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An extensive evaluation of laser tissue welding and soldering biotechnologies: Recent advancements, progress, and applications 广泛评估激光组织焊接和焊锡生物技术:最新进展、进步和应用
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100234
Yuxin Chen , Kehong Wang , Jun Huang , Xiaopeng Li , Yunfeng Rui

In the rapidly advancing field of modern medicine, despite the availability of sophisticated techniques, suturing remains a fundamental procedure in both surgical and internal medicine operations. However, this traditional method inevitably gives rise to issues such as inflammation, fibrosis, or secondary damage. Laser tissue welding and soldering technologies offer a non-contact approach to surgical suturing with advantages including simplicity of operation, reduced fibrosis tendency, and ensured wound closure strength. Nevertheless, its applications have been attempts at clinical trials but no actual implementation. The development and implementation of this technique have the potential to revolutionize both internal and external surgery by enabling automated suture placement. This holds significant importance for ensuring suture quality and postoperative performance. This article provides a detailed summary and discussion on the current applications of this biotechnologies in various organ systems within the human body, as well as an exploration into the interaction mechanisms between tissues and lasers. Additionally, it presents a comprehensive analysis and discussion on laser types suitable for bio tissue laser soldering. Prospects for addressing tissue fibrosis resulting from laser contactless suturing are also explored. These insights will serve as valuable references and guidance for future advancements in utilizing lasers as viable alternatives in human surgical suturing.

在飞速发展的现代医学领域,尽管有了先进的技术,但缝合仍然是外科和内科手术的基本程序。然而,这种传统方法不可避免地会引起炎症、纤维化或二次损伤等问题。激光组织焊接技术为手术缝合提供了一种非接触式方法,其优点包括操作简单、减少纤维化趋势和确保伤口闭合强度。尽管如此,该技术的应用还只是在临床试验中尝试,并未真正实施。这项技术的开发和实施有望通过实现自动缝合置放彻底改变内外科和外科学。这对确保缝合质量和术后效果具有重要意义。本文详细总结和讨论了这种生物技术目前在人体各器官系统中的应用,并探讨了组织与激光之间的相互作用机制。此外,文章还全面分析和讨论了适合生物组织激光焊接的激光类型。此外,还探讨了解决激光非接触缝合造成的组织纤维化问题的前景。这些见解将为未来利用激光作为人体外科缝合的可行替代方法提供有价值的参考和指导。
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引用次数: 0
Antimicrobial activity of (KLAKLAK)–NH2 analogs against pathogenic microbial strains (KLAKLAK)-NH2类似物对病原微生物菌株的抗菌活性
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100236
Sirine Jaber , Yana Evstatieva , Veronica Nemska , Dilyana Nikolova , Emilia Naydenova , Nelly Georgieva , Dancho Danalev

Many microorganisms pose a threat to human health due to the ever-increasing bacterial resistance to conventional drugs. Nowadays, searching for new alternatives to conventional antibiotics to fight bacterial resistance is a main task. Thus, natural molecules such as amino acids and peptides arise as possible solutions to the problem. The antimicrobial activity of targeted compounds was studied by the agar-diffusion method, using the prepared working solutions of the targeted peptides with the corresponding concentrations. The results of the antimicrobial activity against different test pathogens show specificity, as antimicrobial activity against the used test microorganisms was not found in the investigated short-chain synthetic peptides Si6, Si3 and Si13. Antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Staphylococcus epidermidis, Propionibacterium acnes, Escherichia coli, Pseudomonas aeruginosa, and the yeasts Malassezia furfur and Candida albicans was established for the long-chain synthetic peptides Si1, Si5 and Si16, except Si5 which does not show activity against pathogenic fungal strain C. albicans. The compound Si16 where natural Leu in (KLAKLAK)2-NH2 is replaced by unnatural Nle is the best candidate for medical drug due to the combined antibacterial and antiproliferative effect as well as long hydrolytic stability.

