No

PubPeer comments:
 Figure 7a appears to have some image duplications ![file] ,
Carbon nanotubes impregnated with subventricular zone neural progenitor cells promotes recovery from stroke
Authors: Jong Eun Lee
Kiran Kumar Bokara
Sung Ung Moon
Thomas J Webster
Jong Youl Kim
Dongwoo Khang
Jihee Kim
Journal: International journal of nanomedicine (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: biocompatibility; brain; carbon nanotubes; in vivo; stem cell
Affiliations: Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea.

Abstract:  The present in vivo study was conducted to evaluate whether hydrophilic (HL) or hydrophobic (HP) carbon nanotubes (CNTs) impregnated with subventricular zone neural progenitor cells (SVZ NPCs) could repair damaged neural tissue following stroke. For this purpose, stroke damaged rats were transplanted with HL CNT-SVZ NPCs, HP CNT-SVZ NPCs, or SVZ NPCs alone for 1, 3, 5, and 8 weeks. Results showed that the HP CNT-SVZ NPC transplants improved rat behavior and reduced infarct cyst volume and infarct cyst area compared with the experimental control and the HL CNT-SVZ NPC and SVZ NPCs alone groups. The transplantation groups showed an increase in the expression of nestin (cell stemness marker) and proliferation which was evident with the increased number of doublecortin and bromodeoxyuridine double-stained immunopositive cells around the lesion site. But, these effects were more prominent in the HP CNT-SVZ NPC group compared with the other transplantation groups. The HP CNT-SVZ NPC and HL CNT-SVZ NPC transplants increased the number of microtubule-associated protein 2 (marker for neurons) and decreased the number of glial fibrillary acidic protein (marker for astroglial cells) positive cells within the injury epicenter. The majority of the transplanted HP CNT-SVZ NPCs collectively broadened around the ischemic injured region and the SVZ NPCs differentiated into mature neurons, attained the synapse morphology (TUJ1, synaptophysin), and decreased microglial activation (CD11b/c [OX-42]). For these reasons, this study provided the first evidence that CNTs can improve stem cell differentiation to heal stroke damage and, thus, deserve further attention. 

Retracted: No

PubPeer comments:
 Figure 5 * Green boxes: Panels B and F appear to look similar. It is not clear from the legend if they are representing the same samples, though. Could the authors please clarify if panels A through D represent 3 weeks, while E through H represent 5 weeks? ![file] , 
 21 July 2021 The authors have advised Figure 5 on page 2760 is incorrect. Due to an error at the time of figure assembly the images for Figure 5B and 5F were duplicated. The authors did not pick this error up during the proof-reading stage of the publication. The correct Figure 5 is shown in Download Article. The authors apologize for this error and advise that this does not affect the results of the paper. ![file] ,
The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells
Authors: Xianling Feng
Lei Zhou
Mao Niu
Journal: International journal of nanomedicine (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ERK1/2 pathway; dental implant restoration; osteogenic effect; simvastatin-loaded nanomicelles.
Affiliations: Department of Stomatology, School of Medical Technology and Nursing, Shenzhen Polytechnic, Shenzhen, 518055, China., Department of Pathology, School of Medical, Shenzhen University, Shenzhen, 518060, China., Center of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, 510280, China, .

