K. Obayashi, A. Nagamine, H. Yashima, S. Ohshima, C. Uchiyama, E. Takahashi, Y. Takahashi, T. Araki, K. Yamamoto
A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT₃-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.
阿瑞匹坦(APR)联合5-羟色胺3受体拮抗剂(5-HT₃-RA)和地塞米松(DEX)等常规双重止吐疗法，被推荐用于预防化疗引起的卡铂(CBDCA)方案引起的恶心和呕吐。然而，妇科患者APR对紫杉醇与CBDCA联合方案(TC方案)的附加效应尚未达成共识。本回顾性研究探讨了2017年4月至2020年3月在群马大学医院门诊化疗中心接受第一个TC方案周期的妇科癌症患者，帕洛诺司琼联合右美托咪酮(PD治疗)和格拉司琼联合右美托咪酮联合APR (GDA治疗)的止吐效果。结果显示，接受PD治疗的92例患者(PD组)和接受GDA治疗的46例患者(GDA组)的完全缓解率均为80.4% (p = 1.000)， PD组和GDA组的完全控制率分别为78.3%和80.4% (p = 0.828)，差异无统计学意义。此外，我们观察到PD组和GDA组在≥2级恶心、呕吐和厌食症的发生率方面无显著差异(恶心:7.6% vs 0%， p = 0.095;呕吐:4.3% vs. 0%， p = 0.301;厌食症:9.8% vs. 2.2%， p = 0.164)。关于不良事件，与PD组相比，GDA组的≥2级不适发生率显著高于PD组(7.6% vs. 19.6%， p = 0.039)。鉴于PD和GDA治疗的止吐效果没有差异，应考虑不良反应的发生率和与APR的相互作用，仔细选择个别患者的止吐治疗。
{"title":"Comparison of the Antiemetic Effect of Aprepitant/granisetron and Palonosetron Combined with Dexamethasone in Gynecological Cancer Patients Treated with Paclitaxel and Carboplatin Combination Regimen.","authors":"K. Obayashi, A. Nagamine, H. Yashima, S. Ohshima, C. Uchiyama, E. Takahashi, Y. Takahashi, T. Araki, K. Yamamoto","doi":"10.1691/ph.2022.12000","DOIUrl":"https://doi.org/10.1691/ph.2022.12000","url":null,"abstract":"A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT₃-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"465 1","pages":"157-161"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77737922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongxin Sun, Yumiko Urakami -Takebayashi, H. Motohashi, Junya Nagai
Adipose tissue-derived stem cells (AdSCs) are one of the most promising cell types for cell-based therapies. In addition, AdSCs systematically injected into the body have been reported to localize to damaged tissues and certain types of tumor. As an important part of establishing a potent drug delivery system with AdSCs, the mechanism and efficiency of uptake into AdSCs has drawn much research attention. However, this remains to be fully clarified. The aim of this study was to examine the characteristics of endocytosis-mediated uptake in human AdSCs. We used fluorescein isothiocyanate-labeled albumin (FITC-albumin) as a potent marker of endocytosis. FITC-albumin uptake was time- and temperature-dependent. Confocal microscopy showed punctate localization of fluorescence in the cytoplasm. FITC-albumin uptake was inhibited by human serum albumin in a concentration-dependent manner. FITC-albumin uptake was inhibited by a metabolic inhibitor (2,4-dinitrophenol), a microtubule polymerization inhibitor (colchicine), an actin polymerization inhibitor (cytochalasin D), endosomal acidification inhibitors (chloroquine and bafilomycin A1), clathrin-dependent endocytosis inhibitors (chloropromazine, phenylarsine oxide, and Pitstop2), and caveolin-dependent endocytosis inhibitors (nystatin and methyl-β-cyclodextrin). Furthermore, the knockdown of the clathrin heavy chain and caveolin-1 significantly reduced FITC-albumin uptake. These findings suggest that AdSCs take up albumin via endocytic pathways in which clathrin and caveolin are involved.
