Biological & pharmaceutical bulletin最新文献_第2页

Activated Fibroblast Growth Factor Receptor 1 Mitigated Poly-PR-Induced Oxidative Stress and Protein Translational Impairment. 活化成纤维细胞生长因子受体1减轻多聚pr诱导的氧化应激和蛋白质翻译损伤。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00794

Taisei Ito, Kazuki Ohuchi, Hisaka Kurita, Takanori Murakami, Shinnosuke Takizawa, Ayaka Fujimaki, Junya Murata, Yasuhisa Oida, Isao Hozumi, Kiyoyuki Kitaichi, Masatoshi Inden

{"title":"Activated Fibroblast Growth Factor Receptor 1 Mitigated Poly-PR-Induced Oxidative Stress and Protein Translational Impairment.","authors":"Taisei Ito, Kazuki Ohuchi, Hisaka Kurita, Takanori Murakami, Shinnosuke Takizawa, Ayaka Fujimaki, Junya Murata, Yasuhisa Oida, Isao Hozumi, Kiyoyuki Kitaichi, Masatoshi Inden","doi":"10.1248/bpb.b24-00794","DOIUrl":"10.1248/bpb.b24-00794","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron cell death. A GGGGCC hexanucleotide repeat expansion (HRE) within the chromosome 9 open reading frame 72 (C9orf72) gene is a major causative factor in ALS. This abnormal HRE triggers five types of dipeptide repeat protein (DPR), each composed of two alternating amino acid expressions. Among the DPRs, arginine-rich Poly-PR localizes predominantly to the nucleus, exerting particularly strong toxicity on motor and cortical neurons. Several mechanisms have been proposed for poly-PR-induced neurotoxicity. In this study, poly-PR-expressing NSC34 motor neuron-like cells showed an increase in oxidative stress. Fibroblast growth factor receptor 1 (FGFR1) is known to promote neurogenesis and inhibit apoptosis in neurons. However, its neuroprotective effects against DPR-induced toxicity have not been previously reported. Here, we demonstrated that FGFR1 activation reduced oxidative stress by upregulating nuclear factor erythroid 2-related factor 2 (NRF2) expression. Furthermore, we propose that the increase in NRF2 through FGFR1 activation may result from the alleviation of protein translation impairment. Overall, these findings suggest that FGFR1 activation provides neuroprotection against poly-PR toxicity and may represent a potential therapeutic strategy for ALS.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"93-100"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078594","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

Colistin Resistance in Acinetobacter baumannii: Basic and Clinical Insights. 鲍曼不动杆菌的粘菌素耐药性：基础和临床见解。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b23-00642

Go Kamoshida, Noriteru Yamada, Daiki Yamaguchi, Kinnosuke Yahiro, Yuji Morita

{"title":"Colistin Resistance in Acinetobacter baumannii: Basic and Clinical Insights.","authors":"Go Kamoshida, Noriteru Yamada, Daiki Yamaguchi, Kinnosuke Yahiro, Yuji Morita","doi":"10.1248/bpb.b23-00642","DOIUrl":"10.1248/bpb.b23-00642","url":null,"abstract":"The emergence of drug-resistant bacteria has posed a significant problem in medical institutions worldwide. Colistin, which targets lipopolysaccharide (LPS), serves as a last-resort antimicrobial agent against multidrug-resistant Gram-negative bacteria. Nevertheless, Acinetobacter baumannii, a pathogen with a worldwide prevalence of antimicrobial resistance, has been reported to develop resistance to colistin frequently. In this review, we discuss how A. baumannii acquires resistance to colistin, focusing on modification as well as loss of LPS present in its outer membrane, which is the primary mechanism of A. baumannii's resistance to colistin. Basic and clinical insights regarding colistin resistance in A. baumannii have been discussed in isolation. Therefore, we discuss the relationship between these 2 colistin resistance mechanisms in terms of the frequency and fitness of genetic mutations based on the insights from basic studies and clinical settings. We concluded that understanding the detailed mechanisms of colistin drug resistance requires a comprehensive understanding of both the frequency of mutations and the effects of selection pressure. Finally, we highlight the importance of promoting research from both basic science and clinical perspectives.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"213-221"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536429","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

