scholarly journals Potential Anticancer Mechanisms of a Novel EGFR/DNA-Targeting Combi-Molecule (JDF12) against DU145 Prostate Cancer Cells: An iTRAQ-Based Proteomic Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-12
Author(s):  
Haofeng Zheng ◽  
Guancan Liang ◽  
Yanxiong Chen ◽  
Sijie Lin ◽  
Wei Liu ◽  
...  

The development of multitargeting drugs is an emerging trend in cancer research. To promote further development and clinical application of multitargeting drugs, this research was performed. MTT assay and flow cytometry of Annexin V/propidium iodide staining were used to confirm the proapoptotic efficacy of a novel combi-targeting molecule, JDF12, against DU145 prostate cancer (PCa) cells. Differentially expressed proteins between control and JDF12-treated cultures were revealed by isobaric tags for relative and absolute quantitation (iTRAQ), and part of them was confirmed by quantitative PCR. Differentially expressed proteins were further analyzed for function, pathway association, and protein−protein interactions using GO, KEGG, and STRING databases. A total of 119 differentially expressed proteins, 70 upregulated and 49 downregulated, were implicated in the anticancer effects of JDF12. Many of these proteins are involved in biosynthesis, response to stress, energy metabolism, and signal transduction. This study provides important information for understanding the anti-PCa mechanisms of JDF12, and well-designed combi-targeting drugs may possess stronger anticancer efficacy than single-targeting drugs and are thus promising candidates for clinical application.

2020 ◽  
Author(s):  
Nan Zhou ◽  
Jinku Bao ◽  
Yuping Ning

Abstract The ongoing COVID-19 pandemic in the world is caused by SARS-CoV-2, a new coronavirus firstly discovered in the end of 2019. It has led to more than 10 million confirmed cases and more than 500,000 confirmed deaths across 216 countries by 1 July 2020, according to WHO statistics. SARS-CoV-2, SARS-CoV, and MERS-CoV are alike, killing people, impairing economy, and inflicting long-term impacts on the society. However, no specific drug or vaccine has been approved as a cure for these viruses. The efforts to develop antiviral measures are hampered by insufficient understanding of molecular responses of human to viral infections. In this study, we collected experimentally validated human proteins that interact with SARS-CoV-2 proteins, human proteins whose expression, translation and phosphorylation levels experience significantly changes after SARS-CoV-2 or SARS-CoV infection, human proteins that correlate with COVID-19 severity, and human genes whose expression levels significantly changed upon SARS-CoV-2 or MERS-CoV infection. A database, H2V, was then developed for easy access to these data. Currently H2V includes: 332 human-SARS-CoV-2 protein-protein interactions; 65 differentially expressed proteins, 232 differentially translated proteins, 1298 differentially phosphorylated proteins, 204 severity associated proteins, and 4012 differentially expressed genes responding to SARS-CoV-2 infection; 66 differentially expressed proteins responding to SARS-CoV infection; and 6981 differentially expressed genes responding to MERS-CoV infection. H2V can help to understand the cellular responses associated with SARS-CoV-2, SARS-CoV and MERS-CoV infection. It is expected to speed up the development of antiviral agents and shed light on the preparation for potential coronavirus emergency in the future.Database url: http://www.zhounan.org/h2v


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhen Wei ◽  
Zhe Wang ◽  
Xiaoyu Li ◽  
Zhenli Zhao ◽  
Minjie Deng ◽  
...  

Paulownia fortunei is a widely cultivated economic forest tree species that is susceptible to infection with phytoplasma, resulting in Paulownia witches’ broom (PaWB) disease. Diseased P. fortunei is characterized by stunted growth, witches’ broom, shortened internodes, and etiolated and smaller leaves. To understand the molecular mechanism of its pathogenesis, we applied isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography coupled with tandem mass spectrometry approaches to study changes in the proteomes of healthy P. fortunei, PaWB-infected P. fortunei, and PaWB-infected P. fortunei treated with 15 mg·L−1 or 75 mg·L−1 dimethyl sulfate. We identified 2969 proteins and 104 and 32 differentially abundant proteins that were phytoplasma infection responsive and dimethyl sulfate responsive, respectively. Based on our analysis of the different proteomes, 27 PaWB-related proteins were identified. The protein-protein interactions of these 27 proteins were analyzed and classified into four groups (photosynthesis-related, energy-related, ribosome-related, and individual proteins). These PaWB-related proteins may help in developing a deeper understanding of how PaWB affects the morphological characteristics of P. fortunei and further establish the mechanisms involved in the response of P. fortunei to phytoplasma.


