Biological & pharmaceutical bulletin最新文献

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":null,"pages":null},"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

Fentanyl Analogs Exert Antinociceptive Effects via Sodium Channel Blockade in Mice. 芬太尼类似物通过阻断钠通道对小鼠产生抗痛觉作用

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-04-24 DOI: 10.1248/bpb.b24-00048

Satoka Kasai, Natsuki Ogawa, Miho Takagi, Yukino Takahashi, Kosho Makino, Hironobu Arita, Hideyo Takahashi, Kazumi Yoshizawa

{"title":"Fentanyl Analogs Exert Antinociceptive Effects via Sodium Channel Blockade in Mice.","authors":"Satoka Kasai, Natsuki Ogawa, Miho Takagi, Yukino Takahashi, Kosho Makino, Hironobu Arita, Hideyo Takahashi, Kazumi Yoshizawa","doi":"10.1248/bpb.b24-00048","DOIUrl":"https://doi.org/10.1248/bpb.b24-00048","url":null,"abstract":"The formalin test is one approach to studying acute pain in rodents. Similar to formalin, injection with glutamate and veratrine can also produce a nociceptive response. This study investigated whether opioid-related compounds could suppress glutamate- and veratrine-induced nociceptive responses in mice at the same dose. The administration of morphine (3 mg/kg), hydromorphone (0.4 mg/kg), or fentanyl (0.03 mg/kg) suppressed glutamate-induced nociceptive response, but not veratrine-induced nociceptive response at the same doses. However, high doses of morphine (10 mg/kg), hydromorphone (2 mg/kg), or fentanyl (0.1 mg/kg) produced a significant reduction in the veratrine-induced nociceptive response. These results indicate that high doses are required when using morphine, hydromorphone, or fentanyl for sodium channel-related neuropathic pain, such as ectopic activity. As a result, concerns have arisen about overdose and abuse if the dose of opioids is steadily increased to relieve pain. In contrast, trimebutine (100 mg/kg) and fentanyl analog isobutyrylfentanyl (iBF; 0.1 mg/kg) suppressed both glutamate- and veratrine-induced nociceptive response. Furthermore, nor-isobutyrylfentanyl (nor-iBF; 1 mg/kg), which is a metabolite of iBF, suppressed veratrine-induced nociceptive response. Besides, the optimal antinociceptive dose of iBF, unlike fentanyl, only slightly increased locomotor activity and did not slow gastrointestinal transit. Cancer pain is a complex condition driven by inflammatory, neuropathic, and cancer-specific mechanisms. Thus, iBF may have the potential to be a superior analgesic than fentanyl.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664899","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

Carbon Monoxide Alleviates Post-ischemia-reperfusion Skeletal Muscle Injury and Systemic Inflammation. 一氧化碳可缓解缺血再灌注后骨骼肌损伤和全身炎症。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-04-20 DOI: 10.1248/bpb.b23-00917