由于细菌对传统药物的耐药性不断增加,许多微生物对人类健康构成威胁。如今,寻找传统抗生素的新替代品来对抗细菌耐药性已成为一项主要任务。因此,氨基酸和肽等天然分子成为解决问题的可能方案。通过琼脂扩散法,使用制备的相应浓度的目标肽工作溶液研究了目标化合物的抗菌活性。针对不同测试病原体的抗菌活性结果显示出特异性,因为所研究的短链合成肽 Si6、Si3 和 Si13 没有发现针对所用测试微生物的抗菌活性。长链合成肽 Si1、Si5 和 Si16 对蜡样芽孢杆菌、金黄色葡萄球菌、表皮葡萄球菌、痤疮丙酸杆菌、大肠杆菌、铜绿假单胞菌、糠秕马拉色菌和白色念珠菌等酵母菌具有抗菌活性,只有 Si5 对致病真菌白色念珠菌没有活性。在化合物 Si16 中,(KLAKLAK)2-NH2 中的天然 Leu 被非天然 Nle 所取代,由于该化合物具有抗菌和抗增殖的综合效果以及较长的水解稳定性,因此是医疗药物的最佳候选化合物。
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引用次数: 0
Ultrasound-assisted steps for producing biodiesel from microalgae 利用微藻生产生物柴油的超声波辅助步骤
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100251

Biodiesel production from microalgae is considered one of the main candidates to replace conventional fuels. In addition, the use of ultrasound can be crucial to enhance different steps in the industrial production of this biofuel from this type of microorganisms. This review focuses on the potential of ultrasound technology to increase lipid content in microalgae and improve biomass harvesting and lipid extraction, as well as its potential use in oil transesterification. Specifically, the use of ultrasound pulses in the stationary phase of microalgae growth can act as a stimulus to improve lipid content and can oxidise cell walls, improving lipid extraction and subsequent harvesting. Furthermore, if assisted with ultrasound, the reaction time, alcohol/oil molar ratio, separation process, and energy consumption of transesterification can be reduced compared to conventional methods due to the reduction of the interfacial area. Finally, ultrasound technology can be used if some of the previous processes (i.e., in situ transesterification) are coupled to decrease the number of steps in an industrial process. Regarding scale-up, although some ultrasonic reactors working in continuous operation mode have already been proposed, there are still some drawbacks, mainly related to the knowledge of bubble behaviour in different media and their effect on reactions (enzymatic or in situ transesterifications) as well as the energy consumption if ultrasound technology is used in more than one process simultaneously. These facts need to be studied in more detail to introduce this technology in a large-scale process.

利用微藻生产生物柴油被认为是替代传统燃料的主要方法之一。此外,在利用这类微生物工业化生产生物燃料的不同步骤中,超声波的使用至关重要。本综述重点介绍超声波技术在增加微藻脂质含量、改进生物质收割和脂质提取方面的潜力,以及在油类酯交换中的潜在用途。具体来说,在微藻生长的静止期使用超声脉冲可刺激微藻提高脂质含量,并可氧化细胞壁,改善脂质提取和随后的收获。此外,在超声波的辅助下,由于界面面积减小,酯交换反应的反应时间、醇/油摩尔比、分离过程和能耗都会比传统方法减少。最后,如果将之前的一些工艺(即原位酯交换)结合起来使用,可以减少工业工艺中的步骤数量,那么就可以使用超声波技术。关于扩大规模,虽然已经提出了一些连续运行模式的超声波反应器,但仍然存在一些缺点,主要涉及对不同介质中气泡行为的了解、气泡对反应(酶解或原位酯化)的影响以及同时在多个工艺中使用超声波技术时的能耗。要在大规模工艺中采用这种技术,还需要对这些事实进行更详细的研究。
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引用次数: 0
Recent trends in nanozyme research and their potential therapeutic applications 纳米酶研究的最新趋势及其潜在的治疗应用
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100205
Aparajita Sen , Jyoti Oswalia , Sneha Yadav , Meenakshi Vachher , Arti Nigam

