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The Nuclear Factor (Erythroid-Derived 2)-Like 2 Activator TBE-31 Influences Body Weight by Affecting White Adipose Tissue in High Fat Diet-Induced Obesity Mice. 核因子(红细胞衍生2)样2激活剂TBE-31通过影响高脂饮食诱导的肥胖小鼠的白色脂肪组织来影响体重。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00273
Keigo Tsushida, Kohei Yamasaki, Waka Haruyama, Tetsuya Kitayama
{"title":"The Nuclear Factor (Erythroid-Derived 2)-Like 2 Activator TBE-31 Influences Body Weight by Affecting White Adipose Tissue in High Fat Diet-Induced Obesity Mice.","authors":"Keigo Tsushida, Kohei Yamasaki, Waka Haruyama, Tetsuya Kitayama","doi":"10.1248/bpb.b25-00273","DOIUrl":"https://doi.org/10.1248/bpb.b25-00273","url":null,"abstract":"<p><p>The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system plays an important role in defense against oxidative stress, and its involvement has been implicated in body weight reduction under obese conditions. While the effect on white adipose tissue (WAT) has been intensely studied, focusing on the anti-inflammatory and anti-oxidative stress effects exerted by Nrf2 activation, the involvement of skeletal muscle has not been investigated. We assessed the body weight changes induced by Nrf2 activation by comparing its effect on WAT with those on skeletal muscle. We evaluated TBE-31, a potent Nrf2 activator, in a high-fat diet (HFD)-induced obesity model. Notably, TBE-31 significantly suppressed HFD-induced body weight gain compared with vehicle treatment. While treatment with TBE-31 induced a significant WAT weight decrease compared with vehicle, skeletal muscle weight was not affected. In addition, body weight changes were significantly correlated with WAT but not with skeletal muscle. Lipid deposition was remarkably improved in the adipose tissue, but muscle histology was not affected. A gene expression analysis revealed that Ucp-1 was upregulated and Il-6 downregulated by TBE-31 treatment in an Nrf2-dependent manner. Taken together, these findings suggest that pharmacological activation of Nrf2 suppressed HFD-induced body weight gain by affecting WAT.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 9","pages":"1404-1411"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111787","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
FR429 from Polygonum capitatum Demonstrates Potential as an Anti-hepatic Injury Agent by Modulating PI3K/Akt Signaling Pathway. 首蓼FR429通过调节PI3K/Akt信号通路显示抗肝损伤药物的潜力
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00812
Yaru Yang, Lei He, Minghui He, Xu Zhang, Shanggao Liao, Zhu Zeng, Yan Lin, Bo Tu
{"title":"FR429 from Polygonum capitatum Demonstrates Potential as an Anti-hepatic Injury Agent by Modulating PI3K/Akt Signaling Pathway.","authors":"Yaru Yang, Lei He, Minghui He, Xu Zhang, Shanggao Liao, Zhu Zeng, Yan Lin, Bo Tu","doi":"10.1248/bpb.b24-00812","DOIUrl":"https://doi.org/10.1248/bpb.b24-00812","url":null,"abstract":"<p><p>FR429, an ellagitannin isolated and purified from the whole herb Polygonum capitatum (P. capitatum), possesses a robust pharmacological profile, which is particularly noteworthy for its anti-inflammatory and anticancer properties. Despite these established effects, its potential in mitigating hepatic injury remains to be fully explored. The present investigation delineates the hepatoprotective efficacy of FR429 and unveils its underlying molecular mechanisms. Initially, of the tested compounds, 10 compounds (specifically, compounds 2, 4, 5, 6, 7, 8, 9, 12, 13, and 14) exhibited significant protective effects at a concentration of 10 μM, elevating HepG2 (human liver cancer cell) cell viability from 43.4 to 70% following carbon tetrachloride (CCl<sub>4</sub>) exposure. Among them, compounds 2 (FR429, half-maximum effective concentration (EC<sub>50</sub>) = 6.46 μM) and 6 (2\"-O-galloylquercitrin, EC<sub>50</sub> = 5.36 μM) demonstrated the highest cytoprotective activities. In the murine model, FR429 dramatically attenuated serum levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase, indicative of its hepatoprotective potential. Histopathological evaluation further substantiated these findings, as FR429 noticeably mitigated CCl<sub>4</sub>-induced hepatic lesions, involving necrosis, ballooning degeneration, and neutrophil infiltration. Transcriptomic analysis unveiled 178 differentially expressed genes in FR429-treated mice liver tissue, with significant