Biological & pharmaceutical bulletin最新文献

Efficient Loading into and Controlled Release of Lipophilic Compound from Liposomes by Using Cyclodextrin as Novel Trapping Agent. 利用环糊精作为新型诱捕剂，从脂质体中高效装载和控制释放亲脂性化合物

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00558

Sae Akaki, Mika Hosokawa, Saki Maeda, Yusuke Kono, Hideko Maeda, Ken-Ichi Ogawara

{"title":"Efficient Loading into and Controlled Release of Lipophilic Compound from Liposomes by Using Cyclodextrin as Novel Trapping Agent.","authors":"Sae Akaki, Mika Hosokawa, Saki Maeda, Yusuke Kono, Hideko Maeda, Ken-Ichi Ogawara","doi":"10.1248/bpb.b24-00558","DOIUrl":"https://doi.org/10.1248/bpb.b24-00558","url":null,"abstract":"Lipid bilayer vesicles, liposomes are representative drug delivery carriers. High encapsulation efficiency and release control of drugs are essential for clinical application of liposomes. For efficient drug loading into liposomes, remote loading method using driving force like transmembrane gradients of pH and ions are utilized. Ions are called as \"trapping agents,\" which are also critical for the controlled release of drugs loaded into liposomes inside. It is difficult to apply ions as trapping agents to various drugs because of limited physicochemical compatibility between drugs and ions. Cyclodextrins (CDs) with hydrophobic cavity can make inclusion complexes with various hydrophobic compounds. Therefore, we aimed to evaluate the potential of CDs as a novel trapping agent using sulfobutylether-β-cyclodextrin (SBE-β-CD) and ibuprofen (IB), a weak acid hydrophobic drug. Encapsulation efficiency of IB in liposomes with pH gradient was approximately 27%, and it was enhanced by intraliposomal SBE-β-CD inclusion in addition to pH gradient, which was SBE-β-CD concentration-dependent. In liposomes with pH gradient, a large fraction of IB was released in a short time. This early-stage rapid IB release was significantly suppressed by the inclusion of SBE-β-CD inside liposomes. Thus, novel remote loading technology by intraliposomal SBE-β-CD enabled the efficient encapsulation of the hydrophobic drug into the aqueous phase of liposomes as well as their controlled release. This technology should be applied to various drugs that can be included into CDs in order to enhance their therapeutic benefits.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614085","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}

引用次数: 0

Downregulation of Genes for Skeletal Muscle Extracellular Matrix Components by Cisplatin. 顺铂对骨骼肌细胞外基质成分基因的下调作用

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00428

Yu Miyauchi, Miho Kiyama, Shinki Soga, Hayato Nanri, Takayuki Ogiwara, Shiori Yonamine, Risako Kon, Nobutomo Ikarashi, Yoshihiko Chiba, Tomoo Hosoe, Hiroyasu Sakai

{"title":"Downregulation of Genes for Skeletal Muscle Extracellular Matrix Components by Cisplatin.","authors":"Yu Miyauchi, Miho Kiyama, Shinki Soga, Hayato Nanri, Takayuki Ogiwara, Shiori Yonamine, Risako Kon, Nobutomo Ikarashi, Yoshihiko Chiba, Tomoo Hosoe, Hiroyasu Sakai","doi":"10.1248/bpb.b24-00428","DOIUrl":"https://doi.org/10.1248/bpb.b24-00428","url":null,"abstract":"The extracellular matrix (ECM) in skeletal muscle is involved in a variety of physiological functions beyond the mechanical support of muscle tissue, nerves, and blood vessels; however, the role of the ECM in skeletal muscle remains unclear. There is little information regarding changes in the expression of factors comprising the ECM during cisplatin-induced muscle atrophy. In the present study, we examined the changes in gene expressions for skeletal muscle extracellular matrix components in skeletal muscle during cisplatin-induced muscle atrophy. Intraperitoneal administration of cisplatin caused muscle atrophy in mice and during this cisplatin-induced muscle atrophy, the expression of many procollagen genes (Col1a1, Col1a2, Col3a1, Col4a1, Col5a1, and Col5a2), elastin (Eln), fibronectin (Fn1), Laminin (Lama1, Lama2, and Lamb1) decorin (Dcn), heparan sulphate proteoglycans (Hspg2) and integrin (Itgb1) constituting the ECM was suppressed. Additional studies are needed to elucidate the pathological significance and mechanisms of reduced gene expression of ECM components associated with cisplatin-induced muscle atrophy.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614115","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}