Nanozymes are a class of nanoparticles that can mimic enzyme activity and be used for various applications in modern clinical therapy. It has recently been observed that nanozymes have multi-enzyme mimicking activities, are highly stable, versatile and easily modified. Moreover, they have high catalytic efficiency, high recovery rates, improved substrate specificity and are suitable for mass production. The catalytic mechanisms of nanozymes mainly include catalase, peroxidase, oxidase, hydrolase and superoxide dismutase-like activities, which enable nanozymes to be used as potential therapeutics against a plethora of infectious and lifestyle disorders. Nanozymes have been used as therapeutics against cancer, inflammatory diseases, neurodegenerative and neurological disorders, bacterial, fungal and viral infections, wounds and diseases associated with Reactive Oxygen Species. The purpose of writing this review is to provide a comprehensive compilation of novel research work that has taken place in the last few years regarding the use of nanozymes for therapy. We have compiled the various kinds of nanozymes and elaborated on their anti-tumorigenic, antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and neuroprotective roles. Their modes of action and enzymatic targets have also been discussed. The types and mechanisms of synthesis of nanozymes have also been summarized, along with interactions of nanoparticles with nanozymes. Furthermore, strategies to enhance the compatibility between nanoparticles and nanozymes have also been analyzed. Major focus has been laid on therapeutic applications of nanozymes. The challenges and future perspectives of using nanozymes in clinical therapy have also been debated in the later sections.

纳米酶是一类可以模拟酶活性的纳米粒子,可用于现代临床治疗的各种应用。最近的研究发现,纳米酶具有多酶模拟活性、高度稳定性、多功能性和易修饰性。此外,它们还具有催化效率高、回收率高、底物特异性强和适合大规模生产等特点。纳米酶的催化机理主要包括过氧化氢酶、过氧化物酶、氧化酶、水解酶和超氧化物歧化酶类活性,这些活性使纳米酶可作为潜在的治疗药物,用于治疗大量感染性疾病和生活方式疾病。纳米酶已被用作治疗癌症、炎症性疾病、神经退行性疾病和神经系统疾病、细菌、真菌和病毒感染、伤口以及与活性氧有关的疾病的药物。撰写这篇综述的目的是全面汇编过去几年中有关使用纳米酶进行治疗的新研究成果。我们汇编了各种纳米酶,并阐述了它们的抗肿瘤、抗氧化、抗炎、抗菌、抗真菌、抗病毒和神经保护作用。此外,还讨论了它们的作用模式和酶靶标。还总结了纳米酶的类型和合成机制,以及纳米粒子与纳米酶的相互作用。此外,还分析了增强纳米粒子与纳米酶之间兼容性的策略。主要重点是纳米酶的治疗应用。后面的章节还讨论了将纳米酶用于临床治疗所面临的挑战和未来前景。
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引用次数: 0
Peel waste of citrus fruits: A valuable and renewable source of polyphenols for the treatment of diabesity 柑橘类水果的果皮废料:治疗肥胖症的一种宝贵的可再生多酚来源
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100204
Muhammad Ajmal Shah , Savaira Tariq , Syed Muhammad Abuzar , Kainat Ilyas , Irtaza Qadees , Ifat Alsharif , Khairul Anam , Reem T. Almutairi , Khalid A. Al-Regaiey , Ahmad O. Babalghith , Uzma Saleem , Abd. Malik , Mohannad A. Almikhlaf , Yasmene F. Alanazi , Mody Albalawi , Ana Sanches Silva

Diabesity is the concurrence of both diabetes and obesity, and it has become a modern epidemic. It is linked by numerous common pathophysiological mechanisms which can be targeted to combat its harms. The available treatments for diabesity include the medications that are also causing several adverse side effects. The increasing healthcare costs, both direct and indirect, for diabesity management continue to rise, underscoring the urgency to find efficient and cost-effective treatment methods. These circumstances have prompted a shift in research towards exploring natural dietary alternatives for treatment. Among these dietary substitutes, citrus fruits rich in polyphenols have caught the attention of researchers. This review narrates the major interconnection of diabesity and brings out the various mechanisms in which citrus polyphenols can be used for its management. Citrus polyphenols fight against diabesity by targeting adipokines, reactive oxygen species, leptin deficiency, metabolic endotoxemia, peroxisomes proliferator activating receptors, insulin signaling, starch hydrolyzing enzymes, and human islet amyloid polypeptide. The studies on the role of citrus polyphenols in the treatment of diabesity have shown clearly that addressing various physiological systems which can interact with citrus polyphenols can help to manage diabesity and related health concerns.

