Background: Alpha-fetoprotein (AFP) and its isoform AFP-L3 are well-established serum biomarkers for hepatocellular carcinoma (HCC), a common malignancy and a leading cause of cancer-related mortality worldwide. Current methods for measuring these biomarkers are primarily lectin-based assays including the liquid-phase binding assay (LiBA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), both of which have limitations in diagnostic sensitivity and clinical utility for samples with low AFP concentrations. We aimed to develop a lectin-independent LC-MS/MS method for quantifying fucosylated AFP proteins (AFP-Fuc%). Methods: We conducted analytical validation, including method comparisons, over 2 months. The analytical sensitivity and diagnostic performance of this method were evaluated using 525 human serum samples—235 from HCC patients and 290 from non-HCC individuals—and compared with those of LiBA, which measured AFP-L3 levels. Results: The LC-MS/MS method demonstrated acceptable within-laboratory imprecision (CVs < 17.1%) without detectable bias, carryover, or matrix effects. Our method exhibited a broader linear dynamic range (spanning five orders of magnitude) and 10-fold higher analytical sensitivity than LiBA. The diagnostic performance of our method was significantly superior to that of LiBA, particularly in patients with low AFP concentrations ( < 7 ng/mL, P < 0.001), with improved accuracy, sensitivity, and precision at a specificity of 96.2%. Conclusions The validated LC-MS/MS method demonstrated robust analytical performance and superior diagnostic accuracy over LiBA for HCC diagnosis while avoiding the inherent limitations of lectin-based assays. Our LC-MS/MS assay shows promise for early HCC detection and may contribute to enhanced patient care.

Objectives: . Obstructive sleep apnea (OSA) is associated with chronic intermittent hypoxia and systemic inflammation, both of which contribute to vascular and metabolic complications. Monocytes, as key immune cells of innate immunity, have been implicated in this inflammatory state. However, the effect of OSA treatment on monocyte function and inflammatory phenotype remains poorly understood. Methods: . In this prospective cohort study, OSA patients were evaluated before and after 3 months of continuous positive airway pressure (CPAP) therapy. Circulating monocytes were isolated, and inflammatory cytokine production (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) was assessed at baseline and post-treatment, both at rest and after lipopolysaccharide (LPS) stimulation. Monocyte polarization (M1/M2-like marker expression) was measured by flow cytometry. Clinical severity parameters, including the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), were correlated with immune changes. Results: . Following CPAP treatment, LPS-induced inflammatory cytokine secretion and LPS responsiveness, defined as the increase in cytokine levels upon stimulation, both declined after CPAP in proportion to baseline ODI, but not AHI. Apart from TNF-α, baseline IL-1β and IL-6 levels were below the quantifiable range of the assay, which precluded reliable comparison after treatment. This effect may be explained by a parallel post-treatment shift in monocyte phenotype toward an anti-inflammatory M2-like (CD163+CD206+) profile, as demonstrated by our flow cytometry data, which was also significantly associated with baseline ODI. Conclusion . CPAP alleviates systemic inflammation in OSA by reducing hypoxic burden and reprogramming monocytes toward an anti-inflammatory phenotype. The magnitude of immune modulation was more closely linked to ODI than AHI, suggesting that oxygen desaturation burden serves as a meaningful adjunct to AHI in assessing monocyte-driven immune dysregulation in OSA.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

The multiple layers of the skin cover and protect our entire body. Among the skin layers, the epidermis is in direct contact with the outer environment and serves as the first line of defense. The epidermis functions as a physical and immunological barrier. To maintain barrier function, the epidermis continually regenerates and repairs itself when injured. Interactions between tissue-resident immune cells and epithelial cells are essential to sustain epidermal regeneration and repair. In this review, we will dissect the crosstalk between epithelial cells and specific immune cell populations located in the epidermis during homeostasis and wound repair. In addition, we will analyze the contribution of dysregulated immune-epithelial interactions in chronic inflammatory diseases.

