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Genes associated with cell modelling provides new insights into spermiation mechanism in Cyprinus carpio 与细胞建模相关的基因为了解鲤鱼的精子发生机制提供了新的视角
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100262
Spermiation, an act of sperm release, depends on several molecular factors. Despite hormonal administration, spermiation failure is a primary concern in certain fishes. In this study, the molecular mechanisms of spermiation have been analyzed in Cyprinus carpio by comparative transcriptomics. Unigenes for C. carpio control (CCC), which were injected with PBS (Phosphate-buffered saline), and C. carpio treated (CCT), which were injected with ovatide, were 107,616 and 133,435, respectively. A total of 93 genes were identified as involved in the spermiation process, including those related to gonadal steroidogenesis, cell growth, cell adhesion, and cytoplasmic matrix formation. The cd63, CENPS, rasa1a, and genes for gonad steroidogenesis, cell growth, cell adhesion, and cytoplasmic matrix formation were analyzed. Gene expression analysis revealed tubulobulbar complexes mediated disengagement of spermatozoa and JAK2 signaling regulated cyst breakage in teleost for the first time. Analysis was done from the changes at the molecular level to the final act of spermiation. Tissue histology analysis was conducted in accordance with the molecular study, which showed structural changes. Induced breeding in fish plays a key role in seed production in aquaculture sector. However, there are several constraints the sector is still facing due to lack of extensive knowledge regarding the mechanisms of spermiation and species-specific response to hormonal dosage. This study is relevant to understand the molecular mechanisms involved in spermiation and the stages which mark as critical point of sperm release after administrating the inducing agent. This study also lays the groundwork for further exploration of species-specific responses to hormonal treatments, aiding sustainable seed production in the fisheries sector.
精子萌发是一种精子释放行为,取决于多种分子因素。尽管使用了激素,但精子畸形仍是某些鱼类的主要问题。本研究通过比较转录组学分析了鲤鱼精子发生的分子机制。注射磷酸盐缓冲盐水(PBS)的鲤鱼对照组(CCC)和注射卵磷脂的鲤鱼处理组(CCT)的单基因数分别为 107,616 和 133,435 个。经鉴定,共有 93 个基因参与了精子发生过程,包括与性腺类固醇生成、细胞生长、细胞粘附和细胞质基质形成有关的基因。分析了 cd63、CENPS、rasa1a 以及与性腺类固醇生成、细胞生长、细胞粘附和细胞质基质形成有关的基因。基因表达分析首次揭示了管状球复合体介导的精子脱离和 JAK2 信号调控的远洋鱼类囊肿破裂。分析工作从分子水平的变化一直持续到精子的最终形成。根据分子研究结果进行了组织学分析,结果显示了结构上的变化。鱼类诱导育种在水产养殖业的苗种生产中发挥着关键作用。然而,由于缺乏有关精子发生机制和物种对激素剂量特异性反应的广泛知识,该行业仍面临着一些制约因素。这项研究有助于了解精子萌发的分子机制,以及施用诱导剂后精子释放的临界点阶段。这项研究还为进一步探索物种对激素处理的特异性反应奠定了基础,有助于渔业领域的可持续苗种生产。
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引用次数: 0
A new frontier in neuropharmacology: Recent progress in natural products research for blood–brain barrier crossing 神经药理学的新领域:天然产品穿越血脑屏障研究的最新进展
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100235
Ureña-Vacas Isabel , Aznar de la Riera M. Belén , Serrano Dolores R , González-Burgos Elena

Neuropharmacology faces challenges due to the intricate nervous system, diverse neurological disorders, and existence of the blood–brain barrier (BBB), which hinder the development of effective treatments. Although the primary function of the BBB is to expel toxins and pathogens, this structure also prevents optimal drug delivery. Natural products, with their chemical diversity and sustainability, have long been recognized as potential neuroprotective compounds, making BBB permeability studies mandatory. Over the last ten years, biotechnological advances in two-dimensional in vitro BBB models (monoculture and co-culture), in vivo imaging techniques, and pharmacokinetic modeling have contributed to expanding our current knowledge. In this study, we have reviewed the BBB crossing of natural products such as different terpenoids, polyphenolic compounds, and alkaloids. The findings, obtained through in vitro, in vivo, and silico methods, revealed moderate to high permeability for many of these natural products. However, other compounds showed not to be able to reach the brain. To better understand the behavior of natural products in humans and improve their ability to pass across the blood-brainier, the development of new three-dimensional and dynamic models of the BBB, new nanosystems complexes for encapsulation or in-depth studies of the transport mechanism are current and future lines of research.

