Archives of Pharmacal Research最新文献_第9页

Tumor lactic acid: a potential target for cancer therapy 肿瘤乳酸:癌症治疗的潜在靶点

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-02-02 DOI: 10.1007/s12272-023-01431-8

Jun-Kyu Byun

引用次数: 2

Innate immune sensing of pathogens and its post-transcriptional regulations by RNA-binding proteins 病原体的先天免疫感知及其rna结合蛋白的转录后调控

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-02-01 DOI: 10.1007/s12272-023-01429-2

Ka Man Tse, Osamu Takeuchi

{"title":"Innate immune sensing of pathogens and its post-transcriptional regulations by RNA-binding proteins","authors":"Ka Man Tse, Osamu Takeuchi","doi":"10.1007/s12272-023-01429-2","DOIUrl":"10.1007/s12272-023-01429-2","url":null,"abstract":"<div> Innate immunity is one of the most ancient and conserved aspect of the immune system. It is responsible for an anti-infective response and has been intrinsically linked to the generation of inflammation. While the inflammatory response entails signaling to the adaptive immune system, it can be self-perpetuating and over-exaggerated, resulting in deleterious consequences, including cytokine storm, sepsis, and the development of inflammatory and autoimmune diseases. Cytokines are the defining features of the immune system. They are critical to mediation of inflammation and host immune defense, and are tightly regulated at several levels, including transcriptional and post-transcriptional levels. Recently, the role of post-transcriptional regulation in fine-tuning cytokine expression has become more appreciated. This interest has advanced our understanding of how various mechanisms are integrated and regulated to determine the amount of cytokine production in cells during inflammatory responses. Here, we would like to review how innate immunity recognizes and responds to pathogens by pattern-recognition receptors, and the molecular mechanisms regulating inflammatory responses, with a focus on the post-transcriptional regulations of inflammatory mediators by RNA-binding proteins, especially Regnase-1. Finally, we will discuss the regulatory mechanisms of Regnase-1 and highlight therapeutic strategies based on targeting Regnase-1 activity and its turnover as potential treatment options for chronic and autoimmune diseases.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01429-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Distinctive role of inflammation in tissue repair and regeneration 炎症在组织修复和再生中的独特作用

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-01-31 DOI: 10.1007/s12272-023-01428-3

Bokeum Choi, Changjun Lee, Je-Wook Yu

引用次数: 1

Isolation, structure elucidation, total synthesis, and biosynthesis of dermazolium A, an antibacterial imidazolium metabolite of a vaginal bacterium Dermabacter vaginalis 阴道皮杆菌抗菌咪唑代谢物dermazolium A的分离、结构解析、全合成和生物合成

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-01-16 DOI: 10.1007/s12272-022-01424-z

Hye Ryeong Kim, Jonghwan Kim, Jae Sik Yu, Bum Soo Lee, Ki Hyun Kim, Chung Sub Kim

{"title":"Isolation, structure elucidation, total synthesis, and biosynthesis of dermazolium A, an antibacterial imidazolium metabolite of a vaginal bacterium Dermabacter vaginalis","authors":"Hye Ryeong Kim, Jonghwan Kim, Jae Sik Yu, Bum Soo Lee, Ki Hyun Kim, Chung Sub Kim","doi":"10.1007/s12272-022-01424-z","DOIUrl":"10.1007/s12272-022-01424-z","url":null,"abstract":"<div>Dermabacter vaginalis is a human-derived bacterium isolated from vaginal fluid of a Korean female in 2016. Although several human-related species in Dermabacter genus have been reported there are few studies on their bioactive metabolites. Dermazolium A (1), a rare imidazolium metabolite, was isolated from D. vaginalis along with five known metabolites (2–6) and their chemical structures were determined by NMR, HRMS, and MS/MS data analysis. Feeding experiments using predicted precursors and biomimetic total synthesis of 1 corroborated its structure and led to suggestion of biosynthetic pathway of 1. Antibacterial tests on the isolated compounds showed that 1 is a mild antibacterial agent with MIC values of 41 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA) USA300, Lacticaseibacillus paracasei subsp. paracasei KCTC 3510 and Brevibacterium epidermidis KCTC 3090.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-022-01424-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10583373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

