Biol. Pharm. Bull. [JOURNAL]
Sun
200 papers
Possible Involvement of β-Adrenoceptors in the Positive Chronotropic Effects of Mirabegron.
Noguchi K, Nagai A, Kashimoto N … +7 more , Kobayashi R, Okawa K, Shinkuma M, Inoue R, Kanae H, Matsushita M, Ueda C
Biol Pharm Bull · 2026 · PMID 41500611 · Publisher ↗
Mirabegron, a β-adrenoceptor agonist used to treat overactive bladder, is associated with increased heart rate; however, the mechanism underlying its cardiac effect remains unclear. In this study, we investigated the β-a...
Mirabegron, a β-adrenoceptor agonist used to treat overactive bladder, is associated with increased heart rate; however, the mechanism underlying its cardiac effect remains unclear. In this study, we investigated the β-adrenoceptor subtypes that are involved in the chronotropic effects of mirabegron in mouse and guinea pig atria. Mirabegron (0.03-10 μM) produced concentration-dependent positive chronotropic effects in both species, with maximum effects of 75.9% in mice and 27.7% in guinea pigs. Isoproterenol (0.1-100 nM), a nonselective β-adrenoceptor agonist, dobutamine (0.001-100 μM), a β-adrenoceptor agonist, and salbutamol (0.001-100 μM), a β-adrenoceptor agonist, induced concentration-dependent positive chronotropic effects, with the potency order of isoproterenol > dobutamine > mirabegron ≥ salbutamol in mice, and isoproterenol > dobutamine ≥ salbutamol > mirabegron in guinea pigs. Mirabegron-induced positive chronotropic effects were unaffected by 0.1% dimethyl sulfoxide in the mouse atria, but non-competitively antagonized by the selective β-adrenoceptor antagonist L748337 (100-1000 nM), with the slope of the Schild plot being 0.65. The selective β-adrenoceptor antagonist ICI118551 (30 nM) attenuated the positive chronotropic effects of mirabegron, producing a 3-fold rightward shift in the concentration-response curve. Conversely, the selective β-adrenoceptor antagonist CGP20172A (0.03-3 nM) strongly and non-competitively antagonized mirabegron-induced positive chronotropic effects in mouse and guinea pig atria. These results suggest that the positive chronotropic effects of mirabegron are primarily mediated through β-adrenoceptors, with minimal or no involvement of β- and β-adrenoceptors.
SMTP-44D Exerts Renoprotective Effects against Diabetic Nephropathy via Its Anti-inflammatory and Antioxidant Action.
Awane T, Sasaki H, Shibata K … +2 more , Hasumi K, Nobe K
Biol Pharm Bull · 2026 · PMID 41500604 · Publisher ↗
Diabetic nephropathy (DN) is among the most serious diabetes-related microvascular complications, a disease with risks leading to end-stage kidney disease (ESKD). However, only limited DN treatment options are currently...
Diabetic nephropathy (DN) is among the most serious diabetes-related microvascular complications, a disease with risks leading to end-stage kidney disease (ESKD). However, only limited DN treatment options are currently available. DN development and progression involve different pathological mechanisms, including inflammation and oxidative stress. Stachybotrys microspora is a fungus producing the triphenyl phenol SMTP-44D, which exhibits anti-inflammatory and antioxidant properties in several disease models. In this study, we aimed to evaluate the effects of SMTP-44D in a DN mouse model, which was created by removing the right kidney of 6-week-old db/db mice. We administered SMTP-44D for 10 weeks between weeks 6 and 16 of age to observe blood glucose levels, renal function parameters, inflammatory factors, oxidative stress markers, and histopathological characteristics. SMTP-44D treatment did not reduce blood glucose level but significantly decreased serum creatinine and urinary albumin as renal function parameters, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and nicotinamide adenine dinucleotide phosphate oxidase-1 as inflammation and oxidative stress in the kidney. In addition, histopathological assessment revealed its preventive effect against glomerulosclerosis and local regenerative tubule. Therefore, we discovered that SMTP-44D might protect renal function without affecting blood glucose level in DN possibly via suppression of inflammation and oxidative stress. In conclusion, SMTP-44D could be a potential DN treatment agent, even in patients with poor glycemic control.
Tanshinone VI Attenuates the Development of Heart Failure with Preserved Ejection Fraction in Mice.