引用次数: 0

Hua-Zhuo-Jie-Du Decoction Combined with Cisplatin Inhibits the Development of Gastric Cancer Cells by Regulating Immune and Autophagy Signaling. 花椒解毒片联合顺铂通过调节免疫和自噬信号抑制胃癌细胞的发展

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00256

Chun-Xia Sun, De-Hui Li, Ya-Pei Xu, Zhu-Feng Yang, Li-Ying Wei, Yue-Ming Gao, Yi Liu, Cui-Huan Yan, Yong-Zhang Li

{"title":"Hua-Zhuo-Jie-Du Decoction Combined with Cisplatin Inhibits the Development of Gastric Cancer Cells by Regulating Immune and Autophagy Signaling.","authors":"Chun-Xia Sun, De-Hui Li, Ya-Pei Xu, Zhu-Feng Yang, Li-Ying Wei, Yue-Ming Gao, Yi Liu, Cui-Huan Yan, Yong-Zhang Li","doi":"10.1248/bpb.b24-00256","DOIUrl":"https://doi.org/10.1248/bpb.b24-00256","url":null,"abstract":"Host immunity and autophagy of cancer cells markedly impact the development of gastric cancer. Hua-Zhuo-Jie-Du decoction (TDP) has been used in gastritis clinically. This study aimed to evaluate the effects of TDP combined with cisplatin (DDP) on gastric cancer and explore the molecular mechanism. A total of 16 BALB/c nude mice were used to model the SGC7901 cells xenograft and treated with TDP and DDP or both, with the model group as the control. Hematoxylin-Eosin (H&E) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining were performed, and the expression levels of CD31 and Ki-67 were quantified by immunohistochemistry staining. Additionally, cyclooxygenase (COX)-2, matrix metalloproteinas (MMP)-2, and MMP-9 expression levels were quantified using quantitative real-time PCR (qRT-PCR) and Western blotting (WB). WB was used to determine Cleaved-caspase3, Beclin-1, LC3B, and p-p62 levels. Lastly, flow cytometry was employed to evaluate immune responses in mice. TDP and DDP significantly decreased tumor weight and nuclear division, resulting in loosely distributed cells. Besides, TDP and DDP down-regulated the protein expression levels of Ki-67, CD31, COX-2, MMP-2, and MMP-9, as well as decreased the number of CD4+ IL-17+ cells. Conversely, TDP and DDP up-regulated Cleaved-caspase3 expression and the proportion of CD3+/CD4+ and CD8+/CD3+ cells. Notably, optimal effects were achieved using the combination of DDP and TDP. Furthermore, DDP increased the LCII/LCI ratio and the Beclin-1 levels while down-regulating p62 levels. However, TDP alleviated these effects. These results collectively indicated that the combination of TDP with DDP can inhibit the development of gastric cancer cells by mediating the immune and autophagy signaling pathways.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614228","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}

引用次数: 0

Korean Red Ginseng Ameliorates the Level of Serum Uric Acid via Downregulating URAT1 and Upregulating OAT1 and OAT3. 高丽红参通过下调 URAT1 和上调 OAT1 和 OAT3 改善血清尿酸水平

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00293

Soon-Young Lee, Seung-Sik Cho, Kang Min Han, Min-Jae Lee, Taeho Ahn, Byungcheol Han, Chun-Sik Bae, Dae-Hun Park