alterations indicative of a hepatoprotective response. Mechanistic investigations revealed that FR429's hepatoprotective effects involve modulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, evidenced by downregulation of toll-like receptor 2, phosphorylated PI3K, phosphorylated Akt, nuclear factor-kappa-B, interleukin-1 beta, and tumor necrosis factor-alpha expression. Furthermore, FR429 modulated the gene and protein expression levels of apoptotic markers (apoptotic protein (Bax) and B-lymphoblastoma-2 gene (Bcl2)), reinforcing its anti-hepatic damage efficacy. This study represents the first report establishing FR429 as an effective hepatoprotective compound, paving the way for further investigation into its therapeutic applications.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"372-382"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956800","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
Supplementing with Vitamin D during Pregnancy Reduces Inflammation and Prevents Autism-Related Behaviors in Offspring Caused by Maternal Immune Activation. 在怀孕期间补充维生素D可以减少炎症,并预防由母体免疫激活引起的后代自闭症相关行为。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00008
Xiao Wang, Qingqing Li, Zhihong Lyu, Yingying Wu
{"title":"Supplementing with Vitamin D during Pregnancy Reduces Inflammation and Prevents Autism-Related Behaviors in Offspring Caused by Maternal Immune Activation.","authors":"Xiao Wang, Qingqing Li, Zhihong Lyu, Yingying Wu","doi":"10.1248/bpb.b25-00008","DOIUrl":"https://doi.org/10.1248/bpb.b25-00008","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD), a neurodevelopmental disorder of unknown etiology with limited treatment options, has emerged as a significant public health concern. Studies have demonstrated that prenatal vitamin D deficiency is a risk factor for ASD development in offspring; however, the underlying mechanism remains unclear. In this project, vitamin D was administered orally to pregnant mice with/without the subsequent administration of polyriboinosinic polyribocytidylic acid (Poly(I:C)), which induced the maternal immune activation (MIA). Our results showed that vitamin D supplementation during pregnancy alleviated MIA-induced ASD-like behaviors in offspring. Moreover, vitamin D supplementation reduced the MIA-induced elevation of interleukin-6 (IL-6) and IL-17a levels in both the maternal ileum and fetal brains. It also suppressed signal transducer and activator of transcription 3 (Stat3) activation and the elevated expression of serum amyloid A1 and A2 (SAA1/2) in the ileum of MIA-affected pregnant mice. This study revealed that vitamin D may reduce the expression of IL-17a by inhibiting the IL-6/Stat3/SAA signaling pathway, thereby improving ASD-like behavior in offspring mice, and provide a new theoretical support for the prevention and treatment of ASD by scientific dietary interventions and nutritional supplement during pregnancy.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"632-640"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092590","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
Prospective Analysis of Factors Influencing Inter-Individual Variation in Trough Plasma Voriconazole Concentrations in Older Patients-Impact of High α1-Acid Glycoprotein Levels. 老年患者伏立康唑谷血药浓度个体差异影响因素的前瞻性分析——高α1-酸性糖蛋白水平的影响
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00057
Yukako Yasui, Hiroyuki Yasui, Yoshiki Yamamoto, Toshihiko Ishizaka, Kazuo Hatanaka, Waki Imoto, Wataru Shibata, Koichi Yamada, Hiroshi Kakeya
{"title":"Prospective Analysis of Factors Influencing Inter-Individual Variation in Trough Plasma Voriconazole Concentrations in Older Patients-Impact of High α1-Acid Glycoprotein Levels.","authors":"Yukako Yasui, Hiroyuki Yasui, Yoshiki Yamamoto, Toshihiko Ishizaka, Kazuo Hatanaka, Waki Imoto, Wataru Shibata, Koichi Yamada, Hiroshi Kakeya","doi":"10.1248/bpb.b25-00057","DOIUrl":"https://doi.org/10.1248/bpb.b25-00057","url":null,"abstract":"<p><p>Voriconazole (VRCZ), an azole-based, deep-seated antifungal agent, is used as a 1st-line treatment for aspergillosis in Japan. VRCZ exhibits nonlinear pharmacokinetic (PK) behavior with relatively large inter-individual variability in plasma concentration. Additionally, genetic polymorphisms of CYP2C19 have been reported to influence the metabolic variability of VRCZ. The purpose of this study was to search for and identify clinically relevant potential factors