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Levistolide A and periplogenin inhibit the growth of gastric cancer cells in vitro and in vivo 列维stolide A和periplogenin对胃癌细胞生长有体外和体内抑制作用
Pub Date : 2023-03-30 DOI: 10.37349/eds.2023.00006
Jiaqian Guo, Hongshang Hu, S. Lee, Ji Zhong Zhao
Aim: In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, more critically, in vivo, alone or in combination with the therapeutic medication 5-fluorouracil (5-FU).Methods: Methyl thiazolyl tetrazolium (MTT), also known as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were used for the cell viability study. Apoptosis was detected by western blot to detect the cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assays. The nude mice bearing gastric cancer cells were used for the anti-cancer activity detection of LA and its combinational treatment effect with 5-FU.Results: The results in the present study shown that the two compounds were able to inhibit the viability of the cancer cells in a dose- and time-dependent manner by MTT method. They could trigger apoptosis when used alone, and more potently, in combination with 5-FU detected by TUNEL positivity and the cleavage of caspase substrate PARP. In nude mice bearing gastric cancer cells, injection (i.p.) of LA or PPG alone inhibited the growth of the cancer cells. The treatment using one of the compounds in combination with 5-FU inhibited the cancer cell growth at a higher level than the treatment by a compound alone.Conclusions: LA and PPG could inhibit the growth of the cancer cells, alone or in combination with 5-FU, in vitro and in vivo, suggesting that they are promising investigational drugs for therapeutic development.
目的:研究天然产物列维斯托利特A (LA)和periplogenin (PPG)对胃癌细胞生长的体外抑制作用,更重要的是,在体内,单独或与治疗药物5-氟尿嘧啶(5-FU)联合使用。方法:采用甲基噻唑四唑(MTT),也称为3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑进行细胞活力研究。western blot检测caspase底物聚(adp -核糖)聚合酶(PARP)裂解和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸(dUTP)镍端标记(TUNEL)检测细胞凋亡。以胃癌裸鼠为实验对象,检测LA的抗癌活性及其与5-FU的联合治疗效果。结果:MTT法测定两种化合物对肿瘤细胞的抑制作用呈剂量依赖性和时间依赖性。它们单独使用时可以触发细胞凋亡,而与5-FU联合使用时则更有效,通过TUNEL阳性检测和caspase底物PARP的裂解。在携带胃癌细胞的裸鼠中,单独注射LA或PPG均能抑制癌细胞的生长。其中一种化合物与5-FU联合使用的治疗比单独使用一种化合物的治疗更能抑制癌细胞的生长。结论:LA和PPG在体外和体内均可单独或与5-FU联合抑制癌细胞的生长,提示它们是有前景的治疗开发的研究药物。
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引用次数: 0
Essential functions, syntheses and detection of sialyl Lewis X on glycoproteins 唾液酸Lewis X对糖蛋白的基本功能、合成及检测
Pub Date : 2023-02-28 DOI: 10.37349/eds.2023.00004
Qiu-Chen Chen, Han Liu, Xuechen Li
It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX.
普遍认为,sialyl Lewis X (sLeX)通常附着在细胞表面,其组成和链接为n -乙酰神经氨酸(Neu5Ac) α2-3 -半乳糖(Gal) β1-4 [focal (Fuc) α1-3] n -乙酰氨基葡萄糖。它是糖蛋白或糖脂的末端结构,已被证明与多种生物过程有关,如受精和选择素结合。由于sLeX的重要作用,它的合成及其测定方法引起了许多研究者的广泛关注。本文就糖蛋白的sLeX进行综述。首先介绍sLeX在受精发育、免疫、癌症等方面的生物学意义。然后介绍了sLeX的化学和酶合成,包括超过15个国际研究小组的贡献,然后简要介绍了sLeX的检测,重点是单糖和键。这篇综述对那些对sLeX的化学和生物学感兴趣的读者很有价值。
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引用次数: 1
Surface functionalized mesoporous polydopamine nanocomposites for killing tumor cells through collaborative chemo/photothermal/chemodynamic treatment 表面功能化介孔聚多巴胺纳米复合材料通过协同化疗/光热/化学动力学治疗杀死肿瘤细胞
Pub Date : 2023-02-27 DOI: 10.37349/eds.2023.00003
Yi Ouyang, Yan Chen, Ting Xu, Yi Sun, Shenghe Zhao, Chunmei Chen, Yixin Tan, Liang He, Hui Liu
