{"title":"Antipruritic Effects of Single Administration of Paroxetine on Acute and Chronic Itch.","authors":"Kosuke Matsuda, Hikaru Ishisaka, Masahito Sawahata, Toshiaki Kume, Daisuke Uta","doi":"10.1248/bpb.b24-00657","DOIUrl":"10.1248/bpb.b24-00657","url":null,"abstract":"<p><p>Itch is described as an unpleasant sensation, and chronic itch, such as that in atopic dermatitis (AD), often decreases a patient's QOL. There are few effective treatments for various chronic pruritic disorders that are not limited to inflammation. Selective serotonin reuptake inhibitors (SSRIs) are antidepressants used to treat some chronic pruritus disorders. However, there is little evidence from clinical and basic studies using animal models. In this study, we found that paroxetine suppressed acute and chronic itch in mouse models. Single administration of paroxetine (10 mg/kg) inhibited scratching behavior caused by histamine-dependent or histamine-independent itch. Moreover, paroxetine (10 mg/kg) inhibited spontaneous scratching behavior in AD model using NC/Nga mice without affecting locomotor function. These results suggest that paroxetine suppresses chronic itch caused by AD via histamine-dependent and -independent pathways. This study provides one of the few pieces of evidence that SSRIs suppress itch.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"184-187"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jisung Hwang, Deok Yong Sim, Chi-Hoon Ahn, Su-Yeon Park, Jin-Suk Koo, Bum-Sang Shim, Bonglee Kim, Sung-Hoon Kim
{"title":"Inhibition of LGR5/β-Catenin Axis and Activation of miR134 Are Critically Involved in Apoptotic Effect of Sanggenol L in Hepatocellular Carcinoma.","authors":"Jisung Hwang, Deok Yong Sim, Chi-Hoon Ahn, Su-Yeon Park, Jin-Suk Koo, Bum-Sang Shim, Bonglee Kim, Sung-Hoon Kim","doi":"10.1248/bpb.b24-00213","DOIUrl":"10.1248/bpb.b24-00213","url":null,"abstract":"<p><p>Although Sanggenol L (SL), derived from the root bark of Morus alba, has hepatoprotective, neuroprotective, and antitumor effects, the antitumor mechanism of SL remains unclear to date. Thus, in the current work, the apoptotic mechanisms of SL were investigated in HepG2 and Huh hepatocellular carcinoma (HCC) cells in relation to leucine-rich repeat containing G protein-coupled receptor 5 (LGR5)/β-catenin and miR134 signaling axis. Herein, SL significantly incremented cytotoxicity, sub-G1 population, and the number of terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) positive apoptotic bodies and also inhibited proliferation in HCCs. Consistently, SL activated pro-Caspase7 and pro-Caspase3 and induced the cleavage of Poly ADP-ribose polymerase (PARP) in HCCs. Of note, the pivotal role of LGR5/β-catenin signaling was verified in SL-induced apoptosis in LGR5 overexpressed AML-12 cells and LGR5 depleted HepG2 cells. Furthermore, SL upregulated miR134 expression levels in HepG2 cells, while miR134 inhibitors disturbed the capacity of SL to cleave PARP and pro-Caspase3 in HepG2 cells. Taken together, our findings highlight evidence that inhibition of the LGR5/β-catenin axis and upregulation of miR134 play critical roles in SL-induced apoptosis in HCCs.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"126-131"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Antimicrobial Resistance Situation and Mechanisms of Resistance to Key Antimicrobials in Enterotoxigenic Escherichia coli.","authors":"Daichi Morita, Teruo Kuroda","doi":"10.1248/bpb.b24-00649","DOIUrl":"10.1248/bpb.b24-00649","url":null,"abstract":"<p><p>Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in developing countries and is regularly imported into developed countries as a major cause of traveler's diarrhea. ETEC is usually self-limiting and not necessarily treated with antimicrobials, although antimicrobial treatment is recommended in malnourished children, severe cases, and traveler's diarrhea. However, resistant strains to representative therapeutic agents such as ciprofloxacin and azithromycin have been reported in recent years, and multidrug-resistant ETEC has also emerged. This review discusses the recent antimicrobial resistance surveillance in ETEC and the mechanisms of resistance to major antimicrobials.