Modelling premature cardiac aging with induced pluripotent stem cells from a hutchinson-gilford Progeria Syndrome patient.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder that causes accelerated aging and a high risk of cardiovascular complications. However, the underlying mechanisms of cardiac complications of this syndrome are not fully understood. This study modeled HGPS using cardiomyocytes (CM) derived from induced pluripotent stem cells (iPSC) derived from a patient with HGPS and characterized the biophysical, morphological, and molecular changes found in these CM compared to CM derived from a healthy donor. Electrophysiological recordings suggest that the HGPS-CM was functional and had normal electrophysiological properties. Electron tomography showed nuclear morphology alteration, and the 3D reconstruction of electron tomography images suggests structural abnormalities in HGPS-CM mitochondria, however, there was no difference in mitochondrial content as measured by Mitotracker. Immunofluorescence indicates nuclear morphological alteration and confirms the presence of Troponin T. Telomere length was measured using qRT-PCR, and no difference was found in the CM from HGPS when compared to the control. Proteomic analysis was carried out in a high-resolution system using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). The proteomics data show distinct group separations and protein expression differences between HGPS and control-CM, highlighting changes in ribosomal, TCA cycle, and amino acid biosynthesis, among other modifications. Our findings show that iPSC-derived cardiomyocytes from a Progeria Syndrome patient have significant changes in mitochondrial morphology and protein expression, implying novel mechanisms underlying premature cardiac aging.

Development of an analytical method to determine E7130 concentration in mouse plasma by micro-sampling using ultra-performance liquid chromatography-high resolution mass spectrometry.

E7130 is a novel microtubule inhibitor and a promising tumor microenvironment ameliorator. Since the amount of the administration in preclinical study is very small due to the high potency of E7130, this study aimed to establish a sensitive analytical method to measure E7130 concentration in mouse plasma samples obtained via microsampling. A sensitive and validated method was developed based on ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Chromatographic separation was achieved using a Waters ACQUITY UPLC BEH C18 1.7 µm (2.1 × 50 mm) column. Mobile phase A comprised 0.1% formic acid and 10 mM ammonium formate in water, and mobile phase B was methanol. A gradient elution was applied at a flow rate of 0.5 mL/min. The calibration curve drawn was linear in the 0.2-100 ng/mL E7130 concentration range for mouse plasma microsamples (10 µL). Analytical results demonstrated good precision (<6.7%) and accuracy (88.5%-100.0%) in E7130 quantitation, indicating that UHPLC-HRMS is a useful method for pharmacokinetic analysis and a valuable approach for the quantitation of hardly fragmented compounds.

Characterization of Clinical Isolates of Talaromyces marneffei and Related Species, California, USA.

Talaromyces marneffei and other Talaromyces species can cause opportunistic invasive fungal infections. We characterized clinical Talaromyces isolates from patients in California, USA, a non-Talaromyces-endemic area, by a multiphasic approach, including multigene phylogeny, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and phenotypic methods. We identified 10 potentially pathogenic Talaromyces isolates, 2 T. marneffei.

Mass spectrometry imaging to detect lipid biomarkers and disease signatures in cancer.

BACKGROUND: Current methods to identify, classify, and predict tumor behavior mostly rely on histology, immunohistochemistry, and molecular determinants. However, better predictive markers are required for tumor diagnosis and evaluation. Due, in part, to recent technological advancements, metabolomics and lipid biomarkers have become a promising area in cancer research. Therefore, there is a necessity for novel and complementary techniques to identify and visualize these molecular markers within tumors and surrounding tissue. RECENT FINDINGS: Since its introduction, mass spectrometry imaging (MSI) has proven to be a powerful tool for mapping analytes in biological tissues. By adding the label-free specificity of mass spectrometry to the detailed spatial information of traditional histology, hundreds of lipids can be imaged simultaneously within a tumor. MSI provides highly detailed lipid maps for comparing intra-tumor, tumor margin, and healthy regions to identify biomarkers, patterns of disease, and potential therapeutic targets. In this manuscript, recent advancement in sample preparation and MSI technologies are discussed with special emphasis on cancer lipid research to identify tumor biomarkers. CONCLUSION: MSI offers a unique approach for biomolecular characterization of tumor tissues and provides valuable complementary information to histology for lipid biomarker discovery and tumor classification in clinical and research cancer applications.

Photodegradation of fluazaindolizine in aqueous solution with graphitic carbon nitride nanosheets under simulated sunlight illumination.

The photodegradation of fluazaindolizine (FZDL) under simulated sunlight irradiation was accelerated by the catalysis of graphitic carbon nitride (g-C3N4). Under optimum conditions, such as 5 mg of amount and dispersion, the photodegradation half-life was dramatically enhanced to 2.7 h. More importantly, the pathway of degradation by g-C3N4 was different from both direct photolysis and the catalysis by titanium oxide, with particular negative ions of m/z 221 and 195, corresponding to the cleavage of sulfamide bond and the ring opening of imidazole, respectively. In addition, hydroxyl and superoxide radicals played important roles in photodegradation. The results enriched not only the study of FZDL photodegradation but also the application of g-C3N4. It also suggested the possibility of the water purification by photodegradation for pesticide removal in real life.