Biol. Pharm. Bull. [JOURNAL]
Sun
200 papers
Role of the H19/miR-423-5p/DTX3L Axis in Enhancing the Malignant Phenotype of Nasopharyngeal Carcinoma Cells.
Jiang L, Wang C, Hu Q … +2 more , Xu S, Guo Q
Biol Pharm Bull · 2026 · PMID 41882821 · Publisher ↗
Deltex E3 ubiquitin ligase 3L (DTX3L) is a well-established ubiquitin ligase implicated in various cancers, but its role in nasopharyngeal carcinoma (NPC) progression remains elusive. In this study, we confirmed for the...
Deltex E3 ubiquitin ligase 3L (DTX3L) is a well-established ubiquitin ligase implicated in various cancers, but its role in nasopharyngeal carcinoma (NPC) progression remains elusive. In this study, we confirmed for the first time that DTX3L was highly expressed in C666-1 and NPC/HK1 NPC cells. DTX3L overexpression promoted NPC cell proliferation, invasion, and migration. Conversely, DTX3L knockdown suppressed these malignant phenotypes. Notably, DTX3L activated the β-catenin pathway, as evidenced by increased β-catenin nuclear translocation, increased transcriptional activity, and elevated expression of its downstream target c-Myc. Mechanistically, we identified an upstream regulatory axis in which the oncogenic long noncoding RNA H19 acted as a molecular sponge for miR-423-5p, thereby alleviating the miR-423-5p-mediated repression of DTX3L. Dual-luciferase reporter assays confirmed that miR-423-5p directly targeted both DTX3L and H19, supporting the presence of a competitive endogenous RNA (ceRNA) network. Furthermore, rescue experiments demonstrated that DTX3L knockdown largely abolished the proliferative advantage conferred by H19 overexpression. Collectively, the results of our study revealed that the H19/miR-423-5p/DTX3L axis is a novel ceRNA-driven mechanism that promotes NPC progression via activation of β-catenin signaling.
Aldosterone Accelerates Systolic Decline in Volume-Overload Heart Failure.
Cao X, Xie L, Nagasawa Y … +2 more , Aimoto M, Takahara A
Biol Pharm Bull · 2026 · PMID 41882820 · Publisher ↗
High-output heart failure (HF) occurs with sustained volume overload. Hence, clarifying how compensated high-output states transition to maladaptive HF is essential for developing interventions that preserve cardiac func...
High-output heart failure (HF) occurs with sustained volume overload. Hence, clarifying how compensated high-output states transition to maladaptive HF is essential for developing interventions that preserve cardiac function. Therefore, this study investigated the mechanism by which volume overload induced by aortocaval shunt (AVS) and aldosterone (Ald) affects the progression of myocardial function and structural remodeling. AVS was surgically induced in rats, and osmotic mini-pumps delivering Ald (1.0 μg·h) for 4 weeks were intraperitoneally implanted. Cardiac function and structure were serially assessed using echocardiography before surgery and at 4, 12, and 24 weeks under isoflurane. At 23 weeks, atrial natriuretic peptide was analyzed, and at 24 weeks, comprehensive electrophysiological, hemodynamic, morphometric, and histological examinations were performed to characterize cardiopathy. Early diastolic mitral annular velocity (E') remained relatively unchanged after 24 weeks, whereas early diastolic filling wave (E) velocity, atrial contraction wave velocity, and E/E' ratio increased. However, AVS did not markedly reduce systolic function; it was associated with progressive elevation of cardiac output, left ventricular hypertrophy, and dilation. Histological and morphometric analyses confirmed concentric hypertrophy, eccentric remodeling, and focal fibrosis. Ald induced similar diastolic changes and structural remodeling but caused an earlier decline in systolic function at 8 weeks. These findings demonstrate a 2-phase trajectory of high-output stress: an early compensated stage with elevated filling pressure, followed by a decompensated stage with progressive systolic decline. Moreover, Ald accelerates this systolic decline. Therefore, targeting Ald receptors in the early compensation phase may protect against systolic impairment caused by volume overload.
N, N'-Dicyclohexyl-N-linoleic Acylurea, an Unsaturated Fatty Acid Derivative Alleviates Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice.
Zhang T, Mo S, Luo H … +7 more , Ye G, Qin Q, Jiang M, Wang Y, Bi J, Zhang Z, Qi Z
Biol Pharm Bull · 2026 · PMID 41882819 · Publisher ↗
Multiple sclerosis is a chronic inflammatory disease characterized by demyelination in the central nervous system (CNS). The existing drugs for multiple sclerosis treatment carry significant side effects. The aim of this...