Curcumin Is Primarily Distributed in Lung, Spleen and Liver, Metabolized to Glucuronide and Sulfate, and Excreted through Bile and Urine by Using an Amorphous Curcumin Formulation with High Absorbability. 姜黄素主要分布于肺、脾和肝脏，代谢为葡萄糖醛酸盐和硫酸根，并通过胆汁和尿液排出，使用无定形姜黄素配方，具有高吸收性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00877

Tomohiro Nakao, Michiko Nakamura, Kazuya Nagano, Mariko Takeda, Haruna Hirai, Hikaru Maekita, Jian-Qing Gao, Hirofumi Tsujino, Makoto Sakata, Masayuki Nishino, Yuya Haga, Kazuma Higashisaka, Yasuo Tsutsumi

{"title":"Curcumin Is Primarily Distributed in Lung, Spleen and Liver, Metabolized to Glucuronide and Sulfate, and Excreted through Bile and Urine by Using an Amorphous Curcumin Formulation with High Absorbability.","authors":"Tomohiro Nakao, Michiko Nakamura, Kazuya Nagano, Mariko Takeda, Haruna Hirai, Hikaru Maekita, Jian-Qing Gao, Hirofumi Tsujino, Makoto Sakata, Masayuki Nishino, Yuya Haga, Kazuma Higashisaka, Yasuo Tsutsumi","doi":"10.1248/bpb.b24-00877","DOIUrl":"10.1248/bpb.b24-00877","url":null,"abstract":"Curcumin (CUR), a polyphenol, is a promising compound for use in functional foods owing to various biological properties. However, the kinetics of CUR remains unclear because CUR has extremely low water solubility and absorbability. Here, we tried to elucidate the distribution, metabolism, and excretion of CUR by using amorphous CUR, a novel formulation that has dramatically improved water solubility and absorbability. When amorphous CUR was orally administered, CUR was predominantly distributed in the lungs, spleen, and liver, with low levels of accumulation over 24 h. Moreover, most of the CUR metabolites were observed to be glucuronide and sulfate conjugates. Furthermore, CUR was found to be excreted not only in bile but also in urine. Taken together, we have systematically demonstrated the kinetics of CUR by using a highly absorbable CUR formulation. In order to develop functional foods with high quality, it is important to not only evaluate the function and toxicity of CUR but also to correctly understand its kinetics, such as absorption, distribution, accumulation, metabolism, and excretion.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"314-322"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750926","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

Development of a Digital Image-Based Method to Screen Molecules That Regulate Melanization. 一种基于数字图像的方法来筛选调节黑色素化的分子。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00851

Waka Shimosako, Susumu Tanimura, Taiki Baba, Megumi Kuroiwa, Hiroyuki Murota, Kohsuke Takeda

{"title":"Development of a Digital Image-Based Method to Screen Molecules That Regulate Melanization.","authors":"Waka Shimosako, Susumu Tanimura, Taiki Baba, Megumi Kuroiwa, Hiroyuki Murota, Kohsuke Takeda","doi":"10.1248/bpb.b24-00851","DOIUrl":"10.1248/bpb.b24-00851","url":null,"abstract":"Vitiligo vulgaris is an acquired disorder that is thought to arise from the suppression of melanin synthesis by melanocytes in the basal epidermal layer. To develop therapeutic agents for vitiligo vulgaris, it is critical to identify compounds that promote melanization. In this study, we established a digital image-based method to quantify melanization that does not require biochemical procedures. B16F10 cells were seeded in a white-bottom 96-well microplate. After treatment with or without α-melanocyte-stimulating hormone, followed by fixation of the cells, digital images of the microplates were captured, and the total signal intensity of each well on the image was measured. The extent of melanization in the cells in each well was defined after the subtraction of the signal from the corresponding blank well. This method was found to quantify melanization more sensitively than the conventional technique that measures the absorbance of cell lysates at UV-A wavelengths. We obtained statistical parameters showing that this method was applicable to a high-throughput screening assay; thus, this method appears to be useful for screening and identifying molecules that suppress or promote melanization, the latter of which may be developed as therapeutic agents for vitiligo vulgaris.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"308-313"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728345","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

