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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 Q1 CHEMISTRY, MEDICINAL Pub Date : 2023-01-16 DOI: 10.1007/s12272-023-01427-4
Miso Park, Keon Wook Kang, Ji Won Kim

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.

基因表达是通过整合许多调控元件及其相关转录因子(TF)来调节的。TF与特定的DNA序列结合,并激活或抑制转录活性。经过几十年的研究,已经确定了TFs的异常表达或功能异常会导致不受控制的细胞分裂和癌症的发展。癌症转录调控的初步研究主要集中在转录因子作为转录激活因子。然而,最近的研究已经证明了癌症转录抑制的几种不同机制,这可能是开发特定抗癌药物的潜在治疗靶点。在这篇综述的第一部分“转录抑制因子在癌症发展中的新作用”中,我们总结了目前对转录抑制因子及其参与癌症进展分子过程的理解。在接下来的“治疗应用”一节中,我们提供了药物发现的可用治疗靶点的最新概述,并讨论了此类应用的新前沿。
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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 Q1 CHEMISTRY, MEDICINAL 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

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.

E2F 1、2和3a(简称E2F)是E2F转录因子家族的一个亚家族,在细胞周期进程、DNA复制、DNA修复、细胞凋亡和分化中发挥重要作用。虽然E2Fs的转录调控主要集中在口袋蛋白视网膜母细胞瘤蛋白复合物上,但最近的研究表明,E2Fs的翻译后修饰和稳定性调控在多种细胞过程中发挥关键作用。在这项研究中,我们发现FBXO1是s期激酶相关蛋白1 (SKP1)-cullin 1- f -box蛋白(SCF)复合物的一个组分,是E2Fs的结合伙伴。此外,FBXO1与E2Fs结合诱导K48泛素化和随后的E2Fs蛋白酶体降解。结合域分析表明,位于E2F二聚化结构域的Arg (R)/Ile (I)和R/Val (V)基序分别是FBXO1的脱粒基序(DMs),它们分别位于e2f1和3a和E2F2的二聚化结构域。值得注意的是,dm中的RI/AA或RV/AA突变降低了fbxo1介导的泛素化,延长了E2Fs的半衰期。重要的是,E2Fs的稳定性受到位于DMs的RI和RV残基附近的苏氨酸残基磷酸化的影响。磷酸化预测数据库分析和特异性抑制剂分析表明,MEK/ERK信号分子在FBXO1/E2Fs相互作用和调节E2F蛋白周转中发挥关键作用。此外,通过敲低FBXO1上调E2Fs蛋白水平和通过sh-E2F3a下调E2Fs蛋白水平均可延缓G1/S细胞周期转变,从而抑制癌细胞增殖。这些结果表明,FBXO1-E2Fs轴介导的精确E2Fs稳定性调控通过G1/S细胞周期转变在细胞增殖中起关键作用。
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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 Q1 CHEMISTRY, MEDICINAL Pub Date : 2023-01-03 DOI: 10.1007/s12272-022-01425-y
So Hee Nam, Joonhyuck Park, Heebeom Koo

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.

生物细胞膜是活细胞的天然屏障。在过去的几十年里,细胞膜一直是生物活性和治疗药物有效输送的主要障碍。为了提高这些药物的疗效,已经考虑了额外的介质。细胞穿透肽(CPPs)是一系列主要由疏水和/或带正电的侧链组成的寡肽,可以增加与细胞膜的相互作用。基于cpp的递送平台在有效和直接递送各种货物(包括基因、蛋白质和小分子药物)方面显示出巨大的潜力。绕过内吞作用使基于cpp的递送系统比其他药物递送系统更能抵抗基于蛋白质的药物的降解。然而,CPPs的递送表现出本质上的非特异性靶向性,这限制了它们的医学应用。为了使CPPs具有特异性靶向能力,已经报道了ph敏感、酶特异性可切割和多靶向配体的偶联。对于不同大小和表面电荷的药物,仍需对CPPs的长度和序列进行优化。在临床使用之前,应仔细解决基于cpp的给药系统的毒性问题。
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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 Q1 CHEMISTRY, MEDICINAL 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

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.

