Nihon Pharmaceutical University

BackgroundWith no approved pharmacological treatments for non-alcoholic fatty liver disease (NAFLD) in Taiwan, identifying protective and risk factors is crucial for preventing disease progression. Given the clinical heterogeneity of NAFLD, this study aimed to identify clinically meaningful NAFLD phenotypes using electronic medical records (EMRs) and unsupervised clustering, stratify risk across different clusters, identify factors associated with disease progression, and derive a parsimonious set of predictors for high-risk phenotypes.MethodsThis study was a retrospective cohort study conducted in three steps with iterative model training. In step 1, patients diagnosed with NAFLD were identified, and all relevant patient data were extracted, followed by clustering analysis using the k-prototype algorithm. In step 2, survival analysis and Cox regression were applied to perform risk stratification across clusters. In step 3, Lasso regression, logistic regression, and receiver operating characteristic (ROC) curve analysis were used to identify potential protective and risk factors associated with NAFLD and to derive a parsimonious set of predictors for high-risk phenotypes across different risk strata.ResultsStep 1: The analysis of 6,023 patients identified four distinct phenotypic clusters. The first cluster had the most severe disease, the second the least. Step 2: Among 4,998 patients, the first cluster faced the highest risk for all outcomes, with a median survival of 3.06 years, significantly different from the others. There was no significant risk difference between the second and third clusters. Step 3: A comparison of the highest-risk and lowest-risk clusters finally identified 17 potential variables.ConclusionsUsing multiple analytical models, this study identified 17 potential risk factors associated with NAFLD progression. Their combined assessment may inform future risk stratification and hypothesis generation. Further validation is required before clinical application.

Background/Objectives: Oral microbial homeostasis is crucial for overall health. Nonetheless, the relationship between probiotics and the oral environment remains unclear. This study investigated the association between continuous consumption of yogurt containing Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (LbR1 yogurt), salivary antimicrobial proteins (AMPs), tongue-coating microbiota, and upper respiratory tract infection (URTI) frequency. Methods: This observational study was conducted on 53 nursing home care workers, categorized into a group who consumed LbR1 yogurt daily for over 1 year (n = 40, yogurt group) and a non-intake group (n = 13, non-yogurt group). Salivary and tongue-coating samples were collected. Results: The yearly URTI frequency was lower in the yogurt group than in the non-yogurt group (p = 0.003). The salivary β-defensin-2 (HBD2) and β-defensin-3 (HBD3) flow rates were higher in the yogurt group than in the non-yogurt group (p = 0.02 and p = 0.0009, respectively). Fusobacterium nucleatum (F. nucleatum) ssp. animalis abundance was lower in the yogurt group than in the non-yogurt group (p = 0.04). Bayesian network analysis indicated an association between yogurt consumption and the yearly URTI frequency and salivary HBD2 and HBD3 flow rates. Conclusions: Continuous consumption of LbR1 yogurt was associated with elevated salivary HBD2 and HBD3, reduced abundance of F. nucleatum ssp. animalis, and decreased URTI frequency. Thus, LbR1 yogurt intake is associated with modulated oral immunity and microbiota, suggesting a potential link to reduced URTIs. However, as an observational pilot study, its results should be interpreted with caution.

The emergence of SARS-CoV-2, the etiological agent of COVID-19, has resulted in widespread global infection and millions of deaths. Viral entry is initiated by the interaction between the viral spike (S) protein and the host cell receptor ACE2, followed by TMPRSS2-mediated proteolytic activation that facilitates membrane fusion. Bitter melon (Momordica charantia L., MC), a traditional medicinal and edible plant widely used in tropical Asia, possesses notable anti-inflammatory, antioxidant, antitumor, and hypoglycemic properties. In this study, the ethanol extract of bitter melon (EMC) markedly downregulated ACE2 and TMPRSS2 expression in both in vitro and in vivo models without inducing cytotoxicity. Furthermore, phytochemicals isolated from EMC—including p-coumaric acid, rutin, and quercetin—exhibited comparable inhibitory effects. These results indicate that EMC and its bioactive constituents may interfere with SARS-CoV-2 entry by modulating the ACE2/TMPRSS2 axis, highlighting their potential as natural adjuncts for COVID-19 prevention or management.