Multiple sclerosis is a chronic inflammatory disease characterized by demyelination in the central nervous system (CNS). The existing drugs for multiple sclerosis treatment carry significant side effects. The aim of this study was to investigate the safety and effect of a new compound N, N'-dicyclohexyl-N-linoleic acylurea (DCLAA) on experimental autoimmune encephalomyelitis (EAE), the principal multiple sclerosis animal model. Results showed that DCLAA had low toxicity, and DCLAA significantly inhibited the EAE progression and reduced the dosage requirements of methylprednisolone. After DCLAA treatment, the activation of microglia and astrocytes in the CNS was reduced. The expression of proinflammatory cytokines decreased, whereas the expression of anti-inflammatory cytokines increased. DCLAA reduced the number of peripheral T cells and CNS infiltration in EAE mice. Moreover, DCLAA attenuated the proliferation and induced the apoptosis of myelin oligodendrocyte glycoprotein (MOG)-specific T cells. These results indicate that DCLAA exhibit low toxicity and is able to alleviate the clinical symptoms of EAE by reducing neuroinflammation and suppressing the survival of peripheral T cells.
Cigarette Smoke Extract of Heated Tobacco Product Induces Necroptosis via Receptor-Interacting Protein 1-Mediated Phosphorylation of Mixed-Lineage Kinase Domain-Like Protein in Vascular Smooth Muscle Cells.
Shinkai R, Mazaki Y, Hachimori S … +3 more , Hashikura H, Miwa S, Horinouchi T
Biol Pharm Bull · 2026 · PMID 41850815 · Publisher ↗
Heated tobacco products (HTPs) are alternatives to traditional combustible cigarettes and are designed to reduce the generation of substances harmful to health. Recently, we reported that nicotine- and tar-free cigarette...
Heated tobacco products (HTPs) are alternatives to traditional combustible cigarettes and are designed to reduce the generation of substances harmful to health. Recently, we reported that nicotine- and tar-free cigarette smoke extract (CSE) prepared from HTP aerosols (HTP-CSE) induces ferroptosis and non-ferroptotic cell death in rat vascular smooth muscle A7r5 cells. However, the non-ferroptotic mechanism underlying HTP-CSE-induced cell death remains unclear. Here, we demonstrate that HTP-CSE causes necroptosis, a type of programmed cell death mediated by the receptor-interacting protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling pathway. Treatment of A7r5 cells with HTP-CSE at concentrations ranging from 10 to 80% for 4 h decreased mitochondrial metabolic activity and increased lactate dehydrogenase leakage in a concentration-dependent manner. The cytotoxic effects at concentrations of 10 and 20% were partially inhibited by Necrostatin-1s, an RIPK1 inhibitor. Treatment with 20% HTP-CSE for 3 h facilitated MLKL phosphorylation, and the phosphorylation level persisted for up to 6 h after HTP-CSE treatment. The facilitation of MLKL phosphorylation in response to 3 h of exposure to 20% HTP-CSE was almost completely depressed by Necrostatin-1s. These results suggest that HTP-CSE activates the RIPK1/MLKL signaling pathway, resulting in necroptosis associated with mitochondrial dysfunction and cell membrane damage.
Role of P-Glycoprotein Expression and Scaffold Proteins in the Entire Metastasis Process in Lung Cancer Cell Lines.
Liu W, Yajima M, Hariba T … +4 more , Sunakawa H, Yano K, Mizoi K, Ogihara T
Biol Pharm Bull · 2026 · PMID 41850814 · Publisher ↗
Lung cancer metastasis is often associated with poor prognosis for patients. Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are important processes in cancer metastasis and are also a...
Lung cancer metastasis is often associated with poor prognosis for patients. Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are important processes in cancer metastasis and are also associated with multidrug resistance (MDR). P-Glycoprotein (P-gp) is one of the efflux transporters responsible for MDR and is anchored to the cell membrane by a family of proteins called ERM (ezrin, radixin, and moesin). The aim of this study was to elucidate the functional changes in P-gp and their mechanisms by continuously inducing EMT and MET in lung cancer cells. EMT was induced by transfecting HCC827 lung cancer cells with the Snail gene, followed by MET induction via dexamethasone. The results suggested that P-gp membrane expression in lung cancer cells increased due to elevated moesin mRNA expression during EMT, followed by increased ezrin expression during MET. The increase in Msn expression did not change during subsequent MET induction, but that in ezrin expression was thought to be further enhanced by the preceding EMT. Furthermore, P-gp membrane expression increased synergistically with the continuous induction of EMT/MET. This study demonstrated that P-gp expression and activity increase at both the EMT and MET stages in cancer metastasis, suggesting that different mechanisms may be involved at each stage.
