Biological & pharmaceutical bulletin最新文献_第10页

Epigallocatechin-3-gallate Alleviates Ethanol-Induced Endothelia Cells Injury Partly through Alteration of NF-κB Translocation and Activation of the Nrf2 Signaling Pathway. 表没食子儿茶素-3-没食子酸酯部分通过改变NF-κB转位和激活Nrf2信号通路，减轻乙醇诱导的内皮细胞损伤。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-07-05 Epub Date: 2024-06-12 DOI: 10.1248/bpb.b23-00773

Jie Xu, Shouzhu Xu, Jiayin Luo, Shihao Zhang, Dongdong Wu, Qifan Yang, Rourou Fang, Chuandao Shi, Qiling Liu, Jing Zhao

{"title":"Epigallocatechin-3-gallate Alleviates Ethanol-Induced Endothelia Cells Injury Partly through Alteration of NF-κB Translocation and Activation of the Nrf2 Signaling Pathway.","authors":"Jie Xu, Shouzhu Xu, Jiayin Luo, Shihao Zhang, Dongdong Wu, Qifan Yang, Rourou Fang, Chuandao Shi, Qiling Liu, Jing Zhao","doi":"10.1248/bpb.b23-00773","DOIUrl":"10.1248/bpb.b23-00773","url":null,"abstract":"Ethanol (alcohol) is a risk factor that contributes to non-communicable diseases. Chronic abuse of ethanol is toxic to both the heart and overall health, and even results in death. Ethanol and its byproduct acetaldehyde can harm the cardiovascular system by impairing mitochondrial function, causing oxidative damage, and reducing contractile proteins. Endothelial cells are essential components of the cardiovascular system, are highly susceptible to ethanol, either through direct or indirect exposure. Thus, protection against endothelial injury is of great importance for persons who chronic abuse of ethanol. In this study, an in vitro model of endothelial injury was created using ethanol. The findings revealed that a concentration of 20.0 mM of ethanol reduced cell viability and Bcl-2 expression, while increasing cell apoptosis, intracellular reactive oxygen species (ROS) levels, mitochondrial depolarization, and the expression of Bax and cleaved-caspase-3 in endothelial cells. Further study showed that ethanol promoted nuclear translocation of nuclear factor kappa B (NF-κB), increased the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 in the culture medium, and inhibited nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway. The aforementioned findings suggest that ethanol has a harmful impact on endothelial cells. Nevertheless, the application of epigallocatechin-3-gallate (EGCG) to the cells can effectively mitigate the detrimental effects of ethanol on endothelial cells. In conclusion, EGCG alleviates ethanol-induced endothelial injury partly through alteration of NF-κB translocation and activation of the Nrf2 signaling pathway. Therefore, EGCG holds great potential in safeguarding individuals who chronically abuse ethanol from endothelial dysfunction.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"1248-1254"},"PeriodicalIF":1.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309873","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

Effect of Chronic Ethanol Consumption on Exogenous Glucose Metabolism in Rats Using [1-¹³C], [2-¹³C], and [3-¹³C]glucose Breath Tests. 利用[1-13C]、[2-13C]和[3-13C]葡萄糖呼气试验，研究慢性乙醇摄入对大鼠外源性葡萄糖代谢的影响。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-04-17 Epub Date: 2024-03-26 DOI: 10.1248/bpb.b23-00403

Naoyasu Kashima, Yosuke Sasaki, Naoyuki Kawagoe, Tomoyuki Shigeta, Fumiya Komatsu, Yoshihisa Urita