Potentiation of Nicotine-Induced Currents by QO58, a Kv7 Channel Opener, in Intracardiac Ganglion Neurons of Rats. Kv7通道开启剂QO58对大鼠心内神经节神经元尼古丁诱导电流的增强作用

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00498

Shiho Arichi, Kei Eto, Masanori Ogata, Sachie Sasaki-Hamada, Hitoshi Ishibashi

{"title":"Potentiation of Nicotine-Induced Currents by QO58, a Kv7 Channel Opener, in Intracardiac Ganglion Neurons of Rats.","authors":"Shiho Arichi, Kei Eto, Masanori Ogata, Sachie Sasaki-Hamada, Hitoshi Ishibashi","doi":"10.1248/bpb.b24-00498","DOIUrl":"10.1248/bpb.b24-00498","url":null,"abstract":"QO58 (5-(2,6-dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl)-1H-[1,5-a] pyrimidin-7-one) is currently used as a specific activator of the Kv7 (KCNQ) family of K+ channels. Here, we report an unexpected potentiating effect of this drug on nicotinic acetylcholine receptors. We recorded the whole-cell responses to the rapid application of nicotine with the Cs+-based pipette solution in intracardiac ganglion neurons freshly dissociated from the rat heart. Nicotine-induced inward currents were concentration-dependently blocked by mecamylamine, but not by 1 μM atropine at a holding potential of -60 mV. While the application of QO58 per se evoked a persistent inward current at this holding potential, 10 μM QO58 potentiated the peak amplitude of the nicotine-induced current. The QO58-induced inward currents were inhibited by the Kv7 channel blockers XE991 and Ba2+, but not by mecamylamine. On the other hand, the nicotine-induced current potentiated by QO58 was fully inhibited by mecamylamine. The facilitatory action of QO58 on the nicotinic response was unaffected by Ba2+. QO58 did not affect the reversal potential of the nicotine-induced current. QO58 apparently shifted the concentration-response curve of nicotine to the left. The half-maximal effective concentrations for nicotine in the absence and presence of 10 μM QO58 were 10.2 and 4.3 μM, respectively. These results suggest that QO58 acts as a positive allosteric modulator of nicotinic acetylcholine receptors. Given the prevalence of nicotinic receptor signaling, the present observations should be considered in future studies on the roles of Kv7 channels in the function of neural circuits and diseases.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"101-107"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254194","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

Role of Histamine H1 and H3 Receptors in Emotion Regulation in Intermittent Sleep-Deprived Mice. 组胺H1和H3受体在间歇性睡眠剥夺小鼠情绪调节中的作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00028