Glimepiride Modulates LPS-Induced M1 Macrophage Polarization via PPARγ-Mediated Inhibitory Mechanism.
Wang W, Liu H, Yang P
Biol Pharm Bull · 2026 · PMID 41833404 · Publisher ↗
This research intended to explore the role of glimepiride, a sulfonylurea-class medication, in regulating macrophage polarization and clarify its underlying molecular mechanism. In vitro experiments were performed using...
This research intended to explore the role of glimepiride, a sulfonylurea-class medication, in regulating macrophage polarization and clarify its underlying molecular mechanism. In vitro experiments were performed using a lipopolysaccharide (LPS)-induced M1 polarization model in the murine macrophage cell line RAW264.7. Different concentrations (low, medium, and high) of glimepiride were applied to evaluate their effects on the expression of M1 macrophage-specific markers. Transcriptome sequencing was conducted to identify potential regulatory pathways. Small interfering RNA (siRNA) was used to silence target genes, aiming to verify the impacts on downstream signaling pathways and pro-inflammatory cytokine secretion. In vitro experiments revealed that glimepiride markedly suppressed LPS-induced M1 macrophage polarization and diminished the expression levels of M1-specific markers, encompassing cluster of differentiation 86 (CD86) and inducible nitric oxide synthase (iNOS). Transcriptomic profiling indicated that the peroxisome proliferator-activated receptor gamma (PPARγ) pathway was modulated by glimepiride. Functional verification via PPARγ siRNA knockdown revealed that glimepiride mediated its regulatory effects by suppressing the expression of phosphorylated inhibitor of nuclear factor kappa B (IκB)/p65, which in turn restrained M1 macrophage polarization and attenuated pro-inflammatory cytokine release. These findings demonstrate that glimepiride inhibits M1 macrophage polarization through a PPARγ-dependent blockade of the IκB-p65 signaling pathway. This study highlights a novel anti-inflammatory mechanism of glimepiride, providing preclinical evidence for its potential application in anti-inflammatory therapies.
Bortezomib Induces Apoptosis via Upregulation of Abhd4 in Peripheral Nerve Cells.
Konishi Y, Omura T, Ijichi T … +6 more , Nishiguchi H, Hayakawa R, Kitahiro Y, Itohara K, Yamamoto K, Yano I
Biol Pharm Bull · 2026 · PMID 41833403 · Publisher ↗
Bortezomib, a first-in-class proteasome inhibitor, is widely used to treat multiple myeloma and other hematological malignancies. Despite its therapeutic efficacy, bortezomib causes peripheral neuropathy (PN) in approxim...
Bortezomib, a first-in-class proteasome inhibitor, is widely used to treat multiple myeloma and other hematological malignancies. Despite its therapeutic efficacy, bortezomib causes peripheral neuropathy (PN) in approximately 20-30% of patients, often leading to dose reduction or discontinuation. Preventive or therapeutic approaches to bortezomib-induced PN are currently unavailable, as its precise mechanism remains unclear. In this study, we compared the effects of bortezomib and the second-generation proteasome inhibitor carfilzomib on peripheral nerve cells to identify candidate molecules involved in PN development. Transcriptome profiling of differentiated F11 cells, a hybridoma of a rat embryonic dorsal root ganglion and mouse neuroblastoma cell line N18TG2, revealed that bortezomib selectively upregulated α/β-hydrolase containing domain 4 (Abhd4), whereas carfilzomib did not. This finding was confirmed by quantitative RT-PCR and immunoblotting, which demonstrated consistent increases in Abhd4 mRNA and protein levels following bortezomib treatment. Functional analysis further revealed that Abhd4 overexpression promoted early apoptosis, suggesting a mechanistic link between bortezomib-induced Abhd4 elevation and neuronal vulnerability. Therefore, these results suggest that Abhd4 represents a candidate molecular signature associated with bortezomib-induced PN. Although further in vivo validation is needed, these findings warrant further investigation of Abhd4 as a potential contributor to bortezomib-induced PN.
Enhanced Anticancer Immunity Relieves Hypoxia in Tumors Treated with a Combination of Anti-PD-1 and Radiation Therapies.
Nakajima K, Homma M, Suzuki M … +4 more , Yokouchi Y, Hirata K, Kuge Y, Ogawa M
Biol Pharm Bull · 2026 · PMID 41833402 · Publisher ↗
A combination of anti-programmed death-1 (anti-PD-1) immunotherapy and radiation therapy (RT) has shown good clinical outcomes. Previously, we had reported that enhanced anticancer immune response can relieve the hypoxia...