神经药理学面临的挑战包括错综复杂的神经系统、多种神经系统疾病以及血脑屏障(BBB)的存在,这些都阻碍了有效疗法的开发。虽然血脑屏障的主要功能是排出毒素和病原体,但这种结构也阻碍了药物的最佳输送。天然产品具有化学多样性和可持续性,长期以来一直被认为是潜在的神经保护化合物,因此必须进行 BBB 渗透性研究。在过去的十年中,二维体外 BBB 模型(单培养和共培养)、体内成像技术和药代动力学模型等生物技术的进步为拓展我们现有的知识做出了贡献。在本研究中,我们回顾了天然产品(如不同的萜类化合物、多酚化合物和生物碱)的 BBB 穿越情况。通过体外、体内和硅学方法获得的研究结果表明,这些天然产物中的许多都具有中度到高度的渗透性。然而,其他一些化合物则无法进入大脑。为了更好地了解天然产品在人体中的行为,提高其通过血脑屏障的能力,目前和未来的研究方向包括开发新的三维动态 BBB 模型、新的纳米系统封装复合物或深入研究转运机制。
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引用次数: 0
Discovery of novel plant biomass conversion associated fungal transcription factors using a network-based approach 利用基于网络的方法发现新型植物生物量转化相关真菌转录因子
IF 3.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100230
Mao Peng , Astrid Mueller , Joanna E. Kowalczyk , Roland S. Kun , Ronald P. de Vries

Fungal plant biomass conversion (FPBC) is an important component of the global carbon cycle and has been widely applied for the production of biofuels, enzymes and biochemicals. Identification of transcription factors (TFs) governing FPBC is crucial for genetic engineering of industrial fungi towards sustainable production of high-value bioproducts from renewable lignocellulose. Here, we developed a bioinformatics framework for the identification of FPBC related TFs based on reconstructed gene regulatory networks and enrichment analysis of manually curated FPBC gene sets. Applying this approach to model fungi Aspergillus niger and Neurospora crassa, we successfully identified both known TFs and promising candidates. The function of one identified TF, HapX, has been experimentally validated, and several candidates were supported by literature, transcriptome data and initial growth analysis. Our new approach will accelerate the identification of novel TFs involved in FPBC, and facilitate the further improvement of fungal cell factories.

真菌植物生物质转化(FPBC)是全球碳循环的重要组成部分,已被广泛应用于生物燃料、酶和生物化学品的生产。鉴定调控 FPBC 的转录因子(TFs)对于工业真菌的基因工程至关重要,以便从可再生木质纤维素中可持续地生产出高价值的生物产品。在此,我们开发了一个生物信息学框架,用于基于重建的基因调控网络和人工编辑的 FPBC 基因组的富集分析,鉴定与 FPBC 相关的 TFs。将这种方法应用于模式真菌黑曲霉(Aspergillus niger)和蟋蟀神经孢子菌(Neurospora crassa),我们成功地鉴定了已知的 TF 和有希望的候选 TF。其中一个已鉴定的 TF(HapX)的功能已得到实验验证,几个候选基因也得到了文献、转录组数据和初步生长分析的支持。我们的新方法将加速鉴定参与 FPBC 的新型 TF,促进真菌细胞工厂的进一步改进。
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引用次数: 0
Unveiling the potential of marine-derived diterpenes from the order Alcyonacea as promising anti-obesity agents 揭示海藻二萜作为抗肥胖药物的潜力
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100175
Mohamed A. Tammam , Omnia Aly , Florbela Pereira , Aldoushy Mahdy , Amr El-Demerdash