Abstract:  Objectives: The present study aimed to clarify the role of the ERK1/2 pathway in simvastatin (SV)-loaded nanomicelles (SVNs)- and SV-mediated promotion of cell osteogenic differentiation and explore the molecular mechanisms by which SVNs exhibited a greater efficacy in promoting osteogenic differentiation than SV. Materials and methods: SVNs were synthesized using a dialysis method. MG63 cells were treated with 2.5, 0.25, and 0.025 μmol/L of the drug. The optimal drug dosage was determined by examining the proliferative activity and ALP activity of the MG63 cells. Subsequently, Western blot analysis was performed to analyze the levels of the phosphorylated ERK1/2 proteins in each experimental group at various time points. Finally, the inhibitor PD98059 was used to effectively inhibit the ERK1/2 pathway. The resulting changes in the proliferative activity of MG63 cells and the osteogenesis-related markers were analyzed. Results: The SVNs synthesized in the present study had a mean diameter of 27 nm. The encapsulation and drug-loading efficiencies were 52.03% ± 4.05% and 9.42% ± 0.66%, respectively. SVNs and SV exhibited optimum osteogenesis-promoting effects when the drugs were administered at a concentration of 0.25 μmol/L. The drug-induced activation of the ERK1/2 pathway reached a peak at 15 minutes after administration and then declined rapidly. From 24 hours to 7 days, SVNs and SV exerted an inhibitory effect on the ERK1/2 pathway rather than an activating effect. Throughout the whole experimental process, the regulatory effect of SVNs on the ERK1/2 pathway was significantly greater than that of SV. Inhibition of the ERK1/2 pathway by PD98059 markedly reduced the proliferative activity of the cells in all experimental groups. In addition, the ALP activity and the expression levels of the osterix (OSX) and osteocalcin (OC) proteins were drastically increased. Conclusion: SVNs significantly increased the effect of SV-induced osteogenic differentiation by strongly inhibiting the ERK1/2 pathway. 

Retracted: No

PubPeer comments:
 Could the authors examine Figure 6. Should flow cytometry plots look so similar identical? Others on social media say no. *** ![file] *** Full figure ![file] ,
GP73 promotes invasion and metastasis of bladder cancer by regulating the epithelial-mesenchymal transition through the TGF-β1/Smad2 signalling pathway
Authors: Ge-Liang Liu
Bo Liu
Han-Jie Yang
Tian Liu
Journal: Journal of Cellular and Molecular Medicine (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Golgi membrane protein 73; TGF-β1/Smad2 signalling pathway; bladder cancer; epithelial-mesenchymal transition; invasion
Affiliations: Department of Urology; Pingxiang Affiliated, Southern Medical University; Pingxiang China, Department of General Surgery; Xiangya 2nd Hospital of Central South University; Changsha China

Abstract:  This study investigated the effects of Golgi membrane protein 73 (GP73) on the epithelial-mesenchymal transition (EMT) and on bladder cancer cell invasion and metastasis through the TGF-β1/Smad2 signalling pathway. Paired bladder cancer and adjacent tissue samples (102) and normal bladder tissue samples (106) were obtained. Bladder cancer cell lines (T24, 5637, RT4, 253J and J82) were selected and assigned to blank, negative control (NC), TGF-β, thrombospondin-1 (TSP-1), TGF-β1+ TSP-1, GP73-siRNA-1, GP73-siRNA-2, GP73-siRNA-1+ TSP-1, GP73-siRNA-1+ pcDNA-GP73, WT1-siRNA and WT1-siRNA + GP73-siRNA-1 groups. Expressions of GP73, TGF-β1, Smad2, p-Smad2, E-cadherin and vimentin were detected using RT-qPCR and Western blotting. Cell proliferation, migration and invasion were determined using MTT assay, scratch testing and Transwell assay, respectively. Compared with the blank and NC groups, levels of GP73, TGF-β1, Smad2, p-Smad2, N-cadherin and vimentin decreased, and levels of WT1 and E-cadherin increased in the GP73-siRNA-1 and GP73-siRNA-2 groups, while the opposite results were observed in the WT1 siRNA, TGF-β, TSP-1 and TGF-β + TSP-1 groups. Cell proliferation, migration and invasion notably decreased in the GP73-siRNA-1 and GP73-siRNA-2 groups in comparison with the blank and NC groups, while in the WT1 siRNA, TGF-β, TSP-1 and TGF-β + TSP-1 groups, cell migration, invasion and proliferation showed the reduction after the EMT. These results suggest that GP73 promotes bladder cancer invasion and metastasis by inducing the EMT through down-regulating WT1 levels and activating the TGF-β1/Smad2 signalling pathway. 

Retracted: No

PubPeer comments:
 Figure 1. * Red boxes: Two panels in the Smad2 column appear to show an overlap * Blue boxes: Two panels representing different tissue types and protein staining appear to look identical. ![file] , 
 Figure 8. Some groups of cells appear to be visible in multiple panels. ![file] , 
 For some reason, there are two threads for this paper. Here is the other: https: pubpeer.com publications 4D5F92CB9D1E5DF6BED412806F3EC3 ,
YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
Authors: Jie Li
Lei Wu
Meili Pei
Yun Zhang
Journal: Journal of Ovarian Research (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ovarian cancer; YTHDF2; m6A; miR-145.
Affiliations: Department of Pathology, the First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China. ., Department of Gynecology and Obstetrics, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Department of Pathology, the First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.