盐酸托培里森是一种中枢作用的肌肉松弛剂,用于缓解神经性痉挛和与疼痛性运动疾病相关的肌肉痉挛。主要由CYP2D6代谢为无活性代谢物,其次由CYP2C19和CYP1A2代谢。在我们之前的研究中,CYP2D6基因多态性对托哌利松的药代动力学有显著影响,但托哌利松药代动力学的广泛个体间差异并不能仅用CYP2D6基因多态性来解释。因此,我们研究了CYP2C19基因多态性对托培里森酮药代动力学的影响。81名不同CYP2C19基因型的受试者接受单次口服150 mg托培力松加240 mL水,并在给药后12 h采集血样。采用液相色谱-串联质谱联用系统测定托培里森酮的血药浓度。与CYP2C19EM和CYP2C19IM组相比,CYP2C19PM组Cmax显著升高,CL/F显著降低。CYP2C19PM组的auinf分别比CYP2C19EM组和CYP2C19IM组高2.86倍和3.00倍。综上所述,CYP2C19基因多态性显著影响tolperisone药代动力学。
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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 Q1 CHEMISTRY, MEDICINAL 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

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.

托培力松,一种用于中风后痉挛的肌肉松弛剂,据报道具有非常广泛的个体间药代动力学变异性。它主要由CYP2D6代谢,其次由CYP2C19和CYP1A2代谢。CYP2D6是一种高度多态性酶,CYP2D6*wt/*wt、CYP2D6*wt/*10和CYP2D6*10/*10基因型占韩国人群CYP2D6基因型的90%以上。因此,本研究探讨了CYP2D6*10对托培里森酮药代动力学的影响,以阐明个体间差异较大的原因。采用液相色谱-串联质谱法(LC-MS /MS)测定64名健康韩国人口服tolperisone 150 mg的血浆tolperisone浓度。CYP2D6*10/*10和CYP2D6*wt/*10组Cmax显著高于CYP2D6*wt/*wt组,CL/F显著低于CYP2D6*wt/*wt组。CYP2D6*10/*10组和CYP2D6*wt/*10组的AUCinf分别比CYP2D6*wt/*wt组高5.18倍和2.25倍。各基因型组的Cmax和AUC值存在较大差异,且随着CYP2D6活性的降低,差异更大。上述结果提示,CYP2D6基因多态性显著影响托培里松的药代动力学,CYP2D6以外的其他因子也可能对托培里松的药代动力学有显著影响。
{"title":"Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone","authors":"Chang‑Keun Cho,&nbsp;Ji-Young Byeon,&nbsp;Pureum Kang,&nbsp;Jung-In Park,&nbsp;Choon-Gon Jang,&nbsp;Seok-Yong Lee,&nbsp;Chang-Ik Choi,&nbsp;Jung‑Woo Bae,&nbsp;Yun Jeong Lee","doi":"10.1007/s12272-022-01422-1","DOIUrl":"10.1007/s12272-022-01422-1","url":null,"abstract":"<div><p>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 <i>CYP2D6*wt</i>/<i>*wt</i>, <i>CYP2D6*wt/*10</i> and <i>CYP2D6*10/*10</i> genotypes constitute more than 90% of the <i>CYP2D6</i> genotypes in the Korean population. Thus, effects of the <i>CYP2D6*10</i> 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 <i>CYP2D6*10/*10</i> and <i>CYP2D6*wt/*10</i> groups had significantly higher C<sub>max</sub> and lower CL/F values than the <i>CYP2D6*wt/*wt</i> group. The AUC<sub>inf</sub> of <i>CYP2D6*10/*10</i> and <i>CYP2D6*wt/*10</i> groups were 5.18-fold and 2.25-fold higher than the <i>CYP2D6*wt/*wt</i> group, respectively. There were considerable variations in the C<sub>max</sub> 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 <i>CYP2D6</i> significantly affected tolperisone pharmacokinetics and factor(s) other than CYP2D6 may also have significant effects on the pharmacokinetics of tolperisone.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 1","pages":"59 - 64"},"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 Q1 CHEMISTRY, MEDICINAL Pub Date : 2022-12-03 DOI: 10.1007/s12272-022-01421-2
Hyung-Ook Kim

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.

虽然特应性皮炎(AD)主要是一种th2驱动的疾病,但它显示出高度的异质性,根据疾病的亚型,Th22、Th17和Th1通路也有额外的可变贡献。对阿尔茨海默病发病机制的认识和理解不断扩大,促进了许多针对细胞因子及其信号分子的新疗法的发展,以Janus激酶为代表,参与潜在的免疫途径,从而导致治疗的成功和失败。FDA批准的首个药物是靶向生物药dupilumab。尽管这证明了靶向Th2细胞因子在中重度AD中的治疗相关性,但它并不能治疗所有患者,因此需要额外的靶向治疗,通过调节其他细胞因子途径来解决所有亚型的AD。最近fda批准的三种靶向治疗方法和其他几种已开发的靶向治疗方法分别针对Th2、Th22、Th17或Th1途径。本文综述了不同途径中针对细胞因子和信号分子的治疗方法的主要特点和临床结果,并对其治疗意义进行了讨论。未来,AD的治疗应更具有特异性,反映疾病的异质性,但目前靶向治疗的发展在此背景下面临一些挑战,本文也对此进行了讨论。
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引用次数: 2
Non-alcoholic fatty liver disease and liver secretome 非酒精性脂肪性肝病与肝脏分泌组
IF 6.7 3区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2022-11-28 DOI: 10.1007/s12272-022-01419-w
Muhammad Sohaib Khan, Choongho Lee, Sang Geon Kim

