Biol. Pharm. Bull. [JOURNAL]
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200 papers
P2Y12 Receptor Antagonists Decrease the Radiation Resistance of B16 Melanoma by Suppressing DNA Repair.
Mizoguchi Y, Mori N, Kitabatake K … +3 more , Ogawa S, Uchiumi F, Tsukimoto M
Biol Pharm Bull · 2025 · PMID 41260667 · Publisher ↗
Radiation therapy exerts its therapeutic effect by killing cells via the induction of DNA double-strand breaks (DSBs) in malignant tumors, but cancer cells can repair damaged DNA, leading to radiation resistance (radiore...
Radiation therapy exerts its therapeutic effect by killing cells via the induction of DNA double-strand breaks (DSBs) in malignant tumors, but cancer cells can repair damaged DNA, leading to radiation resistance (radioresistance). Therefore, a radiosensitizing effect can be expected by suppressing mechanism(s) involved in DNA repair after irradiation. Here, we show that the P2Y12 receptor is involved in the radioresistance of mouse B16 melanoma cells, and that P2Y12 antagonist treatment decreases the radioresistance both in vitro and in vivo by inhibiting DNA repair after γ-irradiation. P2Y12 receptor antagonists Clopidogrel and PSB0739 increased cellular sites of unrepaired DNA by suppressing the DNA damage response (DDR) after γ-irradiation and enhanced radiation-induced proliferative death in B16 melanoma cells. On the other hand, ADP (a P2Y12 receptor agonist) enhanced DDR after γ-irradiation and increased radioresistance. Knockdown of the P2Y12 receptor resulted in an increase of unrepaired DNA damage and enhanced proliferative death after γ-irradiation. Suppression of the P2Y12 receptor also contributed to the enhancement of the cancer-killing effect of γ-irradiation, even in fractionated irradiation samples in which the cancer-killing effect decreased due to sublethal damage recovery. Finally, PSB0739 significantly enhanced the antitumor effect of γ-irradiation in vivo. Our results suggest that P2Y12 receptor antagonists are promising candidates as radiosensitizers to improve radiation therapy.
Ginsenoside Rb1 Alleviates Asthma Inflammation by Regulating Mitochondrial Dysfunction through SIRT1/PGC-1α and PI3K/AKT Pathways.
Li H, Piao Y, Bai Q … +6 more , Han X, Yinling X, Shen L, Yan G, Song Y, Piao Y
Biol Pharm Bull · 2025 · PMID 41242748 · Publisher ↗
The aim of this study was to investigate whether ginsenoside Rb1 attenuates cockroach extract (CRE)-induced asthma by interfering with mitochondrial dysfunction. After induction with CRE, mice were administered different...
The aim of this study was to investigate whether ginsenoside Rb1 attenuates cockroach extract (CRE)-induced asthma by interfering with mitochondrial dysfunction. After induction with CRE, mice were administered different doses of Rb1. Hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and flow cytometry analysis revealed that inflammatory cell infiltration, total immunoglobulin E (IgE) and CRE-specific IgE in serum, and inflammatory cytokines in bronchoalveolar lavage fluid were effectively inhibited by Rb1. Through Western blot, TUNEL, and immunofluorescence colocalization assays, we observed Rb1 also inhibited endogenous reactive oxygen species (ROS), tightly associated with increased superoxide dismutase, catalase levels, and decreased malondialdehyde levels. Subsequently, the silent information regulator sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) pathway was activated, whereas the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was inhibited. Additionally, Rb1 could rescue mitochondrial dysfunction by promoting the mitochondrial fusion protein mitofusion 1 (MFN1) and inhibiting dynamin-related protein 1 (DRP1) expression and apoptosis in the lungs. In BEAS-2B cells, Rb1 plays a role similar to that of a SIRT1 agonist (SRT1720), including enhancing mitochondrial membrane potential and decreasing mitochondrial ROS and DRP1 translocation to mitochondria. Our findings suggest that Rb1 maintains mitochondrial integrity by activating SIRT1/PGC-1α and inhibiting PI3K/AKT, thereby ameliorating asthmatic airway inflammation.