Abstract:  RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a double-negative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have some overlaps with other papers by the same author ![file] [Li et al 2019](http: pubpeer.com publications 09372199F668DC8D4A2828899366C8) ![file] [Figure 4 of Li et al 2017](http: pubpeer.com publications B00AC97C35BDA0267A1D0C7E61AF6F) ![file] , 
 #1 Thanks so much for pointing out these errors for us. After checking the data, we are so sorry not to notice the duplicated images. Because these experiments were done at the same time, there is a confusion of naming when saving picture, and the images were continuously taken, so there was some overlapamong the images, and it was easy to make a mistake. we will contact the editor as soon as possible to replace these images. Thanks again for your comments. We apologize for these mistakes to the journal editors, reviewers and readers for any inconvenience, and will pay attention to this and not make the same mistakes in the future. Best Wishes. ,
Double-Liposome – Based Dual-Drug Delivery System as Vectors for Effective Management of Peptic Ulcer
Authors: Himanshu Agrawal
Govind P Agrawal
Ashish K Jain
Abhinav Agarwal
Journal: Journal of Liposome Research (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: dual-drug delivery system; vesicular; mucosal ulcer; liposomes; ranitidine bismuth citrate
Affiliations: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar, India.

Abstract:  The aim of the present investigation was to prepare and evaluate a vesicular dual-drug delivery system for effective management of the mucosal ulcer. Inner encapsulating and double liposomes were prepared by the glass-bead and reverse-phase evaporation methods, respectively. The formulation consisted of inner liposomes bearing ranitidine bismuth citrate (RBC) and outer liposomes encapsulating amoxicillin trihydrate (AMOX). The optimized inner liposomes and double liposomes were extensively characterized for vesicle size, morphology, zeta potential, vesicles count, entrapment efficiency, and in vitro drug release. In vitro, the double liposomes demonstrated a sustained release of AMOX and RBC of 93.6 ± 1.9 and 84.1 ± 0.9%, respectively, at the end of 144 hours. Ex vivo studies were conducted on Helicobacter pylori (ATCC26695) bacterial cell lines. Double liposomes showed a more enhanced percent H. pylori growth inhibition than the plain drug combination. Further, in vivo studies illustrated enhanced antisecretory and ulcer-protective activity of double liposomes, as compared to the plain drug combination. Microscopic studies also supported the ulcer-protective action of the formulation. Thus, it may be concluded that double liposomes are instrumental in reducing gastric secretions and targeting ulcer sites with the interception of minimal side effects, thus suggesting their potential in ulcer therapy. 

Retracted: No

PubPeer comments:
  The photographs of open stomach mucosa of animals of group 1, which were administered absolute alcohol (2 mL kg), are shown in Figure 7A, and a number of plethical lesions and deep ulcers were observed throughout the glandular stomach mucosa after 4 hours. Figure 7B shows animals of group 2, which were administered a combination of plain drug solution; somewhat lesser lesions of ulcer spots were found. Figure 7C shows animals of group 3, which were administered the double-liposomal formulation (OL2IL4) before a 30-minute oral dose of absolute alcohol only; minimal lesions were found after 4 hours and depict their potential to protect from ulcers very effectively. Figure 7D shows animals of group 4, which were administered an LP formulation before a 30-minute oral dose of absolute alcohol; the number of lesions were reduced, but to a lesser extent than in OL2IL4.  ![file] What happened here? UDDATE: the delicately-hued woven crystals shown here bear comparison with those appearing in Fig 6 of [Choudhary et al (2016)] : ![] , 
  Figure 1. Freeze-fracture scanning electron microscopy photomicrographs of (A) inner liposomal formulation . Repeated visual elements. ![file] ,
DUXAP8 promotes the proliferation and migration of ovarian cancer cells via down-regulating microRNA-29a-3p expression
Authors: Y-Q Tian
M Ni
S Jin
S-J Hao
L-M Li
Journal: European review for medical and pharmacological sciences (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA DUXAP8; ovarian cancer; microRNA-29a-3p; proliferation; migration
Affiliations: Department of Gynaecology and Obstetrics, Zaozhuang Mining Group Zaozhuang Hospital, Zaozhuang, China. .