2021 ◽  
Vol 15 ◽  
Author(s):  
Zhifeng Qi ◽  
Shuhua Yuan ◽  
Xixi Zhou ◽  
Xunming Ji ◽  
Ke Jian Liu

Hemorrhagic transformation (HT), which occurs with or without reperfusion treatments (thrombolysis and/or thrombectomy), deteriorates the outcomes of ischemic stroke patients. It is essential to find clinically reliable biomarkers that can predict HT. In this study, we screened for potential serum biomarkers from an existing blood bank and database with 243 suspected acute ischemic stroke (AIS) patients. A total of 37 patients were enrolled, who were diagnosed as AIS without receiving reperfusion treatment. They were divided into two groups based on whether they were accompanied with HT or not (five HT and 32 non-HT). Serum samples were labeled by isobaric tags for relative and absolute quantitation (iTRAQ) and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and compared under NCBInr database. A total of 647 proteins in sera samples were captured, and the levels of 17 proteins (12 upregulated and five downregulated) were significantly different. These differentially expressed proteins were further categorized with Gene Ontology functional classification annotation and Kyoto Encyclopedia of Genes and Genomes metabolic pathway analysis into biological processes. Further protein–protein interaction analysis using String database discovered that, among the differentially expressed proteins, 10 pairs of proteins were found to have crosstalk connections, which may have direct (physical) and indirect (functional) interactions for the development of HT. Our findings suggest that these differentially expressed proteins could serve as potential biomarkers for predicting HT after ischemic stroke.


2020 ◽  
Vol 367 (20) ◽  
Author(s):  
Miles D Lange ◽  
Jason Abernathy ◽  
Craig A Shoemaker ◽  
Dunhua Zhang ◽  
Augustus Kirby ◽  
...  

ABSTRACT The Gram-negative bacterium, Aeromonas hydrophila, has been responsible for extensive losses in the catfish industry for over a decade. Due to this impact, there are ongoing efforts to understand the basic mechanisms that contribute to virulent A. hydrophila (vAh) outbreaks. Recent challenge models demonstrated that vAh cultured in the presence of the iron chelating agent deferoxamine mesylate (DFO) were more virulent to channel catfish (Ictalurus punctatus). Interestingly, differential gene expression of select iron acquisition genes was unremarkable between DFO and non-DFO cultures, posing the question: why the increased virulence? The current work sought to evaluate growth characteristics and protein expression of vAh after the addition of DFO. A comparative proteome analysis revealed differentially expressed proteins among tryptic soy broth (TSB) and TSB + DFO treatments. Upregulated proteins identified among the TSB + DFO treatment were enriched for gene ontology groups including iron ion transport, siderophore transport and siderophore uptake transport, all iron acquisition pathways. Protein-protein interactions were also evaluated among the differentially expressed proteins and predicted that many of the upregulated iron acquisition proteins likely form functional physiological networks. The proteome analysis of the vAh reveals valuable information about the basic biological processes likely leading to increased virulence during iron restriction in this organism.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiao Han ◽  
Siyi Zhong ◽  
Pengnan Zhang ◽  
Yanmei Liu ◽  
Sangsang Shi ◽  
...  

AbstractTo investigate the complexity of proteomics in cervical cancer tissues, we used isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry analysis on a panel of normal cervical tissues (N), high-grade squamous intraepithelial lesion tissues (HSIL) and cervical cancer tissues (CC). Total 72 differentially expressed proteins were identified both in CC vs N and CC vs HSIL. The expression of HMGB2 was markedly higher in CC than that in HSIL and N. High HMGB2 expression was significantly correlated with primary tumor size, invasion and tumor stage. The up-regulated HMGB2 was discovered to be associated with human cervical cancer. These findings suggest that HMGB2 may be a potentially prognostic biomarker and a target for the therapy of cervical cancer.


Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110561
Author(s):  
Xuhong Dang ◽  
Haipeng Lin ◽  
Yayi Yuan ◽  
Biao Yang ◽  
Juancong Dong ◽  
...  