Fukie Yaoita, Hiroki Imaizumi, Keigo Kawanami, Masahiro Tsuchiya, Koichi Tan-No

{"title":"Role of Histamine H1 and H3 Receptors in Emotion Regulation in Intermittent Sleep-Deprived Mice.","authors":"Fukie Yaoita, Hiroki Imaizumi, Keigo Kawanami, Masahiro Tsuchiya, Koichi Tan-No","doi":"10.1248/bpb.b25-00028","DOIUrl":"https://doi.org/10.1248/bpb.b25-00028","url":null,"abstract":"The central histamine system is involved in several physiological behaviors and neurological disorders, including the sleep-wake cycle, anxiety-related behaviors (both high and low anxiety), and attention deficit hyperactivity disorder (ADHD). Histamine is synthesized from l-histidine by histidine decarboxylase (HDC) and primarily metabolized by histamine-N-methyltransferase (HNMT) in the central nervous system. We previously reported that mice with intermittent sleep deprivation may exhibit impulsive-like symptoms resembling ADHD and low-anxiety behavior. However, the specific role of histaminergic systems in these behaviors remains unclear. In this study, we evaluated HDC expression levels in the hypothalamus as well as the expression of histamine H1 to H4 receptors and HNMT in the hypothalamus and frontal cortex of sleep-deprived mice. Moreover, the effects of administering histidine, a histamine precursor, and inhibitors of each histamine receptor on sleep deprivation-induced low-anxiety and impulsive-like behaviors were examined using an elevated plus maze test. The expressions of HDC and histamine H1 and H3 receptors in the hypothalamus increased, while that of histamine H1 receptors in the frontal cortex of sleep-deprived mice decreased. The low-anxiety and impulsive-like behaviors in intermittent sleep-deprived mice significantly decreased and increased, respectively, following the administration of histamine H1 and H3 receptor blockers and histidine. Collectively, these findings suggest that the low-anxiety behavior and impulsive-like ADHD symptoms induced by intermittent sleep deprivation may result from the overstimulation of histamine H1 and H3 receptors by elevated histamine, together with increased hypothalamic HDC expression. Furthermore, they suggest that sufficient sleep may contribute to ameliorating ADHD symptoms.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"545-554"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961821","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

Nutritional Availability of Methylated Selenometabolites in Gut Microbiota, Dimethyldiselenide and Dimethylselenide, in Rats. 大鼠肠道微生物群中甲基化硒代谢物的营养有效性，二甲基二硒化物和二甲基硒化物。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00876

Kazuaki Takahashi, Sayano Iijima, Yasumitsu Ogra

{"title":"Nutritional Availability of Methylated Selenometabolites in Gut Microbiota, Dimethyldiselenide and Dimethylselenide, in Rats.","authors":"Kazuaki Takahashi, Sayano Iijima, Yasumitsu Ogra","doi":"10.1248/bpb.b24-00876","DOIUrl":"https://doi.org/10.1248/bpb.b24-00876","url":null,"abstract":"Selenium (Se) is an essential micronutrient for animals. Various chemical forms of Se exist in nature, each with distinct physiological, nutritional, and toxicological properties. In this study, we aimed to determine whether dimethyldiselenide (DMDSe, a monomethylated Se (MMSe) compound) and dimethylselenide (DMSe, a dimethylated Se compound), known gut bacterial metabolites, could serve as Se sources in rats. DMDSe could be utilized for selenoprotein biosynthesis and was metabolized into urinary selenometabolites. By contrast, DMSe was not utilized for selenoprotein biosynthesis but was further methylated to trimethylselenonium ion (TMSe), one of the urinary Se metabolites. Our findings indicate that dimethylated Se is not readily available as an Se source in rats, unlike MMSe. Selenoprotein biosynthesis requires selenide, an unmethylated form of Se, in the metabolic pathway. Our observations support the hypothesis that demethylation occurs on MMSe as a reversible methylation step but not on dimethylated Se. This suggests that the second methylation step is crucial for inactivating Se and plays a significant role in metabolism to maintain Se homeostasis in animals. Gut microbiota, which can synthesize both DMDSe and DMSe, may contribute to host Se metabolism through methylation processes.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"410-414"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958149","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

Evaluation of the Influence of the National Action Plan on Antimicrobial Resistance and the COVID-19 Pandemic on the Consumption of Broad-Spectrum Antimicrobial and Anti-methicillin-resistant Staphylococcus aureus Agents. 《国家抗微生物药物耐药性行动计划》和2019冠状病毒病疫情对广谱抗菌药物和耐甲氧西林金黄色葡萄球菌药物消费的影响评价