Marunouchi T, Kawahara Y, Tanonaka K
Biol Pharm Bull · 2026 · PMID 41485990 · Publisher ↗
Treatments to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) are urgently needed. Tanshinone VI (TanVI) is a compound extracted from the roots of Salvia miltiorrhiza Bunge (Lamiaceae) tha...
Treatments to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) are urgently needed. Tanshinone VI (TanVI) is a compound extracted from the roots of Salvia miltiorrhiza Bunge (Lamiaceae) that exerts inhibitory effects on the development of cardiac remodeling under experimental conditions. However, the therapeutic effects of TanVI on HFpEF remain unclear. The present study aims to investigate the therapeutic effects of TanVI in a mouse model of HFpEF. HFpEF mice were prepared by feeding C57BL/6N mice a high-fat diet and providing water containing N-nitro-L-arginine methyl ester hydrochloride (L-NAME) for 15 weeks, and TanVI (3 mg/kg/d) or vehicle was administered intraperitoneally using an osmotic pump for 5 weeks until the end of the experiment. The administration of a high-fat diet and L-NAME resulted in cardiac diastolic dysfunction with cardiac hypertrophy and fibrosis. In contrast, treatment with TanVI markedly attenuated cardiac hypertrophy and fibrosis and prevented cardiac diastolic dysfunction. In HFpEF mouse hearts, the phosphorylation levels of mitogen-activated protein (MAP) kinases such as c-Raf, MEK1/2, and extracellular signal-regulated kinase 1/2 (ERK1/2), which regulate cardiac hypertrophy and fibrosis, were elevated. In contrast, treatment with TanVI reversed the phosphorylation levels of c-Raf, MEK1/2, and ERK1/2. The present study showed that TanVI prevented the development of HFpEF by reducing cardiac remodeling. Furthermore, our findings suggest, at least in part, that TanVI attenuates the development of HFpEF by inhibiting the MAP kinase signaling pathway.
Antiarrhythmic Potential of the β-Adrenoceptor Blocker Metoprolol against Dofetilide-Induced Torsades de Pointes in Anesthetized Bradycardic Rabbits.
Kawakami S, Ishimaru Y, Aimoto M … +2 more , Nagasawa Y, Takahara A
Biol Pharm Bull · 2026 · PMID 41485989 · Publisher ↗
We have established a proarrhythmic rabbit model of acute atrioventricular block (AVB) with severe bradycardia to detect delayed rectifier K channel current (I) blocker-induced torsade de pointes (TdP). To better underst...
We have established a proarrhythmic rabbit model of acute atrioventricular block (AVB) with severe bradycardia to detect delayed rectifier K channel current (I) blocker-induced torsade de pointes (TdP). To better understand the role of β-adrenoceptors in this model, we investigated the effect of the β-adrenoceptor blocker metoprolol against an I blocker dofetilide-induced TdP. AVB was induced by catheter ablation under isoflurane anesthesia, and the ventricles were electrically paced at a constant rate of 60 beats/min throughout the experiments. Monophasic action potentials (MAPs) were recorded from the right ventricle. In the non-treated control rabbits (n = 5), intravenous administration of an I blocker dofetilide (25 µg/kg) prolonged the MAP duration (MAP) by 90 ± 38 ms, which led to the induction of TdP in four of the five animals. In rabbits receiving the β-adrenoceptor blocker metoprolol (10 µg/kg/min, n = 5), the same dose of dofetilide prolonged MAP by 205 ± 31 ms, whereas TdP did not occur in this group. Meanwhile, the incidence of dofetilide-induced R-on-T-type premature ventricular contractions, representing an arrhythmogenic trigger, was lower in metoprolol-treated rabbits than in non-treated control rabbits. These results indicate that metoprolol exerted an overall antiarrhythmic effect by strongly suppressing TdP generation induced by dofetilide, despite its proarrhythmic action of enhancing repolarization prolongation. This highlights the critical role of β-adrenoceptors in facilitating arrhythmogenic triggers under conditions of excessive repolarization delay.
Photoacoustic Imaging for Monitoring Calcium Dynamics in the Heart.
Kyono D, Matsuzaki R, Kawata D … +6 more , Mikami H, Murano Y, Shoji I, Suzuki H, Nakahara N, Murakami S
Biol Pharm Bull · 2026 · PMID 41485988 · Publisher ↗
Photoacoustic imaging (PAI) is a hybrid imaging modality that captures ultrasound signals produced by thermoelastic expansion when pulsed laser light is absorbed by optical absorbers, enabling visualization of biological...
