Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Featured articles
Displaying 1-20 of 228 articles
  • Volume 46 (2023) Issue 5 Pages 700-706
    Regional Disparity in First-in-Class Anticancer Drug Development in the US, EU, and Japan Read more
    Editor's pick

    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.

  • Volume 46 (2023) Issue 5 Pages 707-712
    Effect of Ointment Base on the Skin Wound-Healing Deficits in Streptozotocin-Induced Diabetic Rat Read more
    Editor's pick

    The authors investigated weather difference ointment bases (absorbent cream, white-, and macrogol-ointment) affect the skin wound healing rate in normal and diabetic models (streptozotocin-induced rat, STZ rat). The wound healing rate was similar in the normal rat treated with three-bases. In contrast of this result, the wound healing in STZ rats treated with macrogol-ointment was delayed in comparison with other two-bases. These results indicate that the wound healing in STZ rats is affected by the properties of ointment base, and the selection of appropriate ointment base according to the skin condition may be important for the wound healing in patients with diabetes.

  • Volume 46 (2023) Issue 5 Pages 713-717
    Rapid Screening Detection of Genetically Modified Papaya by Loop-Mediated Isothermal Amplification Read more
    Editor's pick

    A loop-mediated isothermal amplification (LAMP)-mediated screening detection method for genetically modified (GM) papaya was developed using a Genie II real-time fluorometer. The authors also designed a primer set for the detection of the papaya endogenous reference sequence, chymopapain, and the species-specificity was confirmed. To enhance the simplicity, the authors attempted to develop a lateral flow DNA chromatography to detect LAMP products, and a duplex detection was successfully applied. This simple and quick method for the screening of GM papaya will be useful for the prevention of environmental contamination of unauthorized GM crops.

  • Volume 46 (2023) Issue 5 Pages 718-724
    Strengthening the Competitiveness of Japan’s Pharmaceutical Industry: Analysis of Country Differences in the Origin of New Drugs and Japan’s Highly Productive Firm Read more
    Editor's pick

    The author found that bio-ventures established in the 1990s and 2000s played a crucial role in creating new drugs approved by the FDA from 2017 to 2022 in regions outside of Japan. In contrast, in Japan, all approved drugs were created by old incumbent pharmaceutical companies, highlighting the urgent need to foster drug discovery start-ups in Japan. A case study of the Japanese company that created the largest number of FDA-approved drugs suggests that focused investment in modality technology development, strengthening collaboration with academia in biology, and the reutilizing small-molecule drug discovery capabilities are essential for improving drug discovery productivity.

  • Volume 46 (2023) Issue 4 Pages 574-585
    Anticancer Activity of Methyl Protodioscin against Prostate Cancer by Modulation of Cholesterol-Associated MAPK Signaling Pathway via FOXO1 Induction Read more
    Editor's pick

    High cholesterol concentration can promote the growth of prostate cancer. Methyl protodioscin (MPD), a furostanol saponin found in the rhizomes of Dioscoreaceae, has lipid-lowering and broad anticancer properties. In this research, MPD decreased expression of SREBP1 and SREBP2 by inducing FOXO1, lead to the induction of the expression of cholesterol export pump ABCA1 and reduction of the expression of the rate-limiting enzyme of cholesterol synthesis HMGCR. Reduced cholesterol caused to disrupted lipid rafts and MAPK pathway on it, contributing to MPD anti-prostate cancer activity. Consequently, MPD may be used as an active drug for treatment in prostate cancer.

  • Volume 46 (2023) Issue 4 Pages 592-598
    Prescription Trends for the Antidiabetic Agents Used to Treat Type 2 Diabetes Mellitus in Japan from 2012–2020: a Time-Series Analysis Read more
    Editor's pick

    The authors described prescription trends of the antidiabetic agents used to treat type 2 diabetes mellitus (T2DM) in Japan from 2012 to 2020 using administrative claims data. Noteworthy, this study examined the prescription trends in every line for T2DM treatment, including the combinations of antidiabetic agents, and showed that sodium-glucose cotransporter-2 inhibitors were rapidly introduced into T2DM treatment from several perspectives. Such a descriptive study revealed how T2DM treatment changed in accordance with cumulated evidence and can provide interesting information on public health.

