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Drug discovery and development: A historical overview, current challenges and perspectives 药物发现与开发:历史回顾、当前挑战与展望
Pub Date : 2024-06-08 DOI: 10.28916/lsmb.8.1.2024.137
Chai Xin Yu, C. Tham
The evolution of drug discovery has proceeded for decades. The process has involved the invention of new theories, technologies, disciplines and medicines. These advancements play significant roles in drug discovery today as well as in the future. In this review, the important achievements of ancient Egyptian, Greek, Arabic, Indian, and Chinese medicines were discussed. Then, the development of key concepts, theories or technologies as well as breakthroughs in drug discovery research has been reviewed. Lastly, the current outlook and obstacles in drug discovery studies have been discussed in this article. This review provides an understanding of drug discovery research from a historical perspective and current contexts.
药物发现的演变已经持续了几十年。这一过程涉及新理论、新技术、新学科和新药物的发明。这些进步在当今和未来的药物发现中都发挥着重要作用。在这篇综述中,我们讨论了古埃及、古希腊、阿拉伯、印度和中国医药的重要成就。然后,回顾了药物发现研究中关键概念、理论或技术的发展以及突破。最后,本文讨论了当前药物发现研究的前景和障碍。这篇综述从历史的角度和当前的背景介绍了药物发现研究。
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引用次数: 0
Antihyperlipidemic, hepatoprotective and nephroprotective effects of functional beverages containing soybean (Glycine max L.), sweet potato leaves (Ipomoea batatas L.) and red yeast rice on a high fat diet-induced hyperlipidemia rats 含大豆(Glycine max L.)、甘薯叶(Ipomoea batatas L.)和红麴的功能饮料对高脂饮食诱导的高脂血症大鼠的降血脂、保肝和保肾作用
Pub Date : 2024-04-09 DOI: 10.28916/lsmb.8.1.2024.134
Nurkhasanah Mahfudh, Atika Orchida Sari, Iradatul Ikhtiari, N. Sulistyani, I. D. Kumalasari, Fezah Othman
One of the primary risk factors for hyperlipidemia is an excessively high-fat diet. Due to their phytochemical composition and biological activity, red yeast rice (RYR), sweet potato (Ipomoea batatas L.) leaves and soybeans (Glycine max L.) are known to possess antihyperlipidemia and antioxidants effects. The purpose of this study is to ascertain how beverages containing soybeans, sweet potato leaves, and red yeast rice affect rats fed a high-fat diet in terms of hyperlipidemia, liver damage, and kidney damage. Five groups of rats were used: normal control, positive control using Commercial Smoothie Drink 1 (CSD1), 3.6 ml/day, negative control, and treatment groups receiving beverage doses of 1250 mg/kg and 2500 mg/kg respectively. Following the induction of the high-fat diet in the animals, functional beverage treatment was administered for 14 days starting on day 15 for a total of 28 days. The findings demonstrated that in rats fed a high-fat diet, the administration of functional beverages at a dose of 2500 mg/kg significantly (p<0.05) decreased serum levels of cholesterol, triglyceride, creatinine, blood urea nitrogen, serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT). It is concluded that functional beverages may offer protection against hyperlipidemia, liver, and kidney damage caused by a high-fat diet.
