Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
  • 46 巻 (2023) 9 号 p. 1223-1230
    Therapeutic Effect of Colony Stimulating Factor 1 Receptor Kinase Inhibitor, JTE-952, on Methotrexate-Refractory Pathology in a Rat Model of Rheumatoid Arthritis もっと読む

    Effectively preventing the structural destruction of joints, particularly bone and cartilage, which progresses due to resistance to conventional anti-inflammatory drugs, is one of the unmet medical needs in the treatment of rheumatoid arthritis (RA). In this study, the authors investigated the therapeutic effects of JTE-952, a novel colony-stimulating factor-1 receptor (CSF1R) kinase inhibitor, on methotrexate-resistant joint destruction using a rat model of RA, adjuvant-induced arthritis. Blocking CSF1/CSF1R signaling with JTE-952 did not suppress paw swelling under inflammatory conditions, but it did suppress the destruction of joint structural components, including bone and cartilage, in inflamed joints and may improve subsequent joint dysfunction.

  • 46 巻 (2023) 9 号 p. 1240-1248
    Metallothionein Gene Deficiency Facilitates the Differentiation of C2C12 Myoblasts into Slow-Twitch Myotubes もっと読む

    Fast-to-slow fiber transition in skeletal muscle occurs during aging and has been implicated in muscle atrophy in sarcopenia, but the mechanism is unclear. Authors showed that metallothionein 1 and 2 gene knockout (MTKO) using the CRISPR-Cas9 system promoted to myogenic differentiation of C2C12 myoblasts, which was accompanied by an increased number of slow-twitch myotubes. The increased slow-type myotubes in MTKO cells was inhibited by an antioxidant N-acetylcysteine, suggesting that MT may be involved in specification of skeletal muscle fiber-type due to its antioxidant capacity. This study may help to elucidate the mechanisms of age-related muscle weakness.

  • 46 巻 (2023) 9 号 p. 1296-1303
    Descriptive Study on a Nationwide Exploratory Questionnaire Survey of Emergency Contraceptive Pills and Their Sexual History and Knowledge in Japan もっと読む

    In Japan, the move towards non-prescription emergency contraceptives is under discussion. A nation-wide survey of 4,631 women conducted by the authors revealed that nearly half of them lacked accurate knowledge about emergency contraceptives. Total of 43.6% of women with previous experience needing emergency contraceptives chose not to use them voluntarily. To address this, the authors emphasize the importance of comprehensive sex education, and promoting understanding of emergency contraceptives among women in Japan.

  • 46 巻 (2023) 9 号 p. 1310-1315
    Non-invasive Microneedle Application Increases Ceramide and Natural Moisturizing Factors in a Reconstructed Human Skin Model もっと読む

    Microneedles are microscopic needle structures with lengths of several hundred micrometers, and have attracted attention as one way to improve skin barrier and moisturizing functions as cosmetic product. However, conventional microneedles are thought to work by penetrating the stratum corneum, which carries the risk of side effects. Therefore, in this study, the authors applied microneedles non-invasively without penetrating the stratum corneum and investigated their effects on the skin. The results showed that microneedles can improve skin barrier and moisturizing functions even when applied non-invasively. This study provides valuable insights for the development of new cosmetic techniques using microneedles.

  • 46 巻 (2023) 9 号 p. 1343-1346
    Dietary Zinc Deficiency Induces Cav3.2-Dependent Nociceptive Hypersensitivity in Mice もっと読む

    The activity of Cav3.2 T-type calcium channels expressed in the sensory neurons is reduced by physiological concentrations of zinc. Sulfides including hydrogen sulfide (H2S), a gasotransmitter, enhance the channel activity by removing zinc from Cav3.2, leading to the increased pain sensitivity. Dietary zinc deficiency causes Cav3.2-dependent mechanical allodynia in mice. Exogenously applied sulfides produce Cav3.2-dependent allodynia in the mice fed with normal diet, but do not affect the already developed allodynia in the mice fed with zinc-deficient diet. Thus, the authors suggest that the enhanced Cav3.2 activity participates in the development of pathological pain associated with zinc deficiency.

