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Fundamental Considerations of Targeted Drug Therapies for Breast Cancer 乳腺癌靶向药物治疗的基本考虑
Pub Date : 2023-10-08 DOI: 10.3390/futurepharmacol3040043
Ileana Castillo-Tobías, Lia Berlanga, Joan Poblano, María del C. Rodríguez-Salazar, Hilda Aguayo-Morales, Luis E. Cobos-Puc
Breast cancer is a complex disease for which pharmacological treatment does not guarantee success or cure. In addition, current pharmacological therapies induce unwanted side effects due to their lack of specificity or selectivity. Therefore, it is necessary to develop new therapeutic options to improve these aspects. Currently, phytochemicals with antineoplastic properties have been identified from a wide variety of plant sources, and new therapeutic options have been developed based on the conjugation of drugs with polymeric matrices, resulting in nanoparticles or hydrogels with improved properties. Some antineoplastic drugs have been conjugated with antibodies to improve their selectivity and specificity. One of the most important advances in the treatment of breast cancer has been the development of cyclin inhibitors and gene therapy. This review provides an overview of drugs derived from medicinal plants and polymeric matrices with high potential for use in the treatment of breast cancer. We also highlight the clinical evidence for the use of anti-HER2 monoclonal antibodies and cyclin inhibitors in breast cancer, as well as the advantages of using conjugated antibodies. Finally, we mention some considerations that should be taken into account in the search for new therapeutic agents from phytochemicals, polymers, antibodies, cyclin inhibitors, and gene therapy focused on the treatment of breast cancer.
乳腺癌是一种复杂的疾病,药物治疗不能保证成功或治愈。此外,目前的药物治疗由于缺乏特异性或选择性而引起不必要的副作用。因此,有必要开发新的治疗方案来改善这些方面。目前,具有抗肿瘤特性的植物化学物质已经从各种各样的植物来源中被鉴定出来,并且基于药物与聚合物基质的结合,已经开发出新的治疗选择,从而产生具有改进性能的纳米颗粒或水凝胶。一些抗肿瘤药物已与抗体偶联以提高其选择性和特异性。乳腺癌治疗中最重要的进展之一是细胞周期蛋白抑制剂和基因治疗的发展。本文综述了从药用植物和聚合物基质中提取的药物在乳腺癌治疗中的应用前景。我们还强调了在乳腺癌中使用抗her2单克隆抗体和细胞周期蛋白抑制剂的临床证据,以及使用偶联抗体的优势。最后,我们提到了在寻找新的治疗药物时应该考虑的一些因素,从植物化学物质、聚合物、抗体、细胞周期蛋白抑制剂和基因疗法中寻找新的治疗药物,重点是治疗乳腺癌。
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引用次数: 0
Antioxidant Potential and Known Secondary Metabolites of Rare or Underutilized Plants of Yucatan Region 尤卡坦地区稀有或未充分利用植物的抗氧化潜能和已知次生代谢物
Pub Date : 2023-10-07 DOI: 10.3390/futurepharmacol3040042
Jonatan Jafet Uuh-Narvaez, Maira Rubi Segura-Campos, Oksana Sytar
The screening of rare plants from the Yucatan region and the known native plants in Mexico, that have been successfully introduced worldwide, has been conducted. Based on a literature analysis and a search of English and Spanish scientific information regarding botanical, plant biochemical, and antioxidant potential in databases such as Google Scholar, Scopus, Web of Knowledge, as well as the national databases of Mexico (Flora: Yucatan Peninsula (cicy.mx) and Especies endémicas|Biodiversidad Mexicana), rare or underutilized plants from the Yucatan region with antioxidant potential have been selected. The formulas of the most studied secondary metabolites of these selected rare plants are shown. Among the selected rare plants with antioxidant potential, the families Sapidaceae and Anacardiaceae had the highest number of representatives. Additionally, representatives from the families Annonaceae, Moraceae, Malpighiaceae, Solanaceae, Ebenaceae, Asteraceae, Ranunculaceae, and Leguminosae were also presented. The current scientific data analysis of selected rare plants from the Yucatan region, Mexico, provides significant background for their further use and introduction in not only the Yucatan region of Mexico, but also worldwide.