Photoacoustic imaging (PAI) is a hybrid imaging modality that captures ultrasound signals produced by thermoelastic expansion when pulsed laser light is absorbed by optical absorbers, enabling visualization of biological tissues at greater depths than those of conventional fluorescence imaging. While PAI has been conventionally used for biological, structural, and morphological studies, showing promise for imaging calcium dynamics in cardiac tissue, its practical implementation remains undemonstrated. In this study, we implemented a sectional excitation strategy using a thin, sheet-shaped laser beam to confine optical excitation to defined tissue planes. We applied this approach to photoacoustic imaging of a perfused bullfrog heart loaded with liposome-encapsulated calcium-sensitive dye. We successfully achieved real-time visualization of calcium dynamics within the atrial cross-section, while simultaneous electrocardiographic recordings enabled temporal correlation between photoacoustic signal fluctuations and cardiac electrical activity. This method provides a less-invasive approach to assess calcium transients in deep tissue, and broadens the application of PAI from morphology to physiological function. These findings highlight the potential of this optical-acoustic hybrid modality as a powerful tool for calcium imaging in physiological and pharmacological studies involving deep-tissue organs-particularly in applications such as heart imaging, where conventional optical techniques are limited by shallow penetration depth.
Cardioprotective Role of Neuregulin1-ErbB2 Signaling Pathway: Its Physiological and Onco-Cardiological Roles in the Heart.
Mikami Y, Adachi-Akahane S
Biol Pharm Bull · 2026 · PMID 41485987 · Publisher ↗
Neuregulin 1 (NRG1), a member of the epidermal growth factor (EGF) family, regulates the development, differentiation, proliferation, and plasticity in multiple tissues through its binding to ErbB3 and ErbB4 receptors. I...
Neuregulin 1 (NRG1), a member of the epidermal growth factor (EGF) family, regulates the development, differentiation, proliferation, and plasticity in multiple tissues through its binding to ErbB3 and ErbB4 receptors. In the cardiovascular system, NRG1 plays a crucial role in cardiac development, physiological function, and cell survival. Since NRG1 exerts cardioprotective effects through its interaction with ErbB2/ErbB4 and ErbB4 homodimers on cardiomyocytes, the administration of recombinant human NRG1 has the potential for the treatment of heart failure. ErbB2 is known as human epidermal growth factor receptor 2 (HER2), which is overexpressed in approximately 20% of breast cancers. Trastuzumab (TRZ), a humanized monoclonal antibody targeting ErbB2/HER2, is used for the therapy of HER2-positive breast cancer. However, cardiotoxicity has been observed in approximately 5-10% of patients treated with TRZ. Risk factors for the onset of cardiotoxicity include the use of anthracyclines, hypertension, and diabetes. However, the mechanism linking diabetes and TRZ-induced cardiotoxicity remains unclear. Recently, we reported that the serum levels of NRG1 were elevated in the mouse model of diabetic cardiomyopathy. We found that the up-regulated NRG1 compensates for insulin deficiency to maintain systolic function in the early stage of diabetic cardiomyopathy. This review aims to discuss the physiological roles of NRG1-ErbB2 signaling in the cardiovascular system, the cardioprotective effects of NRG1 and its clinical applications, and the molecular mechanisms of TRZ-induced cardiotoxicity through the blockade of the NRG1-ErbB2 signaling pathway.
Chronotropic, Inotropic, and Lusitropic Effects of Flavonoids.
Noguchi K, Ueda C, Umeda S … +5 more , Kanae H, Seki M, Hamaguchi S, Namekata I, Tanaka H
Biol Pharm Bull · 2026 · PMID 41485986 · Publisher ↗
We summarized the recent findings on the acute myocardial effects of several flavonoids, whose long-term beneficial effects through antioxidant activity has attracted attention. Polymethoxyflavones, such as sudachitin, d...
We summarized the recent findings on the acute myocardial effects of several flavonoids, whose long-term beneficial effects through antioxidant activity has attracted attention. Polymethoxyflavones, such as sudachitin, demethoxysudachitin, and nobiletin, showed chronotropic and inotropic effects; the effects were milder than those of β-adrenoceptor agonists. Their strength of action appeared to be related to the number of methoxy groups in the chemical structure. Sudachitin also showed strong vasorelaxant effect causing full relaxation. Quercetin showed positive lusitropic effects in both normal and diabetic myocardium; this was probably mediated by enhancement of Ca sequestration into the sarcoplasmic reticulum by the Ca ATPase. Hesperetin inhibited the spontaneous firing of action potential in the pulmonary vein myocardium; the chronotropic inotropic and lusitropic effects were weak or not observed. Thus, each flavonoid compound has characteristic pharmacological effects probably through their action on specific cellular targets. Further investigation of their effects would provide insights for the development of therapeutic agents for heart diseases such as heart failure and arrhythmia.
