Fasting Serum Lipid and Dehydroepiandrosterone Sulfate as Important Metabolites for Detecting Isolated Postchallenge Diabetes: Serum Metabolomics via Ultra-High-Performance LC-MS

BACKGROUND Isolated postchallenge diabetes (IPD), a subtype of type 2 diabetes mellitus (T2DM) defined as 2-h postprandial plasma glucose ≥200 mg/dL (≥11.1 mmol/L) and fasting plasma glucose (FPG) &amp;lt;108 mg/dL (&amp;lt;6.0 mmol/L), is often overlooked during screening for diabetes on the basis of FPG concentrations. A key challenge is early identification of IPD by the use of fasting serum, which is critical for large-scale diabetes screening. METHODS We applied a nontargeted metabolomic approach using ultra-high-performance liquid chromatography–quadrupole TOF–mass spectrometry (UPLC-QTOF-MS) to analyze serum samples from 51 patients with IPD, 52 with newly diagnosed T2DM, and 49 healthy individuals. We processed metabolite profiles by multivariate analysis to identify potential metabolites, which were further confirmed by tandem MS (MS/MS). We also used GC-MS and ELISA methods to detect potentially important metabolites. A number of independent samples were selected to validate the identified candidates. RESULTS We selected 15 metabolites with a view to distinguishing patients with IPD, whereas 11 were identified with an authentic standard. The selected metabolites included linoleic acid, oleic acid, phospholipids, and dehydroepiandrosterone sulfate (DHEA-S). In IPD samples, significantly higher linoleic and oleic acid (P &amp;lt; 0.001) and lower DHEA-S (P &amp;lt; 0.001) concentrations were observed, compared with controls. The area under the curve from a combination of linoleic acid, oleic acid, and DHEA-S in the validation study was 0.849 for the IPD group. CONCLUSIONS The current study provides useful information to bridge the gaps in our understanding of the metabolic alterations associated with IPD and might facilitate the characterization of patients with IPD by the use of fasting serum. </jats:sec

Ototoxicity of polystyrene nanoplastics in mice, HEI-OC1 cells and zebrafish

Polystyrene nanoplastics are a novel class of pollutants. They are easily absorbed by living organisms, and their potential toxicity has raised concerns. However, the impact of polystyrene nanoplastics on auditory organs remains unknown. Here, our results showed that polystyrene nanoplastics entered the cochlea of mice, HEI-OC1 cells, and lateral line hair cells of zebrafish, causing cellular injury and increasing apoptosis. Additionally, we found that exposure to polystyrene nanoplastics resulted in a significant elevation in the auditory brainstem response thresholds, a loss of auditory sensory hair cells, stereocilia degeneration and a decrease in expression of Claudin-5 and Occludin proteins at the blood-lymphatic barrier in mice. We also observed a significant decrease in the acoustic alarm response of zebrafish after exposure to polystyrene nanoplastics. Mechanistic analysis revealed that polystyrene nanoplastics induced up-regulation of the Nrf2/HO-1 pathway, increased levels of malondialdehyde, and decreased superoxide dismutase and catalase levels in cochlea and HEI-OC1 cells. Furthermore, we observed that the expression of ferroptosis-related indicators GPX4 and SLC7A11 decreased as well as increased expression of ACLS4 in cochlea and HEI-OC1 cells. This study also revealed that polystyrene nanoplastics exposure led to increased expression of the inflammatory factors TNF-α, IL-1β and COX2 in cochlea and HEI-OC1 cells. Further research found that the cell apoptosis, ferroptosis and inflammatory reactions induced by polystyrene nanoplastics in HEI-OC1 cells was reversed through the pretreatment with N-acetylcysteine, a reactive oxygen species inhibitor. Overall, our study first discovered and systematically revealed the ototoxicity of polystyrene nanoplastics and its underlying mechanism

Gold nanocage-based surface-enhanced Raman scattering probes for long-term monitoring of intracellular microRNA during bone marrow stem cell differentiation

In this study, a hairpin DNA (hpDNA)-conjugated gold nanocages (GNCs) SERS probe was developed for the long-term detection and imaging of miR-144-3p in osteogenic differentiation of bone marrow stem cells.</p

Label-Free Detection of Human Serum Using Surface-Enhanced Raman Spectroscopy Based on Highly Branched Gold Nanoparticle Substrates for Discrimination of Non-Small Cell Lung Cancer

Surface-enhanced Raman spectroscopy (SERS) is a good candidate for the development of fast and easy-to-use diagnostic tools, possibly used on serum in screening tests. In this study, a potential label-free serum test based on SERS spectroscopy was developed to analyze human serum for the diagnosis of the non-small cell lung cancer (NSCLC). We firstly synthesized novel highly branched gold nanoparticles (HGNPs) at high yield through a one-step reduction of HAuCl4 with dopamine hydrochloride at 60°C. Then, HGNP substrates with good reproducibility, uniformity, and high SERS effect were fabricated by the electrostatically assisted (3-aminopropyl) triethoxysilane-(APTES-) functionalized silicon wafer surface-sedimentary self-assembly method. Using as-prepared HGNP substrates as a high-performance sensing platform, SERS spectral data of serum obtained from healthy subjects, lung adenocarcinoma patients, lung squamous carcinoma patients, and large cell lung cancer patients were collected. The difference spectra among different types of NSCLC were compared, and analysis result revealed their intrinsic difference in types and contents of nucleic acids, proteins, carbohydrates, amino acids, and lipids. SERS spectra were analyzed by principal component analysis (PCA), which was able to distinguish different types of NSCLC. Considering its time efficiency, being label-free, and sensitivity, SERS based on HGNP substrates is very promising for mass screening NSCLC and plays an important role in the detection and prevention of other diseases