{"title":"Korean Red Ginseng Ameliorates the Level of Serum Uric Acid via Downregulating URAT1 and Upregulating OAT1 and OAT3.","authors":"Soon-Young Lee, Seung-Sik Cho, Kang Min Han, Min-Jae Lee, Taeho Ahn, Byungcheol Han, Chun-Sik Bae, Dae-Hun Park","doi":"10.1248/bpb.b24-00293","DOIUrl":"https://doi.org/10.1248/bpb.b24-00293","url":null,"abstract":"Hyperuricemia is caused by an imbalance of uric acid and is associated with many diseases. Although gout which is one of hyperuricemia-related diseases is curable with anti-hyperuricemic drugs some medications have side effects, such as hypersensitivity in patients with circulatory system disorders, flare reoccurrences, and increased cardiac risk. This study consisted of test tube (xanthine oxidase's inhibition) and animal study. Animal study using with ICR mice was composed of control, potassium oxonate-induced hyperuricemia, allopurinol, and 3 Korean red ginseng water extract (KRGWE) treatment groups (62.5; 125, and 500 mg/kg). We orally administered KRGWE once a day for 7 d to induce hyperuricemia and injected PO 2 h before the final KRGWE administration. We measured serum uric acid, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen, and creatinine and analyzed the genes such as organic anion transport (OAT)-1, OAT-3, and urate transport (URAT)-1. KRGWE dose-dependently controlled xanthine oxidase activity in the serum and completely inhibited serum uric acid. KRGWE affected both uric acid excretion-related and uric acid reabsorption-related gene expression. KRGWE stimulated uric acid excretion-related gene expressions, such as OAT-1 and OAT-3, but inhibited uric acid reabsorption-related gene expression, such as URAT-1. KRGWE improved liver and kidney functioning. KRGWE improved liver/kidney functioning and is promising anti-hyperuricemic agent which can control serum uric acid via downregulating URAT1 and upregulating OAT1 and OAT3.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646936","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}

引用次数: 0

Evaluating the Associated Hyperuricemia Risk with Sodium-Glucose Cotransporter 2 Inhibitors: A Sequence Symmetry Analysis Using the Japanese Administrative Claims Database. 评估钠-葡萄糖共转运体 2 抑制剂的相关高尿酸血症风险：利用日本行政索赔数据库进行序列对称性分析。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00330

Satoshi Yokoyama, Chihiro Nakagawa, Takaya Uno, Kouichi Hosomi

{"title":"Evaluating the Associated Hyperuricemia Risk with Sodium-Glucose Cotransporter 2 Inhibitors: A Sequence Symmetry Analysis Using the Japanese Administrative Claims Database.","authors":"Satoshi Yokoyama, Chihiro Nakagawa, Takaya Uno, Kouichi Hosomi","doi":"10.1248/bpb.b24-00330","DOIUrl":"https://doi.org/10.1248/bpb.b24-00330","url":null,"abstract":"Hyperuricemia is defined as high uric acid levels within the bloodstream and is commonly associated with gout, type 2 diabetes mellitus, and kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel drugs that prevent glucose reabsorption; additionally, this drug has shown promising results in patients at risk of developing cardiovascular or renal complications by lowering uric acid levels. This study aimed to investigate the association between SGLT2i and hyperuricemia. Here, a self-controlled sequence symmetry analysis using the JMDC administrative claims database (January 2005 to September 2022) consisting of 12396 patients, who were newly prescribed both SGLT2i and hypouricemic agents, was conducted. Trend-adjusted sequence ratios (SR) at intervals of 6, 12, 18, and 24 months were calculated. Significant inverse signals across all intervals were observed between SGLT2i and hypouricemic agents, with the strongest effect observed in the 24-month interval [adjusted SR 0.52 (95% CI 0.49-0.55)]. Significant inverse signals were observed for each of the six types of SGLT2i across all intervals. This indicates that SGLT2i initiation may be associated with a decreased risk of hyperuricemia. Further investigation of the efficacy of SGLT2i is needed in hypothesis-testing designs such as cohort studies.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614102","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}