Metabolism of carbohydrates and lipids and protein degradation occurs in the liver and contributes to the body's homeostasis by secreting a variety of mediators. Any imbalance in this homeostasis due to excess fat consumption and the pathologic events accompanying lipotoxicity, autophagy dysregulation, endoplasmic reticulum stress, and insulin resistance may cause disturbances in the secretion of the proteins from the liver and their physiologic modifications and interactions with others. Since the liver secretome plays a role in the regulation of fuel metabolism and inflammation not only in the liver per se but also in other organs, the proteins belong to the utmost targets for treating metabolic and inflammatory diseases (e.g., COVID-19), depending on the available and feasible approaches to controlling their biological effects. However, in this era, we still come across new liver-derived proteins but are yet unable to entirely understand the pathologic basis underlying disease progression. This review aims to provide an updated overview of liver secretome biology with explanatory mechanisms with regard to the progression of metabolic and inflammatory liver diseases.

碳水化合物和脂质的代谢以及蛋白质的降解发生在肝脏中,并通过分泌多种介质来促进身体的内稳态。由于过量脂肪消耗和伴随脂肪毒性、自噬失调、内质网应激和胰岛素抵抗的病理事件而导致的任何体内平衡失衡,都可能导致肝脏蛋白质分泌紊乱,以及它们的生理改变和相互作用。由于肝脏分泌组不仅在肝脏本身,而且在其他器官中都起着调节燃料代谢和炎症的作用,因此这些蛋白质属于治疗代谢性和炎症性疾病(例如COVID-19)的最大靶点,这取决于控制其生物效应的可用和可行方法。然而,在这个时代,我们仍然发现了新的肝源性蛋白质,但仍无法完全了解疾病进展的病理基础。本文综述了肝脏分泌组生物学的最新进展,以及代谢和炎症性肝病进展的解释机制。
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引用次数: 3
Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms 2019冠状病毒病神经系统疾病:植物和微生物天然产物应用的见解
IF 6.7 3区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2022-11-28 DOI: 10.1007/s12272-022-01420-3
Faezeh Almasi, Wen Dang, Fatemeh Mohammadipanah, Ning Li

In addition to the typical respiratory manifestations, various disorders including involvement of the nerve system have been detected in COVID-19 ranging from 22 to 36%. Although growing records are focusing on neurological aspects of COVID-19, the pathophysiological mechanisms and related therapeutic methods remain obscure. Considering the increased concerns of SARS-CoV-2 potential for more serious neuroinvasion conditions, the present review attempts to focus on the neuroprotective effects of natural compounds as the principle source of therapeutics inhibiting multiple steps of the SARS-CoV-2 infection cycle. The great majority of the natural products with anti-SARS-CoV-2 activity mainly inhibit the attachment, entry and gene expression rather than the replication, assembly, or release. Although microbial-derived natural products comprise 38.5% of the known natural products with neuroprotective effects following viral infection, the neuroprotective potential of the majority of microorganisms is still undiscovered. Among natural products, chrysin, huperzine A, ginsenoside Rg1, pterostilbene, and terrein have shown potent in vitro neuroprotective activity and can be promising for new or repurpose drugs for neurological complications of SARS-CoV-2.

除了典型的呼吸系统表现外,在COVID-19中还发现了包括神经系统受累在内的各种疾病,比例从22%到36%不等。尽管越来越多的记录集中在COVID-19的神经方面,但病理生理机制和相关治疗方法仍然不清楚。考虑到人们越来越关注SARS-CoV-2可能导致更严重的神经侵袭疾病,本综述试图将重点放在天然化合物作为抑制SARS-CoV-2感染周期多个步骤的治疗药物的主要来源的神经保护作用上。绝大多数具有抗sars - cov -2活性的天然产物主要抑制附着、进入和基因表达,而不是抑制复制、组装或释放。尽管微生物衍生的天然产物占已知的病毒感染后具有神经保护作用的天然产物的38.5%,但大多数微生物的神经保护潜力仍未被发现。在天然产物中,大黄素、石杉碱A、人参皂苷Rg1、紫菀芪和人参素已显示出有效的体外神经保护活性,有望成为治疗SARS-CoV-2神经系统并发症的新药物或再用途药物。
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引用次数: 2
Effects of phytoestrogens on reproductive organ health 植物雌激素对生殖器官健康的影响
IF 6.7 3区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2022-11-28 DOI: 10.1007/s12272-022-01417-y
S. Swathi Krishna, Beena Briget Kuriakose, P. K. Lakshmi