糖尿病肥胖症是糖尿病和肥胖症的并发症,已成为现代流行病。它与许多共同的病理生理机制有关,可以针对这些机制消除其危害。现有的肥胖症治疗方法包括药物治疗,但药物治疗也会产生一些不良副作用。用于控制肥胖症的直接和间接医疗费用不断增加,这凸显了寻找高效、经济的治疗方法的紧迫性。这些情况促使研究转向探索治疗糖尿病的天然膳食替代品。在这些膳食替代品中,富含多酚的柑橘类水果引起了研究人员的注意。本综述阐述了肥胖症的主要内在联系,并介绍了柑橘多酚可用于控制肥胖症的各种机制。柑橘多酚通过针对脂肪因子、活性氧、瘦素缺乏、代谢性内毒素血症、过氧化物酶体增殖激活受体、胰岛素信号传导、淀粉水解酶和人类胰岛淀粉样多肽来对抗肥胖症。有关柑橘多酚在治疗肥胖症方面作用的研究清楚地表明,解决与柑橘多酚相互作用的各种生理系统有助于控制肥胖症和相关的健康问题。
{"title":"Peel waste of citrus fruits: A valuable and renewable source of polyphenols for the treatment of diabesity","authors":"Muhammad Ajmal Shah ,&nbsp;Savaira Tariq ,&nbsp;Syed Muhammad Abuzar ,&nbsp;Kainat Ilyas ,&nbsp;Irtaza Qadees ,&nbsp;Ifat Alsharif ,&nbsp;Khairul Anam ,&nbsp;Reem T. Almutairi ,&nbsp;Khalid A. Al-Regaiey ,&nbsp;Ahmad O. Babalghith ,&nbsp;Uzma Saleem ,&nbsp;Abd. Malik ,&nbsp;Mohannad A. Almikhlaf ,&nbsp;Yasmene F. Alanazi ,&nbsp;Mody Albalawi ,&nbsp;Ana Sanches Silva","doi":"10.1016/j.crbiot.2024.100204","DOIUrl":"https://doi.org/10.1016/j.crbiot.2024.100204","url":null,"abstract":"<div><p>Diabesity is the concurrence of both diabetes and obesity, and it has become a modern epidemic. It is linked by numerous common pathophysiological mechanisms which can be targeted to combat its harms. The available treatments for diabesity include the medications that are also causing several adverse side effects. The increasing healthcare costs, both direct and indirect, for diabesity management continue to rise, underscoring the urgency to find efficient and cost-effective treatment methods. These circumstances have prompted a shift in research towards exploring natural dietary alternatives for treatment. Among these dietary substitutes, citrus fruits rich in polyphenols have caught the attention of researchers. This review narrates the major interconnection of diabesity and brings out the various mechanisms in which citrus polyphenols can be used for its management. Citrus polyphenols fight against diabesity by targeting adipokines, reactive oxygen species, leptin deficiency, metabolic endotoxemia, peroxisomes proliferator activating receptors, insulin signaling, starch hydrolyzing enzymes, and human islet amyloid polypeptide. The studies on the role of citrus polyphenols in the treatment of diabesity have shown clearly that addressing various physiological systems which can interact with citrus polyphenols can help to manage diabesity and related health concerns.</p></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590262824000303/pdfft?md5=956c9e0a3d2e055f878894f50e099fb6&pid=1-s2.0-S2590262824000303-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140347076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of influent characteristics and operational parameters on nitrous oxide emissions in wastewater treatment: Strategies for mitigation and microbial insights 污水处理过程中进水特征和运行参数对氧化亚氮排放的影响:缓解策略和微生物见解
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100207
Yi-Wei Zhao , Li-Li Du , Bing Hu , Hong-Yong Lin , Bin Liang , Yun-Peng Song , Yu-Qi Wang , Hong-Wu Wang , Peng-Fei Li , Ai-Jie Wang , Hong-Cheng Wang