Background/Aims: Buspirone shows promise in treating disorders of gut–brain interaction (DGBIs), particularly functional dyspepsia. However, findings have been mixed. Methods: We systematically searched for prospective studies testing buspirone for any upper gastrointestinal DGBI in 4 databases (Cochrane, PubMed, Scopus, and PsycInfo). The primary outcome was any validated measure of gastrointestinal symptoms. Anxiety, depression and adverse events were secondary outcomes. For randomized controlled trials (RCTs), we performed random-effects meta-analysis of the standardized mean difference (SMD) in post-treatment scores between buspirone and control groups. Risk of bias in RCTs was assessed using the Cochrane Common Mental Disorders Depression Anxiety and Neurosis Group (CCDAN) scale. Results: Ten studies (n = 283) met inclusion criteria, comprising 5 RCTs, 1 N-of-1 trial, 1 cohort, 1 case series, and 2 case reports. Tolerability of buspirone was good. In meta-analysis, buspirone produced a non-significant improvement in functional dyspepsia/gastroparesis symptoms compared to placebo (SMD = –0.14; 95% CI, –0.44 to 0.17; P = 0.39; I 2 = 0%; N studies = 3). Of individual symptoms, buspirone improved bloating severity more than placebo (SMD = –0.41; 95% CI, –0.77 to –0.04; P = 0.03; N studies = 2) but did not improve post-prandial fullness (P = 0.24, N studies = 2) or nausea (P = 0.75, N studies = 2). All RCTs included in the meta-analysis were good quality but most treated for only 4 weeks. Conclusions We found that buspirone did not improve functional dyspepsia symptoms more than placebo, though studies were small. Buspirone showed benefit for bloating severity, albeit based on few studies. Larger and longer trials of buspirone, targeting more defined groups such as patients with bloating, are warranted.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Background/Aims: Buspirone shows promise in treating disorders of gut–brain interaction (DGBIs), particularly functional dyspepsia. However, findings have been mixed. Methods: We systematically searched for prospective studies testing buspirone for any upper gastrointestinal DGBI in 4 databases (Cochrane, PubMed, Scopus, and PsycInfo). The primary outcome was any validated measure of gastrointestinal symptoms. Anxiety, depression and adverse events were secondary outcomes. For randomized controlled trials (RCTs), we performed random-effects meta-analysis of the standardized mean difference (SMD) in post-treatment scores between buspirone and control groups. Risk of bias in RCTs was assessed using the Cochrane Common Mental Disorders Depression Anxiety and Neurosis Group (CCDAN) scale. Results: Ten studies (n = 283) met inclusion criteria, comprising 5 RCTs, 1 N-of-1 trial, 1 cohort, 1 case series, and 2 case reports. Tolerability of buspirone was good. In meta-analysis, buspirone produced a non-significant improvement in functional dyspepsia/gastroparesis symptoms compared to placebo (SMD = –0.14; 95% CI, –0.44 to 0.17; P = 0.39; I 2 = 0%; N studies = 3). Of individual symptoms, buspirone improved bloating severity more than placebo (SMD = –0.41; 95% CI, –0.77 to –0.04; P = 0.03; N studies = 2) but did not improve post-prandial fullness (P = 0.24, N studies = 2) or nausea (P = 0.75, N studies = 2). All RCTs included in the meta-analysis were good quality but most treated for only 4 weeks. Conclusions We found that buspirone did not improve functional dyspepsia symptoms more than placebo, though studies were small. Buspirone showed benefit for bloating severity, albeit based on few studies. Larger and longer trials of buspirone, targeting more defined groups such as patients with bloating, are warranted.

The multiple layers of the skin cover and protect our entire body. Among the skin layers, the epidermis is in direct contact with the outer environment and serves as the first line of defense. The epidermis functions as a physical and immunological barrier. To maintain barrier function, the epidermis continually regenerates and repairs itself when injured. Interactions between tissue-resident immune cells and epithelial cells are essential to sustain epidermal regeneration and repair. In this review, we will dissect the crosstalk between epithelial cells and specific immune cell populations located in the epidermis during homeostasis and wound repair. In addition, we will analyze the contribution of dysregulated immune-epithelial interactions in chronic inflammatory diseases.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.