Search Results (110)

Human milk oligosaccharides (HMOs) have garnered significant attention as one of the bioactive components in human milk, with growing applications in infant formula and food products. HMOs enhance butyrate production, which is produced by butyrate-producing bacteria such as Faecalibacterium prausnitzii and contributes to gut health through its diverse biological functions. However, the specific mechanisms by which individual HMOs promote butyrate production remain unclear. In this study, we conducted in vitro co-culture experiments of F. prausnitzii and Bifidobacterium bifidum, examining their relative abundance, fatty acid production, residual sugar levels, and gene expression. Our results revealed that B. bifidum utilizes HMOs and provides the constituent sugars to F. prausnitzii, thereby promoting butyrate production by F. prausnitzii. Furthermore, we found that the underlying mechanisms vary depending on the structure of the HMOs. Specifically, 2′-fucosyllactose and 3′-sialyllactose enhance the butyrate production efficiency of F. prausnitzii, while 6′-sialyllactose primarily promotes the growth of F. prausnitzii. These findings not only deepen our understanding of how HMOs influence infant gut health but also suggest new directions for developing nutritional products that leverage the distinct functional properties of each HMO. Full article

Precious corals from the Corallidae family (Corallium, Hemicorallium, and Pleurocorallium genera) are well known in the high-end jewelry industry due to their colorful and durable axial skeleton. They exist in various colors from white to pink to dark red. One highly appreciated shade is the light pink color, the so-called ‘angel skin’. This color is most often associated with Pleurocorallium elatius and Pleurocorallium secundum, species listed in CITES Appendix III. However, this has been based on an assumption of their visual similarity and has never been underpinned by detailed morphologic or genetic data. In this study, we present the analysis of an ‘angel skin’ coral necklace of exceptional size and homogeneous color and quality. Visual observation and Raman spectroscopy confirmed that the necklace consists of genuine, untreated precious coral material. Following minimally destructive sampling, respectively, drilling 2.2, 2.4, and 2.4 milligrams of material from the existing drill-holes, three randomly selected beads from the necklace were subject to a routine genetic identification assay, which is based on sequencing a short, taxonomically informative mitochondrial region. This genetic analysis identified the coral material as not from P. elatius or P. secundum but from another Pleurocorallium species. We subsequently sequenced additional mitochondrial DNA fragments from one ‘angel skin’ coral bead and compared them against a well-represented, curated reference data set of Pleurocorallium, including the first-ever sequencing of Pleurocorallium gotoense, Pleurocorallium johnsoni, Pleurocorallium cf. pusillum, and Pleurocorallium uchidai. We concluded that the analyzed material of the ‘angel skin’ coral necklace belongs to the Pleurocorallium norfolkicum species complex but is not identical to any hitherto analyzed and published Pleurocorallium specimens. A comparison with further taxonomically unidentified precious coral colony fragments identified a single sample fished in Vietnam to be completely identical to the ‘angel skin’ coral bead in the studied DNA regions. Thus, by the analysis of a high-end jewel, we discovered a species new to the jewelry trade and potentially also unknown to science. This implies that the currently considered list of species present in the precious coral trade is incomplete. Full article

Background: Bronchoalveolar lavage fluid (BALF) analysis is essential for the accurate diagnosis and management of interstitial lung diseases (ILDs). Despite established guidelines, variability in sample handling may affect diagnostic accuracy. This study aimed to evaluate how different storage conditions impact BALF cell counts and differentials to guide optimal sample handling practices. Methods: Forty patients who underwent BAL at Chiba University Hospital from June to December 2024 were included. BALF samples were allocated into five groups based on processing conditions: immediate analysis within 1 h, storage at either at 4 °C or room temperature (RT) for 6 h, or storage at 4 °C or RT for 24 h. Total cell counts (TCC) and differential counts were measured and compared among conditions. Results: TCC remained stable over 24 h at both 4 °C (p = 0.86) and RT (p = 0.90). Similarly, the percentages of eosinophils, lymphocytes, and macrophages did not significantly change at either temperature (all p > 0.05). Notably, neutrophil percentages showed a significant decline over time under both storage conditions—at 4 °C (p = 0.02) and at room temperature (p < 0.01). Post hoc tests revealed a notable decreasing trend at 6 h and significant reductions by 24 h at 4 °C (p = 0.09 and p = 0.02, respectively), and significant decreases at both 6 and 24 h at RT (p = 0.01, <0.01). Conclusions: Among the various cell types in BALF, neutrophil proportions are particularly susceptible to storage conditions, showing a significant decline over time—especially at room temperature—while other cell types remain stable for up to 24 h. Therefore, prompt processing or appropriate refrigeration of BALF is essential to ensure reliable cytological analysis and accurate clinical interpretation. Full article