  • 46 巻 (2023) 8 号 p. 1049-1056
    Inhibitors of the Mechanistic Target of Rapamycin Can Ameliorate Bortezomib-Induced Peripheral Neuropathy もっと読む

    Bortezomib-induced peripheral neuropathy (BIPN), an adverse effect of chemotherapy, can cause patients to suffer from neuropathic pain and lead to drug withdrawal. The authors attempted to explore effective therapeutic targets for BIPN by combining real-world data analysis with in vivo experiments. In the analysis of self-reported adverse event data, mechanistic target of rapamycin (mTOR) inhibitors reduced the incidence of peripheral neuropathy in bortezomib-treated patients. In bortezomib-treated mice, mTOR inhibitors or an inhibitor of ribosomal protein S6 kinase 1 (S6K1), a downstream molecule of mTOR complex 1, showed transient analgesic effects. These results suggest that S6K1 may be a therapeutic target for BIPN.

  • 46 巻 (2023) 8 号 p. 1065-1071
    Pharmacist–Urologist Collaborative Management for Patients with Renal Cell Carcinoma Receiving Pazopanib Monotherapy もっと読む

    The authors established an ambulatory care pharmacy practice that enables pharmacist–urologist collaboration for the treatment of patients with urologic cancer taking oral anti-cancer medications. In this manuscript, the authors sought to investigate the usefulness of pharmacist-urologist collaboration, considering the potential confounding factors, for patients with renal cell carcinoma treating pazopanib monotherapy. The results showed that the time to pazopanib discontinuation was significantly prolonged after the implementation of collaborative management by analyzing the multivariate Cox proportional hazards model. These results clearly indicated that the effectiveness of pharmacist-led team care in pharmacotherapies.

  • 46 巻 (2023) 8 号 p. 1098-1104
    Development of Functional Chimeric Nanoparticles by Membrane Fusion of Small Extracellular Vesicles and Drug-Encapsulated Liposomes もっと読む

    Small extracellular vesicles (sEVs) have been of interest as a drug delivery system (DDS) for various disease treatments, as they possess some advantages in drug delivery. However, certain issues in drug encapsulation, such as low encapsulation efficiency and poor reproducibility, are needed to be addressed. Herein, a new drug encapsulation approach has been developed which utilizes membrane fusion of sEVs and drug encapsulated liposomes composed of phosphatidylserine via the calcium fusion method. The fused-nanoparticles achieved efficient doxorubicin encapsulation as well as increased cellular uptake of liposomes. The present findings are expected to be applied for encapsulation of other therapeutic modalities into sEVs and development of sEV-like nanoparticles.

  • 46 巻 (2023) 8 号 p. 1128-1132
    Effect of a Single Dose of Oxaliplatin on the Induction of Peripheral Neuropathy in a Rat Model: An in Vivo Electrophysiological Study もっと読む

    The anticancer drug oxaliplatin (OXA) is associated with peripheral neuropathy as a side effect accompanied by mechanical and cold allodynia. Authors aimed to record and compare the firing of neurons in the deep and superficial layers of the spinal dorsal horn (SDH) in rats treated with a single dose of OXA. Authors found the comparison of neuronal firing frequencies carried out in the present study of a CIPN rat model treated with a single dose of OXA revealed that pain pathology is reflected more strongly by the superficial than by the deeper layer of the SDH.

  • 46 巻 (2023) 7 号 p. 907-913
    Decreased Analgesic Effect of Tramadol in Japanese Patients with CYP2D6 Intermediate Metabolizers after Orthopedic Surgery もっと読む

    Pharmacogenomic (PGx) testing can predict therapeutic responses or adverse effects based on genetic variants and is expected to be the preemptive precision medicine for patient management. Tramadol is metabolized by CYP2D6 to an active metabolite, which in turn acts as an analgesic. From the retrospective cohort study in Japanese patients with postoperative pain after orthopedic arthroscopic surgery, the authors demonstrated that the analgesic effect in the early postoperative period was depended on CYP2D6 gene polymorphism. These results suggested the clinical utility of preemptive treatment based on the PGx test, which can consider dose adjustment or drug change in advance.

