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A Novel Strategy for the Discovery of Drug Targets: Integrating Clinical Evidence with Molecular Studies
Biol Pharm Bull. 2024;47(2):345-349. doi: 10.1248/bpb.b23-00831.ABSTRACTThe mechanisms of several drugs remain unclear, limiting our understanding of how they exert their effects. Receptor affinities have not been comprehensively measured during drug development, and the safety investigations in humans are limited. Therefore, numerous unknown adverse and beneficial effects of drugs in humans persist. In this review, I highlight our achievements in identifying the unexpected beneficial effects of drugs through the analysis of real-world clinical data, which can contribute to drug repositioning and target finding. (1) Throug...
Source: Biological and Pharmaceutical Bulletin - January 31, 2024 Category: Drugs & Pharmacology Authors: Shuji Kaneko Source Type: research

Drug Discovery Research for Traumatic Brain Injury Focused on Functional Molecules in Astrocytes
Biol Pharm Bull. 2024;47(2):350-360. doi: 10.1248/bpb.b23-00731.ABSTRACTTraumatic brain injury (TBI) is severe damage to the head caused by traffic accidents, falls, and sports. Because TBI-induced disruption of the blood-brain barrier (BBB) causes brain edema and neuroinflammation, which are major causes of death or serious disabilities, protection and recovery of BBB function may be beneficial therapeutic strategies for TBI. Astrocytes are key components of BBB integrity, and astrocyte-derived bioactive factors promote and suppress BBB disruption in TBI. Therefore, the regulation of astrocyte function is essential for BB...
Source: Biological and Pharmaceutical Bulletin - January 31, 2024 Category: Drugs & Pharmacology Authors: Shotaro Michinaga Source Type: research

Inhibitory Actions of Antidepressants, Hypnotics, and Anxiolytics on Recombinant Human Acetylcholinesterase Activity
Biol Pharm Bull. 2024;47(1):328-333. doi: 10.1248/bpb.b23-00719.ABSTRACTAlzheimer's disease (AD) is accompanied by behavioral and psychological symptoms of dementia (BPSD), which is often alleviated by treatment with psychotropic drugs, such as antidepressants, hypnotics, and anxiolytics. If these drugs also inhibit acetylcholinesterase (AChE) activity, they may contribute to the suppression of AD progression by increasing brain acetylcholine concentrations. We tested the potential inhibitory effects of 31 antidepressants, 21 hypnotics, and 12 anxiolytics on recombinant human AChE (rhAChE) activity. At a concentration of 1...
Source: Biological and Pharmaceutical Bulletin - January 31, 2024 Category: Drugs & Pharmacology Authors: Keisuke Obara Haruka Mori Suzune Ihara Kento Yoshioka Yoshio Tanaka Source Type: research

The Mechanism of 5-Fluorouracil-Induced Hyperpigmentation in HRM-2 Hairless Mice: Focus on the Increase of Blood Vessels
In conclusion, this study indicates that 5-FU causes hyperpigmentation by melanin accumulation in a characteristic manner, including an increase in blood vessels.PMID:38281766 | DOI:10.1248/bpb.b23-00584 (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 28, 2024 Category: Drugs & Pharmacology Authors: Atsuo Fujito Shota Tanaka Keiichi Hiramoto Ning Ma Kazuya Ooi Source Type: research

Proteomic Analysis of Staphylococcus aureus Treated with ShangKeHuangShui
This study's primary objective was to delve into the antibacterial properties, potential antibacterial compounds within SKHS, and their associated molecular targets. In vitro SKHS antibacterial assays demonstrated that the minimum inhibitory concentration (MIC) was 8.625 mg/mL and the minimum bactericide concentration (MBC) was 17.25 mg/mL. Proteomic analysis based on tandem mass tag (TMT) showed significant changes in the expression level of 246 proteins in SKHS treated group compared to control group, with 79 proteins upregulated and 167 proteins downregulated (>1.5-fold, p < 0.05). Subsequently, thirteen target pr...
Source: Biological and Pharmaceutical Bulletin - January 28, 2024 Category: Drugs & Pharmacology Authors: Lichu Liu Na Zhao Kuangyang Yang Honghong Liao Xiaofang Liu Ying Wu Yan Wang Xiao Peng Yuanyan Wu Source Type: research

Hydroxytyrosol Alleviates Methotrexate-Induced Pulmonary Fibrosis in Rats: Involvement of TGF- β1, Tissue Factor, and VEGF
Biol Pharm Bull. 2024;47(1):303-310. doi: 10.1248/bpb.b23-00477.ABSTRACTMethotrexate (MTX) is an indispensable drug used for the treatment of many autoimmune and cancerous diseases. However, its clinical use is associated with serious side effects, such as lung fibrosis. The main objective of this study is to test the hypothesis that hydroxytyrosol (HT) can mitigate MTX-induced lung fibrosis in rats while synergizing MTX anticancer effects. Pulmonary fibrosis was induced in the rats using MTX (14 mg/kg/week, per os (p.o.)). The rats were treated with or without HT (10, 20, and 40 mg/kg/d p.o.) or dexamethasone (DEX; 0.5 mg...
Source: Biological and Pharmaceutical Bulletin - January 28, 2024 Category: Drugs & Pharmacology Authors: Mohamed F Manie Hala M Fawzy El-Sayed M El-Sayed Source Type: research