Aim: The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells.Methods: MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO2) coating to construct MPDA-CPT-MnO2 nanocomposites.Results: When uptaken by tumor cells, the nanocomposites can degrade to produce O2, release CPT, and generate manganese (Mn2+) under the stimulation of hydrogen peroxide (H2O2) and acid. The released CPT and Mn2+ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn2+-mediated Fenton-like reaction. After that, the generated Mn4+ can react with glutathione (GSH) through redox reaction to produce Mn2+ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS.Conclusions: The developed MPDA-CPT-MnO2 nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).
目的:开发一种提高疗效的协同策略,在肿瘤治疗中具有很大的前景。本研究旨在开发一种基于功能化介孔聚多巴胺(MPDA)纳米复合材料的杀伤肿瘤细胞的有效协同策略。方法:采用喜树碱(CPT)包覆和二氧化锰(MnO2)包覆制备MPDA-CPT-MnO2纳米复合材料。结果:纳米复合材料被肿瘤细胞摄取后,在过氧化氢(H2O2)和酸的刺激下,可以降解生成O2,释放CPT,生成锰(Mn2+)。释放的CPT和Mn2+可分别作为化疗药物和fenton样药物。4T1肿瘤细胞通过Mn2+介导的fenton样反应产生丰富的活性氧(ROS)。之后,生成的Mn4+与谷胱甘肽(GSH)通过氧化还原反应生成Mn2+,消耗GSH,破坏肿瘤细胞的还原能力,有利于ROS的产生。在激光照射下,纳米复合材料可以产生热疗,促进ROS的产生。结论:制备的MPDA-CPT-MnO2纳米复合材料可通过协同化疗/光热/化学动力治疗(CDT)杀死肿瘤细胞。
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引用次数: 0
Convenient estimation of oxytetracycline and polymyxin B by a novel high-performance liquid chromatography method: development and validation 新型高效液相色谱法测定土霉素和多粘菌素B的方法:建立与验证
Pub Date : 2023-02-24 DOI: 10.37349/eds.2023.00002
T. Chaudhary, Kurmi Balak Das, Dilpreet K Singh
Aim: The aim of this research work was to develop a validated reversed-phase (RP)-high-performance liquid chromatography (HPLC) method for simultaneous estimation of oxytetracycline (OXY) and polymixin B (PMB) in fixed-dose combination.Methods: The HPLC assay method was validated on X-Bridge C18 [250 mm × 4.6 mm intradermal (i.d.), 5 μm], mobile phase consisting of aotearoa co-incidence network (ACN):water containing 0.5% (v/v) orthophosphoric acid (pH 3.5) in the ratio of 80:20 respectively. The flow rate was set at 0.9 mL/min and the column was maintained at room temperature. The RP-HPLC method was validated in terms of the calibration curve (CC), linearity and range, limit of detection (LOD), and limit of quantitation (LOQ), precision, robustness, and accuracy.Results: The method was found to be linear with a concentration range of 5–25 µg/mL. Precision results showed the developed method was found to be precise with a relative standard deviation [RSD (%)] value < 2. Accuracy showed acceptable recovery of prepared concentrations as per intracerebral hemorrhage (ICH) guidelines. Moreover, the developed method was found to be robust and rugged, as per specified ranges. The assay of these two drugs in marketed formulation, i.e., Terramycin® Ointment showed satisfactory recovery, as per ICH guidelines. The results proved that the method can be used for the routine-based estimation of OXY and PMB.Conclusions: Linear CC were obtained with a correlation coefficient (R2 > 0.99) with acceptable results of accuracy and precision.
目的:建立一种有效的反相高效液相色谱法同时测定固定剂量组合中土霉素(OXY)和多霉素B (PMB)含量的方法。方法:采用X-Bridge C18 [250 mm × 4.6 mm皮内(i.d), 5 μm]高效液相色谱法,流动相为aoteoa共入射网络(ACN):含0.5% (v/v)正磷酸(pH 3.5)的水,比例为80:20。流速设置为0.9 mL/min,色谱柱在室温下保持。从校准曲线(CC)、线性范围、检出限(LOD)和定量限(LOQ)、精密度、鲁棒性和准确性等方面对RP-HPLC法进行了验证。结果:该方法在5 ~ 25µg/mL浓度范围内呈线性关系。精密度结果表明,该方法精密度高,相对标准偏差(RSD(%)) < 2。准确度显示,根据脑出血(ICH)指南,制备浓度的恢复是可以接受的。此外,在所规定的范围内,所开发的方法具有鲁棒性和坚固性。根据ICH指南,对这两种已上市制剂(即土霉素软膏)的检测显示回收率令人满意。结果表明,该方法可用于基于常规的氧和PMB估计。结论:获得线性CC,相关系数(R2 > 0.99),准确度和精密度可接受。
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引用次数: 0
Focused ultrasound for treatment of peripheral brain tumors. 聚焦超声治疗外周脑肿瘤。
Pub Date : 2023-01-01 Epub Date: 2023-04-28 DOI: 10.37349/eds.2023.00009
Phillip Mitchell Johansen, Payton Yerke Hansen, Ali A Mohamed, Sarah J Girshfeld, Marc Feldmann, Brandon Lucke-Wold

Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) tumors are classically treated with surgical resection and radiotherapy in addition to adjuvant chemotherapy. However, the therapeutic efficacy of chemotherapeutic agents is limited due to the blood-brain barrier (BBB). Magnetic resonance guided focused ultrasound (MRgFUS) is a new and promising intervention for CNS tumors, which has shown success in preclinical trials. High-intensity focused ultrasound (HIFU) has the capacity to serve as a direct therapeutic agent in the form of thermoablation and mechanical destruction of the tumor. Low-intensity focused ultrasound (LIFU) has been shown to disrupt the BBB and enhance the uptake of therapeutic agents in the brain and CNS. The authors present a review of MRgFUS in the treatment of CNS tumors. This treatment method has shown promising results in preclinical trials including minimal adverse effects, increased infiltration of the therapeutic agents into the CNS, decreased tumor progression, and improved survival rates.

恶性脑肿瘤是儿童癌症相关死亡的主要原因,也是所有人群发病和死亡的重要原因。中枢神经系统(CNS)肿瘤的传统治疗方法是手术切除和放射治疗,以及辅助化疗。然而,由于血脑屏障(BBB)的影响,化疗药物的疗效有限。磁共振引导聚焦超声(MRgFUS)是一种治疗中枢神经系统肿瘤的新型、有前景的干预方法,已在临床前试验中取得成功。高强度聚焦超声(HIFU)能够以热消融和机械破坏肿瘤的形式直接治疗肿瘤。低强度聚焦超声(LIFU)已被证明能破坏BBB,提高大脑和中枢神经系统对治疗药物的吸收。作者回顾了 MRgFUS 在中枢神经系统肿瘤治疗中的应用。这种治疗方法在临床前试验中显示出良好的效果,包括不良反应极小、中枢神经系统对治疗药物的浸润增加、肿瘤进展减少以及生存率提高。
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引用次数: 0
The protective role of GLP-1 in neuro-ophthalmology. GLP-1 在神经眼科中的保护作用。
Pub Date : 2023-01-01 Epub Date: 2023-08-28 DOI: 10.37349/eds.2023.00015
Sohum Sheth, Aashay Patel, Marco Foreman, Mohammed Mumtaz, Akshay Reddy, Ramy Sharaf, Siddharth Sheth, Brandon Lucke-Wold

Despite recent advancements in the field of neuro-ophthalmology, the rising rates of neurological and ophthalmological conditions, mismatches between supply and demand of clinicians, and an aging population underscore the urgent need to explore new therapeutic approaches within the field. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), traditionally used in the treatment of type 2 diabetes, are becoming increasingly appreciated for their diverse applications. Recently, GLP-1RAs have been approved for the treatment of obesity and recognized for their cardioprotective effects. Emerging evidence indicates some GLP-1RAs can cross the blood-brain barrier and may have neuroprotective effects. Therefore, this article aims to review the literature on the neurologic and neuro-ophthalmic role of glucagon-like peptide 1 (GLP-1). This article describes GLP-1 peptide characteristics and the mechanisms mediating its known role in increasing insulin, decreasing glucagon, delaying gastric emptying, and promoting satiety. This article identifies the sources and targets of GLP-1 in the brain and review the mechanisms which mediate its neuroprotective effects, as well as implications for Alzheimer's disease (AD) and Parkinson's disease (PD). Furthermore, the preclinical works which unravel the effects of GLP-1 in ocular dynamics and the preclinical literature regarding GLP-1RA use in the management of several neuro-ophthalmic conditions, including diabetic retinopathy (DR), glaucoma, and idiopathic intracranial hypertension (IIH) are discussed.