influencing the PK and plasma concentration of VRCZ to better inform VRCZ dosing regimens. Thirty patients receiving VRCZ were enrolled. Total (C<sub>t</sub>) and unbound (C<sub>u</sub>) trough plasma concentrations of VRCZ were determined by the HPLC-UV method. Univariate and multivariate correlation analyses were used to evaluate the relationships between C<sub>t</sub> or C<sub>t</sub>/dose per body weight (C<sub>t</sub>/D) and individual demographic and laboratory characteristics. Since the increasing trend of C-reactive protein (CRP) inversely correlated with the classification of CYP2C19 gene polymorphisms, it was suggested that the inflammation counteracted the trend of C<sub>t</sub> according to CYP2C19 gene polymorphisms. Spearman's rank-order correlation analysis showed significant correlations between C<sub>t</sub> and dose per body weight, CRP, and α1-acid glycoprotein (α1-AGP). Multivariate linear regression analysis showed that age, dose per body weight, CRP, and α1-AGP were significant explanatory factors for C<sub>t</sub>. In particular, elevated α1-AGP levels were found to have significant explanatory value for decreased C<sub>t</sub>. Although the present study has critical limitations, such as the patient sample was small in size and being limited to a single medical institution, this finding may explain some of the inter-individual variability in plasma VRCZ concentration.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"694-705"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141221","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
Stress Response Kinase MK2 Induces Non-canonical Activation of EphA2 in EML4-ALK Lung Cancer Cells. 应激反应激酶MK2诱导EML4-ALK肺癌细胞中EphA2的非规范激活
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00747
Fang Zhang, Yue Zhou, Naru Hamada, Akihiro Tanaka, Satoru Yokoyama, Seiji Yano, Kunio Matsumoto, Hiroyuki Mano, Hiroaki Sakurai
{"title":"Stress Response Kinase MK2 Induces Non-canonical Activation of EphA2 in EML4-ALK Lung Cancer Cells.","authors":"Fang Zhang, Yue Zhou, Naru Hamada, Akihiro Tanaka, Satoru Yokoyama, Seiji Yano, Kunio Matsumoto, Hiroyuki Mano, Hiroaki Sakurai","doi":"10.1248/bpb.b24-00747","DOIUrl":"10.1248/bpb.b24-00747","url":null,"abstract":"<p><p>The non-canonical phosphorylation of the receptor tyrosine kinase ephrin type-A receptor 2 (EphA2) at Ser-897 plays crucial roles in tumor progression in a tyrosine kinase-independent manner. This phosphorylation is catalyzed by p90 ribosomal S6 kinase (RSK), a kinase downstream of extracellular signal-regulated kinase (ERK). We recently reported that stress-responsive kinase mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), instead of ERK, regulates RSK under cellular stress conditions; however, the function of MK2 in ERK-activated cells is still unknown. We herein clarified that MK2 regulates the RSK-EphA2 axis in ERK-activated echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) lung cancer cells. In addition, an MK2 inhibitor blocked enhancements in cell motility induced by the constitutively activated RSK-EphA2 axis. The present results reveal the importance of MK2 in the ERK-activated non-canonical activation of EphA2.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"172-176"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536427","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
Astragalus Polysaccharide Alleviates Cognitive Decline in D-Galactose-Induced Aging. 黄芪多糖减轻d -半乳糖诱导衰老的认知能力下降。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00524
Jin Tian, Ran Huo, Yixuan Wang, Jiepeng Wang, Fang Fang, Chaoyi Fang
{"title":"Astragalus Polysaccharide Alleviates Cognitive Decline in D-Galactose-Induced Aging.","authors":"Jin Tian, Ran Huo, Yixuan Wang, Jiepeng Wang, Fang Fang, Chaoyi Fang","doi":"10.1248/bpb.b24-00524","DOIUrl":"https://doi.org/10.1248/bpb.b24-00524","url":null,"abstract":"<p><p>Astragalus polysaccharide (APS) is a biologically active water-soluble polysaccharide extracted from stems or roots, which has been proven to have antiaging effects. The aim of this study was to investigate the effects of APS on cognitive function in d-galactose (d-gal)-induced aging rats and explore the potential underlying molecular mechanisms. The rats were induced to age by intraperitoneal injection with 400 mg/kg/d d-gal for 8 weeks. Aging of rats was assessed through the Morris water maze test, step-down test, open field test, and