A combination of anti-programmed death-1 (anti-PD-1) immunotherapy and radiation therapy (RT) has shown good clinical outcomes. Previously, we had reported that enhanced anticancer immune response can relieve the hypoxia in tumors after treatment with anti-PD-1 agents. In this study, we investigated the relationship between tumor hypoxia and anticancer immunity in the combination therapy. An anti-PD-1 antibody was administered to mice with CT26 tumor on days 0 and 3. Tumors were irradiated with X-rays on days 0, 1, 2, and 3. Hypoxia in tumors was non-invasively examined with a hypoxia positron emission tomography (PET) probe, [F]fluoromisonidazole ([F]FMISO). The percentages of immune and hypoxic cells were analyzed using flow cytometry with pimonidazole. One day after four cycles of irradiation (day 4), no change was observed in the numbers of CD8 T cells and hypoxic cells within the tumor in the combination therapy group. On day 10, a later timepoint, the numbers of CD8 T cells was increased. The number of hypoxic cells was decreased, but [F]FMISO accumulation in the tumors was unchanged. Previous studies had shown that CD8 T cells remodel tumor vasculature in anti-PD-1 therapy, leading to the reduction in hypoxia. Our results also suggest that the recruited CD8 T cells reduced hypoxia in tumors irradiated with X-rays, although [F]FMISO-PET did not indicate these changes. In conclusion, the combination therapy with anti-PD-1 antibody and RT reduced the hypoxic levels in tumors in association with the increased infiltration of CD8 T cells.
Involvement of Ca3.2 T-Type Ca Channels and the Role of Endogenous Estrogen in Pruritus: Evidence from a Fundamental Study and Cross-Sectional Analysis of Pharmacy Claims Data.
Kurahashi S, Miyamoto T, Nishikawa H … +14 more , Mishima E, Matsunaga S, Kino S, Ashida T, Minamino R, Nishiyama I, Yamaguchi M, Yamamoto T, Sakakibara M, Okada T, Toyooka N, Tsubota M, Sekiguchi F, Kawabata A
Biol Pharm Bull · 2026 · PMID 41833401 · Publisher ↗
To clarify the roles of Ca3.2 T-type Ca channels and endogenous estrogen in pruritus, we conducted a fundamental study employing mice and clinical cross-sectional analyses of pharmacy claims data. In mice, intradermal in...
To clarify the roles of Ca3.2 T-type Ca channels and endogenous estrogen in pruritus, we conducted a fundamental study employing mice and clinical cross-sectional analyses of pharmacy claims data. In mice, intradermal injection of sulfide (NaS), a Ca3.2 enhancer, caused itch responses, an effect blocked by KTtp38, a T-type Ca channel inhibitor, and deletion of Ca3.2 gene. KTtp38 also suppressed itch responses following intradermal histamine or chloroquine. The sulfide-induced itch responses in female mice decreased by ovariectomy and/or repeated treatment with letrozole, an aromatase inhibitor. Cross-sectional analyses of pharmacy claims data of 357972 female patients aged 18 years and older, obtained from nationwide branches of a chain pharmacy group, showed significantly lower prescription rates of topical steroids used for treatment of pruritus and/or dermatitis in women 55 years and older than in women under 55 years, and in the users than non-users of estrogen suppressants. Multivariate logistic regression analysis in the users and non-users of estrogen suppressants after propensity score matching indicated significant negative association of topical steroid prescription with the use of estrogen suppressants. Together, the present fundamental and clinical studies suggest the involvement of Ca3.2 and the promotive role of estrogen in pruritus in mice and/or humans.
Natural Language Processing-Based Visualization Framework for Adverse Events Extracted from Clinical Narratives: Towards Enhancing Clinical Interpretability.
Tsuchiya M, Kawazoe Y, Shimamoto K … +10 more , Seki T, Yanagisawa Y, Imai S, Kizaki H, Shinohara E, Yada S, Nishiyama T, Wakamiya S, Aramaki E, Hori S
Biol Pharm Bull · 2026 · PMID 41813137 · Publisher ↗
Subjective adverse events (AEs), such as pain, are often under-recognized when relying solely on structured data. Although natural language processing (NLP) enables the extraction of AEs from narrative electronic health...
