Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
  • 45 巻 (2022) 6 号 p. 703-708
    Effects of Concomitant Administration of PXR Ligand Drugs on the Anticoagulant Effects of Warfarin もっと読む

    Changes in drug-metabolizing activity via pregnane X receptor (PXR) is one of the mechanisms involved in drug-drug interactions. The authors reported cases in which the anticoagulant effects of warfarin were reversibly attenuated by the concomitant administration of rifampicin or bosentan, which are potent PXR ligands. However, no recovery of the response to warfarin was observed in the patients switched from bosentan to macitentan, which is considered not to activate PXR in clinical settings. The authors describe the importance of long-term monitoring and additional examinations to clarify the sustained mechanism for the drug interaction with warfarin, when switching from bosentan to macitentan.

  • 45 巻 (2022) 6 号 p. 709-719
    Comparison of the Concentration of Suspended Particles and Their Chemical Composition near the Ground Surface and Dust Extinction Coefficient by LIDAR もっと読む

    The dust extinction coefficient measured by light detection and ranging (LIDAR) has been used as an indicator of exposure to Asian dust in many epidemiological studies; however, few reports exist which explore the relationship between the dust extinction coefficient and the distribution of airborne particles near the ground surface. In this study, authors repot that the dust extinction coefficient is a useful indicator of Asian dust near the ground surface; however, as harmful air pollutants occasionally move with Asian dust, it is necessary to monitor these pollutants near the ground surface when conducting an epidemiological study on the health effect of airborne particles.

  • 45 巻 (2022) 6 号 p. 751-756
    Diurnal Changes in Protein Expression at the Blood–Brain Barrier in Mice もっと読む

    Circadian rhythms influence various physiological functions, including drug distribution and efficacy. However, the influence of circadian rhythms on the blood-brain barrier (BBB) remains unclear. Ogata et al. comprehensively investigated diurnal protein changes in mouse BBB by quantitative proteomics analysis. Expression of proteins associated with transport and physical barrier at the BBB remained constant throughout the day, whereas expression of proteins involved in protein synthesis, angiogenesis, and energy metabolism varied diurnally. These findings may help predict the biological responses to circadian changes in the BBB and brain drug distribution.

  • 45 巻 (2022) 6 号 p. 763-769
    Prediction Accuracy of Area under the Concentration–Time Curve of Vancomycin by Bayesian Approach Using Creatinine-Based Equations of Estimated Kidney Function in Bedridden Elderly Japanese Patients もっと読む

    An administration plan for vancomycin in bedridden elderly patients has not been established. This study evaluated the prediction accuracy of the Bayesian-derived area under the concentration-time curve (AUC) of vancomycin using creatinine-based equations for estimating kidney function in such patients. In this paper, the authors showed that the Bayesian approach using the estimated creatinine clearance calculated by substituting the serum creatinine level + 0.2 into the Cockcroft-Gault equation has the highest prediction accuracy for the AUC in bedridden elderly patients. These results may contribute to improving the efficacy and safety of vancomycin in such patients.

  • 45 巻 (2022) 6 号 p. 780-792
    Role of Mitochondrial Dysfunction in the Pathogenesis of Cisplatin-Induced Myotube Atrophy もっと読む

    Recently, chemotherapy-induced secondary sarcopenia has emerged as an important clinical issue; however, the underlying mechanisms are poorly understood. In this study, the authors focused on the possible involvement of mitochondrial disturbances in cisplatin-induced muscle atrophy using a cellular model. They concluded that mitochondrial dysfunction and the resultant generation of excessive reactive oxygen species (ROS), but not energy disruption, play a central role in cisplatin-induced C2C12 myotube atrophy. These results suggest that mitochondrial protection and/or ROS scavenging may be promising strategies for preventing muscle atrophy associated with cisplatin-based chemotherapy.