Foreword.
Tanaka H
Biol Pharm Bull · 2026 · PMID 41485985 · Publisher ↗
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Dynamic Feature of Oxidized LDL in Vivo.
Itabe H
Biol Pharm Bull · 2026 · PMID 41485984 · Publisher ↗
Atherosclerosis is a pathological condition that leads to cardiovascular disease and cerebral infarction. Oxidatively modified low-density lipoprotein (LDL), known as oxidized LDL (oxLDL), is one of the major factors for...
Atherosclerosis is a pathological condition that leads to cardiovascular disease and cerebral infarction. Oxidatively modified low-density lipoprotein (LDL), known as oxidized LDL (oxLDL), is one of the major factors for atherogenesis, because it serves as a ligand for scavenger receptors. We and others developed sensitive methods to measure plasma oxLDL levels in the 1990's, and since then, mounting evidence has accumulated demonstrating the relationship between cardiovascular diseases and oxLDL in vivo. Mechanistic insights into the generation, metabolism, and modified structures of oxLDL in vivo have also been obtained. This review focuses on two key issues regarding oxLDL in vivo; its involvement in the initiation of atheromatous lesion development, and the characterization of its modified structures in vivo.
Effects of Kamikihito on the Noradrenergic System and Its Pharmacokinetic Profile.
Oizumi H, Takiyama M, Matsumoto T … +2 more , Nishiyama M, Mizuno K
Biol Pharm Bull · 2025 · PMID 41485925 · Publisher ↗
The presence of treatment-resistant patients underscores the need for novel therapeutic options for affective and anxiety disorders. Kamikihito (KKT), a traditional kampo medicine used to treat mental anxiety and neurosi...
The presence of treatment-resistant patients underscores the need for novel therapeutic options for affective and anxiety disorders. Kamikihito (KKT), a traditional kampo medicine used to treat mental anxiety and neurosis, has recently attracted attention because of its unique mechanism of action as an oxytocin-activating drug. However, the underlying mechanism remains unclear. In particular, for the optimal use of KKT in clinical practice, clarifying whether KKT affects the monoaminergic system, which is the primary target of first-line antidepressants for these disorders, is essential. By evaluating monoaminergic transporter activity in vitro, we found that KKT inhibited the noradrenaline transporter (NAT). In addition, in the tail suspension test, KKT shortened the duration of immobility posture, indicative of behavioral despair, in lipopolysaccharide-injected mice, similar to desipramine, a NAT inhibitor. Furthermore, a reduction in the immobility time following KKT administration was not observed in mice pretreated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenergic neurotoxin, indicating that the antidepressant-like effect of KKT is mediated through the noradrenergic system. To identify the ingredients of KKT that are transferred into the blood and brain, we analyzed the blood and brain tissues of mice after KKT administration using mass spectrometry. Geniposide and formononetin were identified and puerarin, gardoside, 3',7-dihydroxy-4'-methoxyisoflavone 7-O-glucoside, and kazonol N were estimated as ingredients that distribute both in the blood and brain. Although these ingredients did not exhibit NAT inhibitory activity, the information presented in this pharmacokinetic study will be a valuable resource for future studies on the molecular mechanisms of KKT action.
Association between the Expression of Monocarboxylate Transporters in Tumors and Surrounding Stromal Cells and Cancer Prognosis: A Meta-Analysis.