K. Taguchi, Shigeru Ogaki, Hitoshi Maeda, Yu Ishima, Hiroshi Watanabe, Masaki Otagiri, Toru Maruyama

{"title":"Carbon Monoxide Alleviates Post-ischemia-reperfusion Skeletal Muscle Injury and Systemic Inflammation.","authors":"K. Taguchi, Shigeru Ogaki, Hitoshi Maeda, Yu Ishima, Hiroshi Watanabe, Masaki Otagiri, Toru Maruyama","doi":"10.1248/bpb.b23-00917","DOIUrl":"https://doi.org/10.1248/bpb.b23-00917","url":null,"abstract":"Restoration of blood flow in skeletal muscle after a prolonged period of ischemia induces muscular ischemia-reperfusion injury, leading to local injury/dysfunction in muscles followed by systemic inflammatory responses. However, preventive/curative agents for skeletal muscle ischemia injury are unavailable in clinics to date. Increasing evidence has validated that carbon monoxide (CO) prevents the progression of ischemia-reperfusion injury in various organs owing to its versatile bioactivity. Previously, we developed a bioinspired CO donor, CO-bound red blood cells (CO-RBC), which mimics the dynamics of RBC-associated CO in the body. In the present study, we have tested the therapeutic potential of CO-RBC in muscular injury/dysfunction and secondary systemic inflammation induced by skeletal muscle ischemia-reperfusion. The results indicate that CO-RBC rather than RBC alone suppressed elevation of plasma creatine phosphokinase, a marker of muscular injury, in rats subjected to both hind limbs ischemia-reperfusion. In addition, the results of the treadmill walking test revealed a significantly decreased muscular motor function in RBC-treated rats subjected to both hind limbs ischemia-reperfusion than that in healthy rats, however, CO-RBC treatment facilitated sustained muscular motor functions after hind limbs ischemia-reperfusion. Furthermore, CO-RBC rather than RBC suppressed the production of tumour necrosis factor (TNF)-α and interleukin (IL)-6, which were upregulated by muscular ischemia-reperfusion. Interestingly, CO-RBC treatment induced higher levels of IL-10 compared to saline or RBC treatments. Based on these findings, we suggest that CO-RBC exhibits a suppressive effect against skeletal muscle injury/dysfunction and systemic inflammatory responses after skeletal muscle ischemia-reperfusion.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140680299","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

Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period. 模拟咖啡因清除率的发育变化，考虑出生前后的差异

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-04-20 DOI: 10.1248/bpb.b23-00650

Haruka Ide, Yukako Kawasaki, K. Tamura, Taketoshi Yoshida, Ryosuke Fujihara, Akane Hara, Masato Taguchi

{"title":"Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period.","authors":"Haruka Ide, Yukako Kawasaki, K. Tamura, Taketoshi Yoshida, Ryosuke Fujihara, Akane Hara, Masato Taguchi","doi":"10.1248/bpb.b23-00650","DOIUrl":"https://doi.org/10.1248/bpb.b23-00650","url":null,"abstract":"Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140680514","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

Detoxification and Activating Blood Circulation Decoction Promotes Reendothelialization of Damaged Blood Vessels via VEGF Signaling Pathway Activation by miRNA-126. 解毒活血汤通过 miRNA-126 激活血管内皮生长因子信号通路，促进受损血管的再内皮化。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-04-20 DOI: 10.1248/bpb.b23-00858

Zhiming Liu, Guangmie Xie, Zuwei Li, Hanbin Luo, Jianhong Zhou, Jie Cheng, Xiaolin Wang, Xiaoyan Huang, Guohui Zou

{"title":"Detoxification and Activating Blood Circulation Decoction Promotes Reendothelialization of Damaged Blood Vessels via VEGF Signaling Pathway Activation by miRNA-126.","authors":"Zhiming Liu, Guangmie Xie, Zuwei Li, Hanbin Luo, Jianhong Zhou, Jie Cheng, Xiaolin Wang, Xiaoyan Huang, Guohui Zou","doi":"10.1248/bpb.b23-00858","DOIUrl":"https://doi.org/10.1248/bpb.b23-00858","url":null,"abstract":"The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased NO expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of eNOS and the protein expression of VEGF, p-Akt, and p-ERK1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140679831","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 Influence of Emodin Succinyl Ethyl Ester on Non-Alcoholic Steatohepatitis Induced by a Diet High in Fructose, Cholesterol, and Fat in Mice. 大黄素琥珀酰乙酯对高果糖、高胆固醇和高脂肪饮食诱发的小鼠非酒精性脂肪性肝炎的影响

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-04-18 DOI: 10.1248/bpb.b23-00903

Yanxue Wang, Liang Li, Lingling Chen, Jinlei Xia, Tongli Wang, Lei Han, Liang Cao, Zhenzhong Wang, Wei Xiao, Shan Jiang