We demonstrate a rapid and sensitive boron detection method through current amplification mediated by supramolecular interaction. Oxidation peak currents obtained by cyclic voltammetry (CV) measurements of a ferrocene/catechol-functionalized β-cyclodextrin inclusion complex were amplified through an EC’ reaction (where EC’ denotes an electrochemical step followed by a catalytic chemical step). However, the amplified current was decreased by boric acid (the primary form of boron in water) addition at pH 8.6 owing to interactions of boron with the cis-diol structure of dihydroxybenzoic acid-β-cyclodextrin and ferrocene for ester formation. We determined the optimum CyD functionalization sites and measurement conditions and obtained a limit of detection of 0.16 mg B L⁻¹ for ferrocene/3,4-dihydroxybenzoic acid-β-cyclodextrin (Fc/3,4-DHBA-β-CyD). The binding constant (assuming a 1:1 binding model) for the interaction between Fc/3,4-DHBA-β-CyD and boric acid was estimated to be approximately 1500 M⁻¹. Boron concentrations in spiked real samples showed good recoveries and linear calibration curves. The electrochemical response of this system was not significantly affected by the presence of other anions or cations. We also found that an aqueous solution of 3,4-DHBA-β-CyD remained stable for at least 112 days. Full article

Introduction: The significant impact of nonalcoholic fatty liver disease (NAFLD) on public health, combined with the limitations of current diagnostic approaches, demands a more comprehensive and accurate method to identify NAFLD cases in large general populations. Methods: In this cross-sectional study, we recruited 3733 individuals (average age 51.8 years) who underwent health check-ups between October 2015 and October 2016. NAFLD was diagnosed using ultrasound; 114 serum metabolites were measured using gas chromatography–mass spectrometry. We adopted the least absolute shrinkage and selection operator (LASSO) method to build a metabolomic-based diagnostic model. Results: NAFLD was diagnosed in 826 participants. While each metabolite exhibited a limited diagnostic ability for NAFLD when used individually, compared with BMI, the model constructed using the LASSO demonstrated adequate diagnostic power (area under the curve [AUC] 0.866, 95% confidence interval 0.847–0.885 in test set) and even for lean (BMI < 23) populations (AUC for LASSO 0.828, for BMI 0.78). Moreover, the LASSO model-derived ‘pre-NAFLD’ condition showed a potential association with insulin resistance and elevated triglycerides. Conclusions: Our metabolomic-based approach provides a comprehensive evaluation of NAFLD or ‘pre-NAFLD’, both considered parts of a hypothetical ‘NAFLD spectrum’, independent of body type. Metabolomics could offer additional diagnostic benefits and potentially expand the disease concept. Full article

Wind conditions play a significant role in wind power generation. Offshore wind turbines in Japan are located in areas with a shorter fetch compared with those in Europe, raising concerns about more significant coastal effects on offshore wind conditions. Therefore, we conducted observations using unmanned aerial vehicles (UAVs) to investigate coastal effects on offshore wind conditions in Japan, measuring the vertical structure of meteorological parameters at multiple nearshore locations. We explored the application of data pre-processing methods to focus on the spatial variations caused by coastal effects and minimize short-term fluctuations. The results indicated that using ensemble averages of multiple vertical profiles effectively reduced short-term fluctuations. Our UAV observations revealed that stable stratification developed even within the 1300 m fetch region, with rapid growth rates. Additionally, we found that wind speeds were independent of height in some cases, suggesting that the wind profile power law is not suitable for expressing the vertical profiles of wind speed. Full article

