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Approaches for Producing Fungal Cellulases Through Submerged Fermentation. 通过浸没发酵生产真菌纤维素酶的方法。
Pub Date : 2024-01-31 DOI: 10.31083/j.fbe1601005
Madiha Nazir, Attia Iram, Deniz Cekmecelioglu, Ali Demirci

Fungal cellulases are the most sought-after biological molecules produced from microbial sources in the last four decades. Owing to their emerging applications in the bioenergy industry for hydrolyzing cellulose, for which they are the most abundant source on this planet, research trends are shifting heavily toward adapting to submerged fermentation. However, filamentous fungal species, which are efficient cellulase producers, are well-adapted to low-moisture solid support as the substrate, such as in nature. Therefore, various fermentation strategies are currently being investigated to adapt them to submerged fermentation for large and high-quality production of cellulases. Emerging research trends, such as the use of inexpensive feedstocks, nutrient and/or culture optimization, innovative bioreactor designs, microparticle-assisted fungal growth, and innovative genetic engineering approaches, are some of the recent efforts by researchers to exploit the full potential of these biological molecules. This review discusses some of these strategies and their success rates in various research conditions. In addition, specific focus was provided to both increasing the market value of cellulases and the innovative strategies required to enhance their production on an industrial scale.

真菌纤维素酶是近四十年来从微生物来源生产的最受欢迎的生物分子。纤维素是地球上最丰富的资源,由于其在生物能源工业中用于水解纤维素的新兴应用,研究趋势正大量转向适应浸没式发酵。然而,丝状真菌物种是高效的纤维素酶生产者,它们非常适合以低水分的固体支持物作为底物,如自然界中的底物。因此,目前正在研究各种发酵策略,以使它们适应浸没式发酵,从而大量、高质量地生产纤维素酶。新出现的研究趋势,如使用廉价原料、营养和/或培养优化、创新的生物反应器设计、微颗粒辅助真菌生长以及创新的基因工程方法等,都是研究人员近期为充分挖掘这些生物分子的潜力而做出的努力。本综述讨论了其中一些策略及其在各种研究条件下的成功率。此外,还特别关注如何提高纤维素酶的市场价值,以及在工业规模上提高纤维素酶产量所需的创新战略。
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引用次数: 0
Emerging Trends in Wheat (Triticum spp.) Breeding: Implications for the Future. 小麦(Triticum spp.)育种的新趋势:对未来的影响。
Pub Date : 2024-01-31 DOI: 10.31083/j.fbe1601002
Mujahid Alam, P Stephen Baenziger, Katherine Frels

Wheat (Triticum spp and, particularly, T. aestivum L.) is an essential cereal with increased human and animal nutritional demand. Therefore, there is a need to enhance wheat yield and genetic gain using modern breeding technologies alongside proven methods to achieve the necessary increases in productivity. These modern technologies will allow breeders to develop improved wheat cultivars more quickly and efficiently. This review aims to highlight the emerging technological trends used worldwide in wheat breeding, with a focus on enhancing wheat yield. The key technologies for introducing variation (hybridization among the species, synthetic wheat, and hybridization; genetically modified wheat; transgenic and gene-edited), inbreeding (double haploid (DH) and speed breeding (SB)), selection and evaluation (marker-assisted selection (MAS), genomic selection (GS), and machine learning (ML)) and hybrid wheat are discussed to highlight the current opportunities in wheat breeding and for the development of future wheat cultivars.

小麦(Triticum spp,尤其是 T. aestivum L.)是一种重要谷物,对人类和动物的营养需求不断增加。因此,需要利用现代育种技术和成熟的方法来提高小麦产量和遗传增益,以实现必要的生产力增长。这些现代技术将使育种者能够更快、更有效地培育出改良的小麦品种。本综述旨在强调全球小麦育种中使用的新兴技术趋势,重点是提高小麦产量。文中讨论了引入变异(品种间杂交、合成小麦和杂交;转基因小麦;转基因和基因编辑)、近亲繁殖(双单倍体(DH)和速度育种(SB))、选择和评价(标记辅助选择(MAS)、基因组选择(GS)和机器学习(ML))以及杂交小麦的关键技术,以强调当前小麦育种和未来小麦栽培品种开发的机遇。
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引用次数: 0
Isolation and Identification of Phenol-Degrading Bacteria from Iranian Soil and Leaf Samples. 伊朗土壤和叶片样本中苯酚降解细菌的分离与鉴定
Pub Date : 2023-12-12 DOI: 10.31083/j.fbe1504029
Atefehsadat Mortazavi, Mehdi Hassanshahian, Eyhab Ali, Mohammed N Fenjan, Ahmed Alawadi, Ali Alsalamy

Background: By considering the importance and role of soil in the health of humanity, it is important to remove the presence of harmful compounds, such as phenol.