Nitrous oxide (N2O) emissions from the wastewater treatment sector are a significant contributor to global greenhouse gas levels. This investigation delves into the mechanisms of N2O generation and uptake, correlating microbial processes with variables such as influent characteristics and operational parameters. The nature of carbon substrates in the influent profoundly influences microbial consortia and N2O output. Elevating the carbon-to-nitrogen (C/N) ratio has been shown to curtail N2O emissions by alleviating the competitive dynamics among denitrifying enzymes. Optimal activity of N2O reductase is achieved by maintaining a neutral to mildly alkaline pH and stable ambient temperatures. It is imperative to circumvent extreme aeration rates and prolonged aeration periods to reduce N2O release. The study underscores the importance of an effective carbon feed strategy and advocates for prolonged hydraulic retention times (HRT) and sludge retention times (SRT) in activated sludge suspension systems to inhibit N2O escape. Notably, excessive internal recycling, coupled with heightened dissolved oxygen (DO) levels in aerobic zones, intensifies N2O emission risks. Moreover, the presence of hazardous contaminants, such as heavy metals and antibiotics, interferes with nitrogen elimination processes, warranting a comprehensive assessment of consequent N2O emission hazards. This research provides a scientific basis as well as practical management approaches to diminish N2O emissions.

污水处理行业排放的一氧化二氮(N2O)是全球温室气体的重要来源。这项研究深入探讨了一氧化二氮的产生和吸收机制,将微生物过程与进水特征和运行参数等变量联系起来。进水中碳基质的性质对微生物群和一氧化二氮的产生有着深远的影响。提高碳氮比(C/N)可缓解反硝化酶之间的竞争态势,从而减少一氧化二氮的排放。保持中性至弱碱性的 pH 值和稳定的环境温度可使 N2O 还原酶的活性达到最佳状态。必须避免极端曝气速率和延长曝气时间,以减少 N2O 的释放。该研究强调了有效碳进料策略的重要性,并主张在活性污泥悬浮系统中延长水力停留时间(HRT)和污泥停留时间(SRT),以抑制 N2O 逸出。值得注意的是,过度的内部循环,再加上好氧区溶解氧(DO)水平的升高,加剧了一氧化二氮的排放风险。此外,重金属和抗生素等有害污染物的存在也会干扰氮消除过程,因此需要对由此产生的一氧化二氮排放危害进行全面评估。这项研究为减少 N2O 排放提供了科学依据和实用的管理方法。
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引用次数: 0
Lipid droplets dependent or independent cytoprotective activities of unsaturated fatty acids, Lorenzo’s oil and sulfo-N-succinimidyl oleate on 7-ketocholesterol-induced oxidative stress, organelle dysfunction and cell death on 158N and ARPE-19 cells: Cell targets and benefits of sulfo-N-succinimidyl oleate 不饱和脂肪酸、洛伦佐油和 N-琥珀酰亚胺油酸磺酯对 158 N 细胞和 ARPE-19 细胞由 7-酮胆固醇诱导的氧化应激、细胞器功能障碍和细胞死亡的依赖或独立细胞保护活性:N-琥珀酰亚胺油酸的细胞靶标和益处
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100195
Thomas Nury , Imen Ghzaiel , Aziz Hichami , Claudio Caccia , Valerio Leoni , Vivien Pires , Atanas G Atanasov , Amira Zarrouk , Gérard Lizard , Anne Vejux

7-ketocholesterol is a cytotoxic oxysterol which is frequently increased in many chronic inflammatory and age-related diseases. Thus, the inhibition of the toxicity of 7-ketocholesterol is a major challenge to treat these diseases. 158N oligodendrocytes were used to evaluate the cytoprotective effects of lipids: ω-3 and ω-9 fatty acids (α-linolenic acid (C18:3n-3), eicosapentaenoic acid (C20:5n-3), docosahexaenoic acid (C22:6n-3), erucic acid (C22:1n-9) and oleic acid (C18:1n-9)), Lorenzo's oil (a mixture of oleic and erucic acid, 4:1) and sulfo-N-succinimidyl oleate (SSO, a synthetic derivative of oleic acid). On 158N cells, the ability of these molecules to inhibit 7KC-induced oxiapoptophagy (plasma membrane alteration, loss of ΔΨm, peroxisomal dysfunction, reactive oxygen species overproduction, induction of apoptosis and autophagy) were determined. ARPE-19 epithelial retinal cells were also used to evaluate the cytoprotective effect of SSO on 7KC-induced cell death. Unlike ω-3 and ω-9 fatty acids and Lorenzo's oil, sulfo-N-succinimidyl oleate had no cytotoxic effects over a wide range of concentrations. Noteworthy, unlike fatty acids and Lorenzo's oil, the cytoprotective effects of sulfo-N-succinimidyl oleate on 7KC-induced oxiapoptophagy, a caspase-dependent mode of cell death on 158N cells, were not associated with an accumulation of lipid droplets. In addition, on ARPE-19 cells, sulfo-N-succinimidyl oleate prevented 7KC-induced oxidative stress and cell death. These different characteristics of SSO make it possible to envisage its use for therapeutic purposes in diseases where 7-ketocholesterol levels are increased without eventual secondary side effects due to lipid droplets formation.