对尤卡坦地区的珍稀植物和墨西哥已知的已成功引种到世界各地的本土植物进行了筛选。通过文献分析和检索谷歌Scholar、Scopus、Web of Knowledge等数据库以及墨西哥国家数据库(Flora: Yucatan Peninsula (city .mx)和Especies end micas|Biodiversidad Mexicana)中有关植物、植物生化和抗氧化潜力的英文和西班牙文科学信息,选择了尤卡坦地区具有抗氧化潜力的稀有或未被充分利用的植物。本文给出了这些稀有植物中研究最多的次生代谢物的分子式。在所选的具有抗氧化潜力的珍稀植物中,以皂荚科和桔梗科代表数量最多。此外,还介绍了番荔枝科、桑科、麻瓜科、茄科、豆科、菊科、毛茛科和豆科的代表。通过对墨西哥尤卡坦地区珍稀植物的科学数据分析,为其在墨西哥尤卡坦地区乃至世界范围内的进一步利用和引种提供了重要的背景资料。
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引用次数: 0
Moles of Molecules against Mycobacterium abscessus: A Review of Current Research 抗脓肿分枝杆菌分子的研究进展
Pub Date : 2023-09-11 DOI: 10.3390/futurepharmacol3030041
Mario Cocorullo, Christian Bettoni, Sara Foiadelli, Giovanni Stelitano
Mycobacterium abscessus is an emerging opportunistic pathogen that infects mainly the respiratory tract of individuals with pre-existing clinical pictures. In recent years, the incidence of infections of this microorganism has risen, in particular in patients with cystic fibrosis, leading to an exacerbation of their conditions. The actual therapeutic regimen has low efficacy and is extended for long periods since it is mainly based on a combination of repurposed drugs, generally from treatments of Mycobacterium tuberculosis infections. For this reason, it is necessary to develop new drugs or alternative strategies in order to improve the efficacy and shorten the time of treatments. This review aims to give an overview of drugs in the pre-clinical and clinical phases of evaluation against M. abscessus and the molecules that have been in development for the past five years in the early drug-discovery phase.
脓肿分枝杆菌是一种新兴的机会性病原体,主要感染已有临床症状的个体的呼吸道。近年来,这种微生物感染的发生率有所上升,特别是在囊性纤维化患者中,导致其病情恶化。实际的治疗方案疗效低,而且需要长时间延长,因为它主要是基于重新利用的药物组合,通常来自治疗结核分枝杆菌感染。因此,有必要开发新的药物或替代策略,以提高疗效,缩短治疗时间。本文综述了针对脓肿分枝杆菌临床前和临床评价阶段的药物,以及过去5年来在早期药物发现阶段开发的分子。
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引用次数: 0
Aurones as Antidiabetic Agents and Their Prebiotic Activities Aurones作为抗糖尿病药物及其益生元活性
Pub Date : 2023-09-07 DOI: 10.3390/futurepharmacol3030040
Reham M. Samra, Mohamed S. Darwish, Noha A. Abou-Zeid, E. Khojah, V. Imieje, A. Zaki
Cyperus conglomeratus has been utilized in traditional medicine as an emollient, diuretic, analgesic, anthelmintic, and for other diseases. Furthermore, several biological activities have been reported for the plant extract and the isolated metabolites. The chromatographic investigation of an ethyl acetate extract of the aerial parts led to the isolation of three aurone derivatives (1–3) from the plant for the first time. Their structures were identified as aureusidin (1), aureusidin-4-methyl ether (2), and 5-methyl aureusidin (3) using 1D and 2D NMR techniques, along with mass spectrometry. The compounds were tested for their inhibitory activities against enzymes vital in metabolic diseases, especially diabetes, such as α-amylase, α-glucosidase, and glycogen phosphorylase. The results were expressed as percentage inhibition. The inhibitory activity of aurones against the tested enzymes was also analyzed by computational docking studies to provide a rational explanation for the observed results. The tested compounds formed stable interactions in terms of hydrogen bonding and hydrophobic interaction with the active site residues of the tested enzymes, and the results are in agreement with those of the in vitro antidiabetic activity. The compounds were also evaluated for their ability to support the growth and viability of beneficial bacteria in terms of prebiotic activities using two species, Lacticaseibacillus paracasei and Lacticaseibacillus rhamnosus, through the determination of prebiotic activity scores (Pscore). The findings of this study showed that C. conglomeratus is a potential natural source of bioactive agents. There is, however, a need for in vivo testing to evaluate this plant’s efficacy for developing new drug entities in the future.