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00784

Ryota Goto, Ryo Inose, Ryuji Koizumi, Keisuke Sawada, Masahiro Ishikane, Norio Ohmagari, Yuichi Muraki

{"title":"Evaluation of the Influence of the National Action Plan on Antimicrobial Resistance and the COVID-19 Pandemic on the Consumption of Broad-Spectrum Antimicrobial and Anti-methicillin-resistant Staphylococcus aureus Agents.","authors":"Ryota Goto, Ryo Inose, Ryuji Koizumi, Keisuke Sawada, Masahiro Ishikane, Norio Ohmagari, Yuichi Muraki","doi":"10.1248/bpb.b24-00784","DOIUrl":"https://doi.org/10.1248/bpb.b24-00784","url":null,"abstract":"Surveillance of antimicrobial consumption (AMC) is important for controlling antimicrobial resistance (AMR). In recent years, the landscape of infectious diseases has changed due to factors such as the introduction of the National Action Plan (NAP) on AMR and the coronavirus disease 2019 (COVID-19) pandemic. However, their impact on the consumption of broad-spectrum antimicrobial and anti-methicillin-resistant Staphylococcus aureus (MRSA) agents remains unexplored. This study aimed to clarify trends in the consumption of these agents up to 2021, considering the spread of NAP and the COVID-19 pandemic. We used sales data from IQVIA Japan, which were analyzed using an interrupted time-series analysis, with April 2016 (introduction of NAP) and April 2020 (first declaration of a state of emergency) as key change points. The oral broad-spectrum antimicrobial agents consumption decreased, and the spread of the NAP (p-value: 8.15 * 10-3, 95% confidence intervals (95% CI): -7.70 * 10-3 to -2.06 * 10-3) and behavioral restrictions for the COVID-19 pandemic (p value: 1.60 * 10-8, 95% CI: -0.35 to -0.17) were significantly related to this change. Conversely, there was no notable change in the consumption of anti-MRSA agents from 2013 to 2021. Thus, the introduction of NAP and the COVID-19 pandemic may have been more effective in decreasing the consumption of oral broad-spectrum antimicrobial agents. Since antibiotics are used to treat infections across multiple anatomical therapeutic chemical classifications, continuous evaluation based on treatment purposes is important.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"415-421"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964592","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

Nephropathy II Decoction Attenuates Renal Fibrosis via Regulating TLR4 and Gut Microbiota Along the Gut-Kidney Axis. 肾病II汤通过调节TLR4和肠道菌群沿肠肾轴减轻肾纤维化。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00863

Chen Liu, Yujiu Gao, Yirui Chen, Liting Zhu, Fu Rao, Yuhan Huang, Yini Zeng, Rui Cai, Fangyan Wang, Jinguo Cheng