{"title":"Internalization of FITC-albumin in Human Adipose-derived Stem Cells: Involvement of Clathrin and Caveolin.","authors":"Hongxin Sun, Yumiko Urakami -Takebayashi, H. Motohashi, Junya Nagai","doi":"10.1691/ph.2022.2340","DOIUrl":"https://doi.org/10.1691/ph.2022.2340","url":null,"abstract":"Adipose tissue-derived stem cells (AdSCs) are one of the most promising cell types for cell-based therapies. In addition, AdSCs systematically injected into the body have been reported to localize to damaged tissues and certain types of tumor. As an important part of establishing a potent drug delivery system with AdSCs, the mechanism and efficiency of uptake into AdSCs has drawn much research attention. However, this remains to be fully clarified. The aim of this study was to examine the characteristics of endocytosis-mediated uptake in human AdSCs. We used fluorescein isothiocyanate-labeled albumin (FITC-albumin) as a potent marker of endocytosis. FITC-albumin uptake was time- and temperature-dependent. Confocal microscopy showed punctate localization of fluorescence in the cytoplasm. FITC-albumin uptake was inhibited by human serum albumin in a concentration-dependent manner. FITC-albumin uptake was inhibited by a metabolic inhibitor (2,4-dinitrophenol), a microtubule polymerization inhibitor (colchicine), an actin polymerization inhibitor (cytochalasin D), endosomal acidification inhibitors (chloroquine and bafilomycin A1), clathrin-dependent endocytosis inhibitors (chloropromazine, phenylarsine oxide, and Pitstop2), and caveolin-dependent endocytosis inhibitors (nystatin and methyl-β-cyclodextrin). Furthermore, the knockdown of the clathrin heavy chain and caveolin-1 significantly reduced FITC-albumin uptake. These findings suggest that AdSCs take up albumin via endocytic pathways in which clathrin and caveolin are involved.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"38 1","pages":"141-146"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81293516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Kose, H. Endo, H. Hori, S. Hosono, C. Kawamura, Y. Kodama, T. Yamazaki, N. Yasuno
So far, no studies investigated the association between pharmacist intervention and rehabilitation outcomes. The aim of study was to establish whether the pharmacist-led deprescribing intervention affects rehabilitation outcomes. This retrospective, observational, single-center, cohort study included consecutive geriatric patients (n = 448) with pharmacist-led intervention between 2017 and 2019. Participants were divided based on pharmacist-led deprescribing and non deprescribing interventions during hospitalization. Demographic data, laboratory data, the Functional Independence Measure were (FIM) analyzed between the groups. Multiple linear regression analysis was performed to analyze the relationship between pharmacist-led deprescribing and FIM total gain. The primary outcome was FIM total gain. The rate of pharmacist intervention during the study period was 92.4%. A multiple linear regression analysis of FMI-T gain, adjusting for confounding factors, revealed that the pharmacist-led deprescribing intervention was independently correlated with FMI-T gain. Particularly, the use of dyslipidemia drugs, antipsychotic drugs, hypnotics, and nonsteroidal anti-inflammatory drugs significantly decreased during hospitalization. The pharmacist-led deprescribing intervention was independently and significantly associated with FIM-T gain. The pharmacist-led deprescribing intervention improved functional recovery in a rehabilitation setting.