高脂血症的主要风险因素之一是过高的脂肪饮食。红麴(RYR)、甘薯(Ipomoea batatas L.)叶和大豆(Glycine max L.)因其植物化学成分和生物活性而具有抗高脂血症和抗氧化作用。本研究旨在确定含有大豆、甘薯叶和红麴的饮料对高脂饮食大鼠的高脂血症、肝损伤和肾损伤有何影响。研究使用了五组大鼠:正常对照组、使用商业冰沙饮料 1(CSD1)(3.6 毫升/天)的阳性对照组、阴性对照组以及分别接受 1250 毫克/千克和 2500 毫克/千克饮料剂量的治疗组。在诱导动物摄入高脂肪饮食后,从第 15 天开始连续 14 天服用功能饮料,共计 28 天。研究结果表明,在喂食高脂肪饮食的大鼠中,2500 毫克/千克剂量的功能饮料可显著降低血清中胆固醇、甘油三酯、肌酐、血尿素氮、血清谷氨酸丙酮酸转氨酶(SGPT)和血清谷氨酸草酰乙酸转氨酶(SGOT)的水平(p<0.05)。结论是,功能饮料可防止高脂饮食引起的高脂血症、肝脏和肾脏损伤。
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引用次数: 0
4th International Conference on Forensic Sciences, Forensic Medicine and Criminology 2023 (INFOMEC 4.0) 第四届 2023 年法医学和犯罪学国际会议(INFOMEC 4.0)
Pub Date : 2024-04-03 DOI: 10.28916/lsmb.8.1.2024.135
Muhammad Jefri Mohd Yusof, Nurul’Ain Abu Bakar, N. Zainol Abidin, Ke Xin Yu, Chin Shiang Kue, Noor Faradilla Abdullah, Sureshkumar Sampath Rajan
The INFOMEC 2023 organized by the Management and Science University (MSU) is proud to celebrate the 4th anniversary of the International Conference on Forensic Science, Forensic Medicine, and Criminology. This is a premier gathering of experts from around the world who will be sharing their knowledge and expertise, exchange ideas, and discuss the latest advancements and techniques in the field. The conference features a diverse range of topics related to forensic science, forensic medicine, and criminology, including forensic pathology, forensic toxicology, forensic DNA analysis, crime scene investigation, forensic psychology, and criminal profiling, among others. Participants will have the opportunity to attend keynote presentations, poster sessions, and network with colleagues and peers from academia, government, and industry. The conference is an excellent platform for researchers, practitioners, and students to present their research findings and gain valuable feedback from experts in the field. Overall, the International Conference on Forensic Science, Forensic Medicine, and Criminology is an essential event for anyone involved in the fields of forensic science, forensic medicine, and criminology, providing an opportunity to stay up-to-date with the latest trends and developments, and contribute to the advancement of the field.
由管理科学大学(MSU)主办的国际法医学、法医学和犯罪学会议(INFOMEC 2023)将迎来四周年纪念。来自世界各地的专家将汇聚一堂,分享他们的知识和专长,交流思想,讨论该领域的最新进展和技术。会议主题涉及法医学、法医学和犯罪学,包括法医病理学、法医毒理学、法医 DNA 分析、犯罪现场调查、法医心理学和犯罪特征分析等。与会者将有机会参加主题演讲、海报展示,并与来自学术界、政府和行业的同事和同行进行交流。会议为研究人员、从业人员和学生提供了一个绝佳的平台,让他们可以展示自己的研究成果,并从该领域的专家那里获得宝贵的反馈意见。总之,法医学、法医学和犯罪学国际会议对于法医学、法医学和犯罪学领域的从业人员来说是一次不可或缺的盛会,为他们提供了一个了解最新趋势和发展的机会,并为该领域的进步做出贡献。
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引用次数: 0
Diagnostic pitfalls in neonatal hypertyrosinemia: a case report 新生儿高酪氨酸血症的诊断误区:病例报告
Pub Date : 2023-12-28 DOI: 10.28916/lsmb.7.1.2023.139
K. Khalid, Mohd Fazrul Shafiq Kamarudzaman, Siti Nurwani Ahmad Ridzuan, Nurul Izzati Hamzan, Norzahidah Khalid, Noor Hafizah Hassan
Hypertyrosinemia results from abnormality in tyrosine metabolism. Acquired hypertyrosinemia is notably more common than inherited types and typically presents with profile suggestive of secondary aetiology on biochemical testing. Herein, we present an unusual case of a day 16-of-life baby girl who was screened for inborn errors of metabolism (IEM). She presented with jaundice, hypotonia, lethargy and had hepatomegaly on examination. She was treated for sepsis with multiorgan involvement, requiring escalation of intravenous antibiotics and assisted ventilation. Her dried blood spot (DBS) showed moderate elevation of tyrosine (408umol/L, N:10-182) with low Phe:Tyr ratio (0.15mmol/L, N:0.32-3.45). Plasma amino acid showed isolated hypertyrosinemia at 807mmol/L (N:5-167) with mild, non-significant elevations of other liver metabolites. No succinylacetone peak seen with urine organic acids, making the diagnosis of inherited Tyrosinemia type I less likely despite the characteristic findings from DBS, plasma amino acids, and presenting clinical signs. Repeated IEM screening two weeks later revealed a non-diagnostic profile across both DBS and plasma amino acids in light of resolving sepsis and clinical improvement. This case highlights the challenges associated with incompatible biochemical testing in a child with a high index of suspicion for inherited Tyrosinemia. In our case, repeated screening ruled out inherited Tyrosinemia, suggesting the initial picture of hypertyrosinemia to be likely due to liver dysfunction and impaired activity of liver enzymes that are responsible for tyrosine catabolism.