grip strength test. Pathological changes in the hippocampal CA3 and CA1 regions were determined by Hematoxylin and eosin and Nissl staining. The superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) in the serum were measured. Telomere length, dual oxidase 1 (Duox1), dual oxidase 2 (Duox2), peroxiredoxin 1 (Prdx1), p21, p16, p53, telomerase reverse transcriptase (TERT), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), nicotinamide phosphoribosyl transferase (NAMPT), and sirtuin 1 (SIRT1) were detected via real-time PCR, Western blotting, and immunohistochemical staining. The results indicated that APS ameliorated the general status in d-gal-induced aging rats, mitigated neuronal degeneration in the CA3 and CA1 regions, reduced the oxidative stress levels, modulated senescence-related β-GAL and protein expression, and maintained telomere length. Furthermore, APS significantly reduced p53 expression and increased p-PI3K, p-AKT, NAMPT, SIRT1, and TERT expression. Therefore, d-gal-induced aging and cognitive impairment in rats can be prevented by APS, likely through regulation of the TERT/p53 signaling axis via the PI3K/Akt and NAMPT/SIRT1 signaling pathways.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"523-536"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964600","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
Tokishigyakukagoshuyushokyoto (TSGST) Inhibits Aggression Induced by Isolation Rearing in Mice. Tokishigyakukagoshuyushokyoto (TSGST)抑制小鼠分离饲养引起的攻击行为。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00011
Honoka Nakajima, Chisato Wakabayashi
{"title":"Tokishigyakukagoshuyushokyoto (TSGST) Inhibits Aggression Induced by Isolation Rearing in Mice.","authors":"Honoka Nakajima, Chisato Wakabayashi","doi":"10.1248/bpb.b25-00011","DOIUrl":"https://doi.org/10.1248/bpb.b25-00011","url":null,"abstract":"<p><p>Herbal medicines are widely used in clinical practice. Several herbal medicines are prescribed in clinical practice to improve mental symptoms. Yokukansan is an effective prescription for irritability and aggression, which are behavioral and psychological symptoms of dementia (BPSD) or autism spectrum disorder (ASD). However, because herbal medicines contain many components, their pharmacological effects have not been analyzed in detail. Risperidone and quetiapine are prescribed in severe cases; however, their side effects of oversedation are problematic. Tokishigyakukagoshuyushokyoto (TSGST) is a herbal medicine prescribed to improve blood circulation and relieve headaches, back pain, or chilblains associated with hemodynamic insufficiency. Interestingly, most of the individual components of TSGST are known to exert sedative or analgesic effects. In this study, we investigated whether TSGST ameliorates aggressive behavior induced by social isolation in mice. The mice were isolated for 5 or 6 weeks immediately after weaning and given TSGST via a water bottle during this period. Long-term administration of TSGST suppressed the onset of aggression induced by isolation rearing. This aggressive phenotype was significantly reversed by intraperitoneal (i.p.) administration of the 5-hydroxytryptamine 1A (5-HT<sub>1A</sub>) receptor antagonist WAY-100635 in TSGST-isolated mice. We also showed that TSGST had similar effects as risperidone, a commonly used antipsychotic for irritability and aggression. These results suggest that TSGST may be effective for irritability or aggression in BPSD or ASD.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"507-514"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976249","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
Impact of Bridged Nucleic Acid Positions within Blocking Oligonucleotides on DNA Amplification Inhibition in Wild-Type Blocking PCR. 阻断寡核苷酸桥接核酸位置对野生型阻断PCR中DNA扩增抑制的影响。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00113
Takuma Yamashita, Yoshinori Tsukumo, Takenori Yamamoto, Eriko Uchida, Tokuyuki Yoshida, Yasunori Uchida, Takao Inoue