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"222-229"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microfibril-Associated Protein 5 Contributes to the Elastic Fiber Abnormalities in Aged Skin.","authors":"Fumiaki Sato, Teruaki Oku, Yuka Nishigaki, Mana Suzuki, Hiroyasu Sakai, Hideyuki Takeshima, Yoshinori Kato","doi":"10.1248/bpb.b24-00828","DOIUrl":"https://doi.org/10.1248/bpb.b24-00828","url":null,"abstract":"<p><p>Elastic fibers, which contribute to the flexibility of tissues such as the skin, alveoli, and arteries, have a long half-life and are not regenerated once formed during the fetal stage. Consequently, the degradation of elastic fibers due to aging or inflammation can significantly impact tissue function. In the dermis, degeneration of elastic fibers is characterized by degradation in photoaging, driven by UV radiation, and structural abnormalities of elastic fibers in intrinsic aging. However, the mechanisms driving the abnormalities associated with intrinsic aging remain incomplete. This study aimed to identify the factors involved in the elastic fiber abnormalities associated with intrinsic aging of the dermis. Through a comprehensive analysis of gene expression, this study focused on microfibril-associated protein 5 (MFAP5) as a candidate gene responsible for the elastic fiber abnormalities associated with intrinsic aging. Immunofluorescence staining revealed that aged fibroblasts highly expressed MFAP5 and strongly localized it to aggregated elastic fibers. Furthermore, the elimination of MFAP5 expression suppressed elastic fiber aggregation. The exogenous addition of MFAP5 induced thickening and disorganization of elastic fibers, effects that were not observed with the overexpression of MFAP5 in young fibroblasts, which merely express MFAP5. Moreover, MFAP5 inhibited the interaction between latent transforming growth factor β binding protein 4 and fibulin-5, which are crucial for elastic fiber formation. These results suggest that excess MFAP5 expression associated with aging causes abnormalities in elastic fibers. Understanding the role of MFAP5 in elastic fiber abnormalities highlights its potential as a therapeutic target for mitigating intrinsic dermal aging and improving skin elasticity.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"450-456"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cry2 Alleviates Cisplatin-Induced Cytotoxicity in Mouse Renal Cortex Tubular Cell Lines.","authors":"Hiroki Yoshioka, Satoshi Yokota, Shintaro Torimoto, Hanane Horita, Yosuke Tsukiboshi, Tohru Maeda, Nobuhiko Miura","doi":"10.1248/bpb.b24-00811","DOIUrl":"https://doi.org/10.1248/bpb.b24-00811","url":null,"abstract":"<p><p>Cisplatin is a platinum-based drug that is widely used to treat various types of cancer. However, cisplatin is known to cause severe adverse effects, such as nephrotoxicity and ototoxicity. Clock genes, such as Bmal1 and Clock, regulate cisplatin-related homeostasis genes, such as Oct2 and Mate1. Although these clock genes may be involved in cisplatin-induced nephrotoxicity, their associations with other clock genes remain unclear. The aim of the present study was to investigate whether seven clock genes (Ciart, cryptochrome 1 (Cry1), Cry2, Npas2, Per1, Per2, and Per3) regulate cisplatin-induced renal toxicity in a renal cortex tubule cell line (MuRTE61). Cisplatin treatment decreases MuRTE61 cell viability in a dose-dependent manner. Cry2 expression levels increased after treatment with cisplatin for 24 h. Notably, Cry2 overexpression alleviated cisplatin-induced suppression of cell proliferation, apoptosis, and platinum content in MuRTE61 cells. Moreover, Cry2 overexpression upregulated the efflux-related transporters (Atp7a and Mrp2). These results suggest that Cry2 protects against cisplatin toxicity by reducing Pt accumulation and increasing the expression of Atp7a and Mrp2.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"390-398"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Syunki Yamada, Taiki Mihara, Tamaki Kurosawa, Aya Maruyama, Katsuyo Ohashi-Doi, Yuko Mitobe, Masatoshi Hori
{"title":"Delayed Upper Gastrointestinal Motility in Mice Treated with Oral Iron Tablets.","authors":"Syunki Yamada, Taiki Mihara, Tamaki Kurosawa, Aya Maruyama, Katsuyo Ohashi-Doi, Yuko Mitobe, Masatoshi Hori","doi":"10.1248/bpb.b24-00789","DOIUrl":"https://doi.org/10.1248/bpb.b24-00789","url":null,"abstract":"<p><p>Oral iron preparations for iron deficiency anemia have major side effects, such as nausea and vomiting, which are gastrointestinal symptoms widely known to occur with gastrointestinal motility disorders. However, it is unclear whether these symptoms are associated with gastrointestinal motility. This study aimed to explore the correlation between oral iron preparations that cause nausea and vomiting with gastrointestinal motility. Sodium ferrous citrate (SFC), a common ingredient in iron preparations, was