Effects of Metformin on High Glucose- and UVA-Induced Oxidative Stress and Cellular Senescence in Rat Keratinocytes.
Tada T, Sakamoto R, Wajima T
Biol Pharm Bull · 2025 · PMID 41224263 · Publisher ↗
This study investigated the protective effects of metformin against combined high glucose (HG)- and UVA-induced cytotoxicity in fetal rat skin keratinocytes (FRSK cells), a model of diabetic photoaging. HG combined with...
This study investigated the protective effects of metformin against combined high glucose (HG)- and UVA-induced cytotoxicity in fetal rat skin keratinocytes (FRSK cells), a model of diabetic photoaging. HG combined with UVA caused a synergistic loss of cell viability accompanied by marked increases in phosphorylation of AMP-activated protein kinase (p-AMPK), reactive oxygen species (ROS) generation, senescence-associated β-galactosidase (SA-β-Gal) activity, and Sirtuin 1 (SIRT1) expression. HG alone induced moderate cytotoxicity and senescence, whereas UVA alone under normal glucose conditions (NG + UVA) produced negligible ROS and minimal viability loss. Metformin improved cell viability under dual stress conditions in a dose-dependent manner, with maximal protection observed at 8 mM. In UVA-free cultures, metformin increased p-AMPK in both NG and HG, peaking at 8 mM. Under HG + UVA, p-AMPK was higher than in NG + UVA and HG alone, with no additional increase following metformin treatment. ROS accumulation occurred only under HG + UVA and was strongly suppressed by metformin, nearly to baseline at 8 mM. The HG + UVA-induced increases in SA-β-Gal activity and SIRT1 expression were reduced in parallel with ROS suppression. These findings suggest that metformin's cytoprotective effect in this model is primarily mediated by attenuation of ROS rather than by further AMPK activation, indicating an AMPK-independent antioxidant mechanism.
Human Plasma and Urine Concentrations of Triethylamine and Its N-Oxide after Oral Administration Extrapolated Using Pharmacokinetic Modeling: Comparison with Trimethylamine and Its N-Oxide.
Shimizu M, Shimura Y, Yamazaki H
Biol Pharm Bull · 2025 · PMID 41207682 · Publisher ↗
In Japan, the simple N-substituted substances triethylamine and trimethylamine have been designated possibly hazardous air pollutants also requiring further investigation to protect the aquatic environment. Triethylamine...
In Japan, the simple N-substituted substances triethylamine and trimethylamine have been designated possibly hazardous air pollutants also requiring further investigation to protect the aquatic environment. Triethylamine is relevant to human biomonitoring in manufacturing workers because of its possible adverse effects; in contrast, trimethylamine exposure from normal daily dietary consumption is considered nontoxic. Although a role for flavin-containing monooxygenase 3 in the metabolism of triethylamine was recently reported, no simplified physiologically based pharmacokinetic (PBPK) model to estimate human plasma and urinary levels of triethylamine and its N-oxide has currently been developed. In this study, in silico human plasma and urine concentrations of triethylamine were estimated after virtual oral administration using a newly established triethylamine PBPK model. The results were compared with our previously established trimethylamine PBPK model. In silico plasma and urinary concentration curves were generated after single virtual administrations of triethylamine and trimethylamine. After 28 d of daily exposure to reported maximum oral doses of triethylamine and trimethylamine from the public water supply of 0.02 and 0.68 µg/kg body weight/d, respectively, the mean modeled urinary levels for the final day were 3.7 and 1.1 pmol/mL. The proposed occupational standard of 10 mg triethylamine/m of air reportedly corresponds to a urinary excretion of approx. 0.4 nmol/mL. The results of the current forward dosimetry analyses, therefore, indicate at least a two-order safety margin (drinking water versus occupational standard) for triethylamine. The present PBPK model for triethylamine and its N-oxide could estimate daily exposures using forward dosimetry and thereby facilitate risk assessment in humans.
Catheter-Related Bloodstream Infection in Patients Receiving Vitamin-Enriched Peripheral Parenteral Nutrition: A Retrospective Cohort Study.