Metabolic syndrome (MS) represents a global health challenge characterized by various metabolic disorders, including HOMA-IR (insulin resistance), obesity, dyslipidemia, and hypertension. In our pursuit of identifying natural alternatives for the development of effective and safe anti-obesity medications, we examined the potential of the methanolic extract of the Red Sea derived soft coral Sarcophyton glaucum, where serum levels of glucose, insulin, HOMA-IR, lipid profile, fetuin A and B, PTP1Β (Protein tyrosine phosphatase 1B), adropin and omentin were determined. Furthermore, the expression of the UCP1 (Uncoupling protein 1) and PPARGC1A (Peroxisome proliferator–activated receptor-g coactivator-1a) genes have been assessed, to evaluate the anti-obesity potential of S. glaucum organic extract. Our findings demonstrated a significant decrease in glucose, HOMA-IR, cholesterol, triglyceride, LDL-C, fetuin A and B, and PTP1Β levels, accompanied by a significant increase in insulin, HDL-C, adropin, omentin, UCP1, and PPARGC1A expression after treatment with the soft coral extract. These promising outcomes can be attributed to the remarkable ingredients present in the extract, which were further supported by histopathological findings. In addition, a virtual screening protocol including molecular docking (MDock) and Structure-Activity Relationships (SARs) of 27 marine diterpenes was also explored to identify potential PTP1Β inhibitors targeting simultaneously the catalytic site and allosteric site, as well as fetuin A modulators. Moreover, the six most promising predicted marine diterpenes (4, 8, 9, 10, 13 and 14) were investigated for their pharmacokinetic properties, druglike nature and medicinal chemistry friendliness using the SwissADME platform. Of these, four marine diterpenes (4, 8, 9, and 10) were predicted to exhibit the appropriate drug-like properties.

代谢综合征(MS)是一项全球性的健康挑战,以各种代谢紊乱为特征,包括 HOMA-IR(胰岛素抵抗)、肥胖、血脂异常和高血压。为了寻找天然替代品以开发有效、安全的抗肥胖药物,我们研究了红海软珊瑚 Sarcophyton glaucum 的甲醇提取物的潜力,测定了血清中葡萄糖、胰岛素、HOMA-IR、血脂、胎盘素 A 和 B、PTP1Β(蛋白酪氨酸磷酸酶 1B)、阿托品和网膜素的水平。此外,还评估了 UCP1(解偶联蛋白 1)和 PPARGC1A(过氧化物酶体增殖激活受体-g 辅激活剂-1a)基因的表达,以评价 S. glaucum 有机提取物的抗肥胖潜力。我们的研究结果表明,使用软珊瑚提取物治疗后,血糖、HOMA-IR、胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、胎盘素 A 和 B 以及 PTP1Β 的水平明显下降,而胰岛素、高密度脂蛋白胆固醇(HDL-C)、阿糖肽、网织蛋白、UCP1 和 PPARGC1A 的表达则明显增加。这些令人鼓舞的结果可归功于提取物中的卓越成分,而组织病理学研究结果也进一步证实了这一点。此外,还对 27 种海洋二萜进行了虚拟筛选,包括分子对接(MDock)和结构-活性关系(SARs),以确定同时针对催化位点和异构位点的潜在 PTP1Β 抑制剂以及胎盘素 A 调节剂。此外,还利用 SwissADME 平台研究了六种最有前景的预测海洋二萜(4、8、9、10、13 和 14)的药代动力学特性、类药物性质和药物化学友好性。其中,4、8、9 和 10 四种海洋二萜被预测为具有相应的类药物特性。
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引用次数: 0
Coupling electrokinetic remediation with ryegrass for the synergistic remediation of Cd and C14 alkane co-contaminated soil 将电动修复与黑麦草结合起来,协同修复镉和 C14 烷烃共同污染的土壤
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100202
Lizhu Yuan , Shuhai Guo , Yang Wu , Bo Wu , Fenglian Cheng , Jinghao Gao , Xiaowu Huang

Electrokinetic coupled with phytoremediation (EKPR) is an innovative technology to remediate heavy metals or petroleum hydrocarbons polluted soils. However, the feasibility and mechanism of EKPR remediation heavy metals and petroleum hydrocarbons co-contaminated soil are still unknown. This study evaluated the feasibility and potency of coupling EK remediation with Lolium perenne L. (ryegrass) (EKRG) in remediating the cadmium (Cd) and C14 alkane co-contaminated soil. The ryegrass biomass, Cd uptake amount, C14 alkane removal and soil bacterial community were determined for different soil sections of the EKRG treatment. Results indicated that the polarity reversal direct current electric field increased the total Cd uptake amount of ryegrass to 17.95 μg, most likely due to an increase of 41.7 % of the ryegrass shoot biomass. The ryegrass shoots, in the initial anode section of EKRG treatment, acquired an increment in biomass by 82.1 % and Cd uptake amount by 67.1 %, corresponding to 1.02 g and 7.76 μg, respectively. The EKRG treatment boosted the removal of C14 alkane in comparison with the mono-treatment of ryegrass or EK, i.e., increasing by 28.4 % and 36.5 %, respectively. Microbial community analysis suggested that the EKRG treatment promoted the relative abundances of hydrocarbons degrading bacteria, potentially responding to the enhanced removal of C14 alkane. Further, the correlation analysis showed that the removal of C14 alkane was positively correlated with the ryegrass biomass and Cd uptake amount in the EKRG treatment, which again validated that the addition of electric field benefited the remediation of Cd and the removal of C14 alkane. These results together indicated that the electric field assisted phytoremediation would be an effective approach for remediating the Cd and C14 alkane co-contaminated soils.