Subjective adverse events (AEs), such as pain, are often under-recognized when relying solely on structured data. Although natural language processing (NLP) enables the extraction of AEs from narrative electronic health records (EHRs), interpretation of their temporal dynamics is difficult. Visualization methods can bridge this gap by transforming text-derived symptom data into clinically interpretable data. This study aimed to demonstrate the clinical value of a framework integrating NLP-based AE extraction with time-series visualization for otherwise invisible symptoms. Narrative texts, including progress notes, nursing records, and discharge summaries, were processed using MedNERN-CR-JA, a pretrained Japanese BERT-based model for entity recognition. AEs were visualized using Kaplan-Meier curves to represent the time to first onset and heatmaps, displaying all subsequent symptom documentation alongside supportive medication use. Among the 35042 eligible patients, 3094 received paclitaxel (PTX) and were matched to 3094 controls. PTX was associated with a higher risk of musculoskeletal symptoms (hazard ratio, 1.77; 95% confidence interval: 1.57-1.99). Kaplan-Meier curves showed earlier onset in PTX recipients, while heatmaps depicted recurrent documentation and the corresponding analgesic use. Restricting the analyses to the triweekly PTX regimen reduced the heterogeneity between inpatient and outpatient documentation and revealed a clearer alignment between the treatment cycles and acute symptom onset. This framework demonstrates the clinical value of visualizing NLP-extracted AEs from narrative EHRs, improving the resolution of subjective AE data, enhancing monitoring, and supporting patient-centered care and clinical decision making through complementary time-to-event and heatmap visualizations.
Survey of Pharmacy Students' Awareness of Medication Overuse Headache.
Yamada S, Takeda K, Shibata N … +1 more , Nishimura A
Biol Pharm Bull · 2026 · PMID 41795925 · Publisher ↗
Medication overuse headache (MOH) is a condition in which excessive analgesic use induces headache. Recent studies have reported that simple advice significantly reduces the number of days patients use analgesics and the...
Medication overuse headache (MOH) is a condition in which excessive analgesic use induces headache. Recent studies have reported that simple advice significantly reduces the number of days patients use analgesics and the frequency of headaches. Pharmacists are expected to support patient self-medication and contribute to the prevention and treatment of MOH. This study was conducted at Doshisha Women's College of Liberal Arts and Osaka Medical and Pharmaceutical University with the aim of clarifying the current state of pharmacy students' awareness of MOH and related issues. The survey consisted of 28 items, including true or false, open-ended, and multiple-choice questions on MOH. Of the 341 students who responded, 49.9% had heard of the term MOH, and 84.5% recognized the importance of pharmacists in preventing and mitigating MOH. The correct answer rate for the true or false questions was 78.3%, but only 16.4% of the students responded that their current understanding of MOH allows them to provide care to patients, and only 7.9% reported having learned about ways to support patients with MOH. These findings indicate that the knowledge about MOH is not yet fully connected to patient support. Therefore, opportunities to learn about the practical aspects of pharmacist involvement in MOH management on campus may be limited. In the future, universities may consider providing more structured opportunities for pharmacy students to learn the practical aspects of pharmacist-led patient support.
Structural and Functional Diversity of Mitochondria Isolated from Different Cell Types.
Endo Y, Kanai M, Kobayashi M … +4 more , Higami Y, Itakura S, Nishikawa M, Kusamori K
Biol Pharm Bull · 2026 · PMID 41795924 · Publisher ↗
Mitochondria are essential organelles responsible for energy production, autophagy, and apoptosis, and mitochondrial dysfunction has been implicated in various diseases affecting the heart, liver, and kidneys. Mitochondr...
Mitochondria are essential organelles responsible for energy production, autophagy, and apoptosis, and mitochondrial dysfunction has been implicated in various diseases affecting the heart, liver, and kidneys. Mitochondrial transplantation, wherein isolated mitochondria are administered into cells or tissues, has recently emerged as a promising therapeutic approach for restoring cellular functions by enhancing ATP generation and reducing oxidative stress. However, the characteristics and functional diversity of the mitochondria isolated from different cell types remain poorly understood. Here, we aimed to identify the optimal mitochondrial source for transplantation therapy by comparing mitochondria isolated from several mammalian cell types, including mesenchymal stromal, hepatic, muscular, and pluripotent stem cells. Mitochondria were isolated using a streptolysin O-based isolation method and characterized through particle size, zeta potential, protein content, and ATP content. The isolated mitochondria exhibited uniform morphology, negative surface charge, sufficient protein yield, and ATP content, indicating successful preparation of functionally competent organelles suitable for comparative analysis. The mitochondria derived from mesenchymal stromal cells exhibited the highest bioenergetic activity. Adding these mitochondria enhanced cellular proliferation, oxygen consumption, and resistance to oxidative stress in recipient cells. Collectively, these findings demonstrate that mitochondria isolated from autologous mesenchymal stromal cells possess superior bioenergetic properties, highlighting their potential as an optimal source for mitochondrial transplantation therapy and providing new insights into the design of mitochondria-based therapeutics.