{"title":"Association of Pharmacist-led Deprescribing Intervention with the Functional Recovery in Convalescent Setting.","authors":"E. Kose, H. Endo, H. Hori, S. Hosono, C. Kawamura, Y. Kodama, T. Yamazaki, N. Yasuno","doi":"10.1691/ph.2022.2323","DOIUrl":"https://doi.org/10.1691/ph.2022.2323","url":null,"abstract":"So far, no studies investigated the association between pharmacist intervention and rehabilitation outcomes. The aim of study was to establish whether the pharmacist-led deprescribing intervention affects rehabilitation outcomes. This retrospective, observational, single-center, cohort study included consecutive geriatric patients (n = 448) with pharmacist-led intervention between 2017 and 2019. Participants were divided based on pharmacist-led deprescribing and non deprescribing interventions during hospitalization. Demographic data, laboratory data, the Functional Independence Measure were (FIM) analyzed between the groups. Multiple linear regression analysis was performed to analyze the relationship between pharmacist-led deprescribing and FIM total gain. The primary outcome was FIM total gain. The rate of pharmacist intervention during the study period was 92.4%. A multiple linear regression analysis of FMI-T gain, adjusting for confounding factors, revealed that the pharmacist-led deprescribing intervention was independently correlated with FMI-T gain. Particularly, the use of dyslipidemia drugs, antipsychotic drugs, hypnotics, and nonsteroidal anti-inflammatory drugs significantly decreased during hospitalization. The pharmacist-led deprescribing intervention was independently and significantly associated with FIM-T gain. The pharmacist-led deprescribing intervention improved functional recovery in a rehabilitation setting.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"29 1","pages":"165-170"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75681875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, we investigated the immunomodulatory effects of sinensetin (SI) on RAW 264.7 macrophages and cyclophosphamide (CY)-induced immunosuppressed mice. The results showed that SI enhanced macrophage activity and promoted the secretion of NO, IL-1β, and TNF-α in vitro. Compared with the CY-induced immunosuppressed mice, in mice treated with SI, the body weights, organ indices, and total lymphocytes increased. Furthermore, SI promoted the secretion and mRNA expression of IFN-γ, IL-2, and IL-6 and reduced the damage caused by CY to the organs of the immune system. Moreover, it increased the activities of GSH-Px, CAT, SOD, and T-AOC and decreased the level of MDA. This study suggests that SI has the potential to be used as an immunity enhancer in the functional food and healthcare industries.
{"title":"Immunomodulatory Effects of Sinensetin on Macrophage and Cyclophosphamide-induced Immunosuppression in Mice.","authors":"Yi-Lun Wang, Jin-Jie Yang, W. Ni","doi":"10.1691/ph.2022.2321","DOIUrl":"https://doi.org/10.1691/ph.2022.2321","url":null,"abstract":"In this study, we investigated the immunomodulatory effects of sinensetin (SI) on RAW 264.7 macrophages and cyclophosphamide (CY)-induced immunosuppressed mice. The results showed that SI enhanced macrophage activity and promoted the secretion of NO, IL-1β, and TNF-α in vitro. Compared with the CY-induced immunosuppressed mice, in mice treated with SI, the body weights, organ indices, and total lymphocytes increased. Furthermore, SI promoted the secretion and mRNA expression of IFN-γ, IL-2, and IL-6 and reduced the damage caused by CY to the organs of the immune system. Moreover, it increased the activities of GSH-Px, CAT, SOD, and T-AOC and decreased the level of MDA. This study suggests that SI has the potential to be used as an immunity enhancer in the functional food and healthcare industries.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"16 1","pages":"147-151"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79620424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Various chemical reagents containing inhibitors of mitochondrial activity, antioxidants, nuclear factor-kappa B (NF-kB) inhibitor, mammalian target of rapamycin (mTOR) inhibitor and other clinical therapeutics were screened in order to identify those that selectively decrease the viability of senescent human lung fibroblasts. Cell viability was measured using the CCK-8 assay. The results showed that pravastatin, a drug for hyperlipidemia, decreased the viability of senescent cells but not non-senescent cells. The effect of pravastatin on senescent cells is thought to be due to the inhibition of cell proliferation, rather than cell death. The effect of pravastatin was further investigated using the glucose metabolism assay, which showed that glucose consumption was inhibited both in non-senescent and senescent cells and intracellular nicotinamide adenine dinucleotide (NAD) was decreased in senescent cells. Changes to the mRNA expression levels of senescence-associated genes in response to pravastatin treatment were quantified by real-time-qPCR. There were no significant changes in the relative mRNA expression levels of IL-1β, p16, p21, and p53 in pravastatin-treated non-senescent cells, whereas the expression of IL-1β and p16 were increased by pravastatin only in senescent cells. The results of this study suggest that pravastatin does not induce senolysis, but rather selectively inhibits the proliferation of senescent cells and that cellular senescence is enhanced by decreasing intracellular NAD and promoting IL-1β production.