电动耦合植物修复(EKPR)是一种修复重金属或石油碳氢化合物污染土壤的创新技术。然而,EKPR 修复重金属和石油碳氢化合物共污染土壤的可行性和机理尚不清楚。本研究评估了 EK 修复与 Lolium perenne L. (黑麦草)(EKRG)耦合修复镉(Cd)和 C14 烷烃共污染土壤的可行性和有效性。对 EKRG 处理的不同土壤断面进行了黑麦草生物量、镉吸收量、C14 烷烃去除量和土壤细菌群落测定。结果表明,极性反转直流电场将黑麦草对镉的总吸收量提高到 17.95 μg,这很可能是由于黑麦草嫩枝生物量增加了 41.7%。在 EKRG 处理的初始阳极段,黑麦草芽的生物量增加了 82.1%,镉吸收量增加了 67.1%,分别为 1.02 克和 7.76 微克。与黑麦草或 EK 的单一处理相比,EKRG 处理提高了对 C14 烷烃的去除率,分别增加了 28.4% 和 36.5%。微生物群落分析表明,EKRG 处理提高了碳氢化合物降解细菌的相对丰度,这可能与 C14 烷烃去除率的提高有关。此外,相关分析表明,在 EKRG 处理中,C14 烷烃的去除率与黑麦草生物量和镉吸收量呈正相关,这再次验证了电场的加入有利于镉的修复和 C14 烷烃的去除。这些结果共同表明,电场辅助植物修复将是修复镉和 C14 烷共同污染土壤的有效方法。
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引用次数: 0
Changes in chemical composition and fermentation profile in silages from rehydrated grains of maize hybrids during prolonged air exposure 玉米杂交种复水谷青贮饲料在长期空气暴露期间化学成分和发酵曲线的变化
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100206
Kristina Kljak, Veronika Gunjević, Tea Kavčić, Dora Zurak, Marija Duvnjak, Goran Kiš, Darko Grbeša

Most studies investigated the effects of air exposure during the ensiling of whole maize silage and high-moisture maize grains on the chemical composition and fermentation profile, but not of rehydrated grain. The aim of the present study was to investigate the effect of the hybrid and the duration of air exposure on the pH and the content of moisture, main nutrients, fermentation products and nitrogen fractions in silages from three commercial maize hybrids. The grains were rehydrated to 32 % of moisture and ensiled for 63 days with the addition of an inoculant (BIO-SIL®, Dr Pieper Technologie und Produktentwicklung GmbH). After opening, the silages were stored at room temperature for 10 days and samples were taken after 0, 1, 3, 5 and 10 days of air exposure. With increasing duration of air exposure, the content of moisture, lactic and acetic acid and ethanol decreased, while the pH value and the content of water-soluble carbohydrates and ammonia increased. The hybrid affected all the determined properties of the silages except the pH and the ethanol content. There were distinct differences in the contents of moisture, total sugars, water-soluble carbohydrates, lactic, acetic, propionic and isobutyric acids, methanol and ammonia, suggesting that some hybrids may be more susceptible to aerobic spoilage. The majority of the properties remained similar until the fifth day of air exposure, suggesting that the silages of all three hybrids were stable during this period. The only property that increased immediately after air exposure was the content of nitrogen fractions suggesting that proteolysis was occurring, even though pH and lactic acid content remained unchanged. Overall, the results of the study indicate that the behaviour of rehydrated maize silage after exposure to air should be taken into account when selecting maize hybrids.