Miura Y, Oshizaka T, Kawakubo R … +4 more , Mizoguchi M, Mori K, Sugibayashi K, Iizuka Y
Biol Pharm Bull · 2025 · PMID 41207681 · Publisher ↗
In vitro studies have reported that multiple vitamins may promote bacterial growth and infection. In clinical practice, patients receiving peripheral parenteral nutrition (PPN) may develop catheter-related bloodstream in...
In vitro studies have reported that multiple vitamins may promote bacterial growth and infection. In clinical practice, patients receiving peripheral parenteral nutrition (PPN) may develop catheter-related bloodstream infections (CRBSIs). Since some PPN formulations contain multiple vitamins, they may increase the risk of CRBSIs. Therefore, the present study investigated the relationship between PPN infusions containing vitamins and the incidence of CRBSIs and examined the effects of different antiseptics used before catheter insertion. Patients were divided into the following groups: those receiving the BFLUID injection (1 vitamin), those receiving the PAREPLUS injection (9 vitamins), those disinfected with povidone iodine before the PAREPLUS injection, and those disinfected with chlorhexidine alcohol before the PAREPLUS injection. We analyzed infection rates in each group. The PAREPLUS group showed a significantly higher rate of infections by Staphylococcus species. Furthermore, a longer duration of PPN administration (≥2 weeks) was associated with a higher risk of CRBSI across all detected pathogens. Vitamin-enriched PPN increased approximately 2-fold in CRBSI compared with a thiamine-only formulation, independent of infusion duration. However, the incidence of CRBSI did not significantly differ between the different antiseptic groups. These results suggest that proper infection control and careful management are essential during PPN therapy, especially when multiple vitamin products are used over extended periods.
Comparison of the Risk of Paradoxical Psoriasis between Monoclonal Antibody and Non-monoclonal Antibody Tumor Necrosis Factor-α Inhibitors in Patients with Rheumatoid Arthritis: An Observational Study Using a Claims Database.
Shimazaki M, Matsuyama Y, Koide D
Biol Pharm Bull · 2025 · PMID 41192884 · Publisher ↗
Tumor necrosis factor-α inhibitors (TNFis) are associated with a risk of paradoxical psoriasis, but quantitative data remain limited. One proposed mechanism is the induction of interferon (IFN) production following TNFi...
Tumor necrosis factor-α inhibitors (TNFis) are associated with a risk of paradoxical psoriasis, but quantitative data remain limited. One proposed mechanism is the induction of interferon (IFN) production following TNFi administration. Etanercept and certolizumab pegol, which contain immunoglobulin fragments in their structures, reportedly induce IFN production in T cells more than monoclonal antibody (mAb) TNFi agents. Based on this, we hypothesized that non-mAb TNFi agents might carry a higher risk of paradoxical psoriasis than mAb agents. This study compared the risk of paradoxical psoriasis between mAb and non-mAb TNFi agents in rheumatoid arthritis (RA) patients. Using a claims database, we identified 1577 subjects in the mAb group and 1517 in the non-mAb group. Patient characteristics, including sex, age, and prior RA treatment, were extracted, and the onset of psoriasis was identified. Multivariable Cox regression analysis showed the hazard ratio (HR) for psoriasis onset in the mAb group versus the non-mAb group was 1.66 (95% confidence interval [CI]: 0.79-3.48). Subgroup analyses revealed that compared to etanercept, the HR for adalimumab was 1.43 (95% CI: 0.49-4.19), and compared to certolizumab pegol, it was 0.67 (95% CI: 0.19-2.39). These findings suggest that our hypothesis was not supported and that the risk of paradoxical psoriasis may vary even among non-mAb agents, as indicated by differences observed between etanercept and certolizumab pegol.
Development and Stability of a New Transdermal Formulation of Pregabalin for Skin Permeation.
Sakama R, Nagao M, Tajima M … +4 more , Takano M, Yoshikawa M, Sato H, Sugiyama E
Biol Pharm Bull · 2025 · PMID 41192883 · Publisher ↗
Pregabalin is a first-line treatment for neuropathic pain, but its oral use is often limited by central nervous system side effects, which may require dose reduction or discontinuation. A transdermal formulation may help...