沙柏在传统医学中被用作润肤剂、利尿剂、镇痛剂、驱虫药和其他疾病。此外,一些生物活性的植物提取物和分离的代谢物已被报道。对其气相部位的乙酸乙酯提取物进行色谱分析,首次从该植物中分离到3个aurone衍生物(1-3)。它们的结构通过1D和2D NMR技术以及质谱鉴定为金黄色葡萄素(1)、金黄色葡萄素-4-甲基醚(2)和5-甲基金黄色葡萄素(3)。这些化合物对代谢性疾病,特别是糖尿病中至关重要的酶,如α-淀粉酶、α-葡萄糖苷酶和糖原磷酸化酶的抑制活性进行了测试。结果以抑制率表示。通过计算对接研究分析了aurones对所测酶的抑制活性,为观察结果提供了合理的解释。所测化合物与所测酶活性位点残基在氢键和疏水相互作用方面形成稳定的相互作用,结果与体外抗糖尿病活性一致。通过测定益生元活性评分(Pscore),以副干酪乳杆菌(Lacticaseibacillus paracasei)和鼠李糖乳杆菌(lactoaseibacillus rhamnosus)两种益生元活性来评估化合物支持有益菌生长和活力的能力。本研究结果表明,沙棘是一种潜在的天然生物活性物质来源。然而,有必要在体内测试,以评估该植物的功效,为未来开发新的药物实体。
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引用次数: 1
Systemic Inflammasome Biomarkers as Predictors of Diabetic Retinopathy Progression: Evidence from a Pilot Study 系统性炎性体生物标志物作为糖尿病视网膜病变进展的预测因子:来自一项初步研究的证据
Pub Date : 2023-09-07 DOI: 10.3390/futurepharmacol3030039
C. Kuo, I. Rupenthal, Michael Booth, Rinki Murphy, Odunayo O. Mugisho
The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) inflammasome pathway is believed to mediate chronic inflammation in diabetic retinopathy (DR); however, its impact on the progression of DR remains to be elucidated. Therefore, the primary aim of this pilot study was to determine whether systemic inflammasome biomarkers interleukin (IL)-1β and IL-18 can be used to predict DR progression. DR screening results were analyzed against weight, level of glycated hemoglobin (HbA1c), and plasma levels of inflammasome biomarkers (IL-1β and IL-18), as well as general inflammation markers (C-reactive protein (CRP), IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF)) in patients with type 2 diabetes at baseline and 1 year post-bariatric surgery. Cross-sectional analysis demonstrated that weight, HbA1c, CRP, and IL-18 did not correlate with DR severity. The progressed group showed a higher relative change in IL-18 and CRP levels compared to the stable and regressed groups. Furthermore, relative changes in plasma CRP levels correlated with those of IL-18. Although further validation with larger cohorts is necessary, this pilot study supports the hypothesis that systemic inflammasome activation is associated with DR progression.