Methods: In this study, four types of soil and leaf samples were collected from Kerman, Iran, and the amounts of heterotrophic and degradation bacteria were determined using the serial dilution and most probable number (MPN) methods. The amount of removed phenol was investigated using the Gibbs method with different concentrations of phenol. Then, an isolate with the highest percentage of phenol degradation was identified as the superior strain using 16 sRNA sequencing. The effects of the different factors, such as the carbon source (1% molasses and 1 g glucose), nitrogen source (0.1 g yeast extract), mixed culture, and time (14 and 28 days), on the biodegradation ability of the superior strain was investigated.

Results: A total of 18 bacterial strains were isolated from the samples. Isolate B3 had the highest rate (75%) of phenol degradation, at a concentration of 1000 ppm, meaning it was identified as the superior strain. The molecular analysis results identified this isolate as the Comamonas testosteroni strain F4. This bacterium can degrade 89% of the phenol at 30 °C, 180 rpm, and 800 ppm over 28 days. C. testosteroni did not show a favorable phenol degradation ability in the presence of the investigated carbon sources, while this ability was also reduced in mixed cultures.

Conclusions: C. testosteroni bacterial strain isolated from soil samples of pistachio orchards in Kerman, Iran, has a favorable ability to biodegrade phenol.

背景:考虑到土壤对人类健康的重要性和作用,必须去除土壤中的有害化合物,如苯酚:考虑到土壤对人类健康的重要性和作用,必须清除土壤中的有害化合物,如苯酚:本研究从伊朗克尔曼采集了四种类型的土壤和树叶样本,并使用系列稀释法和最可能数(MPN)法测定了异养菌和降解菌的数量。使用吉布斯法对不同浓度的苯酚进行了研究,以确定苯酚的去除量。然后,利用 16 sRNA 测序鉴定出苯酚降解率最高的分离菌株为优良菌株。研究了碳源(1% 糖蜜和 1 克葡萄糖)、氮源(0.1 克酵母提取物)、混合培养和时间(14 天和 28 天)等不同因素对优势菌株生物降解能力的影响:结果:共从样品中分离出 18 种细菌菌株。当苯酚浓度为 1000 ppm 时,分离菌株 B3 的苯酚降解率最高(75%),因此被认定为优势菌株。分子分析结果确定该分离菌株为 Comamonas testosteroni 菌株 F4。在温度为 30 °C、转速为 180 转/分、浓度为 800 ppm 的条件下,该细菌可在 28 天内降解 89% 的苯酚。在所研究的碳源存在下,C. testosteroni菌株没有表现出良好的苯酚降解能力,而在混合培养物中,这种能力也有所下降:结论:从伊朗克尔曼开心果园土壤样本中分离出的 C. testosteroni 细菌菌株具有良好的生物降解苯酚的能力。
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引用次数: 0
Recovery of Phenolic Compounds from Orange Peel Waste by Conventional and Assisted Extraction Techniques Using Sustainable Solvents. 使用可持续溶剂的传统和辅助萃取技术从橘皮废料中回收酚类化合物
Pub Date : 2023-12-12 DOI: 10.31083/j.fbe1504030
Blanca Sáenz de Miera, Raquel Cañadas, María González-Miquel, Emilio J González

Background: The valorization of orange peel waste (OPW) through the extraction of bioactive compounds is a clear example of the circular economy. OPW contains many value-added compounds, among which bioactive phenolic compounds (flavonoids and phenolic acids) could be extracted and used for industrial applications, such as pharmaceuticals or cosmetics.

Methods: In this work, the extraction of phenolic compounds from orange peel was carried out by conventional (orbital shaker) and assisted (ultrasound and microwave) extraction techniques using deionized water, 80% (v/v) ethanol in water, and ethyl acetate as solvents. The effect of temperature, extraction time, and type of technique was evaluated and discussed following spectrophotometric (total phenolic content and total flavonoid content) and high-performance liquid chromatography (HPLC) analyses of the extracts.