{"title":"Effect of Chronic Ethanol Consumption on Exogenous Glucose Metabolism in Rats Using [1-13C], [2-13C], and [3-13C]glucose Breath Tests.","authors":"Naoyasu Kashima, Yosuke Sasaki, Naoyuki Kawagoe, Tomoyuki Shigeta, Fumiya Komatsu, Yoshihisa Urita","doi":"10.1248/bpb.b23-00403","DOIUrl":"10.1248/bpb.b23-00403","url":null,"abstract":"The C3 carbon of glucose molecules becomes the C1 carbon of pyruvate molecules during glycolysis, and the C1 and C2 carbons of glucose molecules are metabolized in the tricarboxylic acid (TCA) cycle. Utilizing this position-dependent metabolism of C atoms in glucose molecules, [1-13C], [2-13C], and [3-13C]glucose breath tests are used to evaluate glucose metabolism. However, the effects of chronic ethanol consumption remain incompletely understood. Therefore, we evaluated glucose metabolism in ethanol-fed rats using [1-13C], [2-13C], and [3-13C]glucose breath tests. Ethanol-fed (ERs) and control rats (CRs) (n = 8 each) were used in this study, and ERs were prepared by replacing drinking water with a 16% ethanol solution. We administered 100 mg/kg of [1-13C], [2-13C], or [3-13C]glucose to rats and collected expired air (at 10-min intervals for 180 min). We compared the 13CO2 levels (Δ13CO2, ‰) of breath measured by IR isotope ratio spectrometry and area under the curve (AUC) values of the 13CO2 levels-time curve between ERs and CRs. 13CO2 levels and AUCs after administration of [1-13C]glucose and [2-13C]glucose were lower in ERs than in CRs. Conversely, the AUC for the [3-13C]glucose breath test showed no significant differences between ERs and CRs, although 13CO2 levels during the 110-120 min interval were significantly high in ERs. These findings indicate that chronic ethanol consumption diminishes glucose oxidation without concomitantly reducing glycolysis. Our study demonstrates the utility of 13C-labeled glucose breath tests as noninvasive and repeatable methods for evaluating glucose metabolism in various subjects, including those with alcoholism or diabetes.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"856-860"},"PeriodicalIF":2.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140304768","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 Effect of Pemafibrate Treatment against Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats. 培马贝特治疗对自发性糖尿病鸟脂鼠糖尿病视网膜病变的保护作用

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-03-27 Epub Date: 2024-03-01 DOI: 10.1248/bpb.b23-00872

Yoshiaki Tanaka, Rina Takagi, Shingen Mitou, Machiko Shimmura, Tetsuya Hasegawa, Jota Amarume, Masami Shinohara, Yasushi Kageyama, Tomohiko Sasase, Takeshi Ohta, Shin-Ichi Muramatsu, Akihiro Kakehashi, Toshikatsu Kaburaki

{"title":"Protective Effect of Pemafibrate Treatment against Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats.","authors":"Yoshiaki Tanaka, Rina Takagi, Shingen Mitou, Machiko Shimmura, Tetsuya Hasegawa, Jota Amarume, Masami Shinohara, Yasushi Kageyama, Tomohiko Sasase, Takeshi Ohta, Shin-Ichi Muramatsu, Akihiro Kakehashi, Toshikatsu Kaburaki","doi":"10.1248/bpb.b23-00872","DOIUrl":"10.1248/bpb.b23-00872","url":null,"abstract":"Diabetic retinopathy (DR) can cause visual impairment and blindness, and the increasing global prevalence of diabetes underscores the need for effective therapies to prevent and treat DR. Therefore, this study aimed to evaluate the protective effect of pemafibrate treatment against DR, using a Spontaneously Diabetic Torii (SDT) fatty rat model of obese type 2 diabetes. SDT fatty rats were fed either a diet supplemented with pemafibrate (0.3 mg/kg/d) for 16 weeks, starting at 8 weeks of age (Pf SDT fatty: study group), or normal chow (SDT fatty: controls). Normal chow was provided to Sprague-Dawley (SD) rats (SD: normal controls). Electroretinography (ERG) was performed at 8 and 24 weeks of age to evaluate the retinal neural function. After sacrifice, retinal thickness, number of retinal folds, and choroidal thickness were evaluated, and immunostaining was performed for aquaporin-4 (AQP4). No significant differences were noted in food consumption, body weight, or blood glucose level after pemafibrate administration. Triglyceride levels were reduced, and high-density lipoprotein cholesterol levels were increased. Extension of oscillatory potential (OP)1 and OP3 waves on ERG was suppressed in the Pf SDT fatty group. Retinal thickness at 1500 microns from the optic disc improved in the Pf SDT fatty group. No significant improvements were noted in choroidal thickness or number of retinal folds. Quantitative analyses showed that AQP4-positive regions in the retinas were significantly larger in the Pf SDT fatty group than in the SDT fatty group. The findings suggest that pemafibrate treatment can exert protective effects against DR.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"713-722"},"PeriodicalIF":2.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020883","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