Pregabalin is a first-line treatment for neuropathic pain, but its oral use is often limited by central nervous system side effects, which may require dose reduction or discontinuation. A transdermal formulation may help minimize this adverse effect. The aim of this study was to improve the skin permeability of pregabalin by assessing the feasibility of in-hospital preparation and evaluating its stability in the early stages of formulation development. A 0.4% pregabalin formulation was prepared using hydrophilic cream, lipophilic cream, and pluronic lecithin organogel (PLO) gel. Ex vivo skin permeation studies were conducted using Franz diffusion cells and excised dorsal skin from hairless male mice (HR-1, 7 weeks old). Samples were collected over time and analyzed by LC-tandem MS. Drug content, pH, and viscosity were assessed under 2 storage conditions (25°C/60% relative humidity [RH] and 40°C/75% RH) to evaluate stability. The hydrophilic cream showed the highest cumulative drug permeation, flux, and permeability coefficient. Penetration enhancers added to the PLO gel did not improve absorption. Drug content remained stable under 25°C/60% RH. An inverse correlation was observed between viscosity and drug permeation, suggesting that lower viscosity facilitated diffusion. pH values remained within the physiological range, indicating low irritation potential. The hydrophilic cream demonstrated superior transdermal delivery characteristics for pregabalin. These findings support its potential as an effective and safe alternative to oral administration for managing neuropathic pain.
Inhibitory Effect of Insulin-Degrading Enzyme-Selective Inhibitor, Ii1, on the Elimination of Amyloid-β(1-40) from Rat Brain.
Shiiki T, Ohtsuki S
Biol Pharm Bull · 2025 · PMID 41192882 · Publisher ↗
Amyloid-β peptide (Aβ) is eliminated from the brain across the blood-brain barrier (BBB) by an insulin-sensitive process. To investigate the involvement of insulin-degrading enzyme (IDE) in this process, the present stud...
Amyloid-β peptide (Aβ) is eliminated from the brain across the blood-brain barrier (BBB) by an insulin-sensitive process. To investigate the involvement of insulin-degrading enzyme (IDE) in this process, the present study was implemented to clarify the effect of a novel IDE-specific inhibitor, Ii1, on the elimination of [I]Aβ(1-40) from rat brain via the brain efflux index method. The results showed that such elimination was significantly inhibited by the co-administration of Ii1. The maximum inhibitory effect of Ii1 and IC were 69.4% and 9.96 µM, respectively. Insulin alone inhibited the elimination of [I]Aβ(1-40), but the inhibitory effect of co-administering insulin and Ii1 was not significantly different from that of Ii1 alone. Meanwhile, thiorphan, an inhibitor of neprilysin, showed an additive inhibitory effect with Ii1. Aβ(1-13) and Aβ(1-14), which are major fragments produced by the degradation of Aβ(1-40) by IDE, and inhibitors of receptor for advanced glycation end products (RAGE) did not significantly inhibit the [I]Aβ(1-40) elimination. These results suggest that IDE is involved in the insulin-sensitive process of [I]Aβ(1-40) elimination across the BBB, to which neprilysin and RAGE make minor contributions. These findings suggest that impairment of IDE may be involved in the onset of sporadic Alzheimer's disease.
Magnetic Delivery of Paclitaxel by Magnetic Anionic Liposome/Atelocollagen Complexes for Targeted Cancer Therapy.
Kono Y, Okada R, Tanaka M … +1 more , Ogawara KI
Biol Pharm Bull · 2025 · PMID 41192881 · Publisher ↗
Magnetic drug carriers are a valuable tool for site-specific drug delivery, utilizing both passive targeting via the enhanced permeability and retention effect and active targeting through magnetic forces. We previously...