Results: The most effective extraction in terms of efficiency was achieved by microwave-assisted extraction using 80% (v/v) ethanol in water as the extraction solvent, at 373 K for 6 min, which obtained 7.2 ± 0.1 mg gallic acid equivalent (GAE)/g OPW and 13.3 ± 0.1 mg quercetin equivalent (QE)/g OPW, with the main bioactive compound extracted being hesperidin (58.2 ± 0.2 mg/g OPW). The most effective extraction in terms of energy consumption was achieved using ultrasound-probe-assisted extraction, yielding 8.8 ± 0.0 mg GAE/g OPW; 17.1 ± 0.1 mg QE/g OPW; 40.0 ± 0.2 mg hesperidin/g OPW, with an energy consumption of 18 kJ.

Conclusions: Ultrasound and microwave-assisted extractions can be considered efficient extraction technologies for the valorization of OPW as they reduce extraction time and energy consumption and increase extraction yield.

背景:通过提取生物活性化合物实现橘皮废料(OPW)的价值化是循环经济的一个明显例子。橘皮废料中含有许多高附加值的化合物,其中生物活性酚类化合物(类黄酮和酚酸)可被提取出来并用于制药或化妆品等工业用途:本研究以去离子水、80%(v/v)乙醇水溶液和乙酸乙酯为溶剂,采用常规(轨道摇床)和辅助(超声波和微波)萃取技术提取橘皮中的酚类化合物。在对提取物进行分光光度法(总酚含量和总黄酮含量)和高效液相色谱法(HPLC)分析后,对温度、提取时间和技术类型的影响进行了评估和讨论:微波辅助萃取的效率最高,萃取溶剂为 80%(v/v)乙醇水溶液,在 373 K 下萃取 6 分钟,可获得 7.2 ± 0.1 毫克没食子酸当量(GAE)/克 OPW 和 13.3 ± 0.1 毫克槲皮素当量(QE)/克 OPW,提取的主要生物活性化合物为橙皮甙(58.2 ± 0.2 毫克/克 OPW)。就能耗而言,超声波探针辅助萃取的效果最好,可获得 8.8 ± 0.0 毫克 GAE/g OPW;17.1 ± 0.1 毫克 QE/g OPW;40.0 ± 0.2 毫克橙皮甙/g OPW,能耗为 18 kJ:结论:超声波和微波辅助萃取可减少萃取时间和能耗,提高萃取率,因此可被视为实现 OPW 价值化的高效萃取技术。
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引用次数: 0
Biological Ammonia Production via Anaerobic Fermentation of Soy Meal Protein. 通过厌氧发酵豆粕蛋白生产生物氨。
Pub Date : 2023-12-05 DOI: 10.31083/j.fbe1504027
Ibrahim Bello, Adewale Adeniyi, Taofeek Mukaila, Ewumbua Monono, Ademola Hammed

Background: Conventional ammonia production methods, notably the energy-intensive Haber-Bosch process, are costly and contribute substantially to about 2% of the world's CO2 emissions. This study focuses on the biological approach to convert protein to ammonia via hyper-ammonia-producing bacteria (HAB) fermentation.

Methods: A consortium of ruminal microbes was employed in this work to ferment soybean meal protein under varying processing conditions. The parameters investigated included pH (7-11), inoculum concentrations (1-10%), substrate concentrations (5-20%), and fermentation time (0-168 h).

Results: Optimal conditions for microbial growth and biological ammonia production were observed at pH 7, fermentation duration of 72 h, inoculum concentration of 10%, and substrate concentration of 10%. ~8000 mg/L biological ammonia was produced following HAB fermentation.

Conclusions: By leveraging the capabilities of rumen HAB, this study contributes to the ongoing efforts to develop environmentally friendly processes for ammonia production that will mitigate both economic and environmental concerns associated with traditional methods.