筛选含有线粒体活性抑制剂、抗氧化剂、核因子- κ B (NF-kB)抑制剂、哺乳动物雷帕霉素靶点(mTOR)抑制剂和其他临床治疗药物的各种化学试剂，以确定那些选择性降低衰老人肺成纤维细胞活力的化学试剂。采用CCK-8法测定细胞活力。结果表明，治疗高脂血症的普伐他汀能降低衰老细胞的活力，但对非衰老细胞没有作用。普伐他汀对衰老细胞的作用被认为是由于抑制细胞增殖，而不是细胞死亡。通过糖代谢实验进一步研究了普伐他汀的作用，结果表明，非衰老细胞和衰老细胞的葡萄糖消耗均受到抑制，衰老细胞的细胞内烟酰胺腺嘌呤二核苷酸(NAD)降低。通过real-time-qPCR定量观察普伐他汀治疗后衰老相关基因mRNA表达水平的变化。非衰老细胞中IL-1β、p16、p21和p53 mRNA的相对表达量在普伐他汀处理后无明显变化，而仅普伐他汀处理后衰老细胞中IL-1β和p16 mRNA的相对表达量增加。本研究结果表明，普伐他汀不会诱导衰老，而是选择性地抑制衰老细胞的增殖，并且通过降低细胞内NAD和促进IL-1β的产生来增强细胞衰老。
{"title":"Selective Growth Suppressive Effect of Pravastatin on Senescent Human Lung Fibroblasts.","authors":"H. Ushijima, A. Onodera","doi":"10.1691/ph.2022.2327","DOIUrl":"https://doi.org/10.1691/ph.2022.2327","url":null,"abstract":"Various chemical reagents containing inhibitors of mitochondrial activity, antioxidants, nuclear factor-kappa B (NF-kB) inhibitor, mammalian target of rapamycin (mTOR) inhibitor and other clinical therapeutics were screened in order to identify those that selectively decrease the viability of senescent human lung fibroblasts. Cell viability was measured using the CCK-8 assay. The results showed that pravastatin, a drug for hyperlipidemia, decreased the viability of senescent cells but not non-senescent cells. The effect of pravastatin on senescent cells is thought to be due to the inhibition of cell proliferation, rather than cell death. The effect of pravastatin was further investigated using the glucose metabolism assay, which showed that glucose consumption was inhibited both in non-senescent and senescent cells and intracellular nicotinamide adenine dinucleotide (NAD) was decreased in senescent cells. Changes to the mRNA expression levels of senescence-associated genes in response to pravastatin treatment were quantified by real-time-qPCR. There were no significant changes in the relative mRNA expression levels of IL-1β, p16, p21, and p53 in pravastatin-treated non-senescent cells, whereas the expression of IL-1β and p16 were increased by pravastatin only in senescent cells. The results of this study suggest that pravastatin does not induce senolysis, but rather selectively inhibits the proliferation of senescent cells and that cellular senescence is enhanced by decreasing intracellular NAD and promoting IL-1β production.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"875 1","pages":"132-136"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72663793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Fukuoka, Y. Yamamoto, E. Usami, H. Hayashi, J. Utsunomiya, M. Kimura, M. Nakamura, T. Yoshimura, Y. Toda
Vincristine (VCR) is an important drug used in R-CHOP regimens for the treatment of non-Hodgkin's lymphoma. The purpose of this study was to examine whether the administration method affects the incidence of VCR-induced peripheral neuropathy. We investigated the ratio of VCR-induced peripheral neuropathy during rapid intravenous infusion and intravenous drip infusion. A total of 71 patients who had received six or more courses of R-CHOP from January, 2015 to December, 2016 at Komaki City Hospital and Ogaki Municipal Hospital were retrospectively investigated. Peripheral neuropathy was observed in 27/39 patients (69 %) and 24/32 (75 %) in rapid intravenous infusion and intravenous drip infusion of VCR, respectively (P = 0.79). Peripheral neuropathy was observed at a high frequency in this study. Additionally, there was no difference in frequency of peripheral neuropathy due to the difference in administration method. In both groups, the degree of peripheral neuropathy was grade 1 and grade 2 in most patients. However, in rapid intravenous infusion, grade 3 peripheral neuropathy was observed. Some cases required dose reduction and discontinuation in rapid intravenous infusion. In contrast, there were no discontinuing patients in the intravenous drip infusion. Therefore, it was suggested that intravenous drip infusion of VCR reduced serious peripheral neuropathy because the ratio requiring dose reduction and discontinuation was less than that in the rapid group. In conclusion, this study is informative as there are few reports focusing on the administration method of vincristine.