Magnetic drug carriers are a valuable tool for site-specific drug delivery, utilizing both passive targeting via the enhanced permeability and retention effect and active targeting through magnetic forces. We previously developed magnetic anionic liposome (Mag-AL)/atelocollagen (ATCOL) complexes and demonstrated their efficient accumulation at the targeted tissue through magnetic attraction and electrostatic interactions. To assess the usefulness of Mag-AL/ATCOL complexes as tumor-targeted drug delivery carriers, we herein prepared paclitaxel (PTX)-loaded Mag-AL/ATCOL complexes and examined their cellular association and cytotoxicity in C26 murine colon adenocarcinoma cells. The biodistribution of the complexes and their antitumor efficacy were also investigated in C26-bearing mice. PTX-Mag-AL/ATCOL complexes exhibited significant binding to C26 cells under an external magnetic field and released PTX in a sustained manner. Consequently, cytotoxic effects against C26 cells were achieved by PTX-Mag-AL/ATCOL complexes with the application of a magnetic field. Moreover, PTX-Mag-AL/ATCOL complexes preferentially distributed in the spleen and liver after their intravenous administration into C26 tumor-bearing mice, while tumor accumulation showed an approximately 2.9-fold augmented by the application of an external magnetic field to the tumor. Due to this magnetic guidance, PTX-Mag-AL/ATCOL complexes significantly inhibited C26 tumor growth. These results indicate that Mag-AL/ATCOL complexes have the potential to improve the therapeutic efficacy of anticancer drugs as magnetic drug carriers.
Notice of Retraction.
Biol Pharm Bull · 2025 · PMID 41183893 · Publisher ↗
Abstract loading — click title to view on PubMed.
Treatment of Experimental Autoimmune Encephalomyelitis with Lipid Nanoparticles Loaded with siRNA Targeting Neogenin.
Shimizu K
Biol Pharm Bull · 2025 · PMID 41183892 · Publisher ↗
Multiple sclerosis (MS) develops due to an abnormal T-cell immune response to autoantigens and control of T-cell activation is a mainstream approach for its treatment. In the present study, neogenin, a key molecule for T...
Multiple sclerosis (MS) develops due to an abnormal T-cell immune response to autoantigens and control of T-cell activation is a mainstream approach for its treatment. In the present study, neogenin, a key molecule for T-cell activation, was used as a targeted molecular gene therapy for MS. Lipid nanoparticles (LNPs) loaded with small interfering RNA (siRNA) targeting neogenin (LNPsiNeo) were prepared, and their therapeutic effect on experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein, a model of MS was evaluated. Neogenin gene expression was reduced by LNPsiNeo in mouse EL-4 cells and splenocytes of LNPsiNeo-treated EAE mouse. Additionally, fluorescence-activated cell sorting (FACS) revealed that the number of CD4 T cells in the splenocytes of EAE mouse decreased after intravenous injection of LNPsiNeo. Furthermore, the progression of encephalomyelitis symptoms was significantly suppressed by LNPsiNeo, whereas the lipid nanoparticle with control siRNA failed to show any effect. The present study suggests that neogenin is a target molecule for EAE gene therapy and LNPsiNeo may be suitable for the MS treatment.
Analysis of the Thermotropic Phase Transitions of Liposomal Phosphatidylcholine Using Differential Scanning Fluorimetry.
Aoki C, Bamba Y, Uchida M … +3 more , Kogure Y, Sugiki T, Sakai-Kato K
Biol Pharm Bull · 2025 · PMID 41183891 · Publisher ↗
Liposomes are small vesicles composed of lipid bilayers, which have been widely studied and are used in drug delivery systems (DDSs). The lipid bilayers, as two-dimensional liquid crystalline structures, show different p...
Liposomes are small vesicles composed of lipid bilayers, which have been widely studied and are used in drug delivery systems (DDSs). The lipid bilayers, as two-dimensional liquid crystalline structures, show different phase states, and temperature-dependent phase transitions occur as a result of the thermotropic alteration of the physicochemical properties of the lipid bilayers, resulting in drastic changes in the morphology and dynamics of the fluctuations of the lipid bilayers. Analysis of the thermotropic phase behavior of the liposomal lipid bilayer is crucial for the development and application of functional liposomes for DDSs. We constructed a differential scanning fluorimetry (DSF) method that enabled observation and analysis of the thermotropic phase transitions and temperatures of liposomal lipid bilayers using a real-time PCR device and solvatochromic dyes, which have fluorescence characteristics that reflect alterations in the polar environment. This DSF method using Nile Red and a tandem thermal sequence enabled analysis of the phase transition temperatures of three liposomal phosphatidylcholines, and not only the T and T, but also the T values, except for the T value of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, were clearly determined. Other solvatochromic dyes could not be used to determine the T values clearly. The measured phase transition temperatures of three liposomal phosphocholines correlated well with the reported values. Our DSF method has several practical advantages over the typical thermal analytical method, differential scanning calorimetry, including reduced sample volume and analytical time, which may contribute to expanding the opportunities for the physicochemical analysis of liposomal lipid bilayers.