  • 46 巻 (2023) 7 号 p. 939-945
    Transient Receptor Potential Ankyrin 1 in Taste Nerve Contributes to the Sense of Sweet Taste in Mice もっと読む

    TRP ankyrin 1 (TRPA1) is present in the afferent sensory neurons and is activated by food-derived ingredients, such as Japanese horseradish, cinnamon, and garlic. The present study aimed to investigate the expression of TRPA1 in taste buds, and determine its functional roles in taste perception using TRPA1-deficient mice. TRPA1-immunoreactivities are detectable in the taste nerve. TRPA1 deficiency significantly reduced sweet sensitivity compared to that in WT mice as per the two-bottle preference tests. Authors found that TRPA1 in the taste nerve contributes to the sense of sweet taste in mice.

  • 46 巻 (2023) 7 号 p. 946-954
    Dimethylglycine, a Methionine Metabolite, Participates in the Suppressive Effect of Methionine on 1-Fluoro-2,4-dinitrobenzene-Induced Dermatitis もっと読む

    Allergic contact dermatitis is a common dermatitis and is induced by contact with allergens. The authors found that methionine suppressed this dermatitis in some strains of mice. They also found that the strength of the effect depended on the suppression of liver betaine homocysteine methyltransferase (Bhmt) expression by the dermatitis. Although the mechanism has not been elucidated, the authors propose that while dermatitis suppresses liver Bhmt expression in some strains of mice, the fact that the metabolic state of the liver affects the suppression of dermatitis suggests that there is at least a skin-liver interaction, especially a dermatitis-liver interaction.

  • 46 巻 (2023) 7 号 p. 955-963
    ACTH/cAMP-Mediated Skin Pigmentation Caused by 5-Fluorouracil Administration もっと読む

    This study aimed to investigate the mechanism underlying the skin pigmentation caused by anticancer drugs using 5-fluorouracil (5-FU), a widely used anticancer drug known to cause this complication. Authors believe our study makes a significant contribution to the literature because anticancer drug-induced skin pigmentation remarkably affects the quality of life of cancer patients, has no established treatment, and has an unknown mechanism. This result provides new insight into the role of the ACTH/cAMP/tyrosinase pathway in 5-FU-mediated skin pigmentation and may help manage this complication.

  • 46 巻 (2023) 7 号 p. 969-978
    An 11-Beta Hydroxysteroid Dehydrogenase Type 1 Inhibitor, JTT-654 Ameliorates Insulin Resistance and Non-obese Type 2 Diabetes もっと読む

    11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is the only enzyme that converts inactive glucocorticoids to active forms and plays an important role in regulating glucocorticoid action in target tissues. Excess glucocorticoids cause insulin resistance in the liver and adipose tissue. Several 11β-HSD1 inhibitors have been reported, but all have been evaluated in obese diabetes models. In the present study, the authors investigated the pharmacological properties of JTT-654, a selective 11β-HSD1 inhibitor, in cortisone-treated rats and non-obese Goto-Kakizaki rats with type 2 diabetes, because many Asians, including Japanese, have non-obese type 2 diabetes. Information gained from detailed analysis of the mechanism of action of JTT-654 may provide a new therapeutic approach for the treatment of non-obese type 2 diabetic patients.

  • 46 巻 (2023) 6 号 p. 746-755
    Extravasation of Noncytotoxic Agents: Skin Injury and Risk Classification もっと読む

    A typical manifestation of iatrogenic injury associated with intravenous injection is extravascular leakage. The severity of injury and treatment for extravascular leakage of cytotoxic agents is well known, however there is insufficient information on non-cytotoxic agents. The authors reviewed human and animal studies of extravascular injury induced by non-cytotoxic agents and classified them based on the severity of injury. The classification of non-cytotoxic agents in the extravasation is useful information in clinical practice to provide appropriate warning of the risk of injury and to prevent worsening of injury.