  • 45 巻 (2022) 5 号 p. 576-582
    The Effects of Sacran, a Sulfated Polysaccharide, on Gut Microbiota Using Chronic Kidney Disease Model Rats もっと読む

    Sacran, a type of new sulfated polysaccharide, is a biomaterial with excellent water solubility and safety, and is expected to be used in pharmaceuticals of the future. In the present study, sacran suppressed oxidative stress and inhibited the progression of chronic kidney disease (CKD). Sacran also had a multifaceted effect on the progression of CKD by altering the mix of intestinal microflora as a prebiotic in addition to the above effects. Thus, sacran is expected to have an effective nephroprotective effect especially when oxidative stress initially appears at the early stage of renal failure.

  • 45 巻 (2022) 5 号 p. 614-624
    PI3K/AKT1 Signaling Pathway Mediates Sinomenine-Induced Hepatocellular Carcinoma Cells Apoptosis: An in Vitro and in Vivo Study もっと読む

    Hepatocellular carcinoma is one of the most frequent cancers. Sinomenine (SIN) is a compound derived from Sinomenium acutum. Authors’ investigations have found that SIN suppressed SK-Hep-1 cells’ proliferation, enhanced the collapse of potential of the mitochondrial membrane, triggered cell apoptosis, down-regulated PI3K p85α, AKT1, BCL-2, Pro-Caspase 9, Pro-Caspase 3 expressions, and up-regulated Cleaved Caspase 9 and Cleaved Caspase 3 expressions. In addition, insulin-like growth factor-1 could reverse the high apoptosis of SK-Hep-1 cells induced by SIN. Therefore, authors revealed that inhibition of PI3K/AKT1 signaling cascade by SIN induced hepatocellular carcinoma cells apoptosis.

  • 45 巻 (2022) 5 号 p. 635-642
    Chronic Volume Overload Caused by Abdominal Aorto-Venocaval Shunt Provides Arrhythmogenic Substrates in the Rat Atrium もっと読む

    Atrial enlargement often provides arrhythmogenic substrates, leading to the induction of atrial fibrillation. The authors examined the anatomical, molecular biological, and electrophysiological characteristics of remodeled atria in rats with 8- and 12-week of aorto-venocaval shunt (AVS). It is noteworthy that marked electrophysiological changes were detected only in the AVS-12W rat despite obvious increments in atrial and ventricular tissue weights and altered gene expression in the AVS-8W rat, which suggests that the electrical remodeling observed in the atrium is preceded by structural remodeling after AVS surgery. These findings provide important information on experimental evidence regarding the timing of generation of arrhythmogenic substrate in the atria.

  • 45 巻 (2022) 5 号 p. 649-658
    Transforming Growth Factor Beta Promotes the Expansion of Cancer Stem Cells via S1PR3 by Ligand-Independent Notch Activation もっと読む

    Breast cancer are originated from cancer stem cells (CSCs), which contribute to drug resistance and recurrence. The authors examined the effects of transforming growth factor beta (TGFβ) signaling on proliferation of breast CSCs. TGFβ induced the proliferation of CSCs via phosphorylation of sphingosine kinase 1 (SphK1) via a Smad-independent manner and subsequent production of sphingosine-1-phosphate (S1P). Moreover, Notch pathway was involved in the S1P response via S1P receptor 3. These results suggest that TGFβ-SphK1-S1P-Notch signaling pathway is a novel therapeutic target in breast cancer.

  • 45 巻 (2022) 5 号 p. 664-667
    Ca2+ Signaling and Proliferation via Ca2+-Sensing Receptors in Human Hepatic Stellate LX-2 Cells もっと読む

    Hepatic stellate cells (HSCs) are a key player in the pathogenesis of hepatic fibrosis including cirrhosis. The development of hepatic fibrosis is associated with enhanced calcium signaling in HSCs. However, the regulatory mechanism of calcium signaling in HSCs is largely unknown. In addition, there is no specific therapeutic drug for hepatic fibrosis currently. This report reveals that calcium-sensing receptors are expressed in human HSCs and function in the regulation of calcium signaling and cell proliferation. These findings help to elucidate the molecular mechanism of hepatic fibrosis and develop a potential therapeutic target for hepatic fibrosis.