Relationship between Phase Transition and Drug Release of Doxorubicin-Encapsulated Liposomes with Different Lipid Compositions Using Raman Spectroscopy.
Yamada R, Sato T, Haneishi K … +5 more , Hisada H, Fujii MY, Hirota K, Koide T, Fukami T
Biol Pharm Bull · 2025 · PMID 41183890 · Publisher ↗
Liposomes have a more complex structure than conventional low-molecular-weight pharmaceuticals, so there is concern that quality evaluation items will be diverse and evaluation methods will be complex. Raman spectroscopy...
Liposomes have a more complex structure than conventional low-molecular-weight pharmaceuticals, so there is concern that quality evaluation items will be diverse and evaluation methods will be complex. Raman spectroscopy has recently attracted attention as a Process Analytical Technology in the pharmaceutical manufacturing, and its application is expected to expand to biopharmaceuticals and other drugs with complex manufacturing in the future. We have demonstrated that the combination of probe-type Raman spectrometer and partial least squares analysis enables real-time quantification of drug inclusion rate and drug release rate from liposomes, and is useful as a new quality assessment method for liposomes. In this study, we evaluated the phase transition of drug-encapsulated liposomes and the accompanying drug release by using Raman spectroscopy. Drug-encapsulated liposomes were prepared by preparing liposomes with different cholesterol (CHOL) ratios. The phase transition and drug release of liposomes were evaluated by using Raman spectroscopy. Raman spectroscopic measurements showed that the peak intensity of the phase transition was large in systems with low CHOL ratios, while it was low in systems with high CHOL ratios. In the drug release test, a decrease in the peak intensity of the drug-derived spectra over time was observed significantly in the low CHOL ratio system compared to the high CHOL ratio system which is supposed to release drug lower due to liquid-ordered phase, suggesting that the drug release property increased in the low CHOL system. Thus, Raman spectroscopy can be used to evaluate the phase transition and the associated drug release properties of liposomes.
Mitochondrial Activation and Therapeutics: Innovations in Cell- and Organelle-Specific Medicine.
Sato I, Shiraishi M, Norota K … +2 more , Shiraki K, Yamada Y
Biol Pharm Bull · 2025 · PMID 41183889 · Publisher ↗
Mitochondria are essential for cellular functions, including ATP production, calcium homeostasis, oxidative stress regulation, and apoptosis. Mitochondrial dysfunction is associated with a variety of diseases, including...
Mitochondria are essential for cellular functions, including ATP production, calcium homeostasis, oxidative stress regulation, and apoptosis. Mitochondrial dysfunction is associated with a variety of diseases, including neurodegenerative disorders, skeletal muscle diseases, and mitochondrial diseases. This review explores the latest mitochondrial-targeted therapeutic approaches across the following key perspectives: (1) technological innovations in mitochondrial transplantation, focusing on tunnel nanotubes and extracellular vesicles; (2) the role of mitochondria in skeletal muscle diseases and therapeutic activation strategies; (3) advances in mitochondrial enhancement techniques within cell therapy, particularly in pediatric applications; and (4) the latest treatment modalities for mitochondrial diseases, such as gene and cell therapies. Taken together, these strategies demonstrate the transformative potential of mitochondrial targeting in cell- and organelle-specific medicine. Additionally, the MITO-Porter system is highlighted as an innovative drug delivery platform contributing to these advances.
Cryogenic Transmission Electron Microscopy for the Evaluation of Lipid-Based Nanomedicines: Principles, Applications, and Challenges.
Takechi-Haraya Y
Biol Pharm Bull · 2025 · PMID 41183888 · Publisher ↗
Lipid-based nanomedicines (LBNs), including liposomes and mRNA-lipid nanoparticles, have propelled modern drug delivery research; however, they possess significant challenges regarding structural characterization. Cryoge...