{"title":"Expression of Vincristin-induced Peripheral Neuropathy Related to Different Administration Methods.","authors":"T. Fukuoka, Y. Yamamoto, E. Usami, H. Hayashi, J. Utsunomiya, M. Kimura, M. Nakamura, T. Yoshimura, Y. Toda","doi":"10.1691/ph.2022.2329","DOIUrl":"https://doi.org/10.1691/ph.2022.2329","url":null,"abstract":"Vincristine (VCR) is an important drug used in R-CHOP regimens for the treatment of non-Hodgkin's lymphoma. The purpose of this study was to examine whether the administration method affects the incidence of VCR-induced peripheral neuropathy. We investigated the ratio of VCR-induced peripheral neuropathy during rapid intravenous infusion and intravenous drip infusion. A total of 71 patients who had received six or more courses of R-CHOP from January, 2015 to December, 2016 at Komaki City Hospital and Ogaki Municipal Hospital were retrospectively investigated. Peripheral neuropathy was observed in 27/39 patients (69 %) and 24/32 (75 %) in rapid intravenous infusion and intravenous drip infusion of VCR, respectively (P = 0.79). Peripheral neuropathy was observed at a high frequency in this study. Additionally, there was no difference in frequency of peripheral neuropathy due to the difference in administration method. In both groups, the degree of peripheral neuropathy was grade 1 and grade 2 in most patients. However, in rapid intravenous infusion, grade 3 peripheral neuropathy was observed. Some cases required dose reduction and discontinuation in rapid intravenous infusion. In contrast, there were no discontinuing patients in the intravenous drip infusion. Therefore, it was suggested that intravenous drip infusion of VCR reduced serious peripheral neuropathy because the ratio requiring dose reduction and discontinuation was less than that in the rapid group. In conclusion, this study is informative as there are few reports focusing on the administration method of vincristine.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"24 1","pages":"162-164"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81076507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Activins belong to the transforming growth factor (TGF)-β superfamily and are involved in the regulation of homeostasis, proliferation, differentiation, and inflammation. In the present study, we examined the mechanism by which activin regulates the transcription of tumor necrosis factor-α (TNF-α)-stimulated cytokines, chemokines, toll-like receptors (TLRs), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in human umbilical vein endothelial cells (HUVECs), and the involvement of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Cell viability was analyzed using MTS/PES solution, mRNA expression was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and protein expression was measured by immunoblotting. TNF-α increased the mRNA expression of cytokines (IL-1β and IL-6), chemokines (IL-8 and MCP-1), and TLR2, as well as the mRNA and protein expression of iNOS and COX-2. Activin decreased TNF-α-induced cytokine, chemokine, and TLR mRNA expression as well as TNF-α-induced iNOS and COX-2 mRNA and protein expression. In addition, activin suppressed the phosphorylation of NF-κB p65 in TNF-α-stimulated HUVECs and reduced TNF-α-induced phosphorylation of AKT, JNK, ERK, and p38 MAPK. Our results demonstrate that the anti-inflammatory effects of activin are mediated by inflammatory response genes through the inhibition of NF-κB and AKT/JNK/MAPK signaling.