Caspase-Independent Cell Death Induced by a Nitric Oxide Donor Derived from Valproic Acid in Human Pancreatic Cancer Cells.
Nishi K, Ueda A, Beppu T … +6 more , Takasaki K, Imoto S, Tsukikawa K, Tokuno M, Otagiri M, Yamasaki K
Biol Pharm Bull · 2026 · PMID 41780936 · Publisher ↗
Nitric oxide (NO) plays diverse roles in tumor biology, including modulation of blood flow and induction of cell death at high concentrations. In this study, we synthesized a novel NO donor derived from valproic acid (NV...
Nitric oxide (NO) plays diverse roles in tumor biology, including modulation of blood flow and induction of cell death at high concentrations. In this study, we synthesized a novel NO donor derived from valproic acid (NVA) and investigated its cytotoxic mechanism in human pancreatic cancer cells. NVA released approximately 40% of its total nitrate/nitrite (NO) immediately after dissolution in phosphate-buffered saline and then remained almost unchanged for 72 h, indicating a rapid initial NO release followed by stabilization. NVA significantly decreased the viability of BxPC-3 cells, whereas valproic acid (VA) alone had little effect. Flow cytometric analysis using Annexin V revealed that NVA-induced cell death was not inhibited by the pan-caspase inhibitor Z-VAD-FMK. Furthermore, Western blotting showed no cleavage of caspase-3 or poly(ADP-ribose) polymerase (PARP) following NVA exposure, suggesting that apoptosis was not the major pathway. These findings indicate that NVA induces NO-dependent, caspase-independent cell death, distinct from classical apoptosis. The present study provides fundamental insights into the potential use of VA-based NO donors as antitumor agents against pancreatic cancer.
The Differences in Gut Microbiota Due to Dietary Habits Affect the Onset of Disease Pathology in a Dextran Sulfate Sodium-Induced Colitis Model.
Takahara C, Tabuchi N, Inoue H … +4 more , Itoh H, Koike Y, Kawazoe K, Takayama K
Biol Pharm Bull · 2026 · PMID 41780935 · Publisher ↗
Ulcerative colitis (UC), an inflammatory bowel disease (IBD) involving colon ulceration and erosion, is challenging to prevent or stop. The findings highlighted the crucial role of gut microbiota imbalance in IBD develop...
Ulcerative colitis (UC), an inflammatory bowel disease (IBD) involving colon ulceration and erosion, is challenging to prevent or stop. The findings highlighted the crucial role of gut microbiota imbalance in IBD development. This study aimed to investigate the influence of five dietary patterns on the onset or progression of UC in a dextran sulfate sodium (DSS)-induced colitis model by altering the gut microbiota. The results showed that the disease condition worsened most significantly in the high-protein diet group, followed by the high-fiber diet group. Before UC induction, these severely affected groups exhibited a higher proportion of Bacteroidota (Bacteroidetes) and a lower proportion of Bacillota (Firmicutes) than the groups in which the condition did not worsen. A reduced Firmicutes/Bacteroidetes ratio has been linked to the onset and progression of IBD. Upon DSS administration, the abundance of Bacteroidota increased in all dietary groups. Analyses revealed that as the disease progressed, the levels of the inflammatory cytokine tumor necrosis factor-α (TNF-α) increased. Specifically, the high-protein group showed elevated expression of interleukin-6 (IL-6) and transforming growth factor β1 (TGF-β1), which are involved in Th17 cell induction, and increased IL-17A secretion, indicating an amplified Th17-mediated inflammatory response. The expression of the tight junction protein occludin was reduced in the high-fiber and high-protein groups. These groups also demonstrated a significant decrease in beneficial short-chain fatty acids, acetate, and propionate. These findings suggest that dietary habits significantly impact the onset and progression of UC, and that the gut microbiota composition before disease onset may play a crucial role in this process.
The Natural Flavonoid Isoscoparin Ameliorates Oxidative Stress and Mitochondrial Dysfunction in C. elegans and Macrophages.
Wang K, Zhang L, Liang GC … +4 more , Duan XM, Zeng C, Jin GJ, Tan YH
Biol Pharm Bull · 2026 · PMID 41780934 · Publisher ↗
The natural flavonoid isoscoparin exhibits potent antioxidant activity, but its protective mechanisms against oxidative stress and mitochondrial dysfunction remain incompletely understood. This study investigated the eff...