{"title":"The Influence of Emodin Succinyl Ethyl Ester on Non-Alcoholic Steatohepatitis Induced by a Diet High in Fructose, Cholesterol, and Fat in Mice.","authors":"Yanxue Wang, Liang Li, Lingling Chen, Jinlei Xia, Tongli Wang, Lei Han, Liang Cao, Zhenzhong Wang, Wei Xiao, Shan Jiang","doi":"10.1248/bpb.b23-00903","DOIUrl":"https://doi.org/10.1248/bpb.b23-00903","url":null,"abstract":"Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/day. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140686850","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":null,"pages":null},"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

Maitake Beta-Glucan Enhances the Therapeutic Effect of Trastuzumab via Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity. 麦门冬β-葡聚糖通过抗体依赖性细胞毒性和补体依赖性细胞毒性增强曲妥珠单抗的治疗效果

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-04-15 DOI: 10.1248/bpb.b23-00802

Yuki Masuda, Shizuka Yamashita, Y. Nakayama, Ryohei Shimizu, M. Konishi

{"title":"Maitake Beta-Glucan Enhances the Therapeutic Effect of Trastuzumab via Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity.","authors":"Yuki Masuda, Shizuka Yamashita, Y. Nakayama, Ryohei Shimizu, M. Konishi","doi":"10.1248/bpb.b23-00802","DOIUrl":"https://doi.org/10.1248/bpb.b23-00802","url":null,"abstract":"Trastuzumab, an anti-HER2 monoclonal antibody, is the mainstay treatment for of HER2-positive breast cancer. However, trastuzumab resistance is often observed during treatment. Therefore, new therapeutic strategies are needed to enhance the clinical benefits of trastuzumab. Maitake β-glucan MD-Fraction, isolated from Grifola frondosa, inhibits tumor growth by enhancing immune responses. In this study, we examined the effect of MD-Fraction on trastuzumab treatment of HER2-positive breast cancer. MD-Fraction did not directly inhibit the survival of HER2-positive breast cancer cells, alone or in the presence of trastuzumab in vitro. In HER2-positive xenograft models, the combination of MD-Fraction and trastuzumab was more effective than trastuzumab alone. Peripheral blood lymphocytes and splenic natural killer cells isolated from BALB/c nu/nu mice treated with MD-Fraction showed enhanced trastuzumab-induced antibody-dependent cellular cytotoxicity (ADCC) ex vivo. MD-Fraction-treated macrophages and neutrophils did not show enhanced trastuzumab cytotoxicity in the presence of heat-inactivated serum, but they showed enhanced cytotoxicity in the presence of native serum. These results suggest that MD-Fraction-treated macrophages and neutrophils enhance trastuzumab-induced complement-dependent cellular cytotoxicity (CDCC). Treatment of HER2-positive breast cancer cells with MD-Fraction in the presence of trastuzumab and native serum increased C3a release and tumor cell lysis in a dose-dependent manner, indicating that MD-Fraction enhanced trastuzumab-induced complement-dependent cytotoxicity (CDC) by activating the complement system. This study demonstrates that the combination of trastuzumab and MD-Fraction exerts a greater antitumor effect than trastuzumab alone by enhancing ADCC, CDCC, and CDC in HER2-positive breast cancer.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140700814","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

Oral Administration of PLGA Nanoparticles to Deliver Antisense Oligonucleotides to Inflammatory Lesions in the Gastrointestinal Tract. 口服聚乳酸乙烯-丙烯酸（PLGA）纳米颗粒将反义寡核苷酸输送到胃肠道炎症病变部位

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-04-15 DOI: 10.1248/bpb.b23-00769

Yuta Yagi, Yiwei Liu, Jinting Li, Shunsuke Shimada, M. Ohkouchi, Yasushi Taguchi, Teruki Nii, Takeshi Mori, Yoshiki Katayama