{"title":"Activin Suppresses the Inflammatory Response of TNF-α -stimulated Human Umbilical Vein Endothelial Cells.","authors":"H. Ko, Young Il Kim, H. Ahn","doi":"10.1691/ph.2022.2330","DOIUrl":"https://doi.org/10.1691/ph.2022.2330","url":null,"abstract":"Activins belong to the transforming growth factor (TGF)-β superfamily and are involved in the regulation of homeostasis, proliferation, differentiation, and inflammation. In the present study, we examined the mechanism by which activin regulates the transcription of tumor necrosis factor-α (TNF-α)-stimulated cytokines, chemokines, toll-like receptors (TLRs), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in human umbilical vein endothelial cells (HUVECs), and the involvement of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Cell viability was analyzed using MTS/PES solution, mRNA expression was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and protein expression was measured by immunoblotting. TNF-α increased the mRNA expression of cytokines (IL-1β and IL-6), chemokines (IL-8 and MCP-1), and TLR2, as well as the mRNA and protein expression of iNOS and COX-2. Activin decreased TNF-α-induced cytokine, chemokine, and TLR mRNA expression as well as TNF-α-induced iNOS and COX-2 mRNA and protein expression. In addition, activin suppressed the phosphorylation of NF-κB p65 in TNF-α-stimulated HUVECs and reduced TNF-α-induced phosphorylation of AKT, JNK, ERK, and p38 MAPK. Our results demonstrate that the anti-inflammatory effects of activin are mediated by inflammatory response genes through the inhibition of NF-κB and AKT/JNK/MAPK signaling.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"17 1","pages":"152-156"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84804630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cardiomyocyte autophagy is closely related to myocardial infarction and hypertrophy. To study the molecular mechanism of autophagy is helpful for the prevention and treatment of these diseases. As a cell surface receptor, the function of ITGB1 gene in cardiomyocyte autophagy is not clear. The purpose of this research was to investigate the function and molecular mechanism of ITGB1 on autophagy. The autophagy-related marker proteins and signaling molecules were detected using western blot with knockdown and overexpression of ITGB1 in H9C2 cells. The results suggested that ITGB1 could inhibit autophagy and the mTORC2/Akt pathway molecules. To further investigate whether the effect of ITGB1 on autophagy might affect myocardial hypertrophy, we constructed AngII induced H9C2 cells and TAC induced rats models. The results showed that ITGB1 inhibited myocardial hypertrophy in both H9C2 cells and heart tissues of disease model. These data highlight the regulation mechanism on autophagy by ITGB1 and the potential usefulness of the gene as a potential target for preventing heart disease.
{"title":"ITGB1 Suppresses Autophagy Through Inhibiting The mTORC2/AKT Signaling Pathway In H9C2 Cells.","authors":"Weiwei Zhou, Weizhe Liu, Dingyan Zhou, Aiying Li","doi":"10.1691/ph.2022.2351","DOIUrl":"https://doi.org/10.1691/ph.2022.2351","url":null,"abstract":"Cardiomyocyte autophagy is closely related to myocardial infarction and hypertrophy. To study the molecular mechanism of autophagy is helpful for the prevention and treatment of these diseases. As a cell surface receptor, the function of ITGB1 gene in cardiomyocyte autophagy is not clear. The purpose of this research was to investigate the function and molecular mechanism of ITGB1 on autophagy. The autophagy-related marker proteins and signaling molecules were detected using western blot with knockdown and overexpression of ITGB1 in H9C2 cells. The results suggested that ITGB1 could inhibit autophagy and the mTORC2/Akt pathway molecules. To further investigate whether the effect of ITGB1 on autophagy might affect myocardial hypertrophy, we constructed AngII induced H9C2 cells and TAC induced rats models. The results showed that ITGB1 inhibited myocardial hypertrophy in both H9C2 cells and heart tissues of disease model. These data highlight the regulation mechanism on autophagy by ITGB1 and the potential usefulness of the gene as a potential target for preventing heart disease.