The natural flavonoid isoscoparin exhibits potent antioxidant activity, but its protective mechanisms against oxidative stress and mitochondrial dysfunction remain incompletely understood. This study investigated the effects of isoscoparin in Caenorhabditis elegans and lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In C. elegans, isoscoparin significantly reduced intracellular reactive oxygen species (ROS) levels and enhanced resistance to paraquat-induced oxidative stress. These effects were associated with upregulation of antioxidant genes (daf-16, skn-1, sod-3, gst-4, ctl-1, ctl-2). In macrophages, isoscoparin not only enhanced the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) while reducing malondialdehyde (MDA) content but also attenuated LPS-induced mitochondrial ROS generation. Furthermore, isoscoparin restored mitochondrial respiratory function by improving basal and maximal respiration, ATP production, and spare respiratory capacity. It also stabilized mitochondrial membrane potential and restored the expression of electron transport chain complexes I-V. These findings demonstrate that isoscoparin alleviates oxidative stress through dual mechanisms: enhancing antioxidant defense via conserved pathways and directly protecting mitochondrial integrity. This study highlights the potential of isoscoparin as a therapeutic candidate for oxidative stress-related diseases.
Clinical Feasibility of Nomogram-Based Vancomycin Dosing Strategy: A Retrospective Study.
Okada N, Yoshii T, Tamura M … +5 more , Baba A, Matsudomi K, Sakiyama T, Goto R, Kitahara T
Biol Pharm Bull · 2026 · PMID 41765476 · Publisher ↗
Vancomycin (VCM) dosing based on the area under the concentration-time curve (AUC)-guided therapeutic drug monitoring is recommended to optimize efficacy and safety; however, pharmacokinetic simulation software is not al...
Vancomycin (VCM) dosing based on the area under the concentration-time curve (AUC)-guided therapeutic drug monitoring is recommended to optimize efficacy and safety; however, pharmacokinetic simulation software is not always available in routine clinical practice. This retrospective study evaluated the usefulness of an AUC-guided nomogram as an alternative approach for VCM dosing strategy. Hospitalized patients who underwent initial VCM serum concentration measurements were categorized into software, nomogram, or non-intervention groups according to VCM dosing strategy. Attainment of pharmacokinetic indices, including first-day AUC (AUC) and safety outcomes, was compared among the groups. The nomogram group demonstrated a significantly higher percentage of achieving the target AUC (55.4%) than the non-intervention group (30.8%) and achieved target attainment comparable to that of the software group (62.0%). Multivariable logistic regression analysis with nomogram-based VCM dosing as the reference identified non-intervention to dosing strategy as a factor associated with failure to achieve the target AUC (odds ratio; 2.82, 95% confidential interval; 1.21, 6.54). The incidence of acute kidney injury did not differ significantly among the groups. In the subgroup of patients with Gram-positive bacteremia, the duration of 50% decrease in C-reactive protein differed significantly among the three groups, with shorter durations observed in the nomogram (median; 4 d) and software groups (median; 4 d) than those in the non-intervention group (median; 9 d). These findings indicate that a nomogram-based VCM dosing strategy can facilitate early attainment of pharmacokinetically appropriate VCM exposure and may serve as a feasible alternative to a software-based VCM dosing strategy.
Efficacy and Safety of Various Antibiotics in Bacteremia Caused by AmpC-Producing Enterobacteriaceae, Comparing Carbapenems: A Systematic Review and Network Meta-analysis.
Mitsuboshi S, Inose R, Yanagisawa R … +3 more , Uemoto K, Mizuno K, Muraki Y
Biol Pharm Bull · 2026 · PMID 41765475 · Publisher ↗
This meta-analysis aimed to evaluate the efficacy and safety of various antibiotics used as definitive therapy for bacteremia caused by AmpC-producing bacteria. MEDLINE via PubMed, the Cochrane Central Register of Contro...
