Comprehensive identification of sphingolipid species by in silico retention time and tandem mass spectral library

Additional file 1. Figure S1 The fragment assignments of 12 sphingolipid classes. The annotations were combinatorially performed by hydrogen rearrangement rules in combination with substantial manual curation. The original spectra were obtained from LC/MS data of some biological samples including human cells, mouse tissues, and plant species

A Simple and Descriptive Assessment of Morphology Based on the Horizontal Plane of the Pediatric Head and Creation of a Normative Database in Japanese Children 6 Years Old and under: Horizontal Vector Analysis

We herein introduce horizontal vector analysis, a simple method for assessing cranial morphology based on measurement of the head’s horizontal plane, and use this method to establish normal cranial morphology in Japanese children Computed tomography scans taken in 2010-2019 in healthy Japanese children aged ≤ 6 years. The two measurement planes were parallel to the orbitomeatal plane: namely, a plane passing through the dorsum sellae (DS) and the plane superior to that with the maximal area (Max plane). A protractor was used to circumferentially measure the lengths from the central point to the outer surface of the skull. A total of 487 images were extracted. The distances between the DS and Max planes were consistently almost 30 mm for each age group, so we fixed the Max plane as the plane 30 mm superior to the DS plane. Finally, we established datasets of normal values for each age group and sex. Using these norms, perioperative evaluation of various cranial deformities could be performed more easily and circumstantially

Prevention of contrast-induced nephropathy by chronic pravastatin treatment in patients with cardiovascular disease and renal insufficiency

SummaryBackgroundContrast-induced nephropathy (CIN) is known to increase morbidity and mortality of cardiovascular disease. Recent studies have shown statins prevented CIN after contrast media exposure, but optimal statin type and dosage are still unknown.PurposeThe aims of the present study were to evaluate whether chronic pravastatin treatment before scheduled coronary angiography or percutaneous coronary intervention could reduce the incidence of CIN and to elucidate the factors related to CIN in patients with renal insufficiency.MethodsWe studied 431 consecutive patients with renal insufficiency. One hundred ninety-four patients were receiving pravastatin treatment as standard chronic treatment of hypercholesterolemia. Serum creatinine levels were measured at baseline (pre-procedure) and within 48h after contrast media exposure (peak post-procedure). CIN was defined as an increase in the serum creatinine values of ≥25% or ≥0.5mg/dl after contrast media exposure. Logistic regression analysis was performed to evaluate the important factors related to CIN using four variables: age, pravastatin, pre-procedure serum creatinine, and contrast volume.ResultsCIN was observed in 36 patients (8.4%). Patients without pravastatin (p<0.01), high level pre-procedure serum creatinine (p<0.01), and high contrast volume (p=0.034) had a significantly higher incidence of CIN. Logistic regression analysis revealed that pravastatin treatment (χ2=6.549, p=0.011, odds ratio=0.34), pre-procedure serum creatinine (χ2=6.294, p=0.009, odds ratio=2.78), and contrast volume (χ2=4.484, p=0.034, odds ratio=1.01) were independently related to the decreased risk of CIN.ConclusionsChronic pravastatin treatment before contrast media exposure was important for preventing CIN in patients with renal insufficiency. Also, reducing the dose of contrast media was important for preventing CIN in patients with high-baseline serum creatinine levels

Inhibition of Plasminogen Activator Inhibitor- 1 Attenuates Transforming Growth Factor- β-Dependent Epithelial Mesenchymal Transition and Differentiation of Fibroblasts to Myofibroblasts

Transforming growth factor-β (TGF-β) is central during the pathogenesis of pulmonary fibrosis, in which the plasminogen activator inhibitor-1 (PAI-1) also has an established role. TGF-β is also known to be the strongest inducer of PAI-1. To investigate the link between PAI-1 and TGF-β in fibrotic processes, we evaluated the effect of SK-216, a PAI-1-specific inhibitor, in TGF-β-dependent epithelial-mesenchymal transition (EMT) and fibroblast to myofibroblast differentiation. In human alveolar epithelial A549 cells, treatment with TGF-β induced EMT, whereas co-treatment with SK-216 attenuated the occurrence of EMT. The inhibition of TGF-β-induced EMT by SK-216 was also confirmed in the experiment using murine epithelial LA-4 cells. Blocking EMT by SK-216 inhibited TGF-β-induced endogenous production of PAI-1 and TGF-β in A549 cells as well. These effects of SK-216 were not likely mediated by suppressing either Smad or ERK pathways. Using human lung fibroblast MRC-5 cells, we demonstrated that SK-216 inhibited TGF-β-dependent differentiation of fibroblasts to myofibroblasts. We also observed this inhibition by SK-216 in human primary lung fibroblasts. Following these in vitro results, we tested oral administration of SK-216 into mice injected intratracheally with bleomycin.We found that SK-216 reduced the degree of bleomycin-induced pulmonary fibrosis in mice. Although the precise mechanisms underlying the link between TGF-β and PAI-1 regarding fibrotic process were not determined, PAI-1 seems to act as a potent downstream effector on the pro-fibrotic property of TGF-β. In addition, inhibition of PAI-1 activity by a PAI-1 inhibitor exerts an antifibrotic effect even in vivo. These data suggest that targeting PAI-1 as a downstream effector of TGF-β could be a promising therapeutic strategy for pulmonary fibrosis