背景:传统的氨生产方法,特别是能源密集型的哈伯-博施工艺,成本高昂,并造成全球约 2% 的二氧化碳排放量。本研究重点关注通过高产氨细菌(HAB)发酵将蛋白质转化为氨的生物方法:方法:本研究采用瘤胃微生物群在不同的加工条件下发酵豆粕蛋白。研究参数包括 pH 值(7-11)、接种物浓度(1-10%)、底物浓度(5-20%)和发酵时间(0-168 小时):结果:在 pH 值为 7、发酵时间为 72 小时、接种物浓度为 10%、底物浓度为 10%的条件下,观察到微生物生长和生物氨产生的最佳条件。HAB 发酵后产生了 ~8000 mg/L 的生物氨:通过利用瘤胃 HAB 的能力,本研究为目前开发环境友好型氨生产工艺的努力做出了贡献,这将减轻与传统方法相关的经济和环境问题。
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引用次数: 0
The Role of the Microbiome in Inflammation and Carcinogenesis. 微生物组在炎症和致癌过程中的作用
Pub Date : 2023-12-05 DOI: 10.31083/j.fbe1504028
Agata Jabłońska-Trypuć

Inflammation has been confirmed to exist in the tumor microenvironment, while the risk of cancer occurrence increases in cases of chronic inflammation. It is estimated that approximately 10% to 20% of cancers are associated with chronic infections and attendant inflammation. Bacteria, both pathogenic and commensal, viruses, and fungi actively participate in the development and maintenance of inflammation and tumor growth in humans. The exposome, which is a sum of human environmental exposures, such as industrial diet, consumed drugs, and toxins, affects the composition and function of the human microbiome, which could lead to dysbiosis and disorders in tissue homeostasis through different mechanisms, including the intensification of the immune response, activation and abnormal proliferation, and disruption to epithelial barrier integrity. Presently, science remains at the stage of revealing the complexity associated with the mechanisms involved in building relationships that cover the microbiome-inflammation-tumor, yet it is already known how important it is to care for microbial homeostasis of the organism.

炎症已被证实存在于肿瘤微环境中,而慢性炎症会增加癌症发生的风险。据估计,约有 10% 到 20% 的癌症与慢性感染和随之而来的炎症有关。细菌(包括致病细菌和共生细菌)、病毒和真菌积极参与人类炎症和肿瘤生长的发展和维持。暴露组是人类环境暴露的总和,如工业饮食、服用的药物和毒素,影响着人类微生物组的组成和功能,可能通过不同的机制导致菌群失调和组织平衡失调,包括免疫反应的加强、激活和异常增殖,以及上皮屏障完整性的破坏。目前,科学仍处于揭示与建立微生物组-炎症-肿瘤关系相关机制的复杂性阶段,但人们已经知道,关注机体的微生物平衡是多么重要。
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引用次数: 0
Degradation of a Model Mixture of PAHs by Bacterial-Fungal Co-Cultures. 细菌-真菌共培养物对多环芳烃模型混合物的降解。
Pub Date : 2023-12-05 DOI: 10.31083/j.fbe1504026
Natalia Pozdnyakova, Anna Muratova, Anastasia Bondarenkova, Olga Turkovskaya

Background: Bacteria and fungi are the most important soil organisms owing to their abundance and the key roles they play in the functioning of ecosystems. We examined possible synergistic and antagonistic effects during the degradation of polycyclic aromatic hydrocarbons (PAHs) by co-cultures of ascomycetes and a plant-growth-promoting bacterium.

Methods: Bacteria and fungi were grown in a liquid nutrient medium supplemented with PAHs. The PAH degradations and the identification of metabolites were checked by high-performance liquid chromatography (HPLC). Enzymatic activities were measured spectrophotometrically using test substrates. All experimental treatments were analyzed using Excel 2019 (Microsoft Office 2019, USA).

Results: The model system included the plant-growth-promoting rhizobacterium (PGPR) Azospirillum brasilense and one of the following ascomycetes: Fusarium oxysporum (plant pathogen), Talaromyces sayulitensis (rhizospheric fungus), Trichoderma viride (plant-growth-promoting fungus, PGPF), and Trichoderma harzianum (PGPF). The notable results are: (1) synergistic effects consisted of more active utilization of the PAH mixture compared to individual compounds, while the PAH mixture was more actively degraded by co-cultures than monocultures; (2) three effects of mutual influence by the studied organisms were also revealed: depressing (F. oxysporum and A. brasilense), partially depressing (T. sayulitensis suppressed the growth of A. brasilense but increased the degradation of anthracene, pyrene, and fluoranthene), and positive effects (A. brasilense and T. viride or T. harzianum); (3) for the first time quinone metabolites of PAH degradation and extracellular oxidase and peroxidase were produced during PAH degradation by T. sayulitensis.Conclusions: The results of the study contribute to the understanding of bacterial-fungal interactions in polluted settings.