7- 酮胆固醇是一种具有细胞毒性的氧杂环醇,在许多慢性炎症和与年龄有关的疾病中经常增加。因此,抑制 7-酮胆固醇的毒性是治疗这些疾病的一大挑战。158N 少突胶质细胞用于评估脂质的细胞保护作用:ω-3 和 ω-9 脂肪酸(α-亚麻酸(C18:3n-3)、二十碳五烯酸(C20:5n-3)、二十二碳六烯酸(C22:6n-3)、芥酸(C22:1n-9)和油酸(C18:1n-9))、洛伦佐油(油酸和芥酸的混合物,4:1)和 N-琥珀酰亚胺油酸磺酸盐(SSO,油酸的合成衍生物)。在 158N 细胞上,测定了这些分子抑制 7KC 诱导的氧凋亡吞噬(质膜改变、ΔΨm 损失、过氧化物酶体功能障碍、活性氧过量产生、诱导细胞凋亡和自噬)的能力。还使用 ARPE-19 上皮视网膜细胞来评估 SSO 对 7KC 诱导的细胞死亡的细胞保护作用。与 ω-3 和 ω-9 脂肪酸以及洛伦佐油不同,N-琥珀酰亚胺基油酸磺酯在广泛的浓度范围内没有细胞毒性作用。值得注意的是,与脂肪酸和洛伦佐油不同,Sulfo-N-琥珀酰亚胺基油酸酯对 7KC 诱导的氧凋亡(一种依赖于 Caspase 的细胞死亡模式)的细胞保护作用与脂滴的积累无关。此外,在 ARPE-19 细胞上,SSO-N-琥珀酰亚胺油酸酯可防止 7KC 诱导的氧化应激和细胞死亡。由于磺基琥珀酰亚胺油酸酯具有这些不同的特性,因此可以设想将其用于治疗 7-酮胆固醇水平升高的疾病,而不会因脂滴的形成而产生副作用。
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引用次数: 0
Nanocarriers for inhaled delivery of RNA therapeutics 用于吸入输送 RNA 疗法的纳米载体
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100200
Sebastian G. Huayamares, Ryan Zenhausern, David Loughrey

RNA therapeutics are promising for the treatment of lung diseases where small molecules and biologics have failed to have much success in the past. While siRNA and mRNA drugs are now FDA-approved for rare diseases in the liver and as vaccines for infectious diseases, they became clinically established only after suitable advances in drug delivery platforms, such as the case of lipid nanoparticles. Localized delivery of RNA therapeutics through nanocarriers optimized for inhaled administration has the potential to address respiratory diseases without toxicity concerns from off-target effects. Here, we review recent clinical and preclinical progress of nanocarriers for inhaled RNA delivery, analyze the properties of nanocarrier-mediated FDA-approved drugs for respiratory diseases, and highlight compelling efficacy endpoints anticipated from ongoing clinical programs. We also present an overview of physiological challenges and opportunities that impact delivery of inhaled RNA therapeutics to the lungs. Finally, we discuss relevant models for preclinical testing, and translational considerations that can be used to help develop future nanocarriers for inhaled administration of RNA therapeutics.