We aimed to specify the characteristics of group A Streptococcus M1 (n = 23) or non-M1 (n = 282) isolates from adult (n = 176) and pediatric (n = 129) populations in central Japan, October 2024-April 2025. Of the speA-possessing fourteen non-M1 isolates, there were seven emm3.93 isolates from six non-invasive samples of pediatric patients and one invasive specimen of an adult patient. We found the distribution of M1 clones containing M1_global (n = 1)/M1_13snps (n = 4)/M1_UK (n = 18)-lineages in central Japan of Tokyo/Chiba/Tochigi/Saitama/Kanagawa. The M1 clones were from twenty-one non-invasive samples of pediatric/adult patients and two invasive specimens of adult patients. Additionally, we determined the sic nucleotide alleles and observed the M1_global/M1_13snps/M1_UK sic clustering. Of the CovS amino acid (AA) mutations among M1, there was an insertion of transposase (ISAs1-like IS1548 transposase, 377 AA) into CovS histidine kinase-like ATPase domain (following AA position 458) of one invasive M1_UK isolate. Our observations suggest that CovS AA mutations of invasive isolates with M1_UK should be specified within its four functional domains to evaluate their hypervirulent properties.

IntroductionHypertension is one of the most critical public health problems in developing countries and a leading cause of mortality and disability. Relevant extrapolations show that the global adult population with high blood pressure will increase significantly. This study utilizes partial data from the Taiwan Biobank to explore the association between clinical examinations and hypertension-related morbidities.MethodsData for this study were sourced from the Taiwan Biobank, which has collected health information since 2012 and serves as a partial source for scientific research into lifestyle and health trends of cardiovascular-related diseases in the general population. This study focused on distinguishing the correlation between blood pressure changes and stability in various age groups and exploring the relationship between environmental exposure factors and health behaviors through stratified analysis.ResultsThe comorbidities identified as significant risk factors for hypertension include hyperlipidemia [odds ratio (OR), 4.0504] and diabetes (OR, 2.1871). Clinical biochemistry examinations also indicated classifiers for hypertension, such as age, heart rate, triglycerides, high-density lipoprotein cholesterol, hyperlipidemia, and diabetes, which were represented as explanatory indicators [the area under the receiver operating characteristic curve (AUROC), 0.8769]. These findings underscore the potential of clinical examinations to predict and prevent hypertension.ConclusionThis study suggested the possibility of developing a risk assessment tool based on these classifiers and investigated the generalizability of these findings using biobank resources. The findings could aid in informing clinical decision-making, enhancing digital health education, and reducing the burden of hypertension.

Abstract Spinal cord injury (SCI) triggers secondary pathophysiological cascades, including glutamate excitotoxicity, that result in neuronal loss and impair functional recovery. We have previously shown that lysophosphatidylethanolamine (LPE), a lysophospholipid, promotes neurite outgrowth and protects against glutamate excitotoxicity in cultured cortical neurons. However, whether these effects extend to spinal cord neurons and occur in vivo has remained unclear. In this study, we compared the effects of different LPE species: myristoyl-LPE (14:0 LPE), palmitoyl-LPE (16:0 LPE), stearoyl-LPE (18:0 LPE), and oleoyl-LPE (18:1 LPE) in cultured spinal commissural neurons, and evaluated their effects in vivo using a mouse model of SCI. In cultured neurons, all LPE species promoted neurite outgrowth. Although several species demonstrated a tendency toward neuroprotection, only 16:0 LPE exhibited a statistically significant protective effect against glutamate-induced excitotoxic cell death. Intrathecal administration of 16:0 LPE after SCI reduced TUNEL-positive cells in the acute phase and attenuated lesion expansion at 8 weeks post-injury. Moreover, 5-HT fluorescence intensity was increased in 16:0 LPE-treated mice, suggesting enhanced serotonergic innervation. Furthermore, administration of 16:0 LPE after SCI significantly improved hind-limb motor performance compared with vehicle controls, as assessed by the Basso Mouse Scale. Collectively, these findings suggest that intrathecal administration of 16:0 LPE reduces secondary injury and promotes functional recovery following SCI. Our findings highlight its potential as a therapeutic candidate for SCI.