Wild-Type DCTN1 Suppresses the Aggregation of DCTN1 Mutants Associated with Perry Disease
In this study, we comprehensively investigated the intracellular distribution of the p150glued mutants in HEK293T cells. We further assessed the effect of co-overexpression of the wild-type p150glued protein with mutants on the formation of mutant aggregates. Notably, overexpression of p150glued mutants identified in healthy controls, which is also associated with amyotrophic lateral sclerosis, showed a thread-like cytoplasmic distribution, similar to the wild-type p150glued. In contrast, p150glued mutants in Perry disease and motor neuron disease caused aggregation. In addition, the co-overexpression of the wild-type prot...
Source: Biological and Pharmaceutical Bulletin - January 24, 2024 Category: Drugs & Pharmacology Authors: Yuto Fukui Hisashi Shirakawa Shuji Kaneko Kazuki Nagayasu Source Type: research

Development of Hollow Gold Nanoparticles for Photothermal Therapy and Their Cytotoxic Effect on a Glioma Cell Line When Combined with Copper Diethyldithiocarbamate
Biol Pharm Bull. 2024;47(1):272-278. doi: 10.1248/bpb.b23-00789.ABSTRACTGold-based nanoparticles hold promise as functional nanomedicines, including in combination with a photothermal effect for cancer therapy in conjunction with chemotherapy. Here, we synthesized hollow gold nanoparticles (HGNPs) exhibiting efficient light absorption in the near-IR (NIR) region. Several synthesis conditions were explored and provided monodisperse HGNPs approximately 95-135 nm in diameter with a light absorbance range of approximately 600-720 nm. The HGNPs were hollow and the surface had protruding structures when prepared using high conce...
Source: Biological and Pharmaceutical Bulletin - January 24, 2024 Category: Drugs & Pharmacology Authors: Jin Liu Tatsuaki Tagami Koki Ogawa Tetsuya Ozeki Source Type: research

Perineural Treatment with High Mobility Group Box-1 Monoclonal Antibody Prevents Initiation of Pain-Like Behaviors in Female Mice with Trigeminal Neuropathy
Biol Pharm Bull. 2024;47(1):221-226. doi: 10.1248/bpb.b23-00729.ABSTRACTPost-traumatic trigeminal neuropathy (PTTN) is a type of chronic pain caused by damage to the trigeminal nerve. A previous study reported that pretreatment with anti-high mobility group box-1 (HMGB1) neutralizing antibodies (nAb) prevented the onset of PTTN following distal infraorbital nerve chronic constriction injury (dIoN-CCI) in male mice. Clinical evidence indicates a high incidence of PTTN in females. Although our previous study found that perineural HMGB1 is crucial in initiation of PTTN in male mice, it is currently unknown whether HMGB1 is al...
Source: Biological and Pharmaceutical Bulletin - January 21, 2024 Category: Drugs & Pharmacology Authors: Simeng Ma Yoki Nakamura Takahiro Kochi Suzuna Uemoto Kazue Hisaoka-Nakashima Dengli Wang Keyue Liu Hidenori Wake Masahiro Nishibori Norimitsu Morioka Source Type: research

Steroid-Insensitive Gene Expression of Extracellular Matrix Components and Pro-fibrotic Factors in the Lung Associated with Airway Hyperresponsiveness in Murine Asthma
In conclusion, steroid-insensitive AHR developed in the 500-µg OVA group and steroid-insensitive genes encoding ECM components and pro-fibrotic factors were identified. Drugs targeting these molecules have potential in the treatment of steroid-resistant asthma.PMID:38246609 | DOI:10.1248/bpb.b23-00768 (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 21, 2024 Category: Drugs & Pharmacology Authors: Hayato Shimora Masaya Matsuda Naoki Takemoto Miku Nomura Junpei Hamaguchi Ryogo Terakawa Miki Inaba Kazuyuki Kitatani Takeshi Nabe Source Type: research