Mukai Y, Yamaguchi A, Suganuma Y … +4 more , Okamoto K, Matsumoto N, Narumi K, Kobayashi M
Biol Pharm Bull · 2025 · PMID 41443841 · Publisher ↗
l-Lactate is not merely a metabolic product of glycolysis but also a molecule that plays an important role in intercellular interactions. Monocarboxylate transporters (MCTs) 1-4 are membrane proteins responsible for tran...
l-Lactate is not merely a metabolic product of glycolysis but also a molecule that plays an important role in intercellular interactions. Monocarboxylate transporters (MCTs) 1-4 are membrane proteins responsible for transporting monocarboxylic acids, such as l-lactate, across the plasma membrane. MCTs have been suggested to be involved in cancer cell invasion, metastasis, and immune evasion. Several studies have reported the relationship between MCT expression in tumor tissues and cancer prognosis. However, the potential for MCTs as poor prognostic factors in cancer remains controversial, and the impacts of different MCT isoforms and cancer types are yet to be fully elucidated. Therefore, we conducted a meta-analysis by pooling previously reported hazard ratios. The expression of MCT1 and MCT4, but not MCT2, in tumors and MCT4 in stromal cells was significantly associated with cancer prognosis. In addition, subgroup analyses revealed that both MCT1 and MCT4 expression were associated with esophageal cancer prognosis, whereas MCT4 expression was associated with hepatocellular carcinoma prognosis. Unlike MCT1, the plasma membrane expression of MCT4 was found to be associated with cancer prognosis. Put together, our findings show that MCT4 is a promising target for the treatment of various cancers. Further integration of basic and clinical research is required to elucidate the mechanisms by which MCTs contribute to poor cancer prognosis, in turn facilitating the development of effective inhibitors.
DNA-Damaging Agents Induce PD-L1 Expression through the Src-STAT1-IRF1 Pathway.
Suzuki Y, Nishibu S, Nohara A … +4 more , Onuma I, Zhou Y, Sakurai H, Yokoyama S
Biol Pharm Bull · 2025 · PMID 41443824 · Publisher ↗
Immune checkpoint inhibitors (ICIs) have been approved for the treatment of various cancers; however, their clinical efficacy remains limited in many patients due to resistance mechanisms. One of the mechanisms underlyin...
Immune checkpoint inhibitors (ICIs) have been approved for the treatment of various cancers; however, their clinical efficacy remains limited in many patients due to resistance mechanisms. One of the mechanisms underlying this resistance is the downregulated expression of programmed cell death-ligand 1 (PD-L1) caused by mutations that impair Janus kinase 1/2 (JAK1/2) function. Therefore, finding an alternative JAK-independent pathway to enhance PD-L1 expression would be highly valuable. In the present study, we found that the chemotherapeutic agents, SN-38 and cisplatin, upregulated the transcription factor interferon regulatory factor 1 (IRF1) and its downstream target PD-L1 in the melanoma cell line A2058. This induction occurred in a JAK-independent, but signal transducer and activator of transcription 1 (STAT1)-dependent manner, with STAT1 activation mediated by the tyrosine kinase Src. Furthermore, SN-38 upregulated PD-L1 expression not only in melanoma but also across multiple cancer types. These results suggest that DNA-damaging chemotherapeutic agents upregulate PD-L1 expression through a Src-STAT1-IRF1 signaling axis, potentially improving the therapeutic efficacy of ICIs, even in tumors with defective JAK signaling.
Patient Education to Prevent Exposure to Anticancer Drugs among Patients and Caregivers during Outpatient Chemotherapy in Japan: A Cross-Sectional Survey.
Tanigawa H, Kanatani Y, Ikesue H … +2 more , Hayashi T, Yamaguchi M
Biol Pharm Bull · 2025 · PMID 41443823 · Publisher ↗
In Japan, education on preventing exposure to anticancer drugs should be conducted for outpatients receiving chemotherapy, based on the "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 E...
In Japan, education on preventing exposure to anticancer drugs should be conducted for outpatients receiving chemotherapy, based on the "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition (guidelines 2019)." However, the educational content at each facility remains unclear. This study aimed to investigate the educational system and content in 461 cancer hospitals nationwide. We conducted a cross-sectional survey using a web questionnaire consisting of 27 questions covering four categories (background, patient educational system, content of patient education handouts, and issues in exposure prevention education). In total, 310 (67.2%) facilities responded, and 306 facilities were surveyed. Among the facilities surveyed, 96.7% (296/306 facilities) provided protection against exposure to injectable anticancer drugs, whereas only 33.4% (99/296 facilities) provided protection against exposure to oral anticancer drugs. Moreover, we analyzed the references and contents of the handouts used at the facilities. A total of 85% (209/244 facilities) of the facilities were creating handouts based on the 2019 guidelines. Approximately 85% of the facilities included "preventing exposure for body fluids and excretions" and "recommended preventing exposure period" in their handouts, but <60% included "handling of injectable agents" and "handling of oral anticancer agents." Furthermore, in the free description section on issues in education, 27 responses mentioned "insufficient of evidence," which was thought to be related to differences in educational content between facilities. In conclusion, it is necessary to establish a system for improving education to prevent exposure to oral anticancer drugs and standardize educational content through the creation of evidence.