This meta-analysis aimed to evaluate the efficacy and safety of various antibiotics used as definitive therapy for bacteremia caused by AmpC-producing bacteria. MEDLINE via PubMed, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov website were comprehensively searched to identify all relevant studies. Carbapenem served as a reference, and the intervention effects of the other antibiotics were compared. Primary outcomes were all-cause mortality, recurrent infections, and adverse events. A frequentist network meta-analysis was performed using a random-effects model to account for any significant heterogeneity between studies. The odds ratios (ORs) and 95% confidence intervals (CIs) for each outcome in comparison with the carbapenem antibiotic were calculated based on the size of the population. Twelve studies were included in this meta-analysis. There were no significant differences in all-cause mortality or recurrent infections between carbapenems and other individual antibiotics. While cefepime significantly reduced the risk of adverse events compared to carbapenem (OR 0.28, 95% CI 0.14-0.57), and piperacillin-tazobactam showed a tendency to increase the risk of adverse events compared to carbapenem (OR 13.41, 95% CI 0.64-280.80). In conclusion, this meta-analysis found that cefepime was associated with comparable efficacy and fewer adverse events than carbapenems in the treatment of bacteremia caused by AmpC-producing bacteria. Additionally, potential concerns identified regarding the therapeutic efficacy of piperacillin-tazobactam, cephalosporins (excluding cefepime), fluoroquinolones, and aminoglycosides.
Evaluation of Antibiotic Use Metrics as Predictors of Clostridioides difficile Infection Onset: A Single-Center, Case-Control Study Assessing the Days of Therapy and the Days of Antibiotic Spectrum Coverage.
Maeda M, Mori N, Hiraide M … +3 more , Oda M, Yamaguchi K, Tokimatsu I
Biol Pharm Bull · 2026 · PMID 41765474 · Publisher ↗
Excessive antibiotic use is a well-known risk factor for the onset of Clostridioides difficile infection (CDI). This study aimed to assess whether antibiotic use metrics such as the days of antibiotic spectrum coverage (...
Excessive antibiotic use is a well-known risk factor for the onset of Clostridioides difficile infection (CDI). This study aimed to assess whether antibiotic use metrics such as the days of antibiotic spectrum coverage (DASC), days of therapy (DOT), and patient antibiotic day (PAD) are useful in predicting the onset of first-episode CDI. A single-center, retrospective, case-control study was conducted at Showa Medical University Hospital. Patients who exhibited an initial episode of CDI (first CDI toxin-positive test result after admission) in our hospital were classified as the case group. Those who obtained CD toxin-negative test results without diarrhea belonged to the control group. A total of 173 patients were included, with 110 in the case group and 63 in the control group. The median values of DASC, DOT, and PAD were significantly higher in the case group than in the control group (54 vs. 120.5, 6.0 vs. 13.0, and 5.0 vs. 11.0, respectively; all: p < 0.05). In a receiver operating characteristic analysis involving DASC, DOT, and PAD, the area under the curve ranged from 0.620 to 0.639. In conclusion, metrics reflecting the duration of antibiotic administration and the antibiotic spectrum appeared to be significant predictors of CDI onset. These findings further support the importance of monitoring these metrics and minimizing the duration of antibiotic use and the use of broad-spectrum agents.
Pharmacist Contributions in Promoting Appropriate Antimicrobial Use toward Combating Antimicrobial Resistance in Japan.
Muraki Y, Ohmagari N
Biol Pharm Bull · 2026 · PMID 41765473 · Publisher ↗
Antimicrobial resistance (AMR) has become a major global health threat, prompting the implementation of antimicrobial stewardship (AS) programs to optimize antimicrobial use. Pharmacists play a vital role in these effort...
Antimicrobial resistance (AMR) has become a major global health threat, prompting the implementation of antimicrobial stewardship (AS) programs to optimize antimicrobial use. Pharmacists play a vital role in these efforts. In Japan, a series of national policy measures has been launched as part of the 2016 National Action Plan on AMR, and systems have been established in parallel to support the active involvement of pharmacists with advanced expertise in infectious diseases. This narrative review provides an overview of the expanding contributions of pharmacists to AS across diverse healthcare settings in Japan. In large hospitals with relatively abundant human resources, pharmacists have promoted post-prescription review, dose optimization, and de-escalation, resulting in reduced use of broad-spectrum antibiotics, shortened treatment durations, cost savings, and even lower resistance rates. Further, in small- and medium-sized hospitals, where infectious disease specialists are often unavailable, pharmacist-led stewardship efforts are gradually emerging. Community pharmacists have also expanded AS efforts outside hospital settings by surveilling outpatient antibiotic prescriptions and identifying leftover antibiotics during home visits. In addition, multicenter collaborative studies and analyses using large-scale administrative claims databases are contributing to the generation of robust real-world evidence, facilitating sustained surveillance and policy evaluation. To maintain and further enhance these efforts, fostering the next generation of AS professionals and developing novel indicators and predictive models are essential. Pharmacist-led AS in Japan is expected to continue progressing, with sustainable contributions needed across healthcare situations of all field.
Foreword.
Kitahara T
Biol Pharm Bull · 2026 · PMID 41765472 · Publisher ↗
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