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"97 1","pages":"137-140"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74805029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A capillary electrophoretic method for the chiral separation and quantification of mitiglinide (MTG) enantiomers is described (less than 9.5 min) with resolution value Rs = 5.25 and with excellent peak shapes after performing the dynamically coating for the bare fused capillary. The study aims to develop and validate a novel and simple method for the separation and quantification of MTG enantiomers using CE after dynamic coating the capillary wall using the hydroxyethyl cellulose (HEC) coating agent. Dynamic coating procedure of the capillary inner surface is conducted via rapid flushes using 0.1 M sodium hydroxide, water, and aqueous solution containing HEC, and hydroxypropyl-γ-cyclodextrin (HP-γ-CD). Besides buffer was used for the dynamic coating process in addition to its use as the separation medium. When the dynamic coating was used, peak symmetry was improved. A bare fused-silica capillary was used throughout the separation after being coated using HEC dissolved in the background electrolyte (BGE) of 50 mM Na₂HPO₄ - 1 M H₃PO₄ solution; pH 8.5; containing 25 25 mg mL-1 of each HP-γ-CD and HEC. The dynamic coating procedure achieved an improvement in migration time as well as peak area precision. The adsorbed coating agent showed slight interactions with MTG, providing efficient separation with outstanding durability and reproducibility at slightly alkaline conditions (pH 8.5). Acceptable validation criteria for selectivity, linearity, precision, and accuracy were also studied. The newly developed method was effectively applied to the assay of enantiomers of MTG in pharmaceutical formulations. Additionally, it was proven to have the advantages of being simple, rapid, and accurate.
本文描述了一种对裸熔融毛细管进行动态涂覆后的米格列尼(MTG)对映体进行手性分离和定量的毛细管电泳方法(小于9.5 min)，分辨率值Rs = 5.25，峰形优异。本研究旨在建立并验证一种新的、简单的、以羟乙基纤维素(HEC)包衣剂动态包衣毛细管壁后，用CE分离和定量MTG对映体的方法。采用0.1 M氢氧化钠、水、含HEC水溶液和羟丙基-γ-环糊精(HP-γ-CD)快速冲洗，对毛细管内表面进行动态涂覆。此外，缓冲液除了用作分离介质外，还用于动态包衣工艺。采用动态涂层后，峰的对称性得到改善。在50 mM Na₂HPO₄- 1 M H₃PO₄溶液的背景电解质(BGE)中涂覆HEC后，采用裸熔融石英毛细管进行分离;pH值8.5;HP-γ-CD和HEC各含25 - 25 mg mL-1。动态镀膜不仅改善了迁移时间，而且提高了峰面积精度。吸附的包衣剂与MTG的相互作用很小，在微碱性条件下(pH 8.5)具有良好的分离性能和重复性。研究了选择性、线性度、精密度和准确度的可接受验证标准。该方法可有效地应用于中药制剂中MTG对映体的测定。此外，它被证明具有简单、快速和准确的优点。
{"title":"A novel and simple dynamic coating capillary electrophoresis method for the chiral separation and quantification of mitiglinide enantiomers using hydroxyethyl cellulose as a dynamic coating agent.","authors":"K. M. Azzam","doi":"10.1691/ph.2022.1166","DOIUrl":"https://doi.org/10.1691/ph.2022.1166","url":null,"abstract":"A capillary electrophoretic method for the chiral separation and quantification of mitiglinide (MTG) enantiomers is described (less than 9.5 min) with resolution value Rs = 5.25 and with excellent peak shapes after performing the dynamically coating for the bare fused capillary. The study aims to develop and validate a novel and simple method for the separation and quantification of MTG enantiomers using CE after dynamic coating the capillary wall using the hydroxyethyl cellulose (HEC) coating agent. Dynamic coating procedure of the capillary inner surface is conducted via rapid flushes using 0.1 M sodium hydroxide, water, and aqueous solution containing HEC, and hydroxypropyl-γ-cyclodextrin (HP-γ-CD). Besides buffer was used for the dynamic coating process in addition to its use as the separation medium. When the dynamic coating was used, peak symmetry was improved. A bare fused-silica capillary was used throughout the separation after being coated using HEC dissolved in the background electrolyte (BGE) of 50 mM Na₂HPO₄ - 1 M H₃PO₄ solution; pH 8.5; containing 25 25 mg mL-1 of each HP-γ-CD and HEC. The dynamic coating procedure achieved an improvement in migration time as well as peak area precision. The adsorbed coating agent showed slight interactions with MTG, providing efficient separation with outstanding durability and reproducibility at slightly alkaline conditions (pH 8.5). Acceptable validation criteria for selectivity, linearity, precision, and accuracy were also studied. The newly developed method was effectively applied to the assay of enantiomers of MTG in pharmaceutical formulations. Additionally, it was proven to have the advantages of being simple, rapid, and accurate.