  • Volume 46 (2023) Issue 4 Pages 599-607
    3,4-Dihydroxybenzalacetone Inhibits the Propagation of Hydrogen Peroxide-Induced Oxidative Effect via Secretory Components from SH-SY5Y Cells Read more
    Editor's pick

    The polyphenol derivative 3,4-dihydroxybenzalacetone (DBL) is the primary antioxidative component of the medicinal folk mushroom Chaga. The authors investigated whether the antioxidative effect of DBL could propagate to recipient cells using extracellular vesicles (EVs)-enriched fractions prepared by sucrose density gradient ultracentrifugation from conditioned medium of SH-SY5Y cells exposed to hydrogen peroxide after pre-exposing DBL. The results obtained from cell-based tests including the radical scavenging and the fluorescent Paul Karl Horan-labeled EVs uptake assays suggest that cell-to-cell communication via bioactive substances, such as EVs propagate the hydrogen peroxide-induced radical scavenging effect, whereas pre-conditioning with DBL inhibits it.

  • Volume 46 (2023) Issue 4 Pages 630-635
    Apigenin Alleviates Endoplasmic Reticulum Stress-Mediated Apoptosis in INS-1 β-Cells Read more
    Editor's pick

    Protection against impaired insulin secretion and β-cell apoptosis is an important strategy to prevent the progression of type 2 diabetes. The authors have reported the effects of apigenin, a dietary trihydroxyflavone, on pancreatic β-cell functions, underlying its anti-diabetic effects. The study demonstrated that apigenin exerts insulinotropic and anti-apoptotic effects in the β-cell line INS-1D. The anti-apoptotic effect of apigenin was further supported by reduced expression of apoptotic signaling proteins and pro-apoptotic protein. The results suggest and provide a basis for the development of apigenin as a potential therapeutic for type 2 diabetes through promoting β-cell survival and function.

  • Volume 46 (2023) Issue 3 Pages 427-431
    Retrospective Analysis of Neutrophil-to-Lymphocyte Ratio in Patients with Melanoma Who Received Ipilimumab Monotherapy or Ipilimumab in Combination with Nivolumab in Japan Read more
    Editor's pick

    Studies have reported an association between elevated neutrophil-to-lymphocyte ratio (NLR) and poor prognosis in patients with melanoma treated with ipilimumab. However, it remains unclear whether NLR is useful in Japanese. Authors retrospectively examined 38 patients, and found that baseline NLR>3.4 was an independent risk factor for ipilimumab discontinuation that was significantly associated with shorter progression-free survival. Because the NLR cut-off value in this study was lower than values in American and European studies, it possibly differs by race. Hence, it should be extrapolated to Japanese patients with caution.

  • Volume 46 (2023) Issue 3 Pages 440-445
    Interference of New Antiseizure Agents with Hospital Transfer of Stroke Patients in Japan: A Retrospective Cohort Study Read more
    Editor's pick

    This investigation of the impact of antiseizure medications (ASMs) on hospital transfer was undertaken because chronic-care hospitals have refused to accept several post-stroke epilepsy patients using novel ASMs from acute-care hospitals. Patients with stroke receiving novel ASMs, i.e., perampanel and lacosamide, had longer times to hospital transfer than patients receiving other ASMs. Furthermore, a weak correlation was found between the cost of a patient's daily medications and the number of days to hospital transfer. These results indicate that considering the availability and cost of ASMs in the transfer destination hospital is important when choosing medications for patients requiring hospital transfer.

