scholarly journals Analysis of ADAM12-Mediated Ephrin-A1 Cleavage and Its Biological Functions

2021 ◽  
Vol 22 (5) ◽  
pp. 2480
Author(s):  
Katsuaki Ieguchi ◽  
Takeshi Tomita ◽  
Toshifumi Takao ◽  
Tsutomu Omori ◽  
Taishi Mishima ◽  
...  
Keyword(s):  
Lung Metastasis ◽  
Biological Activities ◽  
Ionization Mass ◽  
Laser Desorption Ionization ◽  
Biological Functions ◽  
Primary Tumors ◽  
Tumor Bearing ◽  
Potential Biomarker ◽  
Lung Vascular Permeability ◽  
Worse Prognosis

Accumulating evidence indicates that an elevated ephrin-A1 expression is positively correlated with a worse prognosis in some cancers such as colon and liver cancer. The detailed mechanism of an elevated ephrin-A1 expression in a worse prognosis still remains to be fully elucidated. We previously reported that ADAM12-cleaved ephrin-A1 enhanced lung vascular permeability and thereby induced lung metastasis. However, it is still unclear whether or not cleaved forms of ephrin-A1 are derived from primary tumors and have biological activities. We identified the ADAM12-mediated cleavage site of ephrin-A1 by a Matrix-assisted laser desorption ionization mass spectrometry and checked levels of ephrin-A1 in the serum and the urine derived from the primary tumors by using a mouse model. We found elevated levels of tumor-derived ephrin-A1 in the serum and the urine in the tumor-bearing mice. Moreover, inhibition of ADAM-mediated cleavage of ephrin-A1 or antagonization of the EphA receptors resulted in a significant reduction of lung metastasis. The results suggest that tumor-derived ephrin-A1 is not only a potential biomarker to predict lung metastasis from the primary tumor highly expressing ephrin-A1 but also a therapeutic target of lung metastasis.

Rapid quality control of medicine and food dual purpose plant polysaccharides by matrix assisted laser desorption/ionization mass spectrometry

The Analyst ◽  
2020 ◽  
Vol 145 (6) ◽  
pp. 2168-2175 ◽  
Author(s):  
Huiwen Wang ◽  
Xiaoyong Zhao ◽  
Yu Huang ◽  
Jiancong Liao ◽  
Yaqin Liu ◽  
...  
Keyword(s):  
Biological Activities ◽  
Health Benefit ◽  
Laser Desorption ◽  
Ionization Mass ◽  
Laser Desorption Ionization ◽  
Dual Purpose ◽  
Medical Treatments ◽  
Plant Polysaccharides ◽  
Matrix Assisted Laser ◽  
Matrix Assisted Laser Desorption

With their multiple biological activities and health benefit effects, polysaccharides from medicine and food dual purpose plants (MFDPPPs) have been extensively applied in many fields, including in medical treatments, stock farming, and cosmetics.

Sequencing Complex Polysaccharides

Science ◽  
1999 ◽  
Vol 286 (5439) ◽  
pp. 537-542 ◽  
Author(s):  
Ganesh Venkataraman ◽  
Zachary Shriver ◽  
Rahul Raman ◽  
Ram Sasisekharan
Keyword(s):  
Mass Spectrometry ◽  
Biological Activities ◽  
Laser Desorption ◽  
Ionization Mass ◽  
Laser Desorption Ionization ◽  
Notation System ◽  
Desorption Ionization ◽  
Cell Growth And Differentiation ◽  
Matrix Assisted Laser ◽  
Matrix Assisted Laser Desorption

Although rapid sequencing of polynucleotides and polypeptides has become commonplace, it has not been possible to rapidly sequence femto- to picomole amounts of tissue-derived complex polysaccharides. Heparin-like glycosaminoglycans (HLGAGs) were readily sequenced by a combination of matrix-assisted laser desorption ionization mass spectrometry and a notation system for representation of polysaccharide sequences. This will enable identification of sequences that are critical to HLGAG biological activities in anticoagulation, cell growth, and differentiation.