核苷酸结合寡聚化结构域(NOD)样受体(NLR)蛋白3 (NLRP3)炎症小体途径被认为介导糖尿病视网膜病变(DR)的慢性炎症;然而,其对DR进展的影响仍有待阐明。因此,本初步研究的主要目的是确定全身性炎性体生物标志物白介素(IL)-1β和IL-18是否可用于预测DR的进展。将DR筛查结果与2型糖尿病患者在基线和减肥手术后1年的体重、糖化血红蛋白(HbA1c)水平、血浆炎症小体生物标志物(IL-1β和IL-18)水平以及一般炎症标志物(c -反应蛋白(CRP)、IL-6、IL-8、肿瘤坏死因子α (TNF-α)和血管内皮生长因子(VEGF))进行分析。横断面分析显示体重、HbA1c、CRP和IL-18与DR严重程度无关。进展组与稳定组和进展组相比,IL-18和CRP水平的相对变化更高。此外,血浆CRP水平的相对变化与IL-18水平相关。虽然需要更大的队列进一步验证,但该初步研究支持全身性炎性体激活与DR进展相关的假设。
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引用次数: 0
Cyclodextrin in Vaccines: Enhancing Efficacy and Stability 环糊精在疫苗中的应用:增强效力和稳定性
Pub Date : 2023-08-24 DOI: 10.3390/futurepharmacol3030038
Gamze Varan
Cyclodextrins, a family of cyclic oligosaccharides, have received considerable interest in the field of pharmaceuticals due to their unique molecular structure and versatile properties. In the context of vaccines, cyclodextrins can effectively encapsulate antigens, ensuring their protection from degradation and improving their immunogenicity. Cyclodextrins offer stability advantages to vaccines by preventing the degradation of labile vaccine components during storage and transportation. Furthermore, cyclodextrins can serve as adjuvants, potentiating the immune response triggered by vaccines. Their unique structure and interaction with the immune system enhance the recognition of antigens by immune cells, leading to an improved activation of both innate and adaptive immune responses. This adjuvant effect contributes to the development of robust and long-lasting immune protection against targeted pathogens. Owing to the distinctive attributes inherent to nanoparticles, their integration into vaccine formulations has assumed an imperative role. Through the encapsulation of vaccine antigens/adjuvants within cyclodextrin nanoparticles, the potency and stability of vaccines can be notably enhanced. In particular, the capacity of amphiphilic cyclodextrins to form nanoparticles through self-assembly without surfactants or co-solvents is a captivating prospect for their application as carrier systems for antigens. In conclusion, cyclodextrins present a promising platform for enhancing the efficacy and stability of vaccines. Their ability to encapsulate antigens, stabilize labile vaccine components and act as adjuvants demonstrates their potential to revolutionize vaccine formulation and delivery. Further research and development in this field will facilitate the translation of cyclodextrin-based vaccine technologies into practical and impactful immunization strategies, ultimately benefiting global health and disease prevention.
环糊精是一类环低聚糖,由于其独特的分子结构和用途广泛,在制药领域引起了广泛的关注。在疫苗方面,环糊精可以有效地包裹抗原,确保其免受降解并提高其免疫原性。环糊精通过防止不稳定的疫苗成分在储存和运输过程中的降解,为疫苗提供了稳定性优势。此外,环糊精可以作为佐剂,增强疫苗引发的免疫反应。它们独特的结构和与免疫系统的相互作用增强了免疫细胞对抗原的识别,从而改善了先天和适应性免疫反应的激活。这种佐剂作用有助于对目标病原体产生强大而持久的免疫保护。由于纳米颗粒固有的独特属性,将其整合到疫苗配方中已经承担了必不可少的作用。通过将疫苗抗原/佐剂包封在环糊精纳米颗粒内,可以显著提高疫苗的效力和稳定性。特别是,两亲性环糊精在没有表面活性剂或共溶剂的情况下通过自组装形成纳米颗粒的能力是其作为抗原载体系统应用的一个迷人的前景。综上所述,环糊精为提高疫苗的有效性和稳定性提供了一个很有前景的平台。它们包封抗原、稳定不稳定的疫苗成分和充当佐剂的能力表明,它们有可能彻底改变疫苗配方和递送。这一领域的进一步研究和开发将有助于将基于环糊精的疫苗技术转化为实际和有效的免疫战略,最终有利于全球健康和疾病预防。
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引用次数: 0
Preferred Therapy for Patients with Hereditary Angioedema during Pregnancy 妊娠期遗传性血管性水肿患者的首选治疗方法
Pub Date : 2023-08-11 DOI: 10.3390/futurepharmacol3030037
K. Park, A. Yeich, T. Craig
Hereditary angioedema (HAE) is a rare, inherited disease caused by a deficiency (HAE-1) or lack of functional (HAE-2) C1 inhibitor protein. The symptoms present with mucocutaneous swelling of various organ systems, such as the respiratory and gastrointestinal systems, which can manifest as stridor and abdominal pain, respectively. HAE can present with increased frequency and severity of attacks during the pregnancy and lactation period. This is thought to be due to hormonal changes, which may trigger HAE attacks. The management of this condition in pregnant and lactating patients can be challenging for providers due to disease rarity and the lack of data regarding the management of this specific population. This review aims to provide insights for HAE management regarding rescue therapy, short-term prophylaxis, and long-term prophylaxis via the consolidation of the current literature and various international consensus guidelines. Furthermore, this review discusses when to initiate treatment and at what frequency and dosing, as well as the possible side effects that may occur as a result of therapy.