  • Volume 46 (2023) Issue 3 Pages 446-454
    Enhancement of Neprilysin Activity by Natural Polyphenolic Compounds and Their Derivatives in Cultured Neuroglioma Cells Read more
    Editor's pick

    The authors found that amentoflavone, apigenin, kaempferol, and chrysin enhanced the activity and expression of neprilysin, one of the major Aβ-degrading enzymes, by screening a polyphenol library, and that chemical structures involving a double bond between positions 2 and 3 in the C ring of flavones were important for neprilysin enhancement. Moreover, natural compounds, such as quercetin, were not effective per se, but were changed to effective compounds by adding a lipophilic moiety. These findings provide a basis for the development of novel small molecules as disease-modifying drugs for Alzheimer’s disease.

  • Volume 46 (2023) Issue 2 Pages 194-200
    Effect of Severe Renal Dysfunction on the Plasma Levels of DNA-Reactive Platinum after Oxaliplatin Administration Read more
    Editor's pick

    Oxaliplatin is a platinum (Pt)-based chemotherapeutic drug that is widely used to treat gastrointestinal and pancreatic cancers. The authors hypothesized that the DNA-binding capacity is one of the properties of reactive Pt species and aimed to evaluate the contribution of the kidney to the plasma levels of DNA-reactive Pt in an animal model and a hemodialysis patient. The results of this study showed that severe renal dysfunction has a limited effect on the plasma levels of DNA-reactive Pt after oxaliplatin administration.

  • Volume 46 (2023) Issue 2 Pages 263-271
    Microbial Water Quality Assessment of Private Wells Using 16S rRNA Gene Amplicon Sequencing with a Nanopore Sequencer Read more
    Editor's pick

    Private wells are used daily worldwide as convenient household water sources. Comprehensive modern assessment is desirable for securing the microbiological quality of well water. Here, the bacterial community structure was examined using the rapid and portable MinION sequencer, which enabled us to identify bacteria to the species level based on full-length 16S rRNA gene sequences. The analysis method successfully detected bacteria causing opportunistic infections, which are difficult to detect by conventional methods. This approach is expected to be routinely applied in the future as a highly accurate method for assessing the microbiological quality of private well water.

  • Volume 46 (2023) Issue 2 Pages 272-278
    Effect of Topiroxostat on Reducing Oxidative Stress in the Aorta of Streptozotocin-Induced Diabetic Rats Read more
    Editor's pick

    Vascular damage is often seen in patients with diabetes and is thought to be caused by oxidative stress. Xanthine oxidoreductase exists both intracellularly and extracellularly and causes vascular injury by producing reactive oxygen species. The authors investigated the effects of topiroxostat, a xanthine oxidase inhibitor, and its mechanism of action in a rodent model of diabetes. They found that topiroxostat inhibited anchored xanthine oxidase bound to the surface of vascular endothelial cells in the thoracic aorta and suppressed damage to these cells, suggesting that topiroxostat could potentially have a vasoprotective effect in patients with diabetes-induced macrovascular disease.

  • Volume 46 (2023) Issue 2 Pages 301-308
    Use of Iontophoresis Technology for Transdermal Delivery of a Minimal mRNA Vaccine as a Potential Melanoma Therapeutic Read more
    Editor's pick

    mRNA has many challenges including insufficient delivery owing to the high molecular weight and high negative charge. Authors chemically synthesized a minimal mRNA vaccine encoding human gp10025-33 peptide (KVPRNQDWL), as a potential treatment for melanoma and iontophoresis (IP) was used for its delivery into the skin. After combining IP with the newly synthetized minimal mRNA vaccine, successful intradermal and intracellular delivery of the minimal mRNA was achieved. Results showed stimulation of the immune system which led to tumor inhibition and infiltration of cytotoxic CD8+ T cells in the tumor tissue. This is the first report combining IP and chemically synthesized minimal mRNA vaccine.