Identification of Rat Monocarboxylate Transporter 9 as a Low-Affinity Transporter of 1-Methyl-4-phenylpyridinium and Amantadine.
Shinozaki Y, Miki S, Kubo Y … +3 more , Tega Y, Akanuma SI, Hosoya KI
Biol Pharm Bull · 2025 · PMID 41423226 · Publisher ↗
Membrane transporters affect the distribution of drugs in tissues. However, the biological roles of several orphan transporters such as monocarboxylate transporter 9 (MCT9/SLC16A9) have not been elucidated. Since the mol...
Membrane transporters affect the distribution of drugs in tissues. However, the biological roles of several orphan transporters such as monocarboxylate transporter 9 (MCT9/SLC16A9) have not been elucidated. Since the molecules responsible for the distribution of cationic compounds to the retinal, such as 1-methyl-4-phenylpyridinium (MPP) and amantadine, across the blood-retinal barrier (BRB) are not yet fully known, this study aimed to clarify whether MCT9 has transport activity for cationic molecules. MPP was taken up by MCT9 cRNA-injected Xenopus laevis oocytes, with a K value of 24.2 mM. This MPP uptake by the MCT9 cRNA-injected oocytes was significantly reduced in Na-free, low-Cl, and pH 5.0 uptake buffers, whereas it significantly increased in pH 8.4 uptake buffer. In addition, MCT9 cRNA-injected oocytes showed concentration-dependent amantadine uptake with a K value of 9.71 mM. These results indicate that MCT9 is a low-affinity transporter for MPP and amantadine, and contributes to the cellular uptake of these cationic compounds. Although mRNA expression of MCT9 was observed in rat BRB model cells, MCT9 mRNA knockdown by transfection with small interfering RNA did not change amantadine uptake. Despite the expression of MCT9 in the BRB, it is suggested that the contribution of MCT9 to amantadine transport across the BRB is minor. In conclusion, our study first identified the cationic compounds, namely, MPP and amantadine, as substrates transported by MCT9.
Association of Proteinuria as an Observed Side Effect with a Worsening Rate of Renal Function Decline in Patients with Colorectal Cancer Treated with Bevacizumab.
Yamaguchi K, Fujimoto K, Sakurai M … +4 more , Horie T, Takahashi Y, Ishigaki Y, Masauji T
Biol Pharm Bull · 2025 · PMID 41423225 · Publisher ↗
The effect of proteinuria, a side effect of bevacizumab (BV) treatment, on the subsequent rate of renal function decline in patients with colorectal cancer remains inconclusive. In this study, we conducted a retrospectiv...
The effect of proteinuria, a side effect of bevacizumab (BV) treatment, on the subsequent rate of renal function decline in patients with colorectal cancer remains inconclusive. In this study, we conducted a retrospective cohort study of 204 patients with colorectal cancer aged 18 years or older who received BV at Kanazawa Medical University Hospital from January 2014 to October 2024. The patients were classified into 2 groups based on the highest urine protein test values after the start of BV administration: a proteinuria-positive group (urinary protein test 2+ or higher) and a proteinuria-negative group (urinary protein test <1+). The rate of decline in renal function (i.e., estimated glomerular filtration rate [eGFR] slope) from the start of BV to 2 months after completion of BV was compared between the 2 groups using generalized estimating equations. In a model adjusted for confounding factors such as baseline renal function, age, sex, use of drugs or diabetes medications affecting renal function, and total dose of BV, the rate of decline in renal function was significantly greater in the proteinuria-positive group compared with the proteinuria-negative group (eGFR slope in mL/min/1.73 m/year: proteinuria-positive group: -2.80 [95% confidence interval, CI: -5.38 to -0.23]; proteinuria-negative group: -0.13 [95% CI: -2.55 to 2.28], p = 0.03). These results suggest that proteinuria, a side effect of BV treatment, is associated with a subsequent worsening rate of renal function decline in patients with colorectal cancer.
A Retrospective Cohort Study on the Effects of Honeysuckle Chinese Medicine Gargle Use on Postoperative Bleeding and Infection Rates Following Uvulopalatopharyngoplasty.
