Comparative Proteomic Approach Identifies Pkm2 and Cofilin-1 as Potential Diagnostic, Prognostic and Therapeutic Targets for Pulmonary Adenocarcinoma

Abstract BackgroundBaicalin (BCL) is a natural compound with beneficial activities, including antioxidant, anti-inflammatory and immunomodulatory. To investigate the therapeutic action of baicalin treatment in ethanol-induced chronic gastritis. Here, we investigated the proteome changes in the gastric tissue to elucidate the therapeutic targets of baicalin in chronic gastritis by TMT-based quantitative proteomics.ResultsUsing TMT-based quantitative proteomics, a total of the 4,452 proteins were identified and quantified in the gastric antrum tissue of Sprague–Dawley rats. Of these, 107 differentially expressed proteins, including 44 up-regulated and 63 down-regulated proteins, were uncovered in the baicalin-treated group as compared with the untreated group with ethanol-induced gastritis. Furthermore, the expression of TPM2, GIMAP4, and Mpc1 was validated using Western Blot. Baicalin could decrease the production of interleukin (IL)-2, IL-8 and tumor necrosis factor-α (TNF-α), while increase the expression of epidermal growth factor (EGF) and B-cell lymphoma-2 (Bcl-2). Notably, protein-protein interaction network analysis revealed the widespread interactions mediated by baicalin.ConclusionsWe investigated the effects and potential mechanism of baicalin in chronic gastritis. Proteomic technology was used to explore baicalin-affected proteins and some signaling pathways. The results may provide important insights into the discovery of potential target proteins for the treatment of chronic gastritis.

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Proteomic signatures of 16 major types of human cancer reveal universal and cancer-type-specific proteins for the identification of potential therapeutic targets

Journal of Hematology & Oncology ◽

10.1186/s13045-020-01013-x ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Yangying Zhou ◽

T. Mamie Lih ◽

Jianbo Pan ◽

Naseruddin Höti ◽

Mingming Dong ◽

...

Keyword(s):

Large Scale ◽

Human Cancer ◽

Therapeutic Targets ◽

Small Cell ◽

Tissue Type ◽

Cancer Type ◽

Proteomic Profiling ◽

Human Cancers ◽

Proteomic Approach ◽

Specific Proteins

Abstract Background Proteomic characterization of cancers is essential for a comprehensive understanding of key molecular aberrations. However, proteomic profiling of a large cohort of cancer tissues is often limited by the conventional approaches. Methods We present a proteomic landscape of 16 major types of human cancer, based on the analysis of 126 treatment-naïve primary tumor tissues, 94 tumor-matched normal adjacent tissues, and 12 normal tissues, using mass spectrometry-based data-independent acquisition approach. Results In our study, a total of 8527 proteins were mapped to brain, head and neck, breast, lung (both small cell and non-small cell lung cancers), esophagus, stomach, pancreas, liver, colon, kidney, bladder, prostate, uterus and ovary cancers, including 2458 tissue-enriched proteins. Our DIA-based proteomic approach has characterized major human cancers and identified universally expressed proteins as well as tissue-type-specific and cancer-type-specific proteins. In addition, 1139 therapeutic targetable proteins and 21 cancer/testis (CT) antigens were observed. Conclusions Our discoveries not only advance our understanding of human cancers, but also have implications for the design of future large-scale cancer proteomic studies to assist the development of diagnostic and/or therapeutic targets in multiple cancers.

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Characterization of therapeutic targets from Aspergillus fumigates in response to Adjunctive Combination therapy (Ketoconazole with EDTA).

Anti-Infective Agents ◽

10.2174/2211352519666210224095411 ◽

2021 ◽

Vol 19 ◽

Author(s):

Sonam Ruhil ◽

Vikash Kumar ◽

Monika Malik ◽

Meenakshi Balhara ◽

Anil Kumar Chhillar

Keyword(s):

Combination Therapy ◽

Therapeutic Targets ◽

Major Facilitator Superfamily ◽

Fungal Resistance ◽

Sublethal Dose ◽

Fungal Virulence ◽

Peptide Mass ◽

Proteomic Approach ◽

Aspergillus Fumigates ◽

Haemolytic Assay

Background: The Kingdom (Fungi) comprises numerous species that are associated with numerous fungal diseases. Moreover, the fungal resistance, stagnation in the development of antifungal agents and unacceptably high mortality rate associated with some resistant fungus indicates that alternative therapeutic options should consider. Objective: The objective of this study was to find out new therapeutic targets of A.fumigatus in response to adjunctive combination i.e. Ketoconazole (KTZ) plus EDTA. Methods: A.fumigatus was cultured in absence and presence of sublethal dose (MIC 50) of EDTA, KTZ and Combination of KTZ plus EDTA. The cytosolic proteins were extracted by mechanical grinding of fungal cells.The protein profile was studied by using proteomic approach and identification of protein was done by MALDI-TOF/MS. The morphologicaleffect of combination on A. fumigatus was studied by Scanning Electron Microscopy (SEM) and toxic effect on erythrocytes by haemolytic assay. Result: The combination of KTZ with EDTA was non-toxic upto 500 µg/ml by MTT assay. It inhibits the expression offollowing proteins-Glutamatedehydrogenase, Phenyl alanyl t-RNA synhetase POD G, CaO19-5601, AN6454.2 (Conserved domain; MFS (Major Facilitator Superfamily), serine/threonine protein kinase and dipeptidyl peptidase (identified by peptide mass finger printing).Some of these proteins are involved in hyphal development. Morphological defects on development of fungus (like disrupted hyphal tips,phialide) were observed. Conclusion: These targets can be used for novel drug development as some of them are involved in fungal virulence and adjunctive combination therapy can be an optimistic approach.

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