遗传性血管性水肿(HAE)是一种罕见的遗传性疾病,由缺乏(HAE-1)或缺乏功能性(HAE-2) C1抑制蛋白引起。症状表现为各种器官系统的皮肤粘膜肿胀,如呼吸系统和胃肠道系统,分别表现为喘鸣和腹痛。HAE在妊娠期和哺乳期发作的频率和严重程度增加。这被认为是由于激素的变化,这可能引发HAE发作。由于疾病罕见和缺乏有关这一特定人群管理的数据,孕妇和哺乳期患者的这种情况的管理对提供者来说可能是具有挑战性的。本综述旨在通过整合现有文献和各种国际共识指南,为HAE管理提供关于抢救治疗、短期预防和长期预防的见解。此外,本综述还讨论了何时开始治疗,以何种频率和剂量进行治疗,以及治疗可能产生的副作用。
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引用次数: 0
Correction: de Almeida et al. Acute Promyelocytic Leukemia (APL): A Review of the Classic and Emerging Target Therapies towards Molecular Heterogeneity. Future Pharmacol. 2023, 3, 162–179 更正:de Almeida等人。急性早幼粒细胞白血病(APL):经典和新兴靶向治疗分子异质性的综述。中国药理学杂志,2016,32 (3):662 - 669
Pub Date : 2023-08-04 DOI: 10.3390/futurepharmacol3030036
Tâmara Dauare de Almeida, F. Evangelista, A. Sabino
In the original publication [...]
在原出版物中[…]
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引用次数: 0
Design of a Cyclodextrin Bioproduction Process Using Bacillus pseudofirmus and Paenibacillus macerans 假硬芽孢杆菌和芽胞杆菌生产环糊精的工艺设计
Pub Date : 2023-07-11 DOI: 10.3390/futurepharmacol3030035
Alexandre Miguel Guedes, Tiago Filipe Santos Alves, P. Salústio, H. Cabral-Marques, M. Ribeiro
Cyclodextrin (CD) drug delivery systems offer the potential to enhance the desired physicochemical properties and pharmacokinetic parameters of drugs while maintaining their safety. Cyclodextrin-glucosyl-transferase (CGTase) is amongst the most important enzymes used in CD biosynthesis. However, the bioproduction of CDs still faces challenges in terms of optimization and process complexity. This study proposes a novel CD bioproduction system in a batch mode to increase yield and reduce costs. Two bacterial strains were selected: the alkalophilic Bacillus pseudofirmus DSM2517 strain and the neutrophilic Paenibacillus macerans DSM1574 strain. Three different culture media, two temperatures (30 °C and 37 °C), and three scales (shake flasks 20 mL and 100 mL, and bioreactor 3.2 L) were evaluated with respect to bacterial growth kinetics, protein production, and CGTase biosynthesis and activity for β-CD production. Bacterial growth was monitored by measuring optical density (OD600 nm), while CGTase activity was assessed by measuring β-CD production directly in the medium after filtration or in samples after concentration (using a Vivaspin 500® ultrafiltration spin column with a 10 kDa cut-off). β-CD quantification was performed using the phenolphthalein colorimetric method and HPLC. The best conditions for combined growth and protein production, for both microorganisms, in shake flasks were achieved with a medium containing 2% dextrin as the carbohydrate source. Scale-up to the bioreactor displayed improved growth kinetics for both bacteria and higher protein production and CGTase activity for Paenibacillus macerans.