Ren L, Han S, Li Q … +8 more , Dong X, Yan R, Rong T, Yang L, Zhang R, Ma F, Gao Y, Miao Z
Biol Pharm Bull · 2025 · PMID 41423224 · Publisher ↗
To evaluate whether postoperative use of a honeysuckle Chinese medicine gargle solution reduces bleeding and infection rates after uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA). This was a single-cen...
To evaluate whether postoperative use of a honeysuckle Chinese medicine gargle solution reduces bleeding and infection rates after uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA). This was a single-center, retrospective cohort study of patients undergoing UPPP for OSA between 2019 and 2024. Patients were divided into gargle and non-gargle groups based on self-reported honeysuckle Chinese medicine gargle use postoperatively. Propensity score matching was performed to assemble balanced cohorts. The primary outcome was postoperative bleeding within 30 d. Postoperative infection was evaluated as a key secondary outcome. Univariable logistic regression analyses were conducted. A total of 178 patients were included in each matched cohort. Patients using the honeysuckle Chinese medicine gargle had significantly lower rates of postoperative bleeding (8.4 vs. 16.3%, odds ratio [OR] 0.47, 95% confidence interval [CI] 0.25-0.90, p = 0.02) compared to non-gargle users. Postoperative infection rates did not differ significantly between groups (5.6 vs. 8.4%, OR 0.65, 95% CI 0.28-1.47, p = 0.28). Gargle users had higher postoperative platelet counts and lower C-reactive protein levels. No major adverse events related to gargle use were reported. Postoperative honeysuckle Chinese medicine gargle use was associated with reduced bleeding risk after UPPP, plausibly related to hemostatic and anti-inflammatory effects, but did not impact infection rates. This herbal remedy represents a potential preventative strategy to improve surgical outcomes, warranting further investigation.
Differences in the Inhibitory Effects of a Hydrophobic Skin Protectant on Maceration between Aged and Young Skin.
Sasaki A, Horie Y, Akase T
Biol Pharm Bull · 2025 · PMID 41407360 · Publisher ↗
Maceration is a risk factor for pressure ulcers and incontinence-associated dermatitis, and it leads to impaired barrier function, particularly in aged skin. Appropriate care is required for aged skin, but research on th...
Maceration is a risk factor for pressure ulcers and incontinence-associated dermatitis, and it leads to impaired barrier function, particularly in aged skin. Appropriate care is required for aged skin, but research on the effects of hydrophobic skin protectants is lacking. This study evaluated the maceration-suppression effects of the hydrophobic skin protectant Remois Barrier in both young and aged skin. Male ddY mice aged 8 weeks (young) and 6 months (aged) were divided into 4 groups: young and aged mice treated with softening only (non-treated); young and aged mice treated with the skin protectant followed by softening (treated). After hair removal, cotton soaked in saline was fixed with a film for 2 h to induce maceration. Maceration was evaluated by macroscopic observation of the skin, measurement of transepidermal water loss (TEWL), and histological analysis. In the non-treated group, white swelling was observed, whereas in the treated group, water droplets were observed in the area where the hydrophobic skin protectant was applied. TEWL values were significantly decreased in the treated group compared with the non-treated group. Histological analysis indicated that epidermal thickening was suppressed in the treated group. Additionally, the change in TEWL value was significantly higher in the aged group compared with the young group, suggesting that the hydrophobic skin protectant effectively suppresses the decline in barrier function in aged skin. These results indicate that the application of hydrophobic skin protectants is effective in suppressing maceration in older individuals.
Deproteination of Serum-Drug Samples Utilizing a Temperature-Responsive Spin Column Containing Thermoresponsive Polymer Brush-Modified Beads.
Nagase K, Okamoto N, Kanazawa H
Biol Pharm Bull · 2025 · PMID 41407359 · Publisher ↗
Therapeutic drug monitoring requires a straightforward method for deproteinizing serum samples. In this study, a temperature-responsive spin column was developed by employing layers packed with beads modified with a poly...
Therapeutic drug monitoring requires a straightforward method for deproteinizing serum samples. In this study, a temperature-responsive spin column was developed by employing layers packed with beads modified with a poly(N-isopropylacrylamide) (PNIPAAm) copolymer brush. The modification of the silica beads with the PNIPAAm copolymer brush was accomplished through atom transfer radical polymerization, and the modified beads were subsequently packed into empty spin columns. The prepared spin column achieved effective separation of voriconazole and midazolam from serum proteins using pure water as the eluent, with temperature as the sole control parameter. This spin column is particularly advantageous for sample preparation in medical settings, as it eliminates the need for organic solvents and simplifies the process by leveraging temperature control.