引用次数: 0

Decreased Brain pH Underlies Behavioral and Brain Abnormalities Induced by Chronic Exposure to Glucocorticoids in Mice. 脑pH值降低是小鼠长期暴露于糖皮质激素诱发行为和脑异常的基础

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00251

Ryota Araki, Ayami Kita, Takeshi Yabe

{"title":"Decreased Brain pH Underlies Behavioral and Brain Abnormalities Induced by Chronic Exposure to Glucocorticoids in Mice.","authors":"Ryota Araki, Ayami Kita, Takeshi Yabe","doi":"10.1248/bpb.b24-00251","DOIUrl":"https://doi.org/10.1248/bpb.b24-00251","url":null,"abstract":"Depressed patients may exhibit glucocorticoid hypersecretion, suggesting that elevated levels of glucocorticoids may play an important role in the pathophysiology of depression. Some postmortem brain studies have shown decreased pH and increased lactate levels in psychiatric patients, implying involvement of these factors in the pathogenesis. To investigate the effects of glucocorticoids on brain pH and lactate levels, and their roles in depressive symptoms, brain pH and lactate were examined in mice treated with corticosterone (CORT), the major bioactive glucocorticoid in rodents. A single administration of CORT decreased hippocampal pH after 24 h. Three weeks of CORT treatment decreased pH in the prefrontal cortex (PFC), striatum, and hippocampus (HC), whereas intake of pH 9.0 drinking water increased pH in these brain regions. pH and lactate levels were correlated in the PFC and HC of mice treated with CORT for 3 weeks. The suppression of body weight gain and decrease in adrenal weight observed after 3 weeks of CORT treatment were not alleviated by pH 9.0 water. However, an increase in immobility time in the forced swim test and a decrease in neurogenesis in the hippocampus were alleviated. The decrease in brain pH and increase in immobility time in the forced swim test and a decrease in neurogenesis in the hippocampus induced by CORT treatment were abolished by co-treatment with the glucocorticoid receptor (GR) antagonist mifepristone. These findings indicate that decreased brain pH via GRs may be related to glucocorticoid-induced depression-like behavior and decreased hippocampal neurogenesis.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614111","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}

引用次数: 0

The Use of Text Mining to Obtain a Historical Overview of Research on Therapeutic Drug Monitoring. 利用文本挖掘技术了解治疗药物监测研究的历史概况。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00319

Tetsuo Matsuzaki, Hiroyuki Mizoguchi, Kiyofumi Yamada

{"title":"The Use of Text Mining to Obtain a Historical Overview of Research on Therapeutic Drug Monitoring.","authors":"Tetsuo Matsuzaki, Hiroyuki Mizoguchi, Kiyofumi Yamada","doi":"10.1248/bpb.b24-00319","DOIUrl":"https://doi.org/10.1248/bpb.b24-00319","url":null,"abstract":"Therapeutic drug monitoring (TDM) is a routine clinical practice used to individualize drug dosing to maintain drug efficacy and minimize the consequences of overexposure. TDM is applied to many drug classes, including immunosuppressants, antineoplastic agents, and antibiotics. Considerable effort has been made to establish routine TDM practices for each drug. However, because TDM has been developed within the context of specific drugs, there is insufficient understanding of historical trends within the field of TDM research as a whole. In this study, we employed text-mining approaches to explore trends in the TDM research field. We first performed a PubMed search to determine which drugs and drug classes have been extensively studied in the context of TDM. This investigation revealed that the most commonly studied drugs are tacrolimus, followed by cyclosporine and vancomycin. With regard to drug classes, most studies focused on immunosuppressants, antibiotics, and antineoplastic agents. We also subjected PubMed records of TDM-related studies to a series of text-mining pipelines. Our analyses revealed how TDM research has evolved over the years, thereby serving as a cornerstone for forecasting future research trends.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646947","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}

