Background: Inductively coupled plasma mass spectrometry (ICP‐MS) is widely used for the accurate measurement of minerals. However, its application to serum essential mineral measurement has not been fully evaluated. The present study aimed to assess the performance of ICP‐MS for serum minerals by comparing its measurements to those obtained using standard quantification methods.Methods: Cross‐sectional data were collected from 282 participants from a single facility in Japan. Serum concentrations of eight key minerals, namely sodium, potassium, calcium, phosphorus, magnesium, iron, zinc, and copper, measured via ICP‐MS and standard methods were compared using Passing–Bablok regression and Bland–Altman plots.Results: All minerals, except phosphorus, exhibited good agreement with standard methods, with more stable regression coefficients observed for minerals with greater interindividual variability. After systematically filtering outliers, the mean relative errors were approximately −3% for sodium, potassium, calcium, and magnesium; +5% for iron; 0% for zinc; and −19% for copper. The outliers for iron were primarily due to mild hemolysis, whereas those for zinc were largely attributed to nonhemolysis factors. For phosphorus, the serum total phosphorus concentration measured using ICP‐MS was approximately 3.5 times higher than the serum inorganic phosphorus concentration measured using standard methods, with a weak correlation observed between the two methods.Conclusion: This study provides a practical foundation for future research. Understanding ICP‐MS characteristics will facilitate the development of new approaches in clinical diagnostics.
In metastatic renal cell carcinoma (mRCC), the clinical response to immune checkpoint inhibitors (ICIs) is limited in a subset of patients and the need exists to identify non-invasive, blood-based, predictive biomarkers for responses. We performed RNA sequencing using whole-blood samples prospectively collected from 49 patients with mRCC prior to the administration of ipilimumab (IPI) and/or nivolumab (NIVO) to determine whether gene expression profiles were associated with responses. An analysis from 33 mRCC patients with complete responses (n = 5), partial responses (n = 14), and progressive disease (n = 14) showed 460 differentially expressed genes (DEGs) related to immune responses between the responder and non-responder groups with significant differences. A set of 14 genes generated from the initial 460 DEGs accurately classified responders (sensitivity 94.7% and specificity 50.0%) while consensus clustering defined clusters with significantly differing response rates (92.3% and 35.0%). These clustering results were replicated in a cohort featuring 16 additional SD patients (49 total patients): response rates were 95.8% and 48.0%. Collectively, whole-blood gene expression profiles derived from mRCC patients treated with ICIs clearly differed by response and hierarchical clustering using immune response DEGs accurately classified responder patients. These results suggest that such screening may serve as a predictor for ICI responses in mRCC patients.
2 December 2019 in International Journal of Urology
The circadian clock system exists in most organs and regulates diverse physiological processes, including growth. Here, we used a prostate-specific Bmal1-knockout mouse model (pBmal1 KO: PbsnCre+; Bmal1fx/fx) and immortalized human prostate cells (RWPE-1 and WPMY-1) to elucidate the role of the peripheral prostate clock on prostate growth. Bmal1 KO resulted in significantly decreased ventral and dorsolateral lobes with less Ki-67-positive epithelial cells than the controls. Next, the cap analysis of gene expression revealed that genes associated with cell cycles were differentially expressed in the pBmal1 KO prostate. Cdkn1a (coding p21) was diurnally expressed in the control mouse prostate, a rhythm which was disturbed in pBmal1 KO. Meanwhile, the knockdown of BMAL1 in epithelial RWPE-1 and stromal WPMY-1 cell lines decreased proliferation. Furthermore, RWPE-1 BMAL1 knockdown increased G0/G1-phase cell numbers but reduced S-phase numbers. These findings indicate that core clock gene Bmal1 is involved in prostate growth via the modulation of the cell cycle and provide a rationale for further research to link the pathogenesis of benign prostatic hyperplasia or cancer with the circadian clock.
1 January 2024 in Reproductive Medicine and Biology
Purpose: To investigate whether seminal plasma (SP)/serum ratios of multiple trace elements (TEs) can classify patients with male subfertility.Methods: SP/serum ratios of 20 TEs (lithium, sodium, magnesium, phosphorus, sulfur, potassium, calcium, manganese, iron, cobalt, copper, zinc, arsenic, selenium, rubidium, strontium, molybdenum, cesium, barium, and thallium) were calculated for healthy volunteers (n = 4) and those consulting for male subfertility (n = 245). Volunteer semen samples were collected by split ejaculation into early and subsequent fractions, and SP/serum ratio data were compared between fractions. The patients' SP/serum ratio data were used in an unsupervised clustering analysis and qualitatively compared with the data from the fractions of ejaculation from the volunteers. Semen quality parameters and pregnancy outcomes were compared between patient clusters.Results: The early fraction of volunteers was characterized by lower phosphorus and arsenic and 18 other higher TEs than the subsequent fraction. Cluster analysis classified patients into four distinct clusters, one sharing characteristics with the early fraction and another with the subsequent fraction. One cluster with the early fraction characteristics had significantly lower semen volume and higher pregnancy rates from spontaneous pregnancies or intrauterine insemination.Conclusions: Classification of patients based on SP/serum ratios of multiple TEs represents the dominance of fractions of ejaculation samples.