Porcine liver decomposition product (PLDP) is a functional food that enhances delayed memory recall and frontal lobe function in humans and exerts antidepressant and anxiolytic effects. In the present study, the previously unexplored anti-inflammatory effects of PLDP were investigated both in vitro and in vivo. The effects of PLDP on interleukin (IL)-1β production were examined in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and on their transition to an M1 or M2 phenotype. The effects of PLDP administered 30 min before the initiation of a formalin-induced inflammation-related behavior were also evaluated. Furthermore, the effects of PLDP on LPS-induced inflammation related to cytokine production and behavior in vivo were examined. PLDP was orally administered for five consecutive days and 24 h after LPS administration the mice were evaluated in an open field test and plasma cytokine production was measured. PLDP and its lipid fraction, PLDP extracted lipids (PEL) suppressed LPS-induced IL-1β production. Flow cytometry revealed that PEL shifted Raw 264.7 cells to the M2 phenotype. Moreover, PEL reduced phase 2 inflammation-related behavior in formalin-induced inflammation. In the LPS-induced inflammation model, PLDP improved the LPS-attenuated locomotor activity and exploratory behavior and reduced the increased plasma interferon-γ levels. These results suggest that PLDP exerts anti-inflammatory effects and shifts macrophages to the M2 phenotype. Furthermore, our results indicate that the lipid components in PLDP, especially phospholipids, could exert considerable central neuroprotective effects.

Gfi-1B is a hematopoietic transcription factor essential for growth and differentiation of the erythroid/megakaryocytic lineages, and PU.1 is a master regulator for myeloid development. Herein, we demonstrate that PU.1 interacted with Gfi-1B in vivo by immunoprecipitation assay. GST pull-down assays showed that the binding sites were located in the Ets domain of PU.1 and the zinc finger domain of Gfi-1B. Luciferase reporter assays revealed that PU.1 and Gfi-1B antagonized each other's transcriptional activity in a dose-dependent manner. The transduction of Gfi-1B alone in human cord blood progenitor cells strongly enhanced erythroid colony formation. However, the transduction of PU.1 along with Gfi-1B in the progenitors significantly inhibited erythroid colony formation. Co-expression of Gfi-1B with a mutant PU.1, which bound to Gfi-1B but not to GATA1, another erythroid master regulator, also inhibited Gfi-1B-induced erythroid colony formation. Our results suggest that the function of Gfi-1B in the growth and differentiation of erythroid cells is antagonized by the expression of PU.1.

Abstract BackgroundMore than 500 randomized controlled trials (RCTs) were selected from various databases by the evidence‐based medicine committee of the Japan Society for Oriental Medicine (JSOM). Their structured abstracts have been published in Japanese and English in “Evidence Reports of Kampo Treatment.”MethodsFrom among these RCTs, “Kampo Best RCTs” were selected according to impact factor and number of Google Scholar citations.ResultsFour of the authors in this article presented their data at a symposium at the 74th Congress of the JSOM in June 2024. Kazunari Tominaga was elected as the No. 1 author among the best RCTs. His two articles described the effects of rikkunshito on functional dyspepsia and non‐erosive gastroesophageal reflux disease, respectively. Hidekazu Suzuki was elected as No. 2. His article described the effect of rikkunshito on functional dyspepsia. The No. 3 author, Toshimi Kaido, and No. 4 author, Chu Matsuda, described the effects of daikenchuto on adult gastrointestinal disorder following liver transplant and the effects of hangeshashinto on chemotherapy‐induced stomatitis, respectively. These four articles were all based on double‐blind RCTs. Although a range of hardships were encountered during the studies, these RCTs were reported in original articles, providing clinical evidence of high international reputation.ConclusionHere, we describe the details and the hardships encountered by the authors, identify points to note in the interpretation of clinical trial results, and finally mention the current status and future prospects of Kampo RCTs.