高酪氨酸血症源于酪氨酸代谢异常。获得性高酪氨酸血症比遗传性高酪氨酸血症更为常见,通常在生化检测中表现为继发性病因。在此,我们介绍一例不寻常的病例,一名出生 16 天的女婴被筛查出患有先天性代谢异常(IEM)。她出现黄疸、肌张力低下、嗜睡,检查时发现肝脏肿大。她因多器官受累的败血症接受治疗,需要加强静脉注射抗生素和辅助通气。她的干血斑(DBS)显示酪氨酸中度升高(408umol/L,N:10-182),Phe:Tyr比值较低(0.15mmol/L,N:0.32-3.45)。血浆氨基酸显示为 807 毫摩尔/升(N:5-167)的孤立高酪氨酸血症,其他肝脏代谢物轻度升高,但不明显。尿液有机酸中未见琥珀酰丙酮峰值,尽管 DBS、血浆氨基酸和临床表现均有特征性结果,但遗传性酪氨酸血症 I 型的诊断可能性较低。两周后再次进行 IEM 筛查,发现 DBS 和血浆氨基酸均无诊断结果,而败血症已缓解,临床症状也有所改善。本病例强调了对遗传性酪氨酸血症高度怀疑的患儿进行不相容生化检测所面临的挑战。在我们的病例中,反复筛查排除了遗传性酪氨酸血症,提示最初的高酪氨酸血症可能是由于肝功能异常和负责酪氨酸分解代谢的肝酶活性受损所致。
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引用次数: 0
Ellagic acid, a polyphenolic compound synergistically interacts with concanamycin A, an inhibitor of Plasmodium falciparum proton pump 鞣花酸是一种多酚类化合物,它与恶性疟原虫质子泵抑制剂康卡西霉素 A 有协同作用
Pub Date : 2023-12-26 DOI: 10.28916/lsmb.7.1.2023.116
Noor Fardziatun Ujal, Nurul Izzaty Najwa Zahari, N. Abu-Bakar
Ellagic acid is a bioactive phenolic constituent of many plants. Our previous study reported that ellagic acid alkalinised the Plasmodium falciparum digestive vacuole similarly to concanamycin A, a specific inhibitor of V-type H+-ATPase located on the membrane of the malaria parasite’s digestive vacuole. Therefore, this study aimed to determine the interaction of ellagic acid with concanamycin A by using the isobologram analysis of effects on parasite growth. A malarial SBYR Green I fluorescence-based (MSF) assay was conducted prior to the isobologram analysis to determine the antimalarial activity (IC50) of ellagic acid and concanamycin A. Six different combination solutions of the drugs were assigned based on their IC50 values and used in the isobologram analysis. The IC50 of ellagic acid and concanamycin A was 34.0 ± 0.18 nM and 9.2 ± 0.93 nM, respectively and the interaction of both drugs was found to be synergistic that could kill the parasites more effectively. This study suggests that ellagic acid and concanamycin A can be new candidates to be used in combination therapies with artemisinin, a standard antimalarial drug that has been postulated to affect the digestive vacuole pH.