背景:细菌和真菌是最重要的土壤生物,因为它们数量众多,而且在生态系统的运作中发挥着关键作用。我们研究了子囊菌和一种促进植物生长的细菌在降解多环芳烃(PAHs)过程中可能产生的协同和拮抗作用:方法:在添加了多环芳烃的液体营养培养基中培养细菌和真菌。采用高效液相色谱法(HPLC)检测多环芳烃的降解和代谢产物的鉴定。使用测试底物以分光光度法测量酶活性。所有实验处理均使用 Excel 2019(Microsoft Office 2019,美国)进行分析:模型系统包括促进植物生长的根瘤菌(PGPR)巴西天青霉(Azospirillum brasilense)和下列子囊菌之一:Fusarium oxysporum(植物病原体)、Talaromyces sayulitensis(根瘤菌)、Trichoderma viride(植物生长促进真菌,PGPF)和 Trichoderma harzianum(PGPF)。值得注意的结果是(1) 与单个化合物相比,多环芳烃混合物的协同效应包括更积极地利用多环芳烃混合物,而共培养物比单培养物更积极地降解多环芳烃混合物;(2) 研究生物的三种相互影响效应也被揭示出来:抑制(F. oxysporum 和 A. brasilense)、部分抑制(T.sayulitensis抑制了巴西杉的生长,但增加了对蒽,芘和荧蒽的降解),以及积极的影响(巴西杉和 T. viride 或 T. harzianum);(3)首次发现了 T. sayulitensis 在降解 PAH 的过程中产生了 PAH 降解的醌类代谢产物以及细胞外氧化酶和过氧化物酶:结论:研究结果有助于了解污染环境中细菌与真菌之间的相互作用。
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引用次数: 0
Survival of Nematode Larvae after Treatment with Eugenol, Isoeugenol, Thymol, and Carvacrol. 丁香酚、异丁香酚、百里酚和香芹酚处理后线虫幼虫的存活率
Pub Date : 2023-11-17 DOI: 10.31083/j.fbe1504025
Olexandra Boyko, Viktor Brygadyrenko

Background: Helminthiases inflict annual losses on the meat and dairy livestock industries. The commonest species of ruminant parasites are the nematodes: Strongyloides papillosus and Haemonchus contortus, which lay eggs in the intestine and enter the feces. There, the eggs develop into larvae, which when voided with the feces crawl onto plants.

Methods: In our experiment, we evaluated the survivability of the noninvasive and invasive (L1-2 and L3, respectively) larvae of S. papillosus, H. contortus (L3), and Muellerius capillaris (L1) in vitro by subjecting each to natural compounds present in the essential oils of many plants. In the experiment, we used aqueous emulsions of eugenol, isoeugenol, thymol, and carvacrol.

Results: Administering 1% concentrations of those compounds killed 100% of the nematode larvae following 24 h of exposure. Thymol, eugenol, and isoeugenol at a concentration of 0.1% also caused high larvae mortality (over 96%).

Conclusions: Continuous usage of synthetic anthelmintic drugs in veterinary medicine has led to the parasites developing resistance, thus, a search for novel nematicidal drugs is required. Eugenol, isoeugenol, thymol, and carvacrol are promising compounds against nematodes. However, additional research is required regarding peculiarities in their actions toward the bodies of mammals and parasitic nematodes.

背景:螺旋体疾病每年都会给肉类和奶制品畜牧业造成损失。最常见的反刍动物寄生虫是线虫:它们在肠道中产卵并进入粪便。在那里,虫卵发育成幼虫,随粪便排出后爬到植物上:在我们的实验中,我们评估了乳头蝇幼虫(S. papillosus)、鼠疫蝇幼虫(H. contortus)(L3)和恙螨幼虫(Muellerius capillaris)(L1)的非侵入性和侵入性(分别为 L1-2 和 L3)幼虫在体外的存活率,方法是将每种幼虫置于多种植物精油中的天然化合物中。在实验中,我们使用了丁香酚、异丁香酚、百里酚和香芹酚的水乳剂:结果:接触 1%浓度的这些化合物 24 小时后,100% 的线虫幼虫被杀死。浓度为 0.1%的百里酚、丁香酚和异丁香酚也会导致大量幼虫死亡(超过 96%):结论:在兽医领域持续使用合成驱虫药已导致寄生虫产生抗药性,因此需要寻找新型杀线虫药物。丁香酚、异丁香酚、百里酚和香芹酚是很有前途的杀线虫化合物。不过,还需要进一步研究这些化合物对哺乳动物和寄生线虫的特殊作用。
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引用次数: 0
The Role of Multiparametric MRI in the Local Staging of Prostate Cancer. 多参数MRI在癌症前列腺局部分期中的作用。
Pub Date : 2023-09-20 DOI: 10.31083/j.fbe1503021
Tiago Oliveira, Luís Amaral Ferreira, Carlos Miguel Marto, Cristina Marques, Carlos Oliveira, Paulo Donato