大多数研究调查了全株玉米青贮和高水分玉米谷物在贮藏期间暴露于空气中对化学成分和发酵概况的影响,但没有调查再水化谷物的影响。本研究的目的是调查杂交种和空气暴露持续时间对三种商品玉米杂交种青贮饲料的 pH 值、水分含量、主要营养成分、发酵产物和氮组分的影响。谷物被重新水化至 32% 的水分,并在添加接种剂(BIO-SIL®,Dr Pieper Technologie und Produktentwicklung GmbH)后贮存 63 天。青贮打开后,在室温下存放 10 天,分别在暴露于空气 0 天、1 天、3 天、5 天和 10 天后取样。随着空气暴露时间的延长,水分、乳酸、乙酸和乙醇的含量下降,而 pH 值、水溶性碳水化合物和氨的含量上升。除 pH 值和乙醇含量外,杂交种影响了青贮饲料的所有测定特性。水分、总糖、水溶性碳水化合物、乳酸、乙酸、丙酸和异丁酸、甲醇和氨的含量存在明显差异,这表明某些杂交种可能更容易发生有氧腐败。在暴露于空气的第五天之前,大多数特性都保持相似,这表明所有三种杂交种的青贮在此期间都很稳定。唯一在暴露于空气后立即增加的特性是氮组分的含量,这表明发生了蛋白质分解,尽管 pH 值和乳酸含量保持不变。总之,研究结果表明,在选择玉米杂交种时应考虑再水化玉米青贮暴露于空气后的表现。
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引用次数: 0
Postbiotics, a natural feed additive for growth performance, gut microbiota and quality of poultry products 后益生菌,一种促进家禽生长性能、肠道微生物群和产品质量的天然饲料添加剂
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100247

Implementing global strategies for sustainable poultry production is imperative, considering the continuous growth of the human population and the subsequent rise in demand for poultry products, which must be fully safe for future consumers. Identifying and implementing safe, environmentally friendly, and cost-effective alternatives such as postbiotics have become imperative in sustainable poultry farming. This is primarily due to the increasing apprehensions surrounding antimicrobial resistance, the need to minimise or eliminate the use of antibiotic growth promoters, and the growing consumer preference for products that are free from chemicals and antibiotics. Postbiotics refer to bioactive compounds that are synthesised by lactic acid bacteria during the process of metabolising prebiotics. These compounds, also known as biogenics or metabolites, are soluble factors that offer notable health benefits. This concept is a recent development in the field of animal nutrition. Postbiotics possess modes of action and capabilities similar to probiotics, albeit lacking live cells, owing to the presence of probiotic secondary metabolites. These encompass several pharmacologically active compounds that positively influence the performance and quality of poultry products. This article examines the concept, impact and approaches associated with using an innovative solution such as postbiotics in the context of sustainable poultry production.

考虑到人类人口的持续增长以及随之而来的对家禽产品需求的增加,实施可持续家禽生产的全球战略势在必行。在可持续家禽养殖业中,确定并实施安全、环保、经济高效的替代品(如益生元)已势在必行。这主要是由于人们对抗菌素耐药性的担忧与日俱增,需要最大限度地减少或消除抗生素生长促进剂的使用,以及消费者对不含化学品和抗生素的产品的青睐与日俱增。后益生菌是指乳酸菌在代谢益生菌的过程中合成的生物活性化合物。这些化合物也被称为生物原或代谢物,是具有显著健康益处的可溶性因子。这一概念是动物营养领域的最新发展。后益生菌具有与益生菌类似的作用模式和能力,尽管由于益生菌次级代谢产物的存在而缺乏活细胞。它们包括多种药理活性化合物,可对家禽产品的性能和质量产生积极影响。本文探讨了在可持续家禽生产中使用后益生菌等创新解决方案的相关概念、影响和方法。
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引用次数: 0
Anti-Melanoma efficacy of traditional multi-herbal extracts from mongolian ethnomedicine on B16F10 murine cells 蒙古民族医药传统多草药提取物对 B16F10 小鼠细胞的抗黑色素瘤功效
IF 5.6 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100217
Yerkegul Dauletkhan , Tae Young Han , Janbolat Ashim , Shukherdorj Baasanmunkh , Altantsetseg Khajidsuren , Wookyung Yu , Purevjargal Naidansuren , Uteubayeva Gulzada , Kang Duk Choi , Baatartsogt Oyungerel