鞣花酸是许多植物中具有生物活性的酚类成分。我们之前的研究报告指出,鞣花酸对恶性疟原虫消化泡的碱化作用与对位于疟原虫消化泡膜上的 V 型 H+-ATP 酶的特异性抑制剂--康那霉素 A 相似。因此,本研究旨在通过等全息图分析对寄生虫生长的影响,确定鞣花酸与 concanamycin A 的相互作用。在进行等全息图分析之前,先进行了基于 SBYR 绿 I 荧光(MSF)的疟原虫检测,以确定鞣花酸和康那霉素 A 的抗疟活性(IC50)。鞣花酸和金霉素 A 的 IC50 值分别为 34.0 ± 0.18 nM 和 9.2 ± 0.93 nM,两种药物的相互作用具有协同作用,能更有效地杀死寄生虫。这项研究表明,鞣花酸和金刚烷霉素 A 可以作为新的候选药物,与青蒿素(一种标准抗疟药物,据推测会影响消化泡的 pH 值)联合使用。
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引用次数: 0
Time-kill kinetics of Piper betle L. ethanolic leaf extract on methicillin-sensitive Staphylococcus aureus 胡椒槟榔叶乙醇提取物对甲氧西林敏感的金黄色葡萄球菌的时间杀伤动力学
Pub Date : 2023-12-22 DOI: 10.28916/lsmb.7.1.2023.120
Ryan Christopher Co Lao, Ailyn Manglicmot Yabes
Staphylococcus aureus is one of the main pathogens in community and hospital infections that could cause mild skin infections to severe life-threatening bacteremia. Piper betle has shown antibacterial activities against S. aureus but its pharmacodynamics remains unclear despite its widespread availability in many over-the-counter preparations. This study aimed to describe the time-kill kinetics of P. betle extract against methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA). Time-kill kinetics were conducted to describe the killing rate of P. betle extract by its effects on MSSA lag time duration, growth rate, and maximum optical density. The surviving colonies at different time-points after exposure to P. betle extract at minimum bactericidal concentration were also determined. Subinhibitory concentrations elucidated its concentration-dependent antibacterial activity by maintaining a trend of increasing lag time, decreasing growth rate, and decreasing maximum optical density as the concentration increases. In particular, concentration at 1250 μg/mL or 0.5 x minimum inhibitory concentration (MIC) showed consistent significant findings across these parameters. Concentrations at MIC and above did not show growth, indicating MSSA growth inhibition or death. P. betle extract’s bactericidal effect started immediately within two (2) hours and was sustained until no growth was observed from the eighth hour and beyond. P. betle extract maintained antibacterial activities against MSSA at subinhibitory concentrations and has also exhibited immediate and sustained bactericidal effect at minimum bactericidal concentration (MBC).
金黄色葡萄球菌是社区和医院感染的主要病原体之一,可引起轻微的皮肤感染和严重的危及生命的菌血症。胡椒槟榔对金黄色葡萄球菌具有抗菌活性,但其药效学仍不清楚,尽管它在许多非处方制剂中广泛使用。本研究旨在描述蒌蒿提取物对甲氧西林敏感金黄色葡萄球菌 ATCC 29213(MSSA)的时间杀伤动力学。槟榔穗提取物对金黄色葡萄球菌的滞后时间、生长速度和最大光密度都有影响,从而描述了槟榔穗提取物的杀灭率。此外,还测定了暴露于最低杀菌浓度的槟榔箬提取物后不同时间点的存活菌落数。亚抑菌浓度阐明了其抗菌活性的浓度依赖性,即随着浓度的增加,滞后时间延长,生长速度降低,最大光密度减小。尤其是浓度为 1250 μg/mL 或 0.5 x 最低抑菌浓度(MIC)时,这些参数都显示出一致的显著结果。MIC 以上的浓度不显示生长,表明 MSSA 生长受抑制或死亡。槟榔箬叶提取物的杀菌作用在两(2)小时内立即开始,并持续到第 8 小时以后不再生长。槟榔穗提取物在亚抑制浓度下仍能保持对 MSSA 的抗菌活性,在最低杀菌浓度(MBC)下也表现出直接和持续的杀菌效果。
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引用次数: 0
Conditioned medium of IGF-1-induced human synovial membrane mesenchymal stem cells effects on inflammatory response of osteoarthritic in vitro model IGF-1 诱导的人滑膜间充质干细胞调节培养基对骨关节炎体外模型炎症反应的影响
Pub Date : 2023-12-19 DOI: 10.28916/lsmb.7.1.2023.121
M. Marlina, A. Armenia, R. Rahmadian, W. Widodo, Syarifah Fadhlira Haddeline, Maharani Safitri, N. Elida, Wahyu Widowati
Synovial membrane mesenchymal stem cells (SM-MSCs) possess excellent regenerative potential, making them a viable option for osteoarthritis (OA) therapy. Moreover, these cells can be easily obtained from the human body.  Insulin-like growth factor (IGF-1) can be used to decrease the pro-inflammatory marker, these markers can trigger inflammation in OA. These challenges can be addressed by utilizing a conditioned medium (CM) derived from stem cell culture. This study aims to compare the effective way of OA therapy between CM SM-MSC and CM SM-MSC induced by IGF-1 by observe the pro-inflammatory markers such as NF-kB, RANTES, PGE2, COL1 and the anti-inflammatory marker, Aggrecan (ACAN). Chondrocyte cells induced IL-1β as OA model (IL1β-CHON002) treated with IGF-1 15% and 30% and without IGF1-induced SM-MSCs-CM to know its effectiveness in decreasing the pro-inflammatory markers. ELISA and RT-qPCR methods were performed to analyze this effect. Based on the data result, SM-MSCs-CM is estimated to have the potential to treat OA as seen from the content of growth factors in CM, decreasing the markers of inflammation. The most significant reduction in PGE2, RANTES, NF-kB, and COL1 concentration was found in the treatment of SM-MSCs-CM cultured with IGF1 concentrations of 150 ng/mL. The higher aggrecan (ACAN) concentration was found in IGF150 15%. Conclusion: CM from SM-MSCs cultured with IGF150 with concentrations of 15% and 30% resulted in the most effective concentration to decrease the concentration of pro-inflammatory markers and also to increase the anti-inflammatory markers.