{"title":"Impact of Bridged Nucleic Acid Positions within Blocking Oligonucleotides on DNA Amplification Inhibition in Wild-Type Blocking PCR.","authors":"Takuma Yamashita, Yoshinori Tsukumo, Takenori Yamamoto, Eriko Uchida, Tokuyuki Yoshida, Yasunori Uchida, Takao Inoue","doi":"10.1248/bpb.b25-00113","DOIUrl":"https://doi.org/10.1248/bpb.b25-00113","url":null,"abstract":"<p><p>Detecting low-frequency genetic mutations is crucial for genetic testing, especially in cancer diagnostics. Wild-type blocking PCR identifies these genetic mutations using a blocking oligonucleotide that is fully complementary to wild-type DNA. The blocking oligonucleotide selectively binds to wild-type DNA, inhibiting its amplification by DNA polymerase and allowing preferential amplification of mutant DNA. Bridged nucleic acids (BNAs), with high binding affinities for cDNA, are often incorporated into the blocking oligonucleotide to enhance inhibition. However, the effects of BNA positioning within the blocking oligonucleotide on wild-type DNA amplification inhibition are poorly understood. To address this issue, we evaluated the effects of different BNA positions on amplification inhibition efficacy by comparing blocking oligonucleotides with varying numbers of BNAs at the 5' end, 3' end, and central region. Results indicated that BNAs at the 5' end enhanced the inhibition efficacy, whereas BNAs at the 3' end notably diminished the inhibition efficacy. Likewise, increasing the number of BNAs in the central region generally decreased the inhibition efficacy. This is one of the first studies to report the importance of BNA positioning in the amplification inhibition efficacy of blocking oligonucleotides.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"606-612"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075712","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
Dual Anti-inflammatory Actions of a Novel Retinoid X Receptor Agonist Derived from a Natural Compound in Microglial Cells. 天然化合物衍生的新型类视黄醇X受体激动剂在小胶质细胞中的双重抗炎作用。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00037
Koji Tomita, Ken-Ichi Nakashima, Eiji Yamaguchi, Akichika Itoh, Makoto Inoue
{"title":"Dual Anti-inflammatory Actions of a Novel Retinoid X Receptor Agonist Derived from a Natural Compound in Microglial Cells.","authors":"Koji Tomita, Ken-Ichi Nakashima, Eiji Yamaguchi, Akichika Itoh, Makoto Inoue","doi":"10.1248/bpb.b25-00037","DOIUrl":"https://doi.org/10.1248/bpb.b25-00037","url":null,"abstract":"<p><p>Microglia-mediated neuroinflammation plays a critical role in the onset and progression of Alzheimer's disease. In a previous study, we synthesized 6-hydroxy-3'-propyl-[1,1'-biphenyl]-3-propanoic acid (6OHA) based on the structure of magnaldehyde B, a natural compound that our group identified as a retinoid X receptor (RXR) agonist. However, its potential effects on inflammation in microglial cells remain unexplored. In this study, we specifically focused on the early-phase inflammatory responses to lipopolysaccharide (LPS) and evaluated the inhibitory effects of 6OHA on BV-2 microglial cells following 2 h of LPS exposure. Similar to the existing RXR agonist bexarotene (Bex), 6OHA treatment (0.1 and 1 μM) resulted in a dose-dependent decrease in the mRNA levels of proinflammatory mediators, including interleukin-1β (Il1b), Il6, and inducible nitric oxide synthase. However, these effects on proinflammatory mediators were effectively abolished by the RXR antagonist UVI3003. Additionally, 6OHA promoted M2 microglia polarization after 24 h of treatment, as evidenced by the increased mRNA levels of the M2 marker genes arginase-1 (Arg1), C-C motif chemokine ligand 6 (Ccl6), Ccl17, and Ccl22. Notably, 6OHA induced a distinct set of M2 microglial markers compared with IL-4, a known M2 microglial inducer. Furthermore, the transcription of Arg1, a key M2 marker gene, is regulated by retinoic acid receptor/RXR heterodimers and the IL-4 signaling pathway. Collectively, 6OHA suppressed the early inflammatory responses to LPS and promoted M2 microglial polarization through a mechanism distinct from that of IL-4. Therefore, RXR agonists, including 6OHA and Bex, may exhibit dual anti-inflammatory effects and serve as novel modulators of neuroinflammation.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"440-449"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965820","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
Protective Effects of Pleurotus Species on UVB-Induced Skin Disorders at Clinically Relevant Plasma Concentrations of the Antioxidant Ergothioneine in Hairless Mice. 在无毛小鼠抗氧化剂麦角硫因临床相关血浆浓度下,侧耳菌对uvb诱导的皮肤病的保护作用。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00893
Motoki Hanayama, Takahiro Ishimoto, Akira Moritomo, Reiya Yamashita, Junya Kawai, Koichiro Mori, Yukio Kato
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