{"title":"Nephropathy II Decoction Attenuates Renal Fibrosis via Regulating TLR4 and Gut Microbiota Along the Gut-Kidney Axis.","authors":"Chen Liu, Yujiu Gao, Yirui Chen, Liting Zhu, Fu Rao, Yuhan Huang, Yini Zeng, Rui Cai, Fangyan Wang, Jinguo Cheng","doi":"10.1248/bpb.b24-00863","DOIUrl":"https://doi.org/10.1248/bpb.b24-00863","url":null,"abstract":"Nephropathy II Decoction (NED) is a widely used Chinese medicinal formulation for managing chronic kidney disease (CKD). Despite its extensive application, the precise mechanisms underlying its therapeutic effects remain poorly understood. This study aims to elucidate the role of NED in attenuating renal fibrosis and to explore its impact on the gut-kidney axis. The principal constituents of NED were analyzed using ultra-performance LC-tandem mass spectrometry (UPLC-MS/MS). A bilateral renal ischemia-reperfusion injury (bIRI) model was employed to induce fibrosis. RT-qPCR was utilized to assess the expression of mRNA related to the toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) and nuclear factor-κB (NF-κB) signaling pathway. Western blotting analysis was performed to identify changes in renal fibrosis markers, TLR4/MyD88/NF-κB pathway proteins, and the colon proteins ZO-1 and Occludin-1. Serum levels of uremic toxins were quantified using enzyme-linked immunosorbent assay (ELISA), and 16S ribosomal RNA (rRNA) gene sequencing was conducted to explore changes in the gut microbiome of the mice. Our study demonstrated that mice in the NED group exhibited reduced serum creatinine, blood urea nitrogen, and urinary protein levels, alongside improvements in kidney damage and a decrease in renal fibrosis markers. In the bIRI group, TLR4/MyD88/NF-κB protein and mRNA levels, as well as intestinal tight junction proteins and enterogenic uremic toxins, were significantly reduced. NED treatment reversed these changes and modified the gut microbiota. Furthermore, fecal microbial transplantation (FMT) alleviated kidney damage and fibrosis in bIRI mice. In summary, NED ameliorates kidney injury and fibrosis by modulating the gut microbiota and may further attenuate fibrosis through the inhibition of TLR4 expression, thereby influencing the gut-kidney axis.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"577-594"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958559","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

Platelet-Activating Factor (PAF) Induces Strong Mechanical Activities Accompanied by Basal Tension Increases in Esophageal and Gastric Fundus Smooth Muscles from Rat. 血小板活化因子（PAF）诱导大鼠食管和胃底平滑肌强机械活动并伴有基底张力升高。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00125

Keisuke Obara, Sana Takahashi, Miho Otake, Mako Fujiwara, Mio Yamashita, Azusa Murata, Kento Yoshioka, Yoshio Tanaka

{"title":"Platelet-Activating Factor (PAF) Induces Strong Mechanical Activities Accompanied by Basal Tension Increases in Esophageal and Gastric Fundus Smooth Muscles from Rat.","authors":"Keisuke Obara, Sana Takahashi, Miho Otake, Mako Fujiwara, Mio Yamashita, Azusa Murata, Kento Yoshioka, Yoshio Tanaka","doi":"10.1248/bpb.b25-00125","DOIUrl":"https://doi.org/10.1248/bpb.b25-00125","url":null,"abstract":"In rats, platelet-activating factor (PAF) has been reported to increase mechanical activity in various gastrointestinal smooth muscles (SMs) except for esophagus SM. The aim of this study was to examine whether PAF increases mechanical activity in rat esophagus longitudinal SM (LSM) and to compare PAF actions in esophagus LSM with those in other gastrointestinal LSMs. PAF (10-9-10-6 M) increased esophagus LSM mechanical activities in a concentration-dependent manner; PAF mainly elicited basal tension increases that were almost eliminated by a PAF receptor antagonist CV-6209 (10-5 M; against 10-6 M PAF). In the LSM of the gastric fundus, which is similar to esophagus LSM in that it is derived from the foregut during development, PAF (10-6 M) increased basal tension to a comparable, albeit significantly different, magnitude as in esophagus LSM. In contrast, in LSMs of the duodenum-jejunum, ileum, and ascending colon, which are derived from the midgut, and the descending colon, which is derived from the hindgut, the ability of PAF (10-6 M) to increase basal tension was less than that in esophagus and gastric fundus LSMs. Interestingly, in ascending colon LSMs, PAF (10-6 M) induced oscillatory contractions with a small increase in basal tension. PAF-induced contractions were positively correlated with the mRNA expression levels of the PAF-degrading enzymes Pafah2 (R = 0.82) and Pafah1b3 (R = 0.51). These results suggest that PAF strongly stimulates mechanical activities that are mainly accompanied by basal tension increases in rat LSMs of the gastrointestinal tracts that are derived from the foregut during embryogenesis.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"563-570"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952819","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