{"title":"Oral Administration of PLGA Nanoparticles to Deliver Antisense Oligonucleotides to Inflammatory Lesions in the Gastrointestinal Tract.","authors":"Yuta Yagi, Yiwei Liu, Jinting Li, Shunsuke Shimada, M. Ohkouchi, Yasushi Taguchi, Teruki Nii, Takeshi Mori, Yoshiki Katayama","doi":"10.1248/bpb.b23-00769","DOIUrl":"https://doi.org/10.1248/bpb.b23-00769","url":null,"abstract":"In this study, we prepared antisense oligonucleotide (ASO)-encapsulated nanoparticles (NPs) with a suitable profile for oral administration for the treatment of inflammatory bowel disease (IBD). We chose a water-in-oil-in-water (w/o/w) method to prepare the NPs using poly(lactide-co-glycolide) as a matrix and Pluronic as a stabilizer. The obtained NPs had a suitable diameter (158 nm) for the penetration of the mucus layer, endocytic uptake by enterocytes, and accumulation in inflammatory lesions in the intestine. The amount of ASOs in the NPs was relatively large (6.41% (w/w)). When the NPs were stably dispersed in solutions that mimicked gastrointestinal (GI) juice, minimal leakage of ASOs was demonstrated over the required period. The NPs were administered orally to mice with colitis induced by dextran sodium sulfate, which reduced target gene expression in the colons and rectums of the mice, whereas naked ASO administration caused no reduction in gene expression. Thus, the NPs have the potential of promising oral carriers of ASOs for the treatment of IBD that specifically target inflammatory lesions in the GI tract, thereby reducing the non-specific toxic effects of ASOs.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140700284","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 Coptis chinensis Rhizome Extract and Its Constituents (Berberine, Coptisine, and Palmatine) against α-Synuclein Neurotoxicity in Dopaminergic SH-SY5Y Cells. 黄连提取物及其成分（小檗碱、黄连碱和巴马汀）对多巴胺能SH-SY5Y细胞中α-突触核蛋白神经毒性的保护作用

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-04-10 DOI: 10.1248/bpb.b23-00758

Chih-Hsin Lin, Yih-Ru Wu, C. Chao, Kuo-Hsuan Chang, C. Chen, Wan-ling Chen, Pei-Ning Yang, G. Lee-Chen

{"title":"Protective Effects of Coptis chinensis Rhizome Extract and Its Constituents (Berberine, Coptisine, and Palmatine) against α-Synuclein Neurotoxicity in Dopaminergic SH-SY5Y Cells.","authors":"Chih-Hsin Lin, Yih-Ru Wu, C. Chao, Kuo-Hsuan Chang, C. Chen, Wan-ling Chen, Pei-Ning Yang, G. Lee-Chen","doi":"10.1248/bpb.b23-00758","DOIUrl":"https://doi.org/10.1248/bpb.b23-00758","url":null,"abstract":"Parkinson's disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher's disease is caused by homozygous mutations in β-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls. In addition, the protective effects of C. chinensis rhizome extract and its active constituents (berberine, coptisine, and palmatine) against PD were assayed using GBA reporter cells, LC3 reporter cells, and cells expressing mutated (A53T) α-synuclein. Case-control study revealed that GBA L444P carriers had a 3.93-fold increased risk of PD (95% confidence interval (CI): 1.37-11.24, p = 0.006) compared to normal controls. Both C. chinensis rhizome extract and its constituents exhibited chemical chaperone activity to reduce α-synuclein aggregation. Promoter reporter and endogenous GBA protein analyses revealed that C. chinensis rhizome extract and its constituents upregulated GBA expression in 293 cells. In addition, C. chinensis rhizome extract and its constituents induced autophagy in DsRed-LC3-expressing 293 cells. In SH-SY5Y cells expressing A53T α-synuclein, C. chinensis rhizome extract and its constituents reduced α-synuclein aggregation and associated neurotoxicity by upregulating GBA expression and activating autophagy. The results of reducing α-synuclein aggregation, enhancing GBA expression and autophagy, and protecting against α-synuclein neurotoxicity open up the therapeutic potentials of C. chinensis rhizome extract and constituents for PD.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140719428","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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