Abstract:  Objective: To study the role of long-chain non-coding RNA (lncRNA) DUXAP8 in ovarian cancer (OCa) and the underlying potential mechanism. Patients and methods: The expression pattern of DUXAP8 in ovarian cancer was analyzed using the GEPIA database. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of DUXAP8 in OCa tissues; at the same time, OCa cell lines were cultured to complete functional experiments, including cell counting kit-8 (CCK-8), plate cloning experiments and transwell experiments to evaluate the effects of DUXAP8 on the proliferative and migration ability of OCa cell lines. Bioinformatics analysis and Dual-Luciferase reporter genes were used to determine the binding and expression of DUXAP8 to its downstream key gene microRNA-29a-3p in OCa cells. In addition, co-transfection technology and cell function recovery experiments were used to verify the important role of the DUXAP8/microRNA-29a-3p regulatory network in OCa. Results: DUXAP8 was abnormally highly up-regulated in OCa tissues and cell lines, besides, its expression was related to poor prognosis of patients. CCK-8 and plate cloning experiments showed that knockdown of DUXAP8 in OCa cells can significantly inhibit the proliferation of OCa cells. Transwell results suggested that knockdown of DUXAP8 can significantly inhibit OCa cell migration. In addition, it was found that DUXAP8 can bind and negatively regulate the expression of microRNA-29a-3p in OCa. Functional experiments in OCa cells also revealed that microRNA-29a-3p was a key downstream gene that mediated the regulation of DUXAP8 on OCa function. Conclusions: DUXAP8 has abnormally high expression in OCa and can lead to malignant progression of the tumor. 

Retracted: No

PubPeer comments:
  33 pairs of OCa tissues and adjacent normal tissues were collected from the Zaozhuang Mining Group Zaozhuang Hospital.... Clinical data of patients were collected for subsequent experimental research. This investigation was approved by Zaozhuang Mining Group Zaozhuang Hospital Ethics Committee. ... All procedures for the collection and use of the organization followed the ethical standards set out in the Helsinki Declaration . One thing missing here is an explicit declaration of patient **consent**. ,
<p>Silencing circZFR inhibits the proliferation, migration and invasion of human renal carcinoma cells by regulating miR-206</p>
Authors: Jie Liu
Mi Wang
Yisheng Gao
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: circZFR; miR-206; renal carcinoma cells.
Affiliations: Department of Urology, The Second Affiliated Hospital, University of South China, Hengyang 421000, Hunan, People's Republic of China., Department of Urology, Linyi People's Hospital, Linyi 276003, Shandong, People's Republic of China.

Abstract:  Background: Renal cell carcinoma (RCC) is the most prevalent kind of kidney cancer. At present, the most efficient treatment mean is surgery. 40% patients with clear cell RCC (ccRCC) relapse after surgery. Identifying novel therapeutic markers and spots for early detection and treatment of RCC is necessary. Methods: qRT-PCR was utilized to quantify circZFR and miR-206 expression in CAKI-1 and ACHN cells. Cell viability was detected by CCK-8 assay. Colony formation capacity was measured by colony formation assay. Transwell assay was utilized to investigate migration and invasion capacity. Expression of migration and apoptosis-associated proteins was quantified by Western blot. Results: As a result, circZFR was highly expressed in RCC tissues and cells. Si-circZFR suppressed cell growth, migration and invasion of experimental cells. In addition, knockdown of circZFR upregulated miR-206 expression. Moreover, the antigrowth, antimigrating and anti-invasive effects of si-circZFR were attenuated when downregulating miR-206. Furthermore, Met is the target gene of miR-206 in experimental cells. The suppression on these signaling pathways was acted by targeting miR-206/Met axis. Conclusion: The results demonstrated si-circZFR inhibited cell growth, migration and invasion in experimental cells by up-regulating of miR-206. Furthermore, si-circZFR suppressed Wnt/β-catenin and PI3K/AKT pathways via targeting miR-206/Met axis. 