Background/Objectives: Sloths, a group of xenarthran mammals currently comprising six recognized distinct species, have been the focus of much physiological animal research due to their extremely slow metabolisms, deliberate movements, and their status as a species relatively unchanged for over 26 million years. However, despite all the effort aimed at understanding these unique characteristics, the sloth genome remains largely unexplored. Due to the link between genetics and observed traits, such an investigation could potentially lead to insights regarding the genetic basis of unique sloth behaviors and characteristics, such as slow movement, low metabolism, and longevity. Methods: In this exploratory investigation, we performed whole genomic and transcriptomic analysis of a female Choloepus didactylus (Linnaeus’s Two-Toed Sloth). Through whole genome sequencing (WGS), the genetic overlap between female two-toed sloths and female humans was estimated in line with evolutionary biology. Results: Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) showed significant differences between gene expression levels in two-toed sloths and humans related to metabolism, body temperature control, cell cycle regulation, telomere maintenance, circadian rhythm regulation, and cancer prevention. Conclusions: The discovered differences imply a relationship to the low metabolisms, slow movements, and longevity displayed by sloths. Future exploratory research will include additional testing to determine if these findings are universal among all recognized sloth species, as well as to address the relationship between specific gene and protein functions and observed traits. Full article

Background/Objectives: Postoperative analgesia is important for reducing biologically invasive reactions to surgery. In Japan, postoperative analgesia, including indices of analgesia, has not been adequately addressed. This study aimed to determine the relationship between postoperative pain and postoperative course and the importance of analgesia for early recovery. Methods: Patients who underwent any of seven surgical procedures in gastrointestinal, thoracic, and cardiac surgery were enrolled. The primary endpoint was a median Prince Henry Pain Scale score from postoperative days 1 to 3. Secondary endpoints were the quality of recovery on postoperative day 7 (Quality of Recovery-15 [QoR-15]) and the length of postoperative hospital stay. Results: Median postoperative pain levels among surgeries were 3 on day 1, 2 on days 2 and 3, 1 on day 7, and 1 at discharge. In both univariate and multivariate analyses, the use of postoperative epidural analgesia and intravenous patient-controlled analgesia (IV-PCA) were significant predictors of early postoperative pain. Only early postoperative pain was a significant predictor of QoR-15 score. Regular use of acetaminophen, early postoperative pain, no appetite, and postoperative complications were significant in affecting the length of postoperative hospital stay. In the comparison of early postoperative pain according to whether epidural analgesia and IV-PCA were used, the group that used both methods had the least pain. Conclusions: In Japan, early postoperative pain persists after major surgical procedures and affects postoperative quality of recovery and length of hospital stay. The use of epidural analgesia, IV-PCA, or both appeared to be effective in overcoming early postoperative pain, thereby enhancing early postoperative recovery. Full article

The involvement of drug-metabolizing enzymes and transporters in plasma clozapine (CLZ) dynamics has not been well examined in Japanese patients with treatment-resistant schizophrenia (TRS). Therefore, this clinical study investigated the relationship between single nucleotide polymorphisms (SNPs) of various pharmacokinetic factors (drug-metabolizing enzymes and transporters) and dynamic changes in CLZ. Additionally, we aimed to determine whether CLZ acts as a substrate for pharmacokinetic factors using in vitro assays and molecular docking calculations. We found that 6 out of 10 patients with TRS and with multiple organic anion transporting polypeptide (OATP) variants (OATP1B1: *1b, *15; OATP1B3: 334T>G, 699G>A; and OATP2B1: *3, 935G>A, 601G>A, 76_84del) seemed to be highly exposed to CLZ and/or N-desmethyl CLZ. A CLZ uptake study using OATP-expressing HEK293 cells showed that CLZ was a substrate of OATP1B1 with K_m and V_max values of 38.9 µM and 2752 pmol/mg protein/10 min, respectively. The results of molecular docking calculations supported the differences in CLZ uptake among OATP molecules and the weak inhibitory effect of cyclosporine A, which is a strong inhibitor of OATPs, on CLZ uptake via OATP1B1. This is the first study to show that CLZ is an OATP1B1 substrate and that the presence of SNPs in OATPs potentially alters CLZ pharmacokinetic parameters. Full article