滑膜间充质干细胞(SM-MSCs)具有出色的再生潜力,是治疗骨关节炎(OA)的可行选择。此外,这些细胞很容易从人体内获得。 胰岛素样生长因子(IGF-1)可用于降低促炎标记物,而这些标记物会引发 OA 中的炎症。利用干细胞培养基(CM)可以解决这些难题。本研究旨在通过观察NF-kB、RANTES、PGE2、COL1等促炎标记物和抗炎标记物Aggrecan(ACAN),比较CM SM-MSC和IGF-1诱导的CM SM-MSC治疗OA的有效方法。以诱导 IL-1β 的软骨细胞作为 OA 模型(IL1β-CHON002),用 15% 和 30% 的 IGF-1 处理,而不用 IGF1 诱导的 SM-MSCs-CM 处理,以了解其在减少促炎标记物方面的效果。研究人员采用 ELISA 和 RT-qPCR 方法分析了这一效果。根据数据结果,SM-间充质干细胞-CM具有治疗OA的潜力,这一点从CM中生长因子的含量、炎症标志物的减少可以看出。用浓度为150 ng/mL的IGF1培养SM-间充质干细胞-CM时,PGE2、RANTES、NF-kB和COL1浓度的降低最为明显。IGF150浓度为15%时,凝集素(ACAN)浓度较高。结论用浓度为15%和30%的IGF150培养SM-间充质干细胞的CM能最有效地降低促炎标志物的浓度,同时也能增加抗炎标志物的浓度。
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引用次数: 0
Metabolic perturbations in methicillin-resistant Staphylococcus aureus induced by Psidium guajava ethanolic leaf extract 番石榴乙醇叶提取物诱导耐甲氧西林金黄色葡萄球菌发生代谢紊乱
Pub Date : 2023-12-18 DOI: 10.28916/lsmb.7.1.2023.118
Ailyn Manglicmot Yabes, Monica Angelique Orejas Ramos
Psidium guajava ethanolic leaf extract (PGele) showed good antibacterial activity against Staphylococcus aureus in various in vitro and in vivo studies. It was also reported to be efficacious, safe, and well-tolerated in a phase 1/11a clinical trial of the Psidium guajava ointment among volunteer patients with persistent Staphylococcus aureus nasal colonizers. However, its mechanism of antibacterial action is yet to be elucidated. Changes in bacterial metabolism can contribute to the susceptibility of the organism to antibiotics, thus screening for metabolic perturbations induced by PGele can give insight into its mechanism/s of antibacterial action. Minimum inhibitory concentration (MIC) of PGele against methicillin-resistant Staphylococcus aureus (MRSA) was determined using the agar dilution technique. The sole carbon utilization phenotype microarray was used to describe the metabolic perturbations. Psidium guajava ethanolic leaf extract showed antibacterial activity against MRSA with MIC at 1,250 µg/mL. The phenotypic profile of MRSA showed utilization of 51 carbon sources, however, when MRSA was treated with the plant extract at sub-MIC (625 µg /mL), the utilization of carbon sources belonging to carbohydrate group (51.43%), amino acid group (100%) and the group of esters, carboxylic acids and fatty acids (75%) were inhibited. The sub-MIC of PGele induced metabolic perturbations on carbon sources associated with Embden-Meyerhof-Parnas pathway (EMP), pentose phosphate pathway (PPP), and citric acid cycle (TCA) pathways of MRSA. This current study gave an insight into the mechanism of antibacterial action of the Psidium guajava ethanolic leaf extract, a promising plant-derived antibiotic.