Comparing the Efficacy of Fosnetupitant, an NK₁ Receptor Antagonist in CDDP-Based Regimens, with That of Fosaprepitant and Aprepitant: A Retrospective Observational Study. 基于 CDDP 的疗法中 NK1 受体拮抗剂福斯硝普坦与福沙匹坦和阿匹匹坦的疗效比较：一项回顾性观察研究。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-03-25 Epub Date: 2024-02-28 DOI: 10.1248/bpb.b23-00819

Hiroshi Inano, Yoshihito Morimoto, Kanata Kitagawa, Akito Shibuya, Kozue Nakagomi, Tomohiro Ota, Yuri Anzo, Rika Miyauchi, Aiko Shono, Kazuhiro Watanabe, Katsuya Otori

{"title":"Comparing the Efficacy of Fosnetupitant, an NK1 Receptor Antagonist in CDDP-Based Regimens, with That of Fosaprepitant and Aprepitant: A Retrospective Observational Study.","authors":"Hiroshi Inano, Yoshihito Morimoto, Kanata Kitagawa, Akito Shibuya, Kozue Nakagomi, Tomohiro Ota, Yuri Anzo, Rika Miyauchi, Aiko Shono, Kazuhiro Watanabe, Katsuya Otori","doi":"10.1248/bpb.b23-00819","DOIUrl":"10.1248/bpb.b23-00819","url":null,"abstract":"Existing antiemetic therapy against emetic-risk agents across malignancies 24 h post-dose in the acute period in cisplatin (CDDP)-based regimens yields a satisfactory complete response (CR) rate of ≥90%. However, the control rate after 24 h in the delayed period is unsatisfactory. This study compared the efficacy of fosnetupitant (F-NTP), a neurokinin 1 receptor antagonist, with that of fosaprepitant (F-APR) and aprepitant (APR) in the treatment of patients with cancer at high emetic risk due to chemotherapy. In this retrospective case-control study involving patients receiving cisplatin-containing regimens and neurokinin 1 receptor antagonists, patients were divided into three groups based on prophylactic antiemetic therapy: F-NTP, F-APR, and APR. The CR rate was evaluated for each period up to 168 h and further subdivided into acute (0-24 h), delayed (24-120 h), overall (0-120 h), and beyond-delayed (120-168 h) periods. Eighty-eight patients were included in the F-NTP group, 66 in the F-APR group, and 268 in the APR group. The CR rates at 0-168 and 120-168 h after cisplatin administration were significantly higher in the F-NTP group than in the F-APR and APR groups. After adjusting for confounding factors, F-NTP use was an independent factor in the multivariate analysis. Prophylactic antiemetic therapy, including F-NTP, was effective and well-tolerated during the delayed period. The efficacy of F-NTP in managing chemotherapy-induced nausea and vomiting was superior to those of F-APR and APR during the study period.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"692-697"},"PeriodicalIF":2.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989257","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

Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways. Loureirin A 可通过 WNT 和 AKT/mTOR 信号通路促进细胞分化并抑制黑色素瘤细胞的迁移和侵袭。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-02-22 Epub Date: 2024-01-10 DOI: 10.1248/bpb.b23-00415

Zi-Yi Xia, Ling Liu, Chiu-Fai Kuok, Xue-Li Wang, Dan Shi, Quan Ma, Xiao-Yang Cheng, Guo-Li Wang, Min-Jing Li, Qiu-Sheng Zheng, Xiao-Na Liu, De-Fang Li, Bo-Han Li

{"title":"Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.","authors":"Zi-Yi Xia, Ling Liu, Chiu-Fai Kuok, Xue-Li Wang, Dan Shi, Quan Ma, Xiao-Yang Cheng, Guo-Li Wang, Min-Jing Li, Qiu-Sheng Zheng, Xiao-Na Liu, De-Fang Li, Bo-Han Li","doi":"10.1248/bpb.b23-00415","DOIUrl":"10.1248/bpb.b23-00415","url":null,"abstract":"Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"486-498"},"PeriodicalIF":2.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416290","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