Stress and anxiety are significant psychological challenges in modern society, which have led to a rapidly growing market for functional foods, including those reported to relieve stress, as alternatives to psychoactive drugs. Among these, diacyl glyceryl ethers (DAGE) derived from deep-sea shark liver oil have gained attention for their strong antioxidant properties and potential mental health benefits. Building on preliminary evidence suggesting DAGE’s efficacy in enhancing stress resilience and modulating biochemical pathways associated with reduced oxidative stress, the present study aimed to examine their effects on stress responses in two specific mouse strains. Each mouse was fed either a DAGE-infused diet or a control diet for three weeks. Their stress responses were evaluated using three behavioral tests: the elevated plus maze, open-field, and forced swimming tests. The DAGE-fed mice displayed lower stress responses than the control mice in the initial trial of each test. Specifically, DAGE-fed mice demonstrated increased time spent in the open arms in the elevated plus maze and more time spent in the center of the open field, suggesting reduced anxiety. Additionally, in the forced swimming test, DAGE-treated mice displayed reduced immobility times, indicating potential antidepressant effects on the mice. These findings suggest the potential of DAGE to bolster stress resilience in mice, emphasizing their promise for further studies in human stress management. Full article

Background: Acute pancreatitis (AP) severity is correlated with systemic infection incidence in the acute phase, and it is important to assess inflammation during the disease course and to recognize infection at an early stage. As in sepsis, inflammation in AP impairs tissue oxygen metabolism and disrupts microcirculation. We performed a vascular occlusion test (VOT) via near-infrared spectroscopy (NIRS), which noninvasively monitors local oxygen in peripheral tissues, to evaluate tissue oxygen metabolism and blood circulation during the acute AP phase. Methods: Tissue oxygen metabolism was measured via an NIRS probe attached to the thenar eminence at admission and 7 days after admission. The upper arm was wrapped with a sphygmomanometer cuff while avoiding brachial artery compression for 3 min. The minimum desaturation value was defined as the minimum tissue oxygen index (TOI), the maximum reactive hyperemia value after release was defined as the maximum TOI, and the difference was defined as the ∆TOI. The time from the minimum TOI to maximum TOI was defined as the TOI interval. Results: Fifteen healthy volunteers, 13 patients with AP, and 12 patients with sepsis were included. The TOI at baseline and ∆TOI (parameter describing tissue oxygen metabolism) decreased in a stepwise manner, and the TOI interval (measure of peripheral vasodilatory capacity) was protracted in a stepwise manner among the three groups. In a subgroup analysis, no significant differences in the NIRS-derived variables between patients with AP complicated by infection and those without infection were observed at admission; however, after 7 days, the groups significantly differed. Additionally, blood lactate concentrations were significantly correlated with the ∆TOI and TOI. Conclusions: Mild tissue oxygen metabolism impairment and tissue perfusion occurred in AP compared with sepsis, and changes similar to those in sepsis occur in AP complicated by infection. Further research is needed to evaluate whether these values can be applied to treating this group of patients. Full article

In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, its role in pulmonary fibroblasts in hypoxic PH remains unknown. Therefore, we aimed to clarify the mechanistic role of CD26/DPP4 in lung fibroblasts in hypoxic PH. Dpp4 knockout (Dpp4 KO) and wild-type (WT) mice were exposed to hypoxia for 4 weeks. The degree of PH severity and medial wall thickness was augmented in Dpp4 KO mice compared with that in WT mice, suggesting that CD26/DPP4 plays a suppressive role in the development of hypoxic PH. Transcriptome analysis of human lung fibroblasts cultured under hypoxic conditions revealed that TGFB2, TGFB3, and TGFA were all upregulated as differentially expressed genes after DPP4 knockdown with small interfering RNA treatment. These results suggest that CD26/DPP4 plays a suppressive role in TGFβ signal-regulated fibroblast activation under hypoxic conditions. Therefore, CD26/DPP4 may be a potential therapeutic target in patients with PH associated with chronic hypoxia. Full article