引用次数: 0

Sunflower Trypsin Monocyclic Inhibitor Selected for the Main Protease of SARS-CoV-2 by Phage Display. 通过噬菌体展示为 SARS-CoV-2 的主要蛋白酶选择向日葵胰蛋白酶单环抑制剂

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00369

Graziele Cristina Ferreira, Verônica de Moraes Manzato, Debora Noma Okamoto, Livia Rosa Fernandes, Deivid Martins Santos, Gabriel Cerqueira Alves Costa, Fernando Allan Abreu Silva, Ricardo Jose Soares Torquato, Giuseppe Palmisano, Maria Aparecida Juliano, Aparecida Sadae Tanaka

{"title":"Sunflower Trypsin Monocyclic Inhibitor Selected for the Main Protease of SARS-CoV-2 by Phage Display.","authors":"Graziele Cristina Ferreira, Verônica de Moraes Manzato, Debora Noma Okamoto, Livia Rosa Fernandes, Deivid Martins Santos, Gabriel Cerqueira Alves Costa, Fernando Allan Abreu Silva, Ricardo Jose Soares Torquato, Giuseppe Palmisano, Maria Aparecida Juliano, Aparecida Sadae Tanaka","doi":"10.1248/bpb.b24-00369","DOIUrl":"https://doi.org/10.1248/bpb.b24-00369","url":null,"abstract":"Main protease (Mpro), also known as 3-chymotrypsin-like protease (3CLpro), is a nonstructural protein (NSP5) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the cleavage of virus polyproteins during viral replication at 11 sites, which generates 12 functional proteins. Mpro is a cysteine protease that presents specificity for the amino acid residue glutamine (Gln) at the P1 position of the substrate. Due to its essential role in processing the viral polyprotein for viral particle formation (assembly), Mpro inhibition has become an important tool to control coronavirus disease 2019 (COVID-19), since Mpro inhibitors act as antivirals. In this work, we proposed to identify specific inhibitors of the Mpro of SARS-CoV-2 using a monocyclic peptide (sunflower trypsin inhibitor (SFTI)) phage display library. Initially, we expressed, purified and activated recombinant Mpro. The screening of the mutant SFTI phage display library using recombinant Mpro as a receptor resulted in the five most frequent SFTI mutant sequences. Synthetized mutant SFTIs did not inhibit Mpro protease using the fluorogenic substrate. However, the mutant SFTI 4 efficiently decreased the cleavage of recombinant human prothrombin as a substrate by Mpro, as confirmed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). Additionally, SFTI 4 presented a dissociation constant (KD) of 21.66 ± 6.66 µM for Mpro by surface plasmon resonance. Finally, 0.1 µM SFTI 4 reduced VERO cell infection by SARS-CoV-2 wt after 24 and 48 h. In conclusion, we successfully screened a monocyclic peptide library using phage display for the Mpro of SARS-CoV-2, suggesting that this methodology can be useful in identifying new inhibitors of viral enzymes.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614235","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}

引用次数: 0

Expression Profiles of Brain-Derived Neurotrophic Factor Splice Variants in the Hippocampus of Alzheimer's Disease Model Mouse. 脑源性神经营养因子剪接变体在阿尔茨海默氏症模型小鼠海马中的表达谱。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00446