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"2 1","pages":"95-102"},"PeriodicalIF":0.0,"publicationDate":"2022-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87972330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A granulation method using a planetary centrifugal mixer, called planetary centrifugal granulation, has been developed for small-scale production, such as extemporaneous preparation in pharmacies. Although the impact of its operational parameters on granulation is described, the scale effect has not been investigated. Therefore, we aimed to reveal the effects of vessel size and vessel filling rate on granule properties. In this study, ibuprofen 20% granules consisting of lactose, cornstarch, sodium carmellose, and talc were used as model granules. Granulation was performed using geometrically similar containers, 6-58 mL, with a filling rate of 20-70%. After granulation, we monitored the granule properties, for example, median diameter (d50), span of particle size distribution, and sphericity. At filling rates of 40% and 50% in the 58-mL vessel, the granules grew larger in diameter, and at a rate of 30%, the granules showed a higher sphericity. When the filling rate was 30%, d50 became larger and the span decreased as the vessel size increased. The yields of the granules were higher than 95% when using the 12-58 mL vessel. Lastly, the drug content uniformity and drug dissolution behavior of the granules produced in different vessel size were examined. The granules showed similar drug consistencies and drug dissolution profiles. In conclusion, the quality of the products was not affected by changes in vessel size. Thus, pharmacists could prepare and compound the granule formulations with high yield and appropriate quality using an adequate vessel in the same manner.
{"title":"Effect of batch size on the granule properties in planetary centrifugal granulation.","authors":"Y. Miyazaki, T. Uchino, Y. Kagawa","doi":"10.1691/ph.2022.11059","DOIUrl":"https://doi.org/10.1691/ph.2022.11059","url":null,"abstract":"A granulation method using a planetary centrifugal mixer, called planetary centrifugal granulation, has been developed for small-scale production, such as extemporaneous preparation in pharmacies. Although the impact of its operational parameters on granulation is described, the scale effect has not been investigated. Therefore, we aimed to reveal the effects of vessel size and vessel filling rate on granule properties. In this study, ibuprofen 20% granules consisting of lactose, cornstarch, sodium carmellose, and talc were used as model granules. Granulation was performed using geometrically similar containers, 6-58 mL, with a filling rate of 20-70%. After granulation, we monitored the granule properties, for example, median diameter (d50), span of particle size distribution, and sphericity. At filling rates of 40% and 50% in the 58-mL vessel, the granules grew larger in diameter, and at a rate of 30%, the granules showed a higher sphericity. When the filling rate was 30%, d50 became larger and the span decreased as the vessel size increased. The yields of the granules were higher than 95% when using the 12-58 mL vessel. Lastly, the drug content uniformity and drug dissolution behavior of the granules produced in different vessel size were examined. The granules showed similar drug consistencies and drug dissolution profiles. In conclusion, the quality of the products was not affected by changes in vessel size. Thus, pharmacists could prepare and compound the granule formulations with high yield and appropriate quality using an adequate vessel in the same manner.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"4 1","pages":"103-106"},"PeriodicalIF":0.0,"publicationDate":"2022-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91148985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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