The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. However, there is a lack of early warning indicators for radon radiation damage. In this study, mixed serum samples of 3 groups were collected from 27 underground uranium miners and seven aboveground miners according to the radiation exposure dose. The differentially expressed proteins in the serum were identified using the isobaric tags for the relative and absolute quantitation (iTRAQ)-based method. Some differentially expressed proteins were validated by enzyme-linked immunosorbent assay (ELISA) in 84 underground and 32 aboveground miners. A total of 25 co-differentially expressed proteins in 2 underground miner groups were screened, of which 9 were downregulated and 13 were upregulated. Biological process analysis of these proteins using Metascape showed that 5 GO terms were enriched, such as negative regulation of very-low-density lipoprotein particle clearance, endocytosis, and regulated exocytosis. The results of the ELISA for the expression levels of GCN1, CIP2A, and IGHV1-24 in the serum of 116 miners’ serum showed that the levels of GCN1 and CIP2A were consistent with the iTRAQ results. In conclusion, APOC1, APOC2, APOC3, ORM1, ORM2, ANTXR1, GCN1, and CIP2A may be potential early markers of radon radiation damage.


2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Yunke Zhang ◽  
Junhong Yang ◽  
Yingzhe Chen ◽  
Jie Lv ◽  
Jing Zhang ◽  
...  

Myasthenia gravis (MG) is an autoimmune disease. A proportion of MG patients did not get satisfactory results after treatment with pyridostigmine and prednisone. Jia Wei Bu Zhong Yi Qi (Jia Wei BZYQ) decoction, a water extract from multiple herbs, has been demonstrated to be effective in the treatment of multiple “Qi deficiency type” diseases including MG in China. In this text, we investigated protein alterations in the plasma from healthy volunteers (C), MG patients without any treatment (T1), MG patients with routine western medical treatment (T2), and MG patients with combined treatments of Jia Wei BZYQ decoction and routine western medicines (T3) and identified some potential proteins involved in the pathogenesis and treatment of MG. iTRAQ (isobaric tags for relative and absolute quantitation) and 2D-LC-MS/MS (two-dimensional liquid chromatography-tandem mass spectrometry technologies) were employed to screen differentially expressed proteins. The identification, quantification, functional annotation, and interaction of proteins were analyzed by matching software and databases. In our project, 618 proteins were identified, among which 447 proteins had quantitative data. The number of differentially expressed proteins was 110, 117, 143, 115, 86, and 158 in T1 vs. C, T2 vs. C, T2 vs. T1, T3 vs. C, T3 vs. T1, and T3 vs. T2 groups, respectively. Functional annotation results showed that many differentially expressed proteins were closely associated with immune responses. For instance, some key proteins such as C-reactive protein, apolipoprotein C-III, apolipoprotein A-II, alpha-actinin-1, and thrombospondin-1 have been found to be abnormally expressed in T3 group compared to T1 group or T2 group. Interaction network analyses also provided some potential biomarkers or targets for MG management.


2020 ◽  
Author(s):  
Zhao Zhenjie ◽  
Liwei Hu ◽  
Qiansi Chen ◽  
Huaxin Dai ◽  
Xiangyu Meng ◽  
...  

Abstract Background: Carbon nanomaterials (CNMs) have attracted a great deal of research interest for their potential application in plants. Some types of CNMs have exhibited the ability on regulating the growth of plants, which showed a promising future in agriculture. However, detailed mechanism of their application in plants is still not well characterized especially at the molecular level.Methods: The biomass variation of tobacco callus was investigated to exposure of carbon nanoparticles (CNPs). During the incubation period, proteomic profiling in tobacco callus was investigated by using the isobaric tags for relative and absolute quantitation labeling (iTRAQ) coupled with 2D-LC MS/MS. The function of differentially expressed proteins were achieved by using a gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis by InterproScan, and qRT-PCR was used to confirm the results of the proteomic data.Results: The results showed that the growth of tobacco callus was enhanced by CNPs, with the optimal concentration at 50 mg/L. The expression levels of 198 cellular proteins were significantly up- or down- regulated after CNPs treatment. These differentially expressed proteins were involved in mitochondria and calcium-mediated signaling. Conclusions: We demonstrated CNPs have the ability to enhance the growth of tobacco callus. The proteomic profile changes of tobacco callus provided a deeper understanding of the highly complex regulatory mechanisms in tobacco callus exposed to CNPs.


2021 ◽  
Vol 22 (12) ◽  
pp. 6373
Author(s):  
Ahmad Jalloh ◽  
Antwoine Flowers ◽  
Charles Hudson ◽  
Dale Chaput ◽  
Jennifer Guergues ◽  
...  

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.


Sign in / Sign up

Export Citation Format

Share Document