Lipid-based nanomedicines (LBNs), including liposomes and mRNA-lipid nanoparticles, have propelled modern drug delivery research; however, they possess significant challenges regarding structural characterization. Cryogenic transmission electron microscopy (cryo-TEM) preserves LBNs in a near-native, hydrated state, enabling high-resolution imaging of both external and internal features. This review discusses the key principles of cryo-TEM, highlights its advantages in characterizing LBNs, and addresses challenges such as precise sample preparation, beam-induced damage, and complexities in analyzing polydisperse specimens. Nevertheless, ongoing advances in instrumentation and workflow automation continue to expand the accessibility and data quality of cryo-TEM. Standardizing protocols and developing reference materials would further strengthen data reproducibility and facilitate regulatory considerations. By offering unparalleled insight into LBN morphology and functionality, cryo-TEM stands at the forefront of nanomedicine development, guiding both fundamental research and the optimization of next-generation therapeutic carriers.
Foreword.
Sakai-Kato K
Biol Pharm Bull · 2025 · PMID 41183887 · Publisher ↗
Abstract loading — click title to view on PubMed.
Qualitative Changes in Collagen Induced by UV Irradiation Affect Its Interaction with Cells.
Asari A, Sakaue H, Kumagai T … +3 more , Ozeki M, Mizuno K, Sato T
Biol Pharm Bull · 2025 · PMID 41161787 · Publisher ↗
The extracellular matrix (ECM) is a noncellular component in all tissues and organs. Collagen, a component of the ECM, is the most abundant protein in the body. The amount of collagen decreases with aging, leading to wri...
The extracellular matrix (ECM) is a noncellular component in all tissues and organs. Collagen, a component of the ECM, is the most abundant protein in the body. The amount of collagen decreases with aging, leading to wrinkles and skin sagging. Accelerated aging caused by UV radiation is known as photoaging. Skin fibroblasts exposed to UVB have reduced total collagen content due to accelerated production of collagen-degrading enzymes, matrix metalloproteinases (MMPs), and suppression of collagen production. However, the effects of UVB on the ECM surrounding the cell and its interaction with the cell have not been well reported. This study sought to elucidate the effects of UVB-induced changes in the extracellular environment on cells. UVB-irradiated collagen exhibited irradiation-dependent degradation and accelerated carbonylation, resulting in qualitative changes. UVB-induced changes in collagen led to reduced cell-collagen interactions, such as adhesion, proliferation, and contraction. Moreover, UVB-irradiated collagen was more susceptible to collagen degradation by MMP-1. UVB-induced changes in collagen were analyzed using mass spectrometry (LC-MS/MS). Although alternation of post-translational modification was not detected in the cell-bound regions of collagen, multiple sites of carbonylative modification were detected on proline (Pro), arginine (Arg), and lysine (Lys). The numerous carbonylative modifications to Pro, Arg, and Lys in collagen may cause changes in the overall structure of collagen and affect cellular functions that are regulated by the interaction with collagen. Overall, our findings highlight a photoaging mechanism that focuses on the effects of ECM changes on cells.
Evaluation of the Potential Inhibitory Effects of Medications for Detrusor Overactivity on Platelet-Activating Factor (PAF)-Induced Mechanical Activity in Guinea Pig Bladder Smooth Muscle.
Obara K, Makino F, Tanaka M … +4 more , Iwata S, Fujiwara M, Yoshioka K, Tanaka Y
Biol Pharm Bull · 2025 · PMID 41161786 · Publisher ↗
This study aimed to determine whether currently available medications for detrusor overactivity (DO) can inhibit the platelet-activating factor (PAF)-induced increase in the mechanical activity of the urinary bladder smo...