环糊精(CD)给药系统提供了在保持药物安全性的同时增强药物所需的物理化学性质和药代动力学参数的潜力。环糊精-葡萄糖基转移酶(CGTase)是CD生物合成中最重要的酶之一。然而,CDs的生物生产仍然面临着优化和工艺复杂性方面的挑战。本研究提出了一种新的间歇式CD生物生产系统,以提高产量和降低成本。选择嗜碱性假硬芽孢杆菌DSM2517菌株和嗜中性嗜绿芽孢杆菌DSM1574菌株。研究了三种不同的培养基、两种温度(30°C和37°C)和三种天平(摇瓶20 mL和100 mL,生物反应器3.2 L)对细菌生长动力学、蛋白质产量、CGTase生物合成和β-CD生产活性的影响。通过测量光密度(OD600 nm)来监测细菌生长,而通过直接测量过滤后的培养基或浓缩后的样品(使用Vivaspin 500®超滤自旋柱,截止值为10 kDa)中β-CD的产生来评估CGTase活性。采用酚酞比色法和高效液相色谱法对β-CD进行定量。以含有2%糊精的培养基为碳水化合物源,在摇瓶中获得了两种微生物联合生长和蛋白质生产的最佳条件。放大后的生物反应器显示,细菌的生长动力学得到改善,蛋白质产量和CGTase活性均有所提高。
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引用次数: 0
Use of Plant Extracts, Bee-Derived Products, and Probiotic-Related Applications to Fight Multidrug-Resistant Pathogens in the Post-Antibiotic Era 后抗生素时代,植物提取物、蜜蜂衍生产品和益生菌在对抗多重耐药病原体中的应用
Pub Date : 2023-07-04 DOI: 10.3390/futurepharmacol3030034
André G. Machado, Lizbeth Zamora-Mendoza, F. Alexis, J. M. Álvarez-Suarez
The ‘post-antibiotic’ era is near according to the World Health Organization (WHO). It is well known, due to the work of the scientific community, that drugs (antibiotics, antifungals, and other antimicrobial agents) are continuously becoming less effective, and multidrug-resistant (MDR) pathogens are on the rise. This scenario raises concerns of an impending global infectious disease crisis, wherein a simple opportunistic infection could be deadly for humans. The war against MDR pathogens requires innovation and a multidisciplinary approach. The present study provides comprehensive coverage of relevant topics concerning new antimicrobial drugs; it suggests that a combination of different natural products (such as plant extracts, honey, propolis, prebiotics, probiotics, synbiotics, and postbiotics), together with drug therapy, could be used as an adjuvant in standard treatments, thus allowing drug sensitivity in MDR pathogens to be restored, host immunity to be enhanced, and clinical efficiency to be improved. Currently, new and relevant developments in genomics, transcriptomics, and proteomics are available for research, which could lead to the discovery of new antimicrobial drugs and a new generation of antibiotics and non-antibiotics. However, several areas concerning natural products and their combination with standard drugs remain unclear. In an effort to advance new therapies for humankind, these gaps in the literature need to be addressed.
据世界卫生组织(WHO)称,“后抗生素”时代即将来临。众所周知,由于科学界的工作,药物(抗生素、抗真菌药和其他抗菌剂)的效果不断下降,耐多药病原体正在上升。这种情况引起了人们对即将到来的全球传染病危机的担忧,其中简单的机会性感染可能对人类致命。与耐多药病原体的斗争需要创新和多学科方法。本研究全面涵盖了新型抗菌药物的相关课题;建议将不同天然产物(如植物提取物、蜂蜜、蜂胶、益生元、益生菌、合成菌、后生菌等)联合使用,配合药物治疗,作为标准治疗的辅助用药,从而恢复耐多药病原菌的药物敏感性,增强宿主免疫力,提高临床疗效。目前,基因组学、转录组学和蛋白质组学的最新相关进展可供研究,这可能导致新的抗菌药物和新一代抗生素和非抗生素的发现。然而,有关天然产物及其与标准药物的组合的几个领域仍不清楚。在努力推进人类新疗法的过程中,需要解决文献中的这些空白。
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引用次数: 0
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