Association between tranexamic acid administration and mortality based on the trauma phenotype: a retrospective analysis of a nationwide trauma registry in Japan

Tachino J., Seno S., Matsumoto H., et al. Association between tranexamic acid administration and mortality based on the trauma phenotype: a retrospective analysis of a nationwide trauma registry in Japan. Critical Care 28, 89 (2024); https://doi.org/10.1186/s13054-024-04871-w.Background: In trauma systems, criteria for individualised and optimised administration of tranexamic acid (TXA), an antifibrinolytic, are yet to be established. This study used nationwide cohort data from Japan to evaluate the association between TXA and in-hospital mortality among all patients with blunt trauma based on clinical phenotypes (trauma phenotypes). Methods: A retrospective analysis was conducted using data from the Japan Trauma Data Bank (JTDB) spanning 2019 to 2021. Results: Of 80,463 patients with trauma registered in the JTDB, 53,703 met the inclusion criteria, and 8046 (15.0%) received TXA treatment. The patients were categorised into eight trauma phenotypes. After adjusting with inverse probability treatment weighting, in-hospital mortality of the following trauma phenotypes significantly reduced with TXA administration: trauma phenotype 1 (odds ratio [OR] 0.68 [95% confidence interval [CI] 0.57–0.81]), trauma phenotype 2 (OR 0.73 [0.66–0.81]), trauma phenotype 6 (OR 0.52 [0.39–0.70]), and trauma phenotype 8 (OR 0.67 [0.60–0.75]). Conversely, trauma phenotypes 3 (OR 2.62 [1.98–3.47]) and 4 (OR 1.39 [1.11–1.74]) exhibited a significant increase in in-hospital mortality. Conclusions: This is the first study to evaluate the association between TXA administration and survival outcomes based on clinical phenotypes. We found an association between trauma phenotypes and in-hospital mortality, indicating that treatment with TXA could potentially influence this relationship. Further studies are needed to assess the usefulness of these phenotypes. Graphical abstract: (Figure presented.

RNA-binding protein ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with nanos3

Manami SENOO, Hiroshi HOZOJI, Yu ISHIKAWA-YAMAUCHI, Takashi TAKIJIRI, Sho OHTA, Tomoyo UKAI, Mio KABATA, Takuya YAMAMOTO, Yasuhiro YAMADA, Masahito IKAWA, Manabu OZAWA, RNA-binding protein Ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with Nanos3, Journal of Reproduction and Development, 2020, Volume 66, Issue 5, Pages 459-467, Released October 13, 2020, [Advance publication] Released July 06, 2020, Online ISSN 1348-4400, Print ISSN 0916-8818, https://doi.org/10.1262/jrd.2020-060, https://www.jstage.jst.go.jp/article/jrd/66/5/66_2020-060/_article/-char/e

Measurement of Ionized Calcium as Supplementary Marker of Bone Metastasis in Breast Cancer

The serum concentrations of ionized calcium (iCa), corrected automatically for serum pH, were measured in 67 cases with breast cancer (16 positive cases and 51 negative cases for bone metastasis). The serum concentration of iCa in the cases of positive bone metastasis was significantly higher than that in the negative cases (p<0.005). As osteoclastic bone metastasis occurred frequently in breast cancer, the measurements of serum concentrations of iCa might be of help as a supplementary marker of the diagnosis of bone metastasis

Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation

The roles of autoimmune regulator (Aire)–expressing medullary thymic epithelial cells (mTECs) in the organization of the thymic microenvironment for establishing self-tolerance are enigmatic. We sought to monitor the production and maintenance of Aire-expressing mTECs by a fate-mapping strategy in which bacterial artificial chromosome transgenic (Tg) mice expressing Cre recombinase under the control of the Aire regulatory element were crossed with a GFP reporter strain. We found that, in addition to its well recognized expression within mature mTECs, Aire was expressed in the early embryo before emergence of the three germ cell layers. This observation may help to explain the development of ectodermal dystrophy often seen in patients with AIRE deficiency. With the use of one Tg line in which Cre recombinase expression was confined to mTECs, we found that Aire+CD80high mTECs further progressed to an Aire−CD80intermediate stage, suggesting that Aire expression is not constitutive from after its induction until cell death but instead is down-regulated at the beginning of terminal differentiation. We also demonstrated that many mTECs of Aire-expressing lineage are in close contact with thymic dendritic cells. This close proximity may contribute to transfer of tissue-restricted self-antigens expressed by mTECs to professional antigen-presenting cells