Treatment of Inflammatory Bowel Disease with Biologics in Japan: A Single-Center, Retrospective Pharmacoeconomic Study
Biol Pharm Bull. 2024;47(1):232-239. doi: 10.1248/bpb.b23-00682.ABSTRACTBiologics are essential for treating inflammatory bowel disease (IBD); however, only a few studies have validated cost-effective treatment options and patient factors for biologic use using real-world data from Japanese patients with IBD. Here, we aimed to provide pharmacoeconomic evidence to support clinical decisions for IBD treatment using biologics. We assessed 183 cases (127 patients) of IBD treated with biologics between November 2004 and September 2021. Data on patient background, treatment other than biologics, treatment-related medical costs, ...
Source: Biological and Pharmaceutical Bulletin - January 21, 2024 Category: Drugs & Pharmacology Authors: Atsuyuki Saisyo Shinichi Hashimoto Haku Ishida Koichi Kashibe Tomoyuki Oka Yasushi Hirano Miwako Takasago Yutaka Uchida Naoto Okada Taro Takami Takashi Kitahara Source Type: research

Ginsenosides in Panax ginseng Extract Promote Anagen Transition by Suppressing BMP4 Expression and Promote Human Hair Growth by Stimulating Follicle-Cell Proliferation
Biol Pharm Bull. 2024;47(1):240-244. doi: 10.1248/bpb.b23-00276.ABSTRACTStudies showing that Panax ginseng promotes hair growth have largely been conducted using mice; there are few reports on how P. ginseng affects human hair growth. In particular, little is known about its effect on the telogen to anagen transition. To determine the effect of P. ginseng on human hair growth and the transition from the telogen to the anagen phase. The effects of P. ginseng extract (PGE) and the three major ginsenoside components, Rb1, Rg1, and Re, on the proliferation of human dermal papilla cells (DPCs) and human outer root sheath cells ...
Source: Biological and Pharmaceutical Bulletin - January 21, 2024 Category: Drugs & Pharmacology Authors: Tokuro Iwabuchi Kazuki Ogura Kenta Hagiwara Shogo Ueno Hiroaki Kitamura Haruyo Yamanishi Yuki Tsunekawa Akinori Kiso Source Type: research

Development of an Effective Psoriasis Treatment by Combining Tacrolimus-Encapsulated Liposomes and Iontophoresis
In this study, we analyzed the effect of ItP on the expression of various inflammatory cytokines in the skin, and subsequently examined the therapeutic effect of ItP using negatively-charged liposomes encapsulating FK506 (FK-Lipo) in a rat psoriasis model induced by imiquimod. We found that ItP (0.34 mA/cm2, 1 h) did not affect mRNA levels of inflammatory cytokines or epidermis thickness, indicating that ItP is a safe technology for psoriasis treatment. ItP of FK-Lipo suppressed the expression of inflammatory cytokines induced by imiquimod treatment to a greater extent than skin treated with FK506 ointment for 1 h. Further...
Source: Biological and Pharmaceutical Bulletin - January 21, 2024 Category: Drugs & Pharmacology Authors: Seiko Nakamura Mizune Ozono Karen Yanagi Kentaro Kogure Source Type: research

Effect of Anagliptin on Vascular Injury in the Femoral Artery of Type 2 Diabetic Rats
This study aimed to investigate the impact of long-term (6 weeks) anagliptin treatment at a dose of 200 mg/kg/d against oxidative stress in the femoral artery of Otsuka Long-Evans Tokushima Fatty (OLETF) rats using a well-established animal model for type 2 DM. Serum toxic advanced glycation end-products concentrations and blood glucose levels after glucose loading were significantly elevated in OLETF rats compared to Long-Evans Tokushima Otsuka (LETO) rats but were significantly suppressed by anagliptin administration. Plasma glucagon-like peptide-1 concentrations after glucose loading were significantly increased in anag...
Source: Biological and Pharmaceutical Bulletin - January 21, 2024 Category: Drugs & Pharmacology Authors: Masato Noda Chigusa Kikuchi Eisei Hori Takahiro Iwao Chie Nagami Masayoshi Takeuchi Tamihide Matsunaga Source Type: research

Molecular Mechanism of SLC6A8 Dysfunction with c.1699T   & gt;  C (p.S567P) Mutation in Cerebral Creatine Deficiency Syndromes
This study aimed to elucidate the molecular mechanism of SLC6A8 dysfunction caused by the c. 1699T > C missense mutation, which is thought to induce dysfunction through an unidentified mechanism. A study on SLC6A8-expressing oocytes showed that the c.1699T > C mutation decreased creatine uptake compared to that in wild-type (WT) oocytes. In addition, a kinetics study of creatine uptake revealed that the c.1699T > C mutation reduced the maximum uptake rate but not Michaelis-Menten constant. In contrast, the c.1699T > C mutation did not attenuate SLC6A8 protein levels or alter its cellular localization. Based on ...
Source: Biological and Pharmaceutical Bulletin - January 17, 2024 Category: Drugs & Pharmacology Authors: Ryuta Jomura Masaru Sawada Yuma Tega Shin-Ichi Akanuma Masanori Tachikawa Ken-Ichi Hosoya Source Type: research