Retracted: Yes

PubPeer comments:
 Could the authors check the relevance of References [5,6]?  In recent decades, a lot of researches have been carried out on the porous crystal materials, particularly the coordination polymer (CPs) as a signifcant branch for the nanoporous materials [5u20139]. - [5]. Liu W, Li H, Zhu H, Xu P (2020) Materials 13:1180 ** The Interfacial Adhesion Performance and Mechanism of a Modified Asphaltu2013Steel Slag Aggregate ** - [6]. Wang Z, Zhang X, Jiang S, Qu Y, Ou D, Wang J (2020) J Alloy Compd 828:154412 ** Arc erosion dynamic of island- and skeleton-restricted microstructure evolution modes in Agu2013CuO contact materials ** ,
Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury
Authors: Joao Seda Neto
Augustine M K Choi
Takashi Kaizu
Michael A Nalesnik
Kei Kimizuka
Takashi Uchiyama
Leo E Otterbein
Brian S Zuckerbraun
Noriko Murase
Donna B Stolz
Atsunori Nakao
Journal: American Journal Of Pathology (2003)
Discipline: CLINICAL MEDICINE
Keywords: Carbon monoxide; anti-inflammatory effects; intestinal cold ischemia/reperfusion injury; small intestinal transplantation; cytoprotective efficacy
Affiliations: Thomas E. Starzl Transplantation Institute, Departments of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.

Abstract:  Carbon monoxide (CO), a byproduct of heme catalysis by heme oxygenases, has been shown to exert anti-inflammatory effects. This study examines the cytoprotective efficacy of inhaled CO during intestinal cold ischemia/reperfusion injury associated with small intestinal transplantation. Orthotopic syngenic intestinal transplantation was performed in Lewis rats after 6 hours of cold preservation in University of Wisconsin solution. Three groups were examined: normal untreated controls, control intestinal transplant recipients kept in room air, and recipients exposed to CO (250 ppm) for 1 hour before and 24 hours after surgery. In air grafts, mRNA levels for interleukin-6, cyclooxygenase-2, intracellular adhesion molecule (ICAM-1), and inducible nitric oxide synthase rapidly increased after intestinal transplant. Histopathological analysis revealed severe mucosal erosion, villous congestion, and inflammatory infiltrates. CO effectively blocked an early up-regulation of these mediators, showed less severe histopathological changes, and resulted in significantly improved animal survival of 92% from 58% in air-treated controls. CO also significantly reduced mRNA for proapoptotic Bax, while it up-regulated anti-apoptotic Bcl-2. These changes in CO-treated grafts correlated with well-preserved CD31(+) vascular endothelial cells, less frequent apoptosis/necrosis in intestinal epithelial and capillary endothelial cells, and improved graft tissue blood circulation. Protective effects of CO in this study were mediated via soluble guanylyl cyclase, because 1H-(1,2,4)oxadiazole (4,3-alpha) quinoxaline-1-one (soluble guanylyl cyclase inhibitor) completely reversed the beneficial effect conferred by CO. Perioperative CO inhalation at a low concentration resulted in protection against ischemia/reperfusion injury to intestinal grafts with prolonged cold preservation. 

Retracted: No

PubPeer comments:
 Figure 11B. No loading control. Is there any reason for not including a loading control? ,
LncRNA WT1-AS over-expression inhibits non-small cell lung cancer cell stemness by down-regulating TGF-β1
Authors: Lei Fang
Jiong Wang
Xueqin Jiang
Journal: BMC pulmonary medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: Non-small cell lung cancer; Stemness; TGF-β1; lncRNA WT1-AS.
Affiliations: Department of Geriatric Respiratory and Critical Care, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei City, Anhui Province, 230022, People's Republic of China. ., Department of Geriatric Respiratory and Critical Care, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei City, Anhui Province, 230022, People's Republic of China.