Prostate cancer ranks as the second most frequently diagnosed cancer globally among men and stands as the fifth leading cause of cancer-related death in males. Hence, an early and precise diagnosis and staging are critical. Traditional staging is based on clinical nomograms but presents a lower performance than prostate multiparametric magnetic resonance imaging (mpMRI). Since tumor staging serves as the basis for risk stratification, prognosis, and treatment decision-making, the primary objective of mpMRI is to distinguish between organ-confined and locally advanced diseases. Therefore, this imaging modality has emerged as the optimal selection for the local staging of prostate cancer, offering incremental value in evaluating pelvic nodal disease and bone involvement, and supplying supplementary insights regarding the precise location and disease extension. As per the Prostate Imaging Reporting & Data System v2.1 guideline, a comprehensive and accurate mpMRI requires several key sequences, which include T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) for morphological assessment, with T2WI serving as the cornerstone for local staging. Additionally, diffusion-weighted imaging (DWI) and dynamic sequences acquired with intravenous administration of paramagnetic contrast medium (DCE) are crucial components. It is worth noting that while MRI exhibits high specificity, its sensitivity in diagnosing extracapsular extension, seminal vesicle invasion, and lymph node metastases is limited. Moreover, mpMRI has its own constraints and is not as effective in detecting distant metastases or evaluating lymph nodes, for which extended pelvic lymph node dissection remains the gold standard. This review aims to highlight the significance of mpMRI in prostate cancer staging and provide a practical approach to assessing extracapsular extension, seminal vesicle invasions, and the involvement of adjacent organs and lymph nodes.

前列腺癌症是全球男性中诊断频率第二高的癌症,也是男性癌症相关死亡的第五大原因。因此,早期准确的诊断和分期至关重要。传统的分期是基于临床列线图,但其性能低于前列腺多参数磁共振成像(mpMRI)。由于肿瘤分期是风险分层、预后和治疗决策的基础,mpMRI的主要目的是区分器官局限性疾病和局部晚期疾病。因此,这种成像方式已成为癌症局部分期的最佳选择,为评估盆腔淋巴结疾病和骨受累提供了增值价值,并提供了关于精确位置和疾病扩展的补充见解。根据前列腺成像报告和数据系统v2.1指南,全面准确的mpMRI需要几个关键序列,包括用于形态学评估的T1加权成像(T1WI)和T2加权成像(T2WI),T2WI是局部分期的基石。此外,通过静脉注射顺磁造影剂(DCE)获得的扩散加权成像(DWI)和动态序列是至关重要的组成部分。值得注意的是,虽然MRI表现出很高的特异性,但其在诊断囊外扩张、精囊浸润和淋巴结转移方面的敏感性有限。此外,mpMRI有其自身的局限性,在检测远处转移或评估淋巴结方面没有那么有效,而扩大盆腔淋巴结清扫仍然是金标准。这篇综述旨在强调mpMRI在前列腺癌症分期中的意义,并为评估囊外扩张、精囊侵袭以及邻近器官和淋巴结的受累提供一种实用的方法。
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引用次数: 0
Integrating Red Blood Cell Features and Hemoglobin Levels in Metastatic Renal Cell Carcinoma Patients Treated with Pazopanib or Cabozantinib: An Easily Exploitable Prognostic Score. 整合帕唑帕尼或卡博扎替尼治疗的转移性肾癌患者的红细胞特征和血红蛋白水平:一种易于利用的预后评分。
Pub Date : 2023-07-28 DOI: 10.31083/j.fbe1503020
Giulia Mazzaschi, Alessandro Lazzarin, Matteo Santoni, Francesca Trentini, Ugo De Giorgi, Nicole Brighi, Chiara Tommasi, Silvia Puglisi, Orazio Caffo, Stefania Kinspergher, Alessia Mennitto, Carlo Cattrini, Elena Verzoni, Alessandro Rametta, Marco Stellato, Andrea Malgeri, Giandomenico Roviello, Enrico Maria Silini, Pasquale Rescigno, Sara Elena Rebuzzi, Giuseppe Fornarini, Federico Quaini, Giulia Claire Giudice, Giuseppe Luigi Banna, Sebastiano Buti