在各种体外和体内研究中,番石榴乙醇叶提取物(PGele)对金黄色葡萄球菌具有良好的抗菌活性。另据报道,在一项针对金黄色葡萄球菌鼻腔定植者的 1/11a 期临床试验中,番石榴软膏对患有顽固性金黄色葡萄球菌鼻腔定植者的志愿者患者具有良好的疗效、安全性和耐受性。然而,其抗菌作用机制尚待阐明。细菌新陈代谢的变化会导致生物体对抗生素的敏感性,因此,筛选 PGele 引起的新陈代谢扰动可以帮助人们了解其抗菌作用机制。利用琼脂稀释技术测定了 PGele 对耐甲氧西林金黄色葡萄球菌(MRSA)的最小抑菌浓度(MIC)。使用唯一碳利用表型微阵列来描述代谢扰动。番石榴乙醇叶提取物对 MRSA 具有抗菌活性,其 MIC 值为 1,250 µg/mL。MRSA 的表型图显示其利用了 51 种碳源,然而,当 MRSA 使用 MIC 值(625 µg /mL)以下的植物提取物处理时,其对碳水化合物类(51.43%)、氨基酸类(100%)以及酯类、羧酸和脂肪酸类(75%)碳源的利用受到了抑制。PGele 的亚 MIC 诱导了与 MRSA 的恩伯登-梅耶霍夫-帕尔纳斯途径(EMP)、磷酸戊糖途径(PPP)和柠檬酸循环(TCA)途径相关的碳源代谢紊乱。目前的研究深入探讨了番石榴乙醇叶提取物的抗菌作用机制,这是一种很有前景的植物源抗生素。
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引用次数: 0
Alteration of pulmonary mitochondrial oxidation status, inflammation, energy metabolizing enzymes, oncogenic and apoptotic markers in mice model of diisononyl phthalate-induced asthma 邻苯二甲酸二异壬酯诱导哮喘小鼠模型肺线粒体氧化状态、炎症、能量代谢酶、致癌和凋亡标志物的改变
Pub Date : 2023-09-24 DOI: 10.28916/lsmb.7.1.2023.113
Samuel Abiodun Kehinde, Abosede Temitope Olajide, Oyindamola Joy Akinpelu, Sanmi Tunde Ogunsanya
Primary plasticizer used in polyvinyl chloride is diisononyl phthalate (DiNP) and exposure to DiNP has been associated with the development of asthma and allergies. In the current study, how DiNP alters pulmonary antioxidant status, inflammation, energy metabolizing enzymes, oncogenic and apoptotic markers in DiNP-induced asthmatic mice was examined. Male BALB/c mice (n=20, 20-30 g) were divided into 2 groups of 10 mice each: group 1 (control) received saline (0.2ml/kg) orally for 23 days, and group 2 (DiNP) received 50 mg/kg DiNP (Intraperitoneal and intranasal) once per day. After the last administration, mice were sacrificed, lungs were removed and used for biochemical and histopathological analysis. DiNP treated mice experienced alterations in their lung histoarchitecture, levels of oncogenic and apoptotic factors, glycolytic, tricarboxylic acid cycle (TCA), and electron transport chain enzymes (ETC), antioxidant status, and inflammatory biomarkers. DiNP decreased the lungs levels of reduced glutathione and ascorbic acid, and the activities of superoxide dismutase, catalase, and glutathione-s-transferase. In the lungs of DiNP-treated mice compared to the control group, malondialdehyde and inflammatory biomarkers (nitric oxide and myeloperoxidase) were significantly greater (p<0.05). Furthermore, the activities of glycolytic enzymes hexokinase, aldolase, lactate dehydrogenase were downregulated with a concomitant increase in NADase (77%). TCA enzymes and ETC enzymes were significantly reduced as well. CAS-3, p53, Bax, c-MYC, K-Ras increased by 65%, 51%, 70%, 59% and 82% respectively while BCL-2 decreased by 74%. Histopathological analysis revealed distortion of the airway structure characterized by inflammatory cell infiltration, oedema, hemorrhage, and constricted alveoli space. Exposure to DiNP caused oxidative stress which promotes lung inflammation via depletion of antioxidants, pulmonary energy transduction enzymes, levels of oncogenic and apoptotic factors were impaired as well, suggesting that the lungs may not be able to perform its morphological and physiological functions effectively.