尽管神经眼科领域近年来取得了长足的进步,但神经和眼科疾病的发病率不断上升、临床医生供需不匹配以及人口老龄化等问题都凸显了在该领域探索新治疗方法的迫切性。传统上用于治疗 2 型糖尿病的胰高血糖素样肽 1 受体激动剂(GLP-1RAs)因其用途广泛而日益受到重视。最近,GLP-1RAs 已被批准用于治疗肥胖症,其保护心脏的作用也得到了认可。新的证据表明,一些 GLP-1RAs 可以穿过血脑屏障,并可能具有神经保护作用。因此,本文旨在回顾有关胰高血糖素样肽 1(GLP-1)在神经和神经眼科方面作用的文献。本文介绍了 GLP-1 肽的特点及其在增加胰岛素、降低胰高血糖素、延迟胃排空和促进饱腹感方面的已知作用机制。本文确定了 GLP-1 在大脑中的来源和靶点,回顾了介导其神经保护作用的机制,以及对阿尔茨海默病(AD)和帕金森病(PD)的影响。此外,文章还讨论了揭示 GLP-1 对眼部动力学影响的临床前研究,以及有关 GLP-1RA 用于治疗糖尿病视网膜病变 (DR)、青光眼和特发性颅内高压 (IIH) 等几种神经眼科疾病的临床前文献。
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引用次数: 0
Utilizing the Ethereum blockchain for retrieving and archiving augmented reality surgical navigation data. 利用以太坊区块链检索和存档增强现实手术导航数据。
Pub Date : 2023-01-01 Epub Date: 2023-02-28 DOI: 10.37349/eds.2023.00005
Sai Batchu, Michael J Diaz, Lauren Ladehoff, Kevin Root, Brandon Lucke-Wold

Aim: Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author's best knowledge, the present study represents a first-use case of the Interplanetary File Storage protocol for storing and retrieving spine imaging smart contracts.

Methods: The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected.

Results: It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records.

Conclusions: The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

目的:脊柱成像数据共享和存档的传统技术引发了信任和安全问题,人们更多地考虑采用新型方法。以太坊智能合约就是这样一种新方法。以太坊是一个允许使用智能合约的开源平台。智能合约是自动执行的代码包,存在于以太坊状态中,定义了程序化交易的条件。智能合约虽然功能强大,但在展示此类技术的临床实用性方面,尤其是在术前和术后成像领域,所做的尝试还很有限。因此,我们在此提出一个概念验证智能合约,用于存储术中三维(3D)增强现实手术导航(ARSN)数据,并在一个私有的授权证明网络上进行测试。据作者所知,本研究是星际文件存储协议用于存储和检索脊柱成像智能合约的首个使用案例:方法:内容标识符哈希值存储在智能合约中,同时使用星际文件系统(IPFS)有效存储图像文件。插入是通过四个存储映射实现的,以下每个映射一个:虚构患者数据、特定诊断、患者身份证件(ID)和格茨贝恩等级。然后使用通配符对插入的患者观察结果进行查询。收集了不同记录量的插入和检索时间:插入 50 条记录需要 276 毫秒,插入 350 条记录需要 713 毫秒。插入 50 条记录需要 934 兆字节(MB)的内存,而插入 350 条记录几乎需要相同数量的内存。在有 350 条记录的数据库中,检索功能需要约 1,026 MB 的内存来查询一条三个字段都留空的记录,而从有 50 条记录的数据库中获取相同的观察结果只需要 970 MB:本研究提出的概念体现了智能合约和链外数据存储在高效检索/插入 ARSN 数据方面的临床实用性。
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引用次数: 0
Drug discovery: a multifactorial ecosystem 药物发现:一个多因子生态系统
Pub Date : 2022-07-08 DOI: 10.37349/eds.2022.00001
Albericio Fernando
*Correspondence: Fernando Albericio, Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Westville, Durban 4000, South Africa; CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain. albericio@ub.edu; Albericio@ukzn.ac.za Academic Editor: Fernando Albericio, University of KwaZulu-Natal, South Africa; University of Barcelona, Spain Received: June 6, 2022 Accepted: June 10, 2022 Published: January 1, 2023
*通信:Fernando Albericio,肽科学实验室,夸祖鲁-纳塔尔大学化学与物理学院,威斯特维尔,德班4000,南非;西班牙巴塞罗那大学有机化学系生物工程、生物材料和纳米医学网络中心,西班牙巴塞罗那08028albericio@ub.edu;Albericio@ukzn.ac.za学术编辑:Fernando Albericio,夸祖鲁-纳塔尔大学,南非;接收日期:2022年6月6日接收日期:2022年6月10日发布日期:2023年1月1日
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引用次数: 0
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Exploration of drug science
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