  • 46 巻 (2023) 6 号 p. 796-802
    2′-Fucosyllactose Alleviates Early Weaning-Induced Anxiety-Like Behavior, Amygdala Hyperactivity, and Gut Microbiota Changes もっと読む

    Recently, evidence is accumulating on functional communication between the central nervous system (CNS) and the gut microbiota. Given this, early prebiotic treatment may assist the development of the CNS through the gut microbiota. In this study, Araki et al. found that 2'-fucosyllactose (2´-FL), a human milk oligosaccharide, altered the fecal microbiota and reduced anxiety-like behavior and amygdala hyperactivity observed in mice exposed to early weaning stress. These findings suggest that prebiotic treatment with 2´-FL may alleviate the adverse effects of early life stress in the CNS such as anxiety and amygdala hyperactivity.

  • 46 巻 (2023) 6 号 p. 830-839
    Isomerization of Oxidized Linoleate Metabolites with trans/cis Conjugated Diene Moiety to Those with trans/trans One in the Lipoxygenase/Linoleate/Hydrogen Polysulfide System もっと読む

    It is believed that 15-lipoxygenase plays a role in tissue damage under conditions of low oxygen levels through lipid-derived radical chain reactions. The authors of this study discovered that when a higher content of linoleate than oxygen content was stood with 15-lipoxygenase in the presence of hydrogen polysulfides, which are believed to be endogenous bioactive substance in cells, the conjugated diene moiety of the oxidized linoleate derivatives was isomerized from E/Z form to E/E form. Based on these findings, authors proposed a hypothesis that hydrogen polysulfides scavenge lipid-derived radicals, generating thiyl radicals, which then isomerized the conjugated diene moiety.

  • 46 巻 (2023) 6 号 p. 840-847
    Construction of a Temperature-Sensitive Shuttle Vector between Lactic Acid Bacteria and Escherichia coli and Its Application to a Tn10-Based Random Mutagenesis Tool in Lactic Acid Bacteria もっと読む

    Lactic acid bacteria (LABs) are well known as beneficial microorganisms to maintain human health. Although LABs are recognized as probiotics, these bacteria produce many kinds of bioactive compounds. The mechanisms how LABs produce these bioactive substances are not well known. Additionally, unlike the cases of E. coli and yeast, there are not enough commercially available tools for a genetic approach of LABs. Therefore, in the present study, the authors have constructed a new plasmid as an efficient genetic engineering tool for random insertional mutagenesis in LABs using a combination of transposon Tn10 and the temperature-sensitive replication system.

  • 46 巻 (2023) 6 号 p. 856-863
    Plasma and Hepatic Exposures of Celecoxib and Diclofenac Prescribed Alone in Patients with Cytochrome P450 2C9*3 Modeled after Virtual Oral Administrations and Likely Associated with Adverse Drug Events Reported in a Japanese Database もっと読む

    Although the potential for cytochrome P450 2C9 (CYP2C9) to cause drug interactions, there are few cases of information related to the influence of CYP2C9 polymorphism on drug labeling recommendations in Japan. Among the various factors related to adverse events in the database associated with the prescription of celecoxib or diclofenac alone, variations in the in vivo intrinsic clearance of the drug may exist. Virtual hepatic and plasma exposures estimated by pharmacokinetic modeling in patients harboring impaired CYP2C9*3 could represent a causal factor for adverse events induced by celecoxib or diclofenac in a manner similar to that for drug interactions.

  • 46 巻 (2023) 5 号 p. 700-706
    Regional Disparity in First-in-Class Anticancer Drug Development in the US, EU, and Japan もっと読む

    Recent improvement of pharmacotherapy on cancer is remarkable, however cancer is still one of the most devastating diseases for patients and their caregivers. The authors compared the development and approval status of first-in-class (FIC) anticancer drugs between the US, EU, and Japan, and found that approval in Japan lagged substantially behind compared to the other regions (more than 1 year vs the EU and more than 2 years vs the US). Considering the high impact of anticancer drugs on society worldwide, we should work together to reduce drug lag among regions using an improved international cooperative framework.