Yuka Matsuoka, Hibiki Nakasone, Rento Kasahara, Mamoru Fukuchi

{"title":"Expression Profiles of Brain-Derived Neurotrophic Factor Splice Variants in the Hippocampus of Alzheimer's Disease Model Mouse.","authors":"Yuka Matsuoka, Hibiki Nakasone, Rento Kasahara, Mamoru Fukuchi","doi":"10.1248/bpb.b24-00446","DOIUrl":"https://doi.org/10.1248/bpb.b24-00446","url":null,"abstract":"Dysregulation of brain-derived neurotrophic factor (BDNF) has been implicated in Alzheimer's disease (AD). In this study, we investigated the temporal dynamics of BDNF expression in the hippocampus of 5xFAD mice, an AD model, focusing on sex and age differences and Bdnf mRNA splice variants. At 3 months of age, female wild-type (WT) mice exhibited significantly higher Bdnf mRNA levels compared to males. However, this difference was abolished in female 5xFAD mice. At 6 months of age, no sex differences in Bdnf mRNA levels were observed in WT mice, and the levels tended to be lower in female 5xFAD mice. Additionally, a significant decrease in the mRNA levels of full-length tropomyosin-related kinase B (TrkB), a BDNF receptor, was found in female 5xFAD mice at 6 months, while mRNA levels of the truncated TrkB were increased in both male and female 5xFAD mice. Specifically, among the Bdnf mRNA splice variants, the levels of Bdnf exon IIA-IX, exon IIB-IX, exon IIC-IX, and exon IXA mRNA were significantly higher in female WT mice compared to male WT mice at 3 months, but this difference was lost in female 5xFAD mice. These findings suggest that the expression of specific Bdnf splice variants would be maintained at higher levels in the hippocampus of young female mice than in males but may be disrupted in AD model mice. Our study may provide insights into the relationship between sex differences in AD onset and BDNF expression.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614105","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}

引用次数: 0

Upregulation of P-Glycoprotein and Breast Cancer Resistance Protein Activity in Newly Developed in Vitro Rat Blood-Brain Barrier Spheroids Using Advanced Glycation End-Products. 利用高级糖化终产物上调新开发的体外大鼠血脑屏障球体内 P-糖蛋白和乳腺癌抗性蛋白的活性

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00481

Hiroki Endo, Miki Ogasawara, Yuma Tega, Yoshiyuki Kubo, Ken-Ichi Hosoya, Shin-Ichi Akanuma

{"title":"Upregulation of P-Glycoprotein and Breast Cancer Resistance Protein Activity in Newly Developed in Vitro Rat Blood-Brain Barrier Spheroids Using Advanced Glycation End-Products.","authors":"Hiroki Endo, Miki Ogasawara, Yuma Tega, Yoshiyuki Kubo, Ken-Ichi Hosoya, Shin-Ichi Akanuma","doi":"10.1248/bpb.b24-00481","DOIUrl":"https://doi.org/10.1248/bpb.b24-00481","url":null,"abstract":"The blood-brain barrier (BBB) is a dynamic interface controlling the compound translocation between the blood and the brain, thereby maintaining neural homeostasis. There is cumulative evidence that BBB impairment during diabetes mellitus (DM) takes part in the progression of cognitive dementia. As tight junction proteins and ATP-binding cassette (ABC) transporters regulate substance exchange between the circulating blood and brain, the expression and function of these molecules under DM should be fully clarified. To understand the alteration of ABC transporter function in the BBB under DM, in vitro multicellular rat BBB spheroids consisting of conditionally immortalized rat brain capillary endothelial cells, astrocytes, and pericytes were newly developed. Immunostaining and permeability analysis of paracellular transport markers suggested the construction of tight junctions on the surface of the BBB spheroids. Transport analyses using fluorescence substrates of P-glycoprotein (P-gp), the breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 4 (MRP4) indicate the functional expression of these transporters in the spheroids. After treatment with advanced glycation end-products (AGEs), involved in various signals during DM, the mRNA expression of tight junction molecules and ABC transporters in the BBB spheroids was upregulated. Furthermore, the functional changes in P-gp and BCRP in the BBB spheroids exposed to AGEs were canceled by the inhibitors of the receptor for AGEs (RAGE). These results suggest that AGE-RAGE interaction upregulates P-gp and BCRP function in the BBB.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646951","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}

引用次数: 0