The role and application of transcriptional repressors in cancer treatment 转录抑制因子在癌症治疗中的作用及应用

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-01-16 DOI: 10.1007/s12272-023-01427-4

Miso Park, Keon Wook Kang, Ji Won Kim

{"title":"The role and application of transcriptional repressors in cancer treatment","authors":"Miso Park, Keon Wook Kang, Ji Won Kim","doi":"10.1007/s12272-023-01427-4","DOIUrl":"10.1007/s12272-023-01427-4","url":null,"abstract":"<div>Gene expression is modulated through the integration of many regulatory elements and their associated transcription factors (TFs). TFs bind to specific DNA sequences and either activate or repress transcriptional activity. Through decades of research, it has been established that aberrant expression or functional abnormalities of TFs can lead to uncontrolled cell division and the development of cancer. Initial studies on transcriptional regulation in cancer have focused on TFs as transcriptional activators. However, recent studies have demonstrated several different mechanisms of transcriptional repression in cancer, which could be potential therapeutic targets for the development of specific anti-cancer agents. In the first section of this review, “Emerging roles of transcriptional repressors in cancer development,” we summarize the current understanding of transcriptional repressors and their involvement in the molecular processes of cancer progression. In the subsequent section, “Therapeutic applications,” we provide an updated overview of the available therapeutic targets for drug discovery and discuss the new frontier of such applications.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10581178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 1

MEKs/ERKs-mediated FBXO1/E2Fs interaction interference modulates G1/S cell cycle transition and cancer cell proliferation MEKs/ erks介导的FBXO1/E2Fs相互作用干扰调节G1/S细胞周期转变和癌细胞增殖

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-01-06 DOI: 10.1007/s12272-023-01426-5

Ga-Eun Lee, Dohyun Jeung, Weidong Chen, Jiin Byun, Joo Young Lee, Han Chang Kang, Hye Suk Lee, Dae Joon Kim, Jin-Sung Choi, Cheol-Jung Lee, Hyun-Jung An, Yong-Yeon Cho

{"title":"MEKs/ERKs-mediated FBXO1/E2Fs interaction interference modulates G1/S cell cycle transition and cancer cell proliferation","authors":"Ga-Eun Lee, Dohyun Jeung, Weidong Chen, Jiin Byun, Joo Young Lee, Han Chang Kang, Hye Suk Lee, Dae Joon Kim, Jin-Sung Choi, Cheol-Jung Lee, Hyun-Jung An, Yong-Yeon Cho","doi":"10.1007/s12272-023-01426-5","DOIUrl":"10.1007/s12272-023-01426-5","url":null,"abstract":"<div>E2F 1, 2, and 3a, (refer to as E2Fs) are a subfamily of E2F transcription factor family that play essential roles in cell-cycle progression, DNA replication, DNA repair, apoptosis, and differentiation. Although the transcriptional regulation of E2Fs has focused on pocket protein retinoblastoma protein complex, recent studies indicate that post-translational modification and stability regulation of E2Fs play key roles in diverse cellular processes. In this study, we found that FBXO1, a component of S-phase kinase-associated protein 1 (SKP1)-cullin 1-F-box protein (SCF) complex, is an E2Fs binding partner. Furthermore, FBXO1 to E2Fs binding induced K48 ubiquitination and subsequent proteasomal degradation of E2Fs. Binding domain analysis indicated that the Arg (R)/Ile (I) and R/Val (V) motifs, which are located in the dimerization domain of E2Fs, of E2F 1 and 3a and E2F2, respectively, acted as degron motifs (DMs) for FBXO1. Notably, RI/AA or RV/AA mutation in the DMs reduced FBXO1-mediated ubiquitination and prolonged the half-lives of E2Fs. Importantly, the stabilities of E2Fs were affected by phosphorylation of threonine residues located near RI and RV residues of DMs. Phosphorylation prediction database analysis and specific inhibitor analysis revealed that MEK/ERK signaling molecules play key roles in FBXO1/E2Fs’ interaction and modulate E2F protein turnover. Moreover, both elevated E2Fs protein levels by knockdown of FBXO1 and decreased E2Fs protein levels by sh-E2F3a delayed G1/S cell cycle transition, resulting in inhibition of cancer cell proliferation. These results demonstrated that FBXO1-E2Fs axis-mediated precise E2Fs stability regulation plays a key role in cell proliferation via G1/S cell cycle transition.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50020123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Recent advances in selective and targeted drug/gene delivery systems using cell-penetrating peptides 利用细胞穿透肽的选择性和靶向药物/基因传递系统的最新进展