used in this study. Gastrointestinal motility in mice was measured using the <sup>13</sup>C-octanoic acid breath test to determine gastric emptying and colonic transport capacities using the bead expulsion test. SFC significantly delayed gastric emptying. However, it did not affect the colonic transport capacity. Treatment with the antiemetic palonosetron, a 5-hydroxytryptamine 3 (5-HT<sub>3</sub>) receptor inhibitor, abolished the gastric evacuation retardation effect of SFC. However, the additive in the SFC formulation, palonosetron alone, did not affect the gastric emptying capacity. These results suggest that iron preparations cause vagal nausea and vomiting in the upper gastrointestinal tract due to chemical stimulation of the gastrointestinal blood with a concomitant reduction in gastric emptying capacity. Knowledge of the association of delayed gastric emptying with the onset of iron-induced nausea is useful for understanding iron-induced adverse effects.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"432-439"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naoki Tamura, Kanzo Suzuki, Hirono Shiraki, Issei Waguri, Eri Segi-Nishida
{"title":"Production of Adeno-Associated Virus Vector Serotype rh.10 and Optimization of Its Purification via Chloroform Extraction.","authors":"Naoki Tamura, Kanzo Suzuki, Hirono Shiraki, Issei Waguri, Eri Segi-Nishida","doi":"10.1248/bpb.b24-00850","DOIUrl":"https://doi.org/10.1248/bpb.b24-00850","url":null,"abstract":"<p><p>Recombinant adeno-associated virus (AAV) vectors are widely used for manipulating gene expression. AAVrh.10 is a highly infectious AAV serotype for the central nervous system and various tissues. Owing to its potential use in research, we aimed to optimize the production strategy and develop a simple purification protocol for the AAVrh.10 vector. In this study, we explored a simple production and purification strategy for the AAVrh.10 vector via chloroform extraction and ultrafiltration. Initially, we evaluated the optimal conditions for AAVrh.10-CAG-GFP production using AAV-293 cells. AAVrh.10-CAG-GFP was successfully produced in a serum-free medium after plasmid transfection. Moreover, the culture medium contained a substantial amount of the virus. Therefore, both AAVrh.10-containing cell lysate and culture medium should be used to prepare the AAVrh.10 viral vector. To purify and concentrate AAVrh.10-CAG-GFP from the crude lysate and medium, we optimized the chloroform extraction and ultrafiltration strategies. Subsequently, purified AAVrh.10-CAG-GFP was used to infect HEK-293T cells. Overall, this study provides a simple and effective AAVrh.10 vector preparation strategy for basic and preclinical research.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"355-362"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dai Oyama, Masako Okada, Furan Song, Chiori Nitta, Hiroyuki Koide, Sei Yonezawa, Tomohiro Asai
{"title":"Process Optimization of Charge-Reversible Lipid Nanoparticles for Cytosolic Protein Delivery Using the Design-of-Experiment Approach.","authors":"Dai Oyama, Masako Okada, Furan Song, Chiori Nitta, Hiroyuki Koide, Sei Yonezawa, Tomohiro Asai","doi":"10.1248/bpb.b24-00722","DOIUrl":"10.1248/bpb.b24-00722","url":null,"abstract":"<p><p>This study aimed to elucidate the manufacturing process parameters with optimal quality characteristics of protein-encapsulated dioleoylglycerophosphate-diethylenediamine (DOP-DEDA)-based lipid nanoparticles (LNPs) for intracellular protein drug delivery. DOP-DEDA is a pH-responsive and charge-reversible lipid for intracellular cargo delivery. In this study, bovine serum albumin (BSA) was used as a weakly acidic protein model, and LNPs were prepared using microfluidic technology, which has many advantages for practical applications. BSA-encapsulated DOP-DEDA-based LNPs showed pH-responsive charge reversibility and excellent quality characteristics for the intracellular delivery of proteins. A process optimization study was conducted by applying the Box-Behnken design in a design-of-experiment approach. The particle size, ζ-potential, and encapsulation efficiency were evaluated in response to the total flow rate, lipid concentration, and lipid solution ratio. The lipid solution ratio and total flow rate significantly affected the particle size and encapsulation efficiency, respectively. On the contrary, none of the process parameters affected the ζ-potential. Moreover, a map of the predicted values was constructed for the particle size and encapsulation efficiency using a multiple regression equation. In the predicted particle size range of 77-215 nm and encapsulation efficiency of 14-35%, the observed values were close to the predicted values, and 100-nm LNPs were reproduced with an encapsulation efficiency of 27%. Therefore, manufacturing process parameters were established to obtain protein-encapsulated DOP-DEDA-based LNPs with optimal quality characteristics.