Background: Peroral cholangioscopy (POCS) is valuable for assessing malignant biliary strictures; however, biliary drainage prior to POCS often hinders accurate diagnosis. Objectives: This retrospective study aimed to investigate the feasibility of POCS using a newly developed cholangioscope, CHF-B290, during initial endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary strictures. Methods: This multicenter retrospective study included patients who underwent initial ERCP for malignant biliary strictures at two institutions between January 2018 and March 2022. Patients who underwent initial ERCP with POCS were classified into the POCS group, and those without POCS were classified into the non-POCS group. To prevent post-POCS cholangitis, the original irrigation system for CHF-B290 was used in all POCS examinations. The primary endpoint was the rate of post-ERCP biliary infections, and the secondary endpoints were other ERCP-related complications, including pancreatitis, bleeding, and perforation. Results: Overall, 53 and 94 patients were included in the POCS and non-POCS groups, respectively. For the primary endpoint, the rate of post-ERCP biliary infection was not significantly different between the two groups (1.9% vs. 5.3%, p = 0.42). For the secondary endpoints, no significant differences were observed in the rates of post-ERCP pancreatitis (5.7% vs. 6.4%, p = 1.00) and other ERCP-related complications. The overall complication rate was 9.4% in the POCS group and 13% in the non-POCS group (p = 0.60). Conclusions: POCS during the initial ERCP for malignant biliary strictures is feasible. Full article

Atopic dermatitis (AD) is characterized by chronic inflammation, barrier dysfunction, and pruritus, exacerbated by external stimuli, such as scratching. This study investigates the role of extracellular adenosine triphosphate (ATP) in the pathophysiology of AD and assesses the therapeutic potential of clodronate, an ATP release inhibitor. Our research demonstrates that extracellular ATP impairs skin barrier function by reducing the filaggrin expression in the keratinocytes, a critical protein for barrier integrity. Furthermore, ATP release, triggered by IL-4 and mechanical stimuli, amplifies inflammation by promoting cytokine and chemokine production by the immune cells. Clodronate, by inhibiting ATP release, restores the filaggrin levels in the keratinocytes, reduces TARC production in the dendritic cells, and alleviates AD symptoms in a mouse model. These findings suggest that targeting extracellular ATP could offer a novel therapeutic approach to improving skin barrier function and reducing inflammation in AD. Future studies should explore the long-term efficacy and safety of ATP-targeted therapies in clinical settings. Full article

Background: Patients with circulatory failure have high mortality rates and require prompt assessment of microcirculation. Despite the improvement in hemodynamic parameters, microcirculatory dysfunction persists. We measured subcutaneous regional tissue oxygen saturation (rSO₂) with near-infrared spectroscopy (NIRS), which can assess microcirculation in patients with circulatory failure. Methods: A finger-worn oximeter with NIRS measured rSO₂ in the forehead, thenar eminence, thumb, and knees. First, the rSO₂ was measured in healthy adult volunteers (n = 10). Circulatory failure was defined as a systolic blood pressure ≤ 90 mmHg and lactate ≥ 2 mmol/L. The study included 35 patients without circulatory failure and SOFA score of 0 at ICU admission and 38 patients with circulatory failure at ICU admission. Both groups included a single-center prospective study of patients who were transported to the ICU of the Nihon University Hospital. The rSO₂ was measured only on ICU admission in the non-circulatory failure group and later in the circulatory failure group. Results: In the volunteer group, rSO₂ at each site was approximately 58%. The rSO₂ was significantly lower in the circulatory failure group than in the non-circulatory failure group (knee, p < 0.01). In the circulatory failure group, knee rSO₂ showed a significant negative correlation with SOFA score (Day 0, ρ = −0.37, p = 0.02; Day 1, ρ = −0.53, p < 0.01; Day 2, ρ = −0.60, p < 0.01). Conclusions: Subcutaneous knee rSO₂ was associated with SOFA score and was considered an indicator of microcirculatory dysfunction and organ damage. Full article