A Morpholine Derivative N-(4-Morpholinomethylene)ethanesulfonamide Induces Ferroptosis in Tumor Cells by Targeting NRF2. 吗啉衍生物 N-(4-吗啉亚甲基)乙磺酰胺通过靶向 NRF2 诱导肿瘤细胞的铁变态反应。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-02-14 Epub Date: 2024-01-30 DOI: 10.1248/bpb.b23-00544

Bingchun Sun, Ligang Zhang, Binhua Wu, Xiping Luo

{"title":"A Morpholine Derivative N-(4-Morpholinomethylene)ethanesulfonamide Induces Ferroptosis in Tumor Cells by Targeting NRF2.","authors":"Bingchun Sun, Ligang Zhang, Binhua Wu, Xiping Luo","doi":"10.1248/bpb.b23-00544","DOIUrl":"10.1248/bpb.b23-00544","url":null,"abstract":"Small molecule drugs containing morpholine-based moieties have become crucial candidates in the tumor targeted therapy strategies, but the specific molecular mechanisms of these drugs causing tumor cell death require further investigation. The morpholine derivative N-(4-morpholinomethylene)ethanesulfonamide (MESA) was used to stimulate prostate and ovarian cancer cells and we focused on the ferroptosis effects, including the target molecule and signal pathways mediated by MESA. The results showed that MESA could induce ferroptosis to cause the proliferation inhibition and apoptosis effects of tumor cells according to the identification of ferroptosis inhibitor fer-1 and other cell death inhibitors. Further MESA could significantly increase the intracellular malondialdehyde (MDA), reactive oxygen species (ROS) and Fe2+ levels in tumor cells and mediate the dynamic changes of ferroptosis-relative molecules GPX4, nuclear factor erythroid2-related factor 2 (NRF2), ACSL4, SLC7A11 and P62-Kelch-like ECH-associated protein 1 (KEAP1)-NRF2-antioxidant response element (ARE) signal pathways. Further, NRF2 overexpression could reduce the tumor cell death and ROS levels exposure to MESA. Most importantly, it was confirmed that MESA could bind to NRF2 protein through molecular docking and thermal stability assays and NRF2 was a target molecule of MESA for inducing ferroptosis effects in tumor cells. Collectively, our findings indicated the ferroptosis effects of the morpholine derivative MESA in prostate and ovarian cancer cells and its function mechanism including targeted molecule and signal pathways, which would be helpful for developing MESA as a prospective small molecule drug for cancer therapy based on cell ferroptosis.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"417-426"},"PeriodicalIF":2.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721482","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

Icariin Regulates EMT and Stem Cell-Like Character in Breast Cancer through Modulating lncRNA NEAT1/TGFβ/SMAD2 Signaling Pathway. 淫羊藿苷通过调节lncRNA NEAT1/TGFβ/SMAD2信号通路调控乳腺癌的EMT和干细胞样特征

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-02-10 Epub Date: 2024-01-13 DOI: 10.1248/bpb.b23-00668

Bo Song, Fuxia Wei, Jiehao Peng, Xiuhong Wei, Mingran Liu, Zhongbiao Nie, Yanmiao Ma, Tao Peng

{"title":"Icariin Regulates EMT and Stem Cell-Like Character in Breast Cancer through Modulating lncRNA NEAT1/TGFβ/SMAD2 Signaling Pathway.","authors":"Bo Song, Fuxia Wei, Jiehao Peng, Xiuhong Wei, Mingran Liu, Zhongbiao Nie, Yanmiao Ma, Tao Peng","doi":"10.1248/bpb.b23-00668","DOIUrl":"10.1248/bpb.b23-00668","url":null,"abstract":"Metastases and drug resistance are the major risk factors associated with breast cancer (BC), which is the most common type of tumor affecting females. Icariin (ICA) is a traditional Chinese medicine compound that possesses significant anticancer properties. Long non-coding RNAs (lncRNAs) are involved in a wide variety of biological and pathological processes and have been shown to modulate the effectiveness of certain drugs in cancer. The purpose of this study was to examine the potential effect of ICA on epithelial mesenchymal transition (EMT) and stemness articulation in BC cells, as well as the possible relationship between its inhibitory action on EMT and stemness with the NEAT1/transforming growth factor β (TGFβ)/SMAD2 pathway. The effect of ICA on the proliferation (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony assays), EMT (Western blotting, immunofluorescence, and wound healing), and stemness (mammosphere formation assays, Western blotting) of BC cells were examined. According to the findings, ICA suppressed the proliferation, EMT, and stem cell-like in MDA-MB-231 cells, and exerted its inhibitory impact by downregulating the TGFβ/SMAD2 signaling pathway. ICA could significantly downregulate the expression of lncRNA NEAT1, and silencing NEAT1 enhanced the effect of ICA in suppressing EMT and expression of different stem cell markers. In addition, silencing NEAT1 was found to attenuate the TGFβ/SMAD2 signaling pathway, thereby improving the inhibitory impact of ICA on stemness and EMT in BC cells. In conclusion, ICA can potentially inhibit the metastasis of BC via affecting the NEAT1/TGFβ/SMAD2 pathway, which provides a theoretical foundation for understanding the mechanisms involved in potential application of ICA for BC therapy.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"399-410"},"PeriodicalIF":2.0,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466070","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