RNA 疗法在治疗肺部疾病方面大有可为,因为过去小分子药物和生物制剂在治疗肺部疾病方面一直不甚成功。虽然 siRNA 和 mRNA 药物目前已被美国食品及药物管理局批准用于治疗肝脏罕见疾病和作为传染病疫苗,但它们只是在药物输送平台(如脂质纳米颗粒)取得适当进展后才开始在临床上应用。通过针对吸入给药进行优化的纳米载体局部给药 RNA 疗法有可能在解决呼吸系统疾病问题的同时避免脱靶效应带来的毒性问题。在此,我们回顾了用于吸入 RNA 给药的纳米载体的最新临床和临床前研究进展,分析了 FDA 批准的用于治疗呼吸系统疾病的纳米载体药物的特性,并重点介绍了正在进行的临床项目中预期的令人信服的疗效终点。我们还概述了影响将 RNA 治疗药物吸入肺部的生理挑战和机遇。最后,我们讨论了临床前测试的相关模型,以及可用于帮助开发未来用于吸入给药 RNA 治疗的纳米载体的转化考虑因素。
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引用次数: 0
Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2 法维拉韦与去铁酮:同分异构体、光物理、体外生物学研究以及与 SARS-Cov-2-MPro/ACE2 的结合相互作用
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100176
Nikolay T. Tzvetkov , Martina I. Peeva , Maya G. Georgieva , Vera Deneva , Aneliya A. Balacheva , Ivan P. Bogdanov , Maria Ponticelli , Luigi Milella , Kiril Kirilov , Maima Matin , Hans-Georg Stammler , Atanas G. Atanasov , Liudmil Antonov

Coronavirus disease 2019 (COVID-19) still remains the most disastrous infection continuously affecting millions of people worldwide. Herein, we performed a comparative study between the anti-influenza drug favipiravir (FAV) and the anti-thalassemia drug deferiprone (DFP) in order to examine their potential as basic scaffolds for the generation of most effective and structurally novel antivirals. To conduct the initial molecular modelling and virtual screening steps, our recently proposed single crystal X-ray diffraction (SCXRD)/HYdrogen DEssolvation (HYDE) technology platform has been used. This platform allows molecular design, interactive prioritization and virtual evaluation of newly designed molecules, simultaneously affecting two COVID-related targets, including angiotensin-converting enzyme 2 (ACE2) as a host-cellular receptor (host-based approach) and the main protease (Mpro) enzyme of the spike glycoprotein of SARS-Cov-2 (virus-based approach). Based on the molecular docking results, DFP has shown higher binding affinity (Ki HYDE values) over FAV towards both biological targets. The tautomeric, physicochemical, and biological properties of FAV and DFP have been studied both experimentally and theoretically using molecular spectroscopy (UV–VIS absorption), parallel artificial membrane permeability assay, and cell biology (PAMPA and MTT assay), as well as DFT quantum chemical calculations. According to the obtained results, the enol tautomers of both compounds are considerably more stable in different organic solvents. However, the keto tautomer of FAV was estimated to be most preferable under physiological conditions, which is in good agreement with the molecular docking studies. The isolated crystal structure of DFP is in an excellent agreement with the computation in respect of the most stable tautomer. Combined single X-ray/molecular modeling studies including HYDE analyses provided not only insights into the protein–ligand interactions within the binding site of SARS-Cov-2-ACE2 and SARS-Cov-2-Mpro, but also a valuable information regarding the most stable enol tautomeric form of DFP that contributes to its estimated higher potency against these targets.

2019年冠状病毒病(COVID-19)仍然是影响全球数百万人的最具灾难性的传染病。在此,我们对抗流感药物法非比拉韦(FAV)和抗地中海贫血药物去铁酮(DFP)进行了比较研究,以考察它们作为生成最有效和结构新颖的抗病毒药物的基本支架的潜力。为了进行最初的分子建模和虚拟筛选步骤,我们使用了最近提出的单晶 X 射线衍射(SCXRD)/氢溶解(HYDE)技术平台。该平台可对新设计的分子进行分子设计、交互式优先排序和虚拟评估,同时影响两个与 COVID 相关的靶点,包括作为宿主细胞受体的血管紧张素转换酶 2(ACE2)(基于宿主的方法)和 SARS-Cov-2 穗糖蛋白的主蛋白酶(Mpro)(基于病毒的方法)。根据分子对接结果,DFP 对这两个生物靶标的结合亲和力(Ki HYDE 值)高于 FAV。通过分子光谱(紫外-可见吸收)、平行人工膜渗透性检测、细胞生物学(PAMPA 和 MTT 检测)以及 DFT 量子化学计算,对 FAV 和 DFP 的同分异构体、物理化学和生物学特性进行了实验和理论研究。结果表明,这两种化合物的烯醇同系物在不同的有机溶剂中都更为稳定。然而,据估计,FAV 的酮同系物在生理条件下最为理想,这与分子对接研究结果十分吻合。就最稳定的同分异构体而言,DFP 的分离晶体结构与计算结果非常吻合。包括 HYDE 分析在内的单 X 射线/分子建模综合研究不仅深入揭示了 SARS-Cov-2-ACE2 和 SARS-Cov-2-Mpro 结合位点内蛋白质与配体之间的相互作用,而且还提供了有关 DFP 最稳定的烯醇同分异构体形式的宝贵信息,这些信息有助于估计 DFP 对这些靶标具有更高的效力。
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引用次数: 0
Proteomics characterization of biofilm formation by salt-tolerant Schwannyomyces etchellsii in seawater-based growth medium 耐盐壳斗霉菌在海水生长培养基中形成生物膜的蛋白质组学特征分析
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100242