  • 45 巻 (2022) 4 号 p. 382-393
    Clinical Aspects of Drug–Drug Interaction and Drug Nephrotoxicity at Renal Organic Cation Transporters 2 (OCT2) and Multidrug and Toxin Exclusion 1, and 2-K (MATE1/MATE2-K) もっと読む

    Organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 and 2-K (MATE1/2-K) are critically involved in renal secretion, pharmacokinetics (PK), and toxicity of cationic drugs. Drug-drug interactions (DDIs) at OCT2 and/or MATE1/2-K have been shown to result in clinical impacts on PK, therapeutic efficacy and are probably involved in the renal accumulation of drugs. In this work, an overview of OCT2 and MATE1/2-K is presented. The primary structure, membrane location, functional properties, and clinical impact of OCT2 and MATE1/2-K are described. In addition, clinical aspects of DDIs in OCT2 and MATE1/2-K and their involvement in drug nephrotoxicity are compiled.

  • 45 巻 (2022) 4 号 p. 394-396
    Simultaneous Screening of SARS-CoV-2 Omicron and Delta Variants Using High-Resolution Melting Analysis もっと読む

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has multiple receptor-binding domain (RBD) mutations. Some of these mutations can increase infectivity and reduce antibody affinity. In this study, the authors successfully developed a rapid screening assay to simultaneously identify RBD mutations in the Omicron and Delta variants using high-resolution melting (HRM) analysis. As this HRM-based genotyping assay does not require sequence-specific probes, unlike the TaqMan probe assay, it is easy to perform and cost-effective. This simple method may contribute to the rapid identification and prevention of the potential widespread infection of SARS-CoV-2 variants.

  • 45 巻 (2022) 4 号 p. 491-496
    Influence of the Th1 Cytokine Environment on CCL5 Production from Langerhans Cells もっと読む

    It has long been known that the chronic skin lesions of atopic dermatitis (AD) patients show increased amounts of Th1 cells in addition to Th2 cells. However, it has remained unclear whether these Th1 cells actually participate in the exacerbation of skin inflammation. In this paper, the authors showed that Langerhans cells (LCs) augmented CCL5 production by responding to Th1 cytokine, IFN-g while presenting antigen to Th cells, and that this augmentation of CCL5 production would contribute to infiltration of eosinophils and other Th1 cells into skin lesions, followed by expansion of chronic inflammation in the skin.

  • 45 巻 (2022) 4 号 p. 508-516
    Sex, Organ, and Breed Differences in the mRNA Expression of Drug Transporters in the Liver and Kidney of Pigs もっと読む

    Breed and organ-dependent sex differences in the mRNA amounts of several drug transporters in the liver and kidney were found in pigs. In Meishan pigs, the sex differences in the amounts of hepatic MDR1, OATP1B3, and OCT1 mRNAs and in those of renal MRP2, OAT1, OAT2, OAT3, and OCT2 mRNAs were found. However, no such sex differences were observed in Landrace pigs. Furthermore, additional experiments using castrated and/or testosterone propionate-treated pigs suggested that breed-dependent sex differences in the gene expression of drug transporters, especially hepatic OCT1 and renal OAT1, were primarily due to the difference in serum testosterone concentration.

  • 45 巻 (2022) 4 号 p. 528-533
    Nobiletin and 3′-Demethyl Nobiletin Activate Brown Adipocytes upon β-Adrenergic Stimulation もっと読む

    Brown adipose tissue (BAT) specifically regulates energy expenditure via heat production. Hence, BAT may have the potential to combat obesity in humans. The activity of BAT is directly regulated by β-adrenergic stimulation. In this study, the authors report the effects of Nobiletin (NOB), a natural polymethoxylated flavone present in citrus fruits, on BAT activation using β-adrenergic agonists. NOB can enhance the thermogenic functions of brown adipocytes and promote brown adipokine secretion due to enhanced β-adrenergic stimulation. NOB could be a promising candidate for activating BAT under β-adrenergic stimulation and preventing the onset of obesity.