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"286-297"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trends of Strong and Weak Opioid Prescriptions in Japan: A Cross-Sectional Study Based on Open Data from the National Database and Hospital Claims Data from Fiscal Years 2015 to 2021.","authors":"Tomokazu Shoji, Manabu Akazawa, Nonoka Nakagomi, Miwako Kobayashi, Fumihiko Kitta, Ryo Inose, Yuichi Muraki, Tetsuya Iijima, Takaaki Suzuki","doi":"10.1248/bpb.b24-00584","DOIUrl":"10.1248/bpb.b24-00584","url":null,"abstract":"<p><p>Trends in opioid use for patients with cancer in Japan remain unclear. This study investigated the prescription trends of strong and weak opioids in Japan and the prescription trends among patients with or without support from a palliative care team. Open data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) and administrative claims data from the University of Yamanashi Hospital from fiscal years 2015 to 2021 were used. Opioid consumption was reported using the defined daily dose (DDD) per 1000 inhabitants per day (DID) and DDD per 100 bed-days. The NDB open data showed a decrease from 0.3111 to 0.2271 in the DID for inpatients (p = 0.0001) and an increase from 0.5971 to 0.8597 in the DID for outpatients (p = 0.0003). Consumption of tramadol, a weak opioid, increased in both inpatient and outpatient settings. In University of Yamanashi Hospital, the annual percentage of opioid consumption changed little among strong opioids (98.1-97.1%) and weak opioids (1.8-2.8%) for patients supported by a palliative care team (p = 0.2842), but changed more noticeably among strong opioids (86.6-69.6%) and weak opioids (13.3-30.3%) for patients without support from a palliative care team (p < 0.001). Opioid prescription patterns in Japan changed during the 7-year study period, which indicated shifts in the types of opioids used. Additionally, the trend in opioid prescriptions was characterized by the presence or absence of palliative care team support.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"279-285"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hui-Hsin Cheng, Ming-Che Liu, Chih-Han Lin, Shu-Yu Kuo
{"title":"Integrated Clinical Trial Management System: Establishment and Efficiency Assessment.","authors":"Hui-Hsin Cheng, Ming-Che Liu, Chih-Han Lin, Shu-Yu Kuo","doi":"10.1248/bpb.b25-00110","DOIUrl":"https://doi.org/10.1248/bpb.b25-00110","url":null,"abstract":"<p><p>In the hospital settings, performing clinical trials is an intricate process that is generally hampered by several institutional, technical, and record-keeping challenges. Hence, we evaluated the effectiveness and efficiency of our established integrated clinical trial management system (CTMS) in terms of analyzing core functionalities, assessing integration with existing systems, measuring time, and cost efficiency. Our CTMS (version 10.1, August 2024) is integrated into one of the largest teaching hospitals with the human research audit system, biobank management system, biological sample management system, enterprise resource system service, institutional review, and single sign-on system. The total number of trials, subjects enrolled, products developed, investigators, new drug and indication, devices, and new medical technology are found to be 913, 53969, 851, 159, 784, and 98, respectively, with a total budget of 3539846777 New Taiwan Dollar (approx. 106881045 US$). Our CTMS is efficient in updating data, with improved user interface experience, and controlled access according to the defined policy. Integrating CTMS with other components provides effective tracking and monitoring of the clinical study. Conclusively, our integrated CTMS is designed for comprehensive evaluation and supervision of clinical trials, supporting full-process data management and seamless integration with clinical systems of hospitals through a unified interface. The increasing number of trials, subjects enrolled, products developed, investigators, new drugs and indications, devices, and new medical technology indicates its robustness and efficacy.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"782-790"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}