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-01-03 DOI: 10.1007/s12272-022-01425-y

So Hee Nam, Joonhyuck Park, Heebeom Koo

{"title":"Recent advances in selective and targeted drug/gene delivery systems using cell-penetrating peptides","authors":"So Hee Nam, Joonhyuck Park, Heebeom Koo","doi":"10.1007/s12272-022-01425-y","DOIUrl":"10.1007/s12272-022-01425-y","url":null,"abstract":"<div>Biological cell membranes are a natural barrier for living cells. In the last few decades, the cell membrane has been the main hurdle in the efficient delivery of bioactive and therapeutic agents. To increase the drug efficacy of these agents, additional mediators have been considered. Cell-penetrating peptides (CPPs), a series of oligopeptides composed of mostly hydrophobic and/or positively charged side chains, can increase the interaction with the cell membrane. CPP-based delivery platforms have shown great potential for the efficient and direct cytosol delivery of various cargos, including genes, proteins, and small molecule drugs. Bypassing endocytosis allows the CPP-based delivery systems greater defense against the degradation of protein-based drugs than other drug delivery systems. However, the delivery of CPPs exhibits intrinsically non-specific targeting, which limits their medical applications. To endow CPPs with specific targeting ability, the conjugation of pH-sensitive, enzyme-specific cleavable, and multiple targeting ligands has been reported. Optimization of the length and sequence of CPPs is still needed for various drugs of different sizes and surface charges. Toxicity issues in CPP-based delivery systems should be addressed carefully before clinical use.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-022-01425-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10635928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Effects of CYP2C19 genetic polymorphism on the pharmacokinetics of tolperisone in healthy subjects CYP2C19基因多态性对健康受试者托培里松药代动力学的影响

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-12-23 DOI: 10.1007/s12272-022-01423-0

Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Hye-Jung Park, Eunvin Ko, Chou Yen Mu, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee

{"title":"Effects of CYP2C19 genetic polymorphism on the pharmacokinetics of tolperisone in healthy subjects","authors":"Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Hye-Jung Park, Eunvin Ko, Chou Yen Mu, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee","doi":"10.1007/s12272-022-01423-0","DOIUrl":"10.1007/s12272-022-01423-0","url":null,"abstract":"<div>Tolperisone hydrochloride is a centrally-acting muscle relaxant used for relieving spasticities of neurological origin and muscle spasms associated with painful locomotor diseases. It is metabolized to the inactive metabolite mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. In our previous study, the pharmacokinetics of tolperisone was significantly affected by the genetic polymorphism of CYP2D6, but the wide interindividual variation of tolperisone pharmacokinetics was not explained by genetic polymorphism of CYP2D6 alone. Thus, we studied the effects of CYP2C19 genetic polymorphism on tolperisone pharmacokinetics. Eighty-one subjects with different CYP2C19 genotypes received a single oral dose of 150 mg tolperisone with 240 mL of water, and blood samples were collected up to 12 h after dosing. The plasma concentration of tolperisone was measured by a liquid chromatography-tandem mass spectrometry system. The CYP2C19PM group had significantly higher Cmax and lower CL/F values than the CYP2C19EM and CYP2C19IM groups. The AUCinf of the CYP2C19PM group was 2.86-fold and 3.00-fold higher than the CYP2C19EM and CYP2C19IM groups, respectively. In conclusion, the genetic polymorphism of CYP2C19 significantly affected tolperisone pharmacokinetics.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 3

Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone CYP2D6*10等位基因对托培里松药动学的影响

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-12-21 DOI: 10.1007/s12272-022-01422-1

Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Jung-In Park, Choon-Gon Jang, Seok-Yong Lee, Chang-Ik Choi, Jung‑Woo Bae, Yun Jeong Lee

{"title":"Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone","authors":"Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Jung-In Park, Choon-Gon Jang, Seok-Yong Lee, Chang-Ik Choi, Jung‑Woo Bae, Yun Jeong Lee","doi":"10.1007/s12272-022-01422-1","DOIUrl":"10.1007/s12272-022-01422-1","url":null,"abstract":"<div>Tolperisone, a muscle relaxant used for post-stroke spasticity, has been reported to have a very wide interindividual pharmacokinetic variability. It is metabolized mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. CYP2D6 is a highly polymorphic enzyme, and CYP2D6*wt/*wt, CYP2D6*wt/*10 and CYP2D6*10/*10 genotypes constitute more than 90% of the CYP2D6 genotypes in the Korean population. Thus, effects of the CYP2D6*10 on tolperisone pharmacokinetics were investigated in this study to elucidate the reasons for the wide interindividual variability. Oral tolperisone 150 mg was given to sixty-four healthy Koreans, and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS). The CYP2D6*10/*10 and CYP2D6*wt/*10 groups had significantly higher Cmax and lower CL/F values than the CYP2D6*wt/*wt group. The AUCinf of CYP2D6*10/*10 and CYP2D6*wt/*10 groups were 5.18-fold and 2.25-fold higher than the CYP2D6*wt/*wt group, respectively. There were considerable variations in the Cmax and AUC values within each genotype group, and the variations were greater as the activity of CYP2D6 decreased. These results suggest that the genetic polymorphism of CYP2D6 significantly affected tolperisone pharmacokinetics and factor(s) other than CYP2D6 may also have significant effects on the pharmacokinetics of tolperisone.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-022-01422-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10657760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Targeting cytokines and signaling molecules related to immune pathways in atopic dermatitis: therapeutic implications and challenges 靶向细胞因子和信号分子相关的免疫途径在特应性皮炎:治疗意义和挑战

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-12-03 DOI: 10.1007/s12272-022-01421-2

Hyung-Ook Kim

{"title":"Targeting cytokines and signaling molecules related to immune pathways in atopic dermatitis: therapeutic implications and challenges","authors":"Hyung-Ook Kim","doi":"10.1007/s12272-022-01421-2","DOIUrl":"10.1007/s12272-022-01421-2","url":null,"abstract":"<div>Although atopic dermatitis (AD) is primarily a Th2-driven disease, it shows high heterogeneity with additional variable contributions of the Th22, Th17, and Th1 pathways, depending on the subtype of the disease. Expanding knowledge and understanding of AD pathogenesis has promoted the development of numerous novel therapeutics that target cytokines and their signaling molecules, representatively, Janus kinases, involved in the underlying immune pathways, resulting in therapeutic success and failure. The first FDA approval was for the targeted biologic dupilumab. Although this proved the therapeutic relevance of targeting Th2 cytokines in moderate-to-severe forms of AD, it did not treat all patients, necessitating additional targeted therapeutics that modulate other cytokine pathways to resolve AD in all subtypes. Three more recently FDA-approved targeted therapeutics and several others that have been developed represent different targeted approaches directed to the Th2, Th22, Th17, or Th1 pathways. This review summarizes the main features and clinical outcomes of various approaches targeting cytokines and signaling molecules in these different pathways in view of both successful and failed cases, with a discussion of their therapeutic implications. In future, AD should be treated with more specific treatments reflecting the disease heterogeneity, but the current development of targeted therapeutics has faced some challenges in this context, which is also discussed.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10374383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 2