Quantitative Analysis of Therapeutic Antibody Interactions with Fcγ Receptors Using High-Speed Atomic Force Microscopy. 利用高速原子力显微镜定量分析治疗性抗体与 Fcγ 受体之间的相互作用。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-31 Epub Date: 2023-12-22 DOI: 10.1248/bpb.b23-00751

Saeko Yanaka, Hiroki Watanabe, Rina Yogo, Mesayamas Kongsema, Sachiko Kondo, Hirokazu Yagi, Takayuki Uchihashi, Koichi Kato

{"title":"Quantitative Analysis of Therapeutic Antibody Interactions with Fcγ Receptors Using High-Speed Atomic Force Microscopy.","authors":"Saeko Yanaka, Hiroki Watanabe, Rina Yogo, Mesayamas Kongsema, Sachiko Kondo, Hirokazu Yagi, Takayuki Uchihashi, Koichi Kato","doi":"10.1248/bpb.b23-00751","DOIUrl":"10.1248/bpb.b23-00751","url":null,"abstract":"This study employed high-speed atomic force microscopy to quantitatively analyze the interactions between therapeutic antibodies and Fcγ receptors (FcγRs). Antibodies are essential components of the immune system and are integral to biopharmaceuticals. The focus of this study was on immunoglobulin G molecules, which are crucial for antigen binding via the Fab segments and cytotoxic functions through their Fc portions. We conducted real-time, label-free observations of the interactions of rituximab and mogamulizumab with the recombinant FcγRIIIa and FcγRIIa. The dwell times of FcγR binding were measured at the single-molecule level, which revealed an extended interaction duration of mogamulizumab with FcγRIIIa compared with that of rituximab. This is linked to enhanced antibody-dependent cellular cytotoxicity that is attributed to the absence of the core fucosylation of Fc-linked N-glycan. This study also emphasizes the crucial role of the Fab segments in the interaction with FcγRIIa as well as that with FcγRIIIa. This approach provided quantitative insight into therapeutic antibody interactions and exemplified kinetic proofreading, where cellular discrimination relies on ligand residence times. Observing the dwell times of antibodies on the effector molecules has emerged as a robust indicator of therapeutic antibody efficacy. Ultimately, these findings pave the way for the development of refined therapeutic antibodies with tailored interactions with specific FcγRs. This research contributes to the advancement of biopharmaceutical antibody design and optimizing antibody-based treatments for enhanced efficacy and precision.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"334-338"},"PeriodicalIF":2.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032143","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

Quantitative Assessment of the Post-translational Modifications of Human Serum Albumin by Dimethyl Trisulfide. 二甲基三硫醚对人类血清白蛋白翻译后修饰的定量评估

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-27 Epub Date: 2023-12-27 DOI: 10.1248/bpb.b23-00793