Background: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis still play a key role. The aim of the present study was to explore the prognostic performance of an integrated blood score, based on hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and red cell distribution width (RDW), in mRCC patients treated with anti-VEGF TKIs. The primary endpoint was to correlate Hb, MCV, and RDW with progression-free survival (PFS) and overall survival (OS).

Materials and methods: Our multicenter retrospective observational study involved mRCC patients treated with pazopanib or cabozantinib from January 2012 to December 2020 in nine Italian centers. Clinical records and laboratory data, including Hb levels, MCV, and RDW, were collected at baseline. Descriptive statistics and univariate and multivariate analyses were performed.

Results: We enrolled 301 mRCC patients of which 179 (59%) underwent pazopanib, and 122 (41%) cabozantinib. We considered baseline Hb ≥12 g/dL, MCV >87 fL, and RDW ≤16% as good prognostic factors; hence, developing a multiparametric score capable of delineating 4 different categories. The number of good prognostic factors was associated with significantly longer PFS and OS (p < 0.001 for both). Therefore, we developed a red blood cell-based score by stratifying cases into two groups (2-3 versus 0-1, good factors). The impact on PFS and OS was even more striking (median PFS (mPFS): 16.3 vs 7.9 months; median OS (mOS): 33.7 vs 14.1 months)), regardless of the TKI agent. When challenged with univariate and multivariate analysis, the blood score maintained its high prognostic significance in terms of OS (multivariate analysis HR for OS: 0.53, 95% CI 0.39-0.75; p < 0.001, respectively), while the impact on PFS resulted in borderline significance.

Conclusions: Our analyses demonstrate the prognostic role of a multiparametric score based on easily exploitable blood parameters, such as Hb concentration, MCV, and RDW. The red blood cell-based score may underlie the upregulation of the HIF-1α pathway and VEGF axis, thereby identifying a selected population who is likely to benefit from TKI therapy.

背景:免疫检查点抑制剂(ICIs)的出现彻底改变了转移性肾细胞癌(mRCC)的治疗前景。尽管如此,靶向血管内皮生长因子(VEGF)轴的酪氨酸激酶抑制剂(TKIs)仍然发挥着关键作用。本研究的目的是探讨在接受抗VEGF TKIs治疗的mRCC患者中,基于血红蛋白(Hb)浓度、平均红细胞体积(MCV)和红细胞分布宽度(RDW)的综合血液评分的预后表现。主要终点是将Hb、MCV和RDW与无进展生存期(PFS)和总生存期(OS)相关联。材料和方法:我们的多中心回顾性观察性研究涉及2012年1月至2020年12月在九个意大利中心接受帕唑帕尼或卡博扎替尼治疗的mRCC患者。在基线时收集临床记录和实验室数据,包括Hb水平、MCV和RDW。进行描述性统计和单变量和多变量分析。结果:我们纳入了301例mRCC患者,其中179例(59%)接受了帕唑帕尼治疗,122例(41%)接受了卡博扎替尼治疗。我们认为基线Hb≥12 g/dL、MCV>87 fL和RDW≤16%是良好的预后因素;因此,开发了能够描绘4个不同类别的多参数评分。良好预后因素的数量与显著延长的PFS和OS相关(两者均为0.001)。因此,我们通过将病例分为两组(2-3对0-1,好因素),制定了基于红细胞的评分。对PFS和OS的影响更为显著(中位PFS(mPFS):16.3个月对7.9个月;中位OS(mOS):33.7 vs 14.1个月)。当单变量和多变量分析挑战时,血液评分在OS方面保持其较高的预后意义(OS的多变量分析HR:0.53,95%CI 0.39-0.75;p<0.001),而对PFS的影响导致临界意义。结论:我们的分析证明了基于易于利用的血液参数(如Hb浓度、MCV和RDW)的多参数评分的预后作用。基于红细胞的评分可能是HIF-1α通路和VEGF轴上调的基础,从而确定可能受益于TKI治疗的选定人群。
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Frontiers in bioscience (Elite edition)
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