Effect of PEGylated Liposomalization of Oxaliplatin on the Gut Microbiota in Mice.
Mogi K, Morimoto H, Yasukawa T … +3 more , Uozumi Y, Ishida T, Nagasawa K
Biol Pharm Bull · 2025 · PMID 41407346 · Publisher ↗
Dysbiosis is a contributing factor in various conditions, including depressive disorder and irritable bowel syndrome. Key drivers of dysbiosis include stress exposure, chronic unbalanced diet, and exposure to certain pha...
Dysbiosis is a contributing factor in various conditions, including depressive disorder and irritable bowel syndrome. Key drivers of dysbiosis include stress exposure, chronic unbalanced diet, and exposure to certain pharmacological medications. While the platinum-based anticancer agent oxaliplatin (l-OHP) induces dysbiosis, it remains unclear whether liposomal encapsulation impacts this microbiota disruption. Here, we evaluated characteristics of the colonic microbiota in male C57BL/6J mice administered l-OHP or its PEGylated liposomal formulation (Lipo-l-OHP). On Day 7 following treatment with l-OHP or Lipo-l-OHP (total dose: 16 mg/kg), all mice developed mechanical allodynia, while those receiving l-OHP, but not Lipo-l-OHP, exhibited reduced body weight gain. On Day 7, mice treated with l-OHP or Lipo-l-OHP showed a trend toward reduced α-diversity of the colonic microbiota compared with untreated mice in a control group; however, α-diversity remained significantly higher in the Lipo-l-OHP group than in the l-OHP group. β-Diversity analysis revealed the distinct patterns in microbiota composition among the 3 groups. At the bacterial genus level, the relative abundances of unclassified Muribaculaceae spp., Lachnospiraceae NK4A136 group spp., Bacteroides spp., and Clostridium sensu stricto 1 spp. were significantly altered in the l-OHP group, but not in the Lipo-l-OHP group, compared with those in the control group. Interestingly, the abundances of unclassified Muribaculaceae spp. and Lachnospiraceae NK4A136 group spp. were positively correlated, and Bacteroides spp. was negatively correlated, with body weight changes in mice on Day 7. Collectively, our findings demonstrated that PEGylated liposomalization of l-OHP partially ameliorates l-OHP-induced dysbiosis in mice.
Effect of Probiotics on Immunosuppressive Drug Pharmacokinetics: Interaction between Bacillus subtilis and Tacrolimus in Mice.
Tsuchiya Y, Yamamoto N, Yamamoto T … +4 more , Ogura Y, Hirota T, Ieiri I, Uchida M
Biol Pharm Bull · 2025 · PMID 41391856 · Publisher ↗
The pharmacokinetics of drugs significantly affects their efficacy and adverse effects. Clarifying and predicting individual pharmacokinetic differences is crucial for the appropriate use of pharmaceuticals. Recent studi...
The pharmacokinetics of drugs significantly affects their efficacy and adverse effects. Clarifying and predicting individual pharmacokinetic differences is crucial for the appropriate use of pharmaceuticals. Recent studies have suggested that the metabolic potential of intestinal bacteria may influence individual differences in pharmacokinetics. The consumption of probiotics, including supplements and fermented foods, has increased as a recent health trend. However, probiotics may also influence drug pharmacokinetics. In this study, we focused on the immunosuppressive drugs tacrolimus, everolimus, and cyclosporin A, which require careful dosing regimens, and investigated their interactions with microorganisms present in probiotics. Among the evaluated microorganisms, Bacillus subtilis exhibited a particularly strong drug degradation activity, with B. subtilis TO-A reducing the residual rates of tacrolimus and everolimus by 8 and 17%, respectively, in vitro. In a nonclinical pharmacokinetic trial, mice administered B. subtilis TO-A showed a significant reduction in the maximum blood concentration of tacrolimus. The concentration was 86.36 ± 63.61 ng/mL, much lower than that (212.8 ± 67.40 ng/mL) observed in the non-administered group. Based on these results, we can infer that orally ingested microorganisms can metabolize pharmaceuticals before reaching the small intestine, which is the primary site of absorption. These findings strongly suggest the need for caution when concurrently administering tacrolimus and probiotics in humans.
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