聚氯乙烯中使用的主要增塑剂是邻苯二甲酸二异壬酯(DiNP),接触DiNP与哮喘和过敏的发生有关。本研究检测了DiNP对哮喘小鼠肺抗氧化状态、炎症、能量代谢酶、致癌和凋亡标志物的影响。雄性BALB/c小鼠(n=20, 20-30 g)分为2组,每组10只:1组(对照组)给予生理盐水(0.2ml/kg)口服,连续23 d; 2组(DiNP)给予DiNP 50 mg/kg(腹腔和鼻内),每天1次。末次给药后处死小鼠,取肺进行生化和组织病理学分析。DiNP处理小鼠的肺组织结构、致癌因子和凋亡因子、糖酵解、三羧酸循环(TCA)和电子传递链酶(ETC)水平、抗氧化状态和炎症生物标志物发生了变化。DiNP降低肺部还原型谷胱甘肽和抗坏血酸水平,降低超氧化物歧化酶、过氧化氢酶和谷胱甘肽s-转移酶的活性。与对照组相比,在dinp处理的小鼠肺中,丙二醛和炎症生物标志物(一氧化氮和髓过氧化物酶)显著增加(p < 0.05)。此外,糖酵解酶己糖激酶、醛缩酶、乳酸脱氢酶活性下调,NADase随之升高(77%)。TCA酶和ETC酶也显著降低。CAS-3、p53、Bax、c-MYC、K-Ras分别升高65%、51%、70%、59%、82%,BCL-2降低74%。组织病理学分析显示气道结构扭曲,表现为炎症细胞浸润、水肿、出血和肺泡空间收缩。暴露于DiNP引起氧化应激,通过消耗抗氧化剂、肺能量转导酶、致癌因子和凋亡因子水平受损而促进肺部炎症,表明肺可能无法有效发挥其形态和生理功能。
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引用次数: 0
Fabrication of ciprofloxacin loaded alginate/cockle shell powder nanobiocomposite bone scaffold 载藻酸盐/贝壳粉环丙沙星纳米生物复合骨支架的制备
Pub Date : 2023-09-04 DOI: 10.28916/lsmb.7.1.2023.111
Huai Li Wong, J. Santhanam, Shiow Fern Ng, B. H. Bharatham
Orthopedic implant infection is one of the most challenging issues in bone tissue engineering industry. Hence, local delivery of antibiotics incorporated into a fabricated bone scaffold possibly provides a more rapid bacteria inhibitory effect. In this study, pure ciprofloxacin loaded alginate/cockle shell powder nanobiocomposite bone scaffolds are fabricated with 5 wt% and 10 wt% ciprofloxacin respectively and tested for drug encapsulation, drug release and antibacterial properties towards common implant infecting bacterial strains (Staphylococcus aureus and Pseudomonas aeruginosa). Results from the studies showed a low drug encapsulation and drug release regardless of the concentration of drugs loaded with no significant differences noted (p<0.05). However, bacterial inhibition studies through direct contact and using eluted samples from drug release studies showed some inhibitory effects towards the growth of both bacterial strains tested. These findings were further justified with microscopy observations on biofilm and bacterial colony formation. Mineralization studies conducted additionally indicated that the scaffolds characteristics was not compromised due to drug loading. Although pure ciprofloxacin may not be the most suitable antibiotic to be incorporated into the nanobiocomposite bone scaffold, the study did provide some insight to the possible use of the scaffold for future drug delivery applications.
骨科植入物感染是骨组织工程领域最具挑战性的问题之一。因此,局部递送掺入人造骨支架的抗生素可能提供更快速的细菌抑制效果。本研究分别以5%和10%的环丙沙星含量制备了纯环丙沙星负载藻酸盐/鸟壳粉纳米复合骨支架,并对常见种植体感染菌株(金黄色葡萄球菌和铜绿假单胞菌)进行了药物包封、药物释放和抗菌性能测试。研究结果表明,无论载药浓度如何,药物的包封度和释放度都很低,但差异无统计学意义(p<0.05)。然而,通过直接接触和使用药物释放研究中洗脱的样品进行的细菌抑制研究表明,对两种细菌菌株的生长都有一定的抑制作用。这些发现进一步证实了显微镜观察的生物膜和细菌菌落形成。另外进行的矿化研究表明,支架的特性不受药物负荷的影响。虽然纯环丙沙星可能不是纳米生物复合骨支架中最合适的抗生素,但该研究确实为该支架在未来药物输送应用中的可能用途提供了一些见解。
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Life Sciences, Medicine and Biomedicine
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