Abstract:  Background: LncRNA WT1-AS is a recently identified potential tumor suppressor in gastric cancer. This study mainly explored the role of WT1-AS in non-small cell lung cancer (NSCLC). Methods: WT1-AS and TGF-β1 mRNA in two types of tissues of 74 NSCLC patients were detected by performing RT-qPCR experiments. WT1-AS and TGF-β1 expression vectors were established using the pcDNA3.1 vector. Protein concentration was measured by BCA assay. Mean values in this study were calculated using the data of three biological replicates of each experiment. Results: We found that WT1-AS was down-regulated, while TGF-β1 was upregulated in NSCLC tissues. Survival analysis showed that low levels of WT1-AS expression predicted poor survival of NSCLC patients. WT1-AS and TGF-β1 were inversely correlated in NSCLC tissues. Over-expression experiments revealed down-regulated TGF-β1 after WT1-AS over-expression, while TGF-β1 over-expression failed to affect WT1-AS. WT1-AS over-expression resulted in inhibited cancer cell stemness. TGF-β1 over-expression played an opposite role and attenuated the effects of TGF-β1 over-expression. Conclusion: Therefore, WT1-AS over-expression may inhibit non-small cell lung cancer cell stemness by down-regulating TGF-β1. Trial registration: The First Affiliated Hospital of Anhui Medical University Ethics committee approved this study (AHMU20101009). 

Retracted: No

PubPeer comments:
 Now uncertain about comment; reconsidering. ,
Metformin reduces pancreatic cancer cell proliferation and increases apoptosis through MTOR signaling pathway and its dose-effect relationship
Authors: J-Q Zhao
H-W Zhao
N Zhou
R Wang
F Jin
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Metformin; proliferation; apoptosis; pancreatic cancer cells; dose-effect relationship
Affiliations: Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, China. .

Abstract:  Objective: To study the influences of metformin on the proliferation and apoptosis of pancreatic cancer cells and its dose-effect relationship and crucial molecular mechanism. Materials and methods: With human pancreatic cancer cell line PANC-1 as the study object, different concentrations of metformin were added for intervention. Then, the proliferation of PANC-1 cells was detected via methyl thiazolyl tetrazolium (MTT) assay to determine the dose-effect relationship of metformin in PANC-1 cell proliferation. PANC-1 cells were treated with metformin at three appropriate concentrations as Metformin treatment groups, and an equal amount of dimethyl sulfoxide (DMSO) was added in Control group. Flow cytometry was performed to detect PANC-1 cell cycle and apoptosis, and the apoptosis of PANC-1 cells was also evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Caspase-3 protein localization and expression in PANC-1 cells were detected using immunofluorescence assay. Besides, the expressions of the apoptosis-associated proteins Caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2 associated X protein (Bax) and phosphatidylinositol 3-hydroxy kinase (PI3K), phosphorylated protein kinase B (p-Akt), and p-mammalian target of rapamycin (mTOR) proteins related to the mTOR pathway were detected using Western blotting. Results: Metformin repressed the proliferation of human pancreatic cancer PANC-1 cells in a concentration-dependent and time-dependent manner. Compared with Control group, Metformin treatment groups (0, 20 and 40 mM) exhibited a higher proportion of PANC-1 cells in G0/G1 phases, and a lower proportion of PANC-1 cells in S phase (p&lt;0.05), and the change in the proportion of cells in G2/M phase was not statistically significant (p&gt;0.05). Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p&lt;0.05). Conclusions: Metformin modulates the mTOR signaling pathway to reduce the proliferation of pancreatic cancer cell, but increase their apoptosis. 

Retracted: No

PubPeer comments:
 Figure 7C may show signs of a possible splice. Some on social media suggest the authors post an image of the complete gel to clarify. *** Contrast enhanced ![file] , 
 Additionally, an image in Figures 5 and 8 appear to overlap, however it appears they are described differently. Could the authors please check? *** ![file] *** ![file] ,
Myostatin induces insulin resistance via Casitas B-lineage lymphoma b (Cblb)-mediated degradation of insulin receptor substrate 1 (IRS1) protein in response to high calorie diet intake
Authors: Mridula Sharma
Ravi Kambadur
Craig McFarlane
Sudarsanareddy Lokireddy
Sabeera Bonala
Sreekanth Patnam
Journal: Journal of Biological Chemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cblb; Diabetes; High Fat Diet; High Glucose; IRS1
Affiliations: From the School of Biological Sciences, Nanyang Technological University, Singapore 637551.