Ichiro Koshiishi, Seiya Nagai, Yasushi Yuzawa, Yuta Takigawa

{"title":"Quantitative Assessment of the Post-translational Modifications of Human Serum Albumin by Dimethyl Trisulfide.","authors":"Ichiro Koshiishi, Seiya Nagai, Yasushi Yuzawa, Yuta Takigawa","doi":"10.1248/bpb.b23-00793","DOIUrl":"10.1248/bpb.b23-00793","url":null,"abstract":"Some bacteria, such as Fusobacterium nucleatum, act as dimethyl trisulfide (DMTS) producers in the host in vivo. DMTS acts as a sulfane sulfur donor and chemically modifies the sulfhydryl groups. This study explored the post-translational modifications of human serum albumin using DMTS. Quantitative assessments were conducted on mixed disulfides of mercaptoalbumin with mercaptomethane (Alb-SS-CH3) and albumin hydropersulfide (Alb-SSH) as post-translationally modified species. The hydropersulfide group was alkylated with iodoacetamide, resulting in the formation of an albumin-mercaptoacetamide mixed disulfide. The mixed disulfides were subsequently reduced with tris(2-carboxyethyl)phosphine, and the liberated mercaptomethane and mercaptoacetamide were fluorescently labeled with 4-fluoro-7-sulfamoylbenzofurazan (ABD-F). Quantification was performed using HPLC with fluorescence detection. Using this methodology, we examined the formation of Alb-SS-CH3 and Alb-SSH via the reaction between 4% human serum albumin and DMTS at 10-100 µM concentrations. Approximately two molecules of Alb-SS-CH3 and one molecule of Alb-SSH were generated from one DMTS molecule. Moreover, hydrogen sulfide was identified as an intermediate, suggesting its generation and subsequent reaction with intraprotein disulfide bonds, leading to the production of Alb-SSH. These results suggest the production of DMTS in humans in vivo should be involved in the elevation of Alb-SS-CH3 and Alb-SSH contents in plasma samples.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"318-327"},"PeriodicalIF":2.0,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039494","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

Tanshinone IIA Alleviates Early Brain Injury after Subarachnoid Hemorrhage in Rats by Inhibiting the Activation of NF-κB/NLRP3 Inflammasome. 丹参酮IIA通过抑制NF-κB/NLRP3炎性体的激活，减轻大鼠蛛网膜下腔出血后早期脑损伤。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-26 Epub Date: 2023-12-06 DOI: 10.1248/bpb.b23-00519

Fanhui Yang, Ningshuai Ma, Suping Li, Fei Chen, Xiaohong Huang, Li Zhao, Lingzhi Cao

{"title":"Tanshinone IIA Alleviates Early Brain Injury after Subarachnoid Hemorrhage in Rats by Inhibiting the Activation of NF-κB/NLRP3 Inflammasome.","authors":"Fanhui Yang, Ningshuai Ma, Suping Li, Fei Chen, Xiaohong Huang, Li Zhao, Lingzhi Cao","doi":"10.1248/bpb.b23-00519","DOIUrl":"10.1248/bpb.b23-00519","url":null,"abstract":"The abnormal activation of the nuclear factor-kappa B (NF-κB)/nod-like receptor family-pyrin domain-containing 3 (NLRP3) signaling pathway is closely related to early brain injury after subarachnoid hemorrhage (SAH). Targeting the NLRP3-inflammasome has been considered an efficient therapy for the local inflammatory response after SAH. Tanshinone IIA (Tan IIA), a major component extracted from Salvia miltiorrhiza, has been reported to have anti-inflammatory effects. The aim of this study was to investigate the effect and mechanism of Tan IIA on early brain injury after SAH. In vivo SAH injury was established by endovascular perforation technique in Sprague-Dawley rats. Limb-placement test and corner turning test were used to measure the behavior. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, hematoxylin-eosin (H&E) staining, and immunofluorescence were used to evaluate the nerve damage. Real-time RT quantitative PCR (RT-qPCR) was used to quantify the levels of inflammatory factors. Western blot was performed for the activation of the NF-κB/NLRP3 pathway. An in vitro SAH model was used to validate the conclusion. We found that the neurobehavioral impairment and cerebral edema in SAH model rats given Tan IIA were alleviated. Further study demonstrated that Tan IIA could inhibit SAH-secondary neuronal apoptosis around hematoma and alleviate brain injury. Tan IIA down-regulated the expression of interleukin-6 (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-α, and inhibited the activation of NF-κB. And the overexpression of pro-inflammatory factors NLRP3, IL-1β, and IL-18 induced after SAH was also reversed by Tan IIA. In conclusions, Tan IIA could inhibit the NF-κB/NLRP3 inflammasome activation to protect and ameliorate SAH-followed early brain injury, and may be a preventive and therapeutic strategy against SAH.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"279-291"},"PeriodicalIF":2.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497752","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}

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