  • 45 巻 (2022) 3 号 p. 323-332
    Infliximab Treatment Persistence among Japanese Patients with Chronic Inflammatory Diseases: A Retrospective Japanese Claims Data Study もっと読む

    This report reveals that the persistence rates of infliximab therapy differed across chronic inflammatory diseases in real-world practice. Although infliximab has contributed to the treatment of Crohn’s disease, ulcerative colitis, psoriasis, and rheumatoid arthritis, loss of response to long-term therapy has been a major problem. The authors described the persistence rates of infliximab therapy using the Japanese claims data to estimate its long-term effectiveness. Factors associated with the longer persistence were identified in each disease group. These results could facilitate the proper use of infliximab for persistent successful treatment.

  • 45 巻 (2022) 3 号 p. 339-353
    Betulin Attenuates TGF-β1- and PGE2-Mediated Inhibition of NK Cell Activity to Suppress Tumor Progression and Metastasis in Mice もっと読む

    This study reveals that a natural compound, betulin, inhibits the growth of B16 melanoma by enhancing natural killer cell activity through attenuating transforming growth factor (TGF)-b1- and prostaglandin E2 (PGE2)-induced immunosuppression in the tumor microenvironment. No report has shown such compounds that target TGF-b1- and PGE2-induced immunosuppressive activities so far. Additionally, it is intriguing that the mechanism-of-action of betulin differs from that of TGF-b1 type I receptor kinase inhibitors. Targeting TGF-b1 activity is a promising strategy for cancer therapy. Findings of this study provide new insight to develop drugs for immune checkpoint therapy in an immunosuppressive tumor microenvironment.

  • 45 巻 (2022) 3 号 p. 354-359
    Activation of Host Immune Cells by Probiotic-Derived Extracellular Vesicles via TLR2-Mediated Signaling Pathways もっと読む

    Live microorganisms with positive effects on the host are known as probiotics. Probiotics secrete extracellular vesicles (EVs) that activate immune response. The authors investigated the involvement of Toll-like receptor 2 (TLR2) and its downstream signaling of immune cells in cytokines production elicited by EVs from probiotics. TLR2 is a key molecule in EV-mediated immune activation. Furthermore, JNK/MAPK as well as NF-κB signaling pathways play important roles in cytokines production from EV-treated immune cells. These findings offer a promising perspective for the understanding of the host biological function induced by probiotic-derived EVs, which is helpful for developing an EV-based immunotherapeutic system.

  • 45 巻 (2022) 3 号 p. 360-363
    Fosphenytoin Alleviates Herpes Simplex Virus Infection-Induced Provoked and Spontaneous Pain-Like Behaviors in Mice もっと読む

    Spontaneous pain in acute herpes zoster (HZ) is severe, autonomous and inescapable, which makes the patient very uncomfortable. In this study, the authors demonstrated that intravenous injection of fosphenytoin (fPHT), a water-soluble prodrug of phenytoin, suppressed spontaneous pain-related behavior in mice model of acute HZ induced by cutaneous infection with herpes simplex virus type-1. The suppressive effects were more potent than diclofenac or pregabalin. Intravenous fPHT may become a viable option for an acute HZ pain, especially for spontaneous pain.

  • 45 巻 (2022) 3 号 p. 374-377
    Trends in Investigator-Initiated Clinical Studies at a University Hospital after Enforcement of the 2018 Clinical Trials Act in Japan もっと読む

    The Clinical Trials Act was enforced in 2018 with the aim of ensuring public trust in clinical research. The authors examined the activity of interventional research before and after the enforcement of the law, using the number of applications to the ethics committees as an indicator at a university hospital with a certified review board. It was found that the number of applications tended to decrease with the enforcement of the law. Possible way to promote clinical studies in the new Clinical Trials Act era should be further examined.