This study aimed to determine whether currently available medications for detrusor overactivity (DO) can inhibit the platelet-activating factor (PAF)-induced increase in the mechanical activity of the urinary bladder smooth muscle (UBSM) in guinea pigs. Ten clinically used DO drugs-oxybutynin, tolterodine, fesoterodine, propiverine, propantheline, solifenacin, imidafenacin, flavoxate, urapidil, and clenbuterol-were tested at a concentration of 10 μM, exceeding typical therapeutic plasma levels. Among these, oxybutynin exerted the most pronounced inhibitory effect, reducing the PAF (1 μM)-induced increase in basal tone by approximately 60%. Furthermore, oxybutynin (10 μM) also decreased 60 mM KCl-induced contractions by a similar extent and nearly abolished acetylcholine (ACh, 10 μM)-induced contractions. These findings suggest that oxybutynin suppresses PAF-induced UBSM hyperactivity through a mechanism distinct from its anticholinergic effect, likely mediated by blockade of voltage-dependent Ca channels (VDCCs).
Safety Assessment of Air-Ultrafine Bubbles Measured, Transported, and Stored According to ISO Standards for Dermal, Ocular, and Oral Applications.
Morishita R, Suwabe S, Takeda-Morishita M
Biol Pharm Bull · 2025 · PMID 41161785 · Publisher ↗
Fine bubbles (FBs), which are microscopic bubbles with a particle size less than 100 μm, have been increasingly utilized in industrial fields. They have been widely adopted across various industries including agriculture...
Fine bubbles (FBs), which are microscopic bubbles with a particle size less than 100 μm, have been increasingly utilized in industrial fields. They have been widely adopted across various industries including agriculture, fisheries, and cleaning. Furthermore, FBs are negatively charged colloids that can encapsulate various gases, leading to their potential use in the medical field. However, information on the biological safety of ultrafine bubbles (UFBs) remains limited. In particular, no safety evaluations of UFBs have been reported using internationally standardized protocols. Therefore, this study comprehensively evaluated the biological safety of air-UFB water that was measured, transported, and stored according to International Organization for Standardization (ISO) standards. To this end, in vitro skin irritation and eye irritation tests, as well as an in vivo 28-d repeated-dose oral toxicity test, were conducted in accordance with international protocols. The results of both in vitro tests showed that UFB water was classified as "Not classified" under the United Nations Globally Harmonized System of Classification and Labelling of Chemicals and was considered non-irritating and not seriously damaging to the skin or the eyes. Similarly, the abnormal changes attributable to the administration of UFB water were not observed in blood biochemistry and hematology tests, organ weights and histopathological evaluations on the in vivo test. These results, in which no toxicity attributable to UFBs was observed in dermal, ocular, or oral tests, support the fundamental safety of ISO-certified air-UFB water.
Oligodendroglia Generate Vascular Mural Cells and Neurons in the Adult Mouse Brain.
Xu T, Yu Q, Huang M … +4 more , Yang K, Yang Z, He X, Yuan F
Biol Pharm Bull · 2025 · PMID 41161784 · Publisher ↗
Oligodendroglia encompass oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs). In the grey matter of the cortex, nearly all OPCs divide slowly, yet they do not differentiate solely into mature OLs, leaving...
Oligodendroglia encompass oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs). In the grey matter of the cortex, nearly all OPCs divide slowly, yet they do not differentiate solely into mature OLs, leaving the exact role of these OPCs in the grey matter enigmatic. Oligodendroglia were traced using the sex-determining region Y-related high mobility group-box 10 (Sox10) Cre-ER reporter mice. We compared the effect of tamoxifen dissolved in different solvents on the fate of Sox10 cells. We also compared the effect of tamoxifen dosage on the fate of Sox10 cells. The differentiation of labeled red fluorescent protein (RFP) cells was analyzed using immunofluorescence staining. Two groups of RFP cells, type A Sox10 (Sox10-A) cells and type B Sox10 (Sox10-B) cells, were identified in the cortex, striatum, hippocampus, thalamus, and hypothalamus. Sox10-A cells differentiate into platelet-derived growth factor receptor-β+, CD13+ pericytes, and smooth muscle myosin heavy chain 11+ smooth muscle cells when the mice received ethanol or high-dose tamoxifen. Sox10-B cells transform into glutamatergic neurons when the mice received high-dose tamoxifen. Sox10-B cells include perineuronal OPCs and OLs. This investigation provides evidence that a substantial proportion of oligodendroglia in the grey matter serve as mural cell precursors and neuronal precursors. These two phenomena may contribute to our understanding of the fate of oligodendroglia.
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