  • Volume 46 (2023) Issue 2 Pages 320-333
    Plantainoside B in Bacopa monniera Binds to Aβ Aggregates Attenuating Neuronal Damage and Memory Deficits Induced by Aβ Read more
    Editor's pick

    Cholinergic neurons in the basal forebrain are known to degenerate early stage of Alzheimer's disease (AD), and amyloid-β (Aβ) oligomers are suggested to be deeply involved in AD pathogenesis. Authors here established an Aβ oligomer-induced neurodegeneration model using human induced pluripotent stem cell-derived cholinergic neurons and demonstrated the neuroprotective effect of plantainoside B identified from herbal extracts as an Aβ-binding small molecule. Radioisotope-labeled plantainoside B showed affinities to Aβ oligomers and brain sections from a mouse model of AD. Results suggest the potential of developing “theranostics” in AD that simultaneously performs diagnoses (Aβ detection) and therapy (neuroprotection).

  • Volume 46 (2023) Issue 1 Pages 1-11
    Chemical Activation of Piezo1 Alters Biomechanical Behaviors toward Relaxation of Cultured Airway Smooth Muscle Cells Read more
    Editor's pick

    Inspired by the well-known phenomenon of stretch-induced airway dilation in normal lung and the emerging stretch-responsive Piezo1 channels, the authors in this study demonstrated that chemical activation of Piezo1 channels by agonist YODA1 dramatically reduced the contractility of cultured ASMCs in terms of cells stiffness, traction force, migration, and expression of molecules associated with cell mechanics. These findings indicate that chemical activation of Piezo1 can indeed modulate biomechanical behaviors of ASMCs towards relaxation. And this novel regulatory mechanism as alternative to the conventional b2-adrenergic receptor for relaxation of ASMCs may provide a potentially new target for bronchodilation in asthma therapy.

  • Volume 46 (2023) Issue 1 Pages 19-25
    Impact of Drugs and Patient Characteristics on Life Expectancy during the Induction Phase of Dialysis Read more
    Editor's pick

    Various factors affect the prognosis of dialysis patients. Analysis of the drugs used and clinical and demographic characteristics of the patient at the time of dialysis initiation is a useful means of estimating prognosis. The authors investigated the drugs used by dialysis patients during the induction phase of dialysis and performed a detailed analysis of variables predictive of prognosis. As a result, antihypertensives, hemoglobin, and age at start of dialysis were found to have significant effects on dialysis duration. It was posited that antihypertensives prolong dialysis duration, thereby improving life expectancy. These findings may be used to improve drug adherence in dialysis patients and guide physicians in their treatment.

  • Volume 46 (2023) Issue 1 Pages 86-94
    Altered Pharmacological Efficacy of Phenobarbital with the Treatment of 7,8-Dihydroxyflavone, an Agonist of Tropomyosin Receptor Kinase B, in Rats Read more
    Editor's pick

    Tropomyosin receptor kinase B (TrkB) may be a key modulator of the pharmacological effects of barbiturates. Suzuki, et al., used a TrkB agonist 7,8-dihydroxyflavone (DHF) in the animal study for phenobarbital-induced general anesthesia, demonstrating that rats receiving the DHF pretreatment readily fell into anesthesia in a shorter time than those without the pretreatment. They then showed that DHF promotes the TrkB to be phosphorylated and that the protein expression of the potassium chloride transporter KCC2 was consequently suppressed. It was thus revealed that DHF potentiates the pharmacological effects of phenobarbital as it causes the functional activation of the TrkB.

  • Volume 46 (2023) Issue 1 Pages 102-110
    Specific Cellular Effects of Low Bortezomib Concentrations on Purified Cultures of Schwann Cells, Satellite Glial Cells, Macrophages, and Dorsal Root Ganglion Neurons Read more
    Editor's pick

    Bortezomib is widely used in treating multiple myeloma, but causes serious adverse effects, such as peripheral neuropathy, leading to discontinuation of Bortezomib treatment. To explore the mechanism, the authors, unlike previous reports, applied relatively low concentrations of bortezomib at clinical concentration, to primary cultured Schwann cells, satellite glial cells, macrophages, and dorsal root ganglion neurons. The results showed that bortezomib caused Schwann cell dedifferentiation, increased GFAP levels in satellite glial cells without inducing inflammatory responses, and decreased ion channel expression in dorsal root ganglion neurons. This may explain the mechanism of bortezomib-induced peripheral neuropathy.