Multi-herbal formulation is an attractive approach to developing novel therapeutic strategies to manage advanced forms of melanoma. This research aims to evaluate the anti-melanoma potential of Traditional Multi-Herbal (G4) Extracts sourced from Mongolian Ethnomedicine utilizing both cellular and xenograft models. In vitro and ex vivo experiments employing B16F10 melanoma cells were conducted to evaluate the anti-cancer effect of the G4 extract. Furthermore, in vivo experiments utilizing BALB/C nu/nu mice xenograft models were carried out to gauge the extract's effectiveness. A comprehensive analysis encompassing various assays, such as cell viability, migration and invasion assays, cellular phase analysis, and key indicators of apoptosis, was performed. These indicators included activation of the caspase-3 cascade, genomic DNA fragmentation, nuclear staining alterations, and levels of cell cycle and apoptotic regulatory markers analysis. Our Results showed that the G4 extract exhibited potent anti-cancer effects on B16F10 melanoma cells, notably inhibiting cell migration and vascular sprouting in a concentration-dependent manner, suggesting its potential to impede melanoma metastasis. This investigation underscores the promising anti-cancer potential of the G4 extract against melanoma cells through the modulation of apoptotic pathways and suppression of tumor xenograft growth. Ultimately, our findings suggest that the G4 extract holds promise as a candidate for the development of future melanoma chemotherapeutics.

多种草药配方是开发新型治疗策略以控制晚期黑色素瘤的一种有吸引力的方法。本研究旨在利用细胞和异种移植模型,评估来自蒙古民族医药的传统多草药(G4)提取物的抗黑色素瘤潜力。采用 B16F10 黑色素瘤细胞进行体外和体内实验,以评估 G4 提取物的抗癌效果。此外,还利用 BALB/C nu/nu 小鼠异种移植模型进行了体内实验,以评估提取物的有效性。实验进行了全面的分析,包括各种检测方法,如细胞活力、迁移和侵袭检测、细胞期分析以及细胞凋亡的关键指标。这些指标包括 Caspase-3 级联的激活、基因组 DNA 断裂、核染色改变以及细胞周期和凋亡调控标志物水平分析。我们的研究结果表明,G4 提取物对 B16F10 黑色素瘤细胞有很强的抗癌作用,特别是以浓度依赖的方式抑制细胞迁移和血管萌发,这表明它具有阻碍黑色素瘤转移的潜力。这项研究强调了 G4 提取物通过调节细胞凋亡途径和抑制肿瘤异种移植生长,对黑色素瘤细胞具有良好的抗癌潜力。最终,我们的研究结果表明,G4 提取物有望成为开发未来黑色素瘤化疗药物的候选物质。
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引用次数: 0
From circadian sleep disruption to Neuroprotection: The potential of VIP/PACAP in Alzheimer’s disease treatment 从昼夜节律睡眠干扰到神经保护:VIP/PACAP在阿尔茨海默病治疗中的潜力
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100254

Alzheimer’s Disease (AD) represents a significant neurodegenerative challenge with current therapeutic strategies primarily focused on symptomatic management. This review explores the relationship between disrupted circadian rhythms, AD and the critical involvement of vasoactive intestinal peptide (VIP) and adenylate cyclase-activating polypeptide (PACAP) signaling pathways. These pathways hold promise for new drug development and provide insights into the complex pathogenesis of AD. Enhancement of brain bioavailability through advanced drug delivery systems is proposed and reviewed.