Microbial biofilms are complex communities with cells embedded in an extracellular matrix. We previously discovered that salt-tolerant yeasts Debaryomyces fabryi, Schwanniomyces etchellsii, Schwanniomyces polymorphus and Kluyveromyces marxianus were able to form biofilms when grown in seawater- but not in freshwater-based media. The extracellular matrices of these biofilms were composed mainly of carbohydrates and proteins involved in metabolic processes and the response to stimuli. We herein focus on one of these yeasts, S. etchellsii, to explore its molecular determinants for biofilm formation in depth. We describe new analyses in which the proteome of cells in the biofilm network formed in seawater-based media is compared to that of the planktonic cells co-existing with them and with cells suspended in freshwater-based growth media. According to our data, in both cases biofilms cells contain overexpressed proteins involved in protein biosynthesis, in membrane structures and in transport mediated by vesicles. The great number of proteins with higher expression in these cells participating in translation and located in ribosomes indicate that they are more engaged in protein biosynthesis than their counterparts. Analyses carried out with the STRING database reinforced these results. Cell viability was also wider in biofilm cells. Our analyses have also allowed us to detect in S. etchellsii a homolog of the Candida albicans Spf1p. This protein is an ion transporter P-type ATPase in this microorganism, which participates in several processes, including cellular adhesion and cell wall organization and biogenesis. Our work provides a dataset with a large number of unknown proteins of S. etchellsii that show sequence similarity to proteins from other yeasts; this knowledge will help to better understand the proteome of this yeast and to look for future biotechnological applications.

微生物生物膜是细胞嵌入细胞外基质的复杂群落。我们之前发现,耐盐酵母菌 Debaryomyces fabryi、Schwanniomyces etchellsii、Schwanniomyces polymorphus 和 Kluyveromyces marxianus 在海水培养基中生长时能够形成生物膜,而在淡水培养基中则不能。这些生物膜的胞外基质主要由碳水化合物和蛋白质组成,参与新陈代谢过程并对刺激做出反应。在本文中,我们将重点关注其中一种酵母菌 S. etchellsii,深入探讨其形成生物膜的分子决定因素。我们描述了新的分析方法,将在海水培养基中形成的生物膜网络中的细胞的蛋白质组与与之共存的浮游细胞的蛋白质组以及悬浮在淡水培养基中的细胞的蛋白质组进行了比较。根据我们的数据,在这两种情况下,生物膜细胞都含有参与蛋白质生物合成、膜结构和囊泡运输的高表达蛋白质。在这些细胞中,大量参与翻译和位于核糖体中的蛋白质表达量较高,这表明它们比同类细胞更多地参与蛋白质的生物合成。利用 STRING 数据库进行的分析进一步证实了这些结果。生物膜细胞的存活率也更高。通过分析,我们还在 S. etchellsii 中发现了白色念珠菌 Spf1p 的同源物。这种蛋白质是该微生物的一种离子转运P型ATP酶,参与了多个过程,包括细胞粘附、细胞壁组织和生物生成。我们的工作提供了一个数据集,其中包含了大量与其他酵母蛋白质序列相似的 S. etchellsii 未知蛋白质;这些知识将有助于更好地了解这种酵母的蛋白质组,并寻找未来的生物技术应用。
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引用次数: 0
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Current Research in Biotechnology
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