Abstract:  To date a plethora of evidence has clearly demonstrated that continued high calorie intake leads to insulin resistance and type-2 diabetes with or without obesity. However, the necessary signals that initiate insulin resistance during high calorie intake remain largely unknown. Our results here show that in response to a regimen of high fat or high glucose diets, Mstn levels were induced in muscle and liver of mice. High glucose- or fat-mediated induction of Mstn was controlled at the level of transcription, as highly conserved carbohydrate response and sterol-responsive (E-box) elements were present in the Mstn promoter and were revealed to be critical for ChREBP (carbohydrate-responsive element-binding protein) or SREBP1c (sterol regulatory element-binding protein 1c) regulation of Mstn expression. Further molecular analysis suggested that the increased Mstn levels (due to high glucose or fatty acid loading) resulted in increased expression of Cblb in a Smad3-dependent manner. Casitas B-lineage lymphoma b (Cblb) is an ubiquitin E3 ligase that has been shown to specifically degrade insulin receptor substrate 1 (IRS1) protein. Consistent with this, our results revealed that elevated Mstn levels specifically up-regulated Cblb, resulting in enhanced ubiquitin proteasome-mediated degradation of IRS1. In addition, over expression or knock down of Cblb had a major impact on IRS1 and pAkt levels in the presence or absence of insulin. Collectively, these observations strongly suggest that increased glucose levels and high fat diet, both, result in increased circulatory Mstn levels. The increased Mstn in turn is a potent inducer of insulin resistance by degrading IRS1 protein via the E3 ligase, Cblb, in a Smad3-dependent manner. 

Retracted: Yes

PubPeer comments:
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 https: www.straitstimes.com singapore 3-spore-based-scientists-linked-to-research-fraud ,
Potential of stem cell‐derived exosomes to regenerate β islets through Pdx‐1 dependent mechanism in a rat model of type 1 diabetes
Authors: Zahra Salmasi
Elahe Mahdipour
Nona Sabeti
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: exosome; menstrual blood; mesenchymal stem cell; pancreas; type 1 diabetes
Affiliations: Department of Medical BiotechnologyFaculty of Medicine, Mashhad University of Medical SciencesMashhad Iran, Nanotechnology Research CenterPharmaceutical Technology Institute, Mashhad University of Medical SciencesMashhad Iran, Faculty of MedicineMashhad University of Medical SciencesMashhad Iran

Abstract:  Type 1 diabetes, has been recognized as an autoimmune disease. Like other immunological conditions, regulation of immune response is a key strategy to control the autoimmunity in diabetic patients. Mesenchymal stem cells have been shown to have a distinct potential in modulating the immune reactions. However, treatment with stem cells is combined with concerns about safety issues. To overcome these concerns, in this study, we have utilized the regenerative potential of exosomes isolated from menstrual blood-derived mesenchymal stem cells to restore the β-cell mass and insulin production in type 1 diabetes. Exosomes are nanovesicles containing various cargos involved in cellular communications. Streptozotocin was used to induce islet destruction and diabetes in male Wistar rats. Then, exosomes were intravenously injected into animals at different time points and in a single or repeated therapeutic doses. After about 6 weeks, animals were euthanized and the pancreas was analyzed for the presence of the regenerated β islets as well as the insulin secretion. The non-fasting blood glucose and the serum insulin level were also monitored during the study. Our results represented that menstrual blood-derived mesenchymal stem cell-derived exosomes enhance the β-cell mass and insulin production in the pancreas of diabetic animals that received repeated doses of exosomes. Immunohistochemistry analysis also confirmed the presence of insulin in the islets of treated animals. Further investigations proposed that exosomes induce the islet regeneration through pancreatic and duodenal homeobox 1 pathway. The exosome tracking also revealed the homing of injected exosomes to the pancreas. 

Retracted: No

PubPeer comments:
 ![file] , 
 Continuation figure 2C. ![file] , 
 For clarity. ![file] , 
 Two sets of images in Figure 5C appear to overlap, although the dimensions seem to be different, suggesting that this was not merely the wrong images selected during figure assembly. *** ![file] ,