阿尔茨海默病(AD)是神经退行性病变的重大挑战,目前的治疗策略主要侧重于对症治疗。这篇综述探讨了昼夜节律紊乱与阿尔茨海默病之间的关系,以及血管活性肠肽(VIP)和腺苷酸环化酶激活多肽(PACAP)信号通路的重要参与。这些途径为新药开发带来了希望,并为了解复杂的注意力缺失症发病机制提供了线索。本文提出并综述了通过先进的给药系统提高大脑生物利用度的建议。
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引用次数: 0
Biocompatible, controlled-release remdesivir-loaded liposomes tackling the telomerase activity of Non-Small cell lung cancer cells: Preparation, characterization, in vitro biological evaluation, and molecular docking analysis 具有生物相容性的控释雷米替韦脂质体可抑制非小细胞肺癌细胞的端粒酶活性:制备、表征、体外生物学评价和分子对接分析
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crbiot.2024.100256
Non-small cell lung cancer (NSCLC) is a global leading cause of cancer mortality. Herein, remdesivir (RDV) was loaded into biocompatible liposomes (RDV-Lips) composed of 1,2-dipalmitoyl-sn‑glycero-3-phosphocholine (DPPC), cholesterol, and polyethylene glycol hexadecyl ether (Brij-58) to enhance its solubility and anticancer efficiency. The study highlighted the possible RDV-induced underlying events, emphasizing its inhibitory potential of telomerase activity through in-silico docking and in vitro studies. RDV-Lips were developed using thin-film hydration and then subjected to physicochemical characterizations. The selected formulations were evaluated for their stability, in vitro release, and in vitro anticancer activity. The size range of RDV-Lips was 83.8–157.9 nm with a polydispersity index (PDI) lower than 0.23 and entrapment exceeded 93%. The cholesterol content of RDV-Lips offered a control point of RDV release, where high and low concentrations exerted slow and fast release patterns, respectively. RDV-Lips showed enhanced anticancer activity and selectivity. They inhibited colony formation, increased lipid peroxidation, induced apoptosis, and inhibited the telomerase activity in a dose-dependent manner. In conclusion, RDV-Lips overcame RDV solubility problems and enhanced its anticancer efficiency. RDV could be a potential therapy against NSCLC via induction of oxidative stress and inhibition of the telomerase activity, which, in turn, restricts unlimited cellular proliferation and apoptosis induction.
非小细胞肺癌(NSCLC)是全球癌症死亡的主要原因。在本研究中,雷米替韦(RDV)被载入由1,2-二棕榈酰-sn-甘油-3-磷酸胆碱(DPPC)、胆固醇和聚乙二醇十六烷基醚(Brij-58)组成的生物相容性脂质体(RDV-Lips)中,以提高其溶解度和抗癌效率。该研究强调了 RDV 可能诱导的基本事件,并通过室内对接和体外研究强调了其抑制端粒酶活性的潜力。研究人员利用薄膜水合技术开发了 RDV-Lips,并对其进行了理化表征。对所选制剂的稳定性、体外释放和体外抗癌活性进行了评估。RDV-Lips 的尺寸范围为 83.8-157.9 nm,多分散指数(PDI)低于 0.23,夹带率超过 93%。RDV-Lips 的胆固醇含量提供了一个 RDV 释放的控制点,高浓度和低浓度分别具有缓慢和快速的释放模式。RDV-Lips 显示出更强的抗癌活性和选择性。它们以剂量依赖的方式抑制了癌细胞的形成,增加了脂质过氧化,诱导了细胞凋亡,并抑制了端粒酶的活性。总之,RDV-Lips 克服了 RDV 的溶解性问题,提高了其抗癌效率。RDV 可以通过诱导氧化应激和抑制端粒酶活性,进而限制细胞无限增殖和诱导细胞凋亡,成为一种潜在的治疗 NSCLC 的方法。
{"title":"Biocompatible, controlled-release remdesivir-loaded liposomes tackling the telomerase activity of Non-Small cell lung cancer cells: Preparation, characterization, in vitro biological evaluation, and molecular docking analysis","authors":"","doi":"10.1016/j.crbiot.2024.100256","DOIUrl":"10.1016/j.crbiot.2024.100256","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is a global leading cause of cancer mortality. Herein, remdesivir (RDV) was loaded into biocompatible liposomes (RDV-Lips) composed of 1,2-dipalmitoyl-sn‑glycero-3-phosphocholine (DPPC), cholesterol, and polyethylene glycol hexadecyl ether (Brij-58) to enhance its solubility and anticancer efficiency. The study highlighted the possible RDV-induced underlying events, emphasizing its inhibitory potential of telomerase activity through in-silico docking and in vitro studies. RDV-Lips were developed using thin-film hydration and then subjected to physicochemical characterizations. The selected formulations were evaluated for their stability, in vitro release, and in vitro anticancer activity. The size range of RDV-Lips was 83.8–157.9 nm with a polydispersity index (PDI) lower than 0.23 and entrapment exceeded 93%. The cholesterol content of RDV-Lips offered a control point of RDV release, where high and low concentrations exerted slow and fast release patterns, respectively. RDV-Lips showed enhanced anticancer activity and selectivity. They inhibited colony formation, increased lipid peroxidation, induced apoptosis, and inhibited the telomerase activity in a dose-dependent manner. In conclusion, RDV-Lips overcame RDV solubility problems and enhanced its anticancer efficiency. RDV could be a potential therapy against NSCLC via induction of oxidative stress and inhibition of the telomerase activity, which, in turn, restricts unlimited cellular proliferation and apoptosis induction.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421325","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}
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Current Research in Biotechnology
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