Phytoestrogens are non-steroidal, polyphenolic compounds that are derived from plants and have biological properties similar to those of human estrogens. Their bioactivity, which is based on the core ring system, is caused by their structural resemblance to estrogen. Flavonoids, coumestans, lignans, and stilbenes are the four major categories into which they can be divided. They are structurally and functionally related to ovarian and placental estrogens, which are essential in female reproductive processes. Phytoestrogens are present in numerous dietary supplements and find application in hormone replacement therapy as an alternative to synthetic hormones. In addition, they provide health benefits for osteoporosis, heart disease, breast cancer, and prostate cancer. There is a growing interest in using phytoestrogen as preventative medicine in the form of nutraceuticals. This literature provides comprehensive information about the types, sources, and biological actions of phytoestrogens in the reproductive system.

植物雌激素是从植物中提取的非甾体多酚类化合物,具有与人类雌激素相似的生物学特性。它们的生物活性基于核心环系统,是由它们与雌激素的结构相似性引起的。类黄酮、库米斯坦、木脂素和二苯乙烯是它们可以分为的四大类。它们在结构和功能上与卵巢和胎盘雌激素相关,而卵巢和胎盘雌激素在女性生殖过程中是必不可少的。植物雌激素存在于许多膳食补充剂中,并作为合成激素的替代品在激素替代疗法中得到应用。此外,它们对骨质疏松症、心脏病、乳腺癌和前列腺癌都有健康益处。人们对使用植物雌激素作为营养保健品的预防药物越来越感兴趣。这篇文献提供了关于植物雌激素在生殖系统中的类型、来源和生物作用的全面信息。
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引用次数: 8
Scope and challenges of nanoparticle-based mRNA delivery in cancer treatment 基于纳米颗粒的mRNA递送在癌症治疗中的范围和挑战
IF 6.7 3区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2022-11-24 DOI: 10.1007/s12272-022-01418-x
Md. Emranul Karim, Sheikh Tanzina Haque, Hamed Al-Busaidi, Athirah Bakhtiar, Kyi Kyi Tha, Mark M. Banaszak Holl, Ezharul Hoque Chowdhury

Messenger RNA (mRNA) recently emerged as an appealing alternative to treat and prevent diseases ranging from cancer and Alzheimer’s disease to COVID-19 with significant clinical outputs. The in vitro-transcribed mRNA has been engineered to mimic the structure of natural mRNA for vaccination, cancer immunotherapy and protein replacement therapy. In past decades, significant progress has been noticed in unveiling the molecular pathways of mRNA, controlling its translatability and stability, and its evolutionary defense mechanism. However, numerous unsolved structural, biological, and technical difficulties hamper the successful implementation of systemic delivery of mRNA for safer human consumption. Advances in designing and manufacturing mRNA and selecting innovative delivery vehicles are mandatory to address the unresolved issues and achieve the full potential of mRNA drugs. Despite the substantial efforts made to improve the intracellular delivery of mRNA drugs, challenges associated with diverse applications in different routes still exist. This study examines the current progress of mRNA therapeutics and advancements in designing biomaterials and delivery strategies, the existing translational challenges of clinical tractability and the prospects of overcoming any challenges related to mRNA.

信使RNA (mRNA)最近成为治疗和预防从癌症、阿尔茨海默病到COVID-19等疾病的一种有吸引力的替代方案,并取得了显著的临床成果。体外转录的mRNA已被改造成模拟天然mRNA的结构,用于疫苗接种、癌症免疫治疗和蛋白质替代治疗。近几十年来,在揭示mRNA的分子通路、控制其可译性和稳定性、及其进化防御机制等方面取得了重大进展。然而,许多未解决的结构、生物学和技术难题阻碍了mRNA系统递送的成功实施,从而使人类更安全地食用。设计和制造mRNA以及选择创新的递送工具的进展是解决未解决问题和充分发挥mRNA药物潜力的必要条件。尽管在改善mRNA药物的细胞内递送方面做出了大量努力,但不同途径的不同应用仍然存在挑战。本研究探讨了mRNA治疗学的最新进展、设计生物材料和递送策略的进展、临床可处理性的现有转化挑战以及克服任何与mRNA相关的挑战的前景。
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引用次数: 8
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Archives of Pharmacal Research
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