CDK12 Promotes Breast Cancer Progression and Maintains Stemness by Activating c-myc/β -catenin Signaling

2020 ◽  
Vol 20 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Fang Peng ◽  
Chuansheng Yang ◽  
Yanan Kong ◽  
Xiaojia Huang ◽  
Yanyu Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Lung Metastasis ◽  
Xenograft Model ◽  
Breast Cancer Cell Lines ◽  
Cell Renewal ◽  
Cancer Stemness ◽  
Mesenchymal Transition ◽  
Potential Biomarker

Background: CDK12 is a promising therapeutic target in breast cancer with an effective ability of maintaining cancer cell stemness. Objective: We aim to investigate the mechanism of CDK12 in maintaining breast cancer stemness. Methods: CDK12 expression level was accessed by using RT-qPCR and IHC. CDK12-altered breast cancer cell lines MDA-MB-231-shCDK12 and SkBr-3-CDK12 were then established. CCK8, colony formation assays, and xenograft model were used to value the effect of CDK12 on tumorigenicity. Transwell assay, mammosphere formation, FACS, and lung metastasis model in vivo were determined. Western blot further characterized the mechanism of CDK12 in breast cancer stemness through the c-myc/β-catenin pathway. Results: Our results showed a higher level of CDK12 exhibited in breast cancer samples. Tumor formation, cancer cell mobility, spheroid forming, and the epithelial-mesenchymal transition will be enhanced in the CDK12high group. In addition, CDK12 was associated with lung metastasis and maintained breast cancer cell stemness. CDK12high cancer cells presented higher tumorigenicity and a population of CD44+ subset compared with CDK12low cells. Our study demonstrated c-myc positively expressed with CDK12. The c-myc/β-catenin signaling was activated by CDK12, which is a potential mechanism to initiate breast cancer stem cell renewal and may serve as a potential biomarker of breast cancer prognosis. Conclusion: CDK12 overexpression promotes breast cancer tumorigenesis and maintains the stemness of breast cancer by activating c-myc/β-catenin signaling. Inhibiting CDK12 expression may become a potential therapy for breast cancer.

scholarly journals Diagnosis of Agglomeration and Crystallinity of Active Pharmaceutical Ingredients in Over the Counter Headache Medication by Electrospray Laser Desorption Ionization Mass Spectrometry Imaging

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 610
Author(s):  
Mariann Inga Van Meter ◽  
Salah M. Khan ◽  
Brynne V. Taulbee-Cotton ◽  
Nathan H. Dimmitt ◽  
Nathan D. Hubbard ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Laser Desorption ◽  
Ionization Mass Spectrometry ◽  
Ionization Mass ◽  
Active Pharmaceutical Ingredients ◽  
Laser Desorption Ionization ◽  
Over The Counter ◽  
Pharmaceutical Ingredients ◽  
Desorption Ionization

Agglomeration of active pharmaceutical ingredients (API) in tablets can lead to decreased bioavailability in some enabling formulations. In a previous study, we determined that crystalline APIs can be detected as agglomeration in tablets formulated with amorphous acetaminophen tablets. Multiple method advancements are presented to better resolve agglomeration caused by crystallinity in standard tablets. In this study, we also evaluate three “budget” over-the-counter headache medications (subsequently labeled as brands A, B, and C) for agglomeration of the three APIs in the formulation: Acetaminophen, aspirin, and caffeine. Electrospray laser desorption ionization mass spectrometry imaging (ELDI-MSI) was used to diagnose agglomeration in the tablets by creating molecular images and observing the spatial distributions of the APIs. Brand A had virtually no agglomeration or clustering of the active ingredients. Brand B had extensive clustering of aspirin and caffeine, but acetaminophen was observed in near equal abundance across the tablet. Brand C also had extensive clustering of aspirin and caffeine, and minor clustering of acetaminophen. These results show that agglomeration with active ingredients in over-the-counter tablets can be simultaneously detected using ELDI-MS imaging.

Analysis of microbial lipids deposited on Mars Global Simulant (MGS-1) by geomatrix-assisted laser desorption/ionization-mass spectrometry

2021 ◽  
pp. 1-7
Author(s):  
Alef dos Santos ◽  
Edson Rodrigues-Filho ◽  
Manoel Gustavo Petrucelli Homem
Keyword(s):  
Mass Spectrometry ◽  
Laser Desorption ◽  
Ionization Mass Spectrometry ◽  
Ionization Mass ◽  
Laser Desorption Ionization ◽  
Organic Substances ◽  
Microbial Lipids ◽  
Desorption Ionization ◽  
Martian Soil ◽  
Planetary Missions

Abstract Lipids are among the organic substances that can work as biosignatures, indicating life in an environment. We present an experimental investigation concerning analysis of lipids from a microbial source deposited on the Mars Global Simulant (MGS-1) regolith by geomatrix-assisted laser desorption/ionization-mass spectrometry (GALDI-MS). Our results indicate that lipids from intact microbial cells of a black yeast strain can be detected in these mimetic samples of Martian soil. These lipid molecules are predominantly associated with the occurrence of adducts in the GALDI-MS spectra. The results can be helpful in the planning of future planetary missions.

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