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Wnt Signaling in the Gastrointestinal Tract in Health and Disease Wnt信号在健康和疾病胃肠道中的作用
Pub Date : 2023-02-09 DOI: 10.3390/physiologia3010007
Negar Taheri, Egan L. Choi, V. T. Nguyen, Abhishek Chandra, Y. Hayashi
Wnt signaling involves multiple pathways that contribute to organ development, cell fate, inflammation, and normal stem cell renewal and maintenance. Although the homeostasis of stem cells in the gastrointestinal (GI) tract highly depends on the Wnt signaling pathway, this regulation is impaired in cancers and in aging. Overactive (uncontrolled) Wnt signaling can induce GI epithelial cancers such as colon and gastric cancer. Overactive Wnt signaling can also contribute to the initiation and progression of gastrointestinal stromal tumor, which is the most common human sarcoma occurring in the walls of the digestive organs, mainly the stomach and small intestine. Wnt expression is positively associated not only with the progression of oncogenesis but also with resistance to chemotherapy and radiotherapy. Of note, recent reports show that decreased Wnt signaling is related to intestinal stem cell aging and that overactivated Wnt signaling leads to gastric pacemaker stem cell aging in tunica muscularis. These findings indicate that Wnt signaling has different crucial aspects of cell fate determination with age in GI tunica mucosa and muscularis. In this review, we summarize the most recent advances in our understanding of Wnt signaling pathways and their role in regulating key aspects during development, carcinogenesis, inflammation, and aging, with the ultimate goal of identifying novel therapies.
Wnt信号传导涉及多种途径,有助于器官发育、细胞命运、炎症以及正常干细胞的更新和维持。尽管干细胞在胃肠道(GI)中的稳态高度依赖于Wnt信号通路,但这种调节在癌症和衰老中受损。过度活跃(不受控制)的Wnt信号可诱导胃肠道上皮癌,如结肠癌和癌症。过度活跃的Wnt信号传导也有助于胃肠道间质瘤的发生和发展,胃肠道基质瘤是发生在消化器官壁(主要是胃和小肠)的最常见的人类肉瘤。Wnt的表达不仅与肿瘤发生的进展呈正相关,而且与化疗和放疗的耐药性呈正相关。值得注意的是,最近的报道表明,Wnt信号传导减少与肠道干细胞衰老有关,而Wnt信号转导过度激活导致肌层中胃起搏器干细胞衰老。这些发现表明,随着年龄的增长,Wnt信号在胃肠道粘膜和肌层的细胞命运决定中具有不同的关键方面。在这篇综述中,我们总结了我们对Wnt信号通路及其在发育、致癌、炎症和衰老过程中调节关键方面的作用的理解的最新进展,最终目标是确定新的治疗方法。
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引用次数: 1
Effects of Culture System and Substrate Composition on Micropropagated Plantlets of Two Varieties of Stevia rebaudiana Bert 栽培体系和基质组成对两个甜菊品种微繁殖植株的影响
Pub Date : 2023-02-02 DOI: 10.3390/physiologia3010006
Susana Vilariño, M. Florido, José Luis García, M. Cantos
Background: Secondary metabolites in stevia leaves offer important therapeutic benefits. The germination problems of stevia seeds and the high heterogeneity of the resulting populations make micropropagation the preferred tool for obtaining a large number of plants in a short time. Until now, studies have focused on optimizing the action of growth regulators for the improvement of stevia micropropagated plantlets. In this project, we study alternative mineral nutrients in the substrate and two culture systems on micropropagated stevia plantlets to obtain proper amounts of enhanced plantlets. Methods: Criolla and Morita varieties; MS, MSM, and G substrates, and temporary immersion (TIS) and agar-medium systems were used. Biometric variables and damage to the cell membrane of the resulting plantlets were tested. Results: More productivity in the Criolla plantlets growing in MS solid medium and TIS. The Morita plantlets presented higher productivity in the solid MS, MSM, and G substrates and TIS. The explants growing in MS and MSM presented the highest productivity. The solid substrate was generally better than TIS. No damage to the cell membrane was found. Conclusions: The micropropagation efficiency of stevia plantlets of the two varieties has been enhanced without negative effects on their physiological condition. Consequently, any of the culture systems used, including bioreactors, can be of industrial application on a large scale.
背景:甜菊叶中的次生代谢产物具有重要的治疗作用。甜叶菊种子的发芽问题和由此产生的种群的高度异质性使得微繁殖成为在短时间内获得大量植物的首选工具。到目前为止,研究的重点是优化生长调节剂的作用,以改善甜菊微繁殖植株。在本项目中,我们研究了基质中的替代矿物质营养素和两种培养系统对微繁殖甜菊植株的培养,以获得适当数量的增强植株。方法:Criolla和Morita两个品种;使用MS、MSM和G基质,以及临时浸泡(TIS)和琼脂培养基系统。测试了生物特征变量和对所得植株细胞膜的损伤。结果:在MS固体培养基和TIS培养基上生长的Criolla植株生产力较高。森田植株在固体MS、MSM、G基质和TIS中表现出较高的生产力。在MS和MSM中生长的外植体表现出最高的生产力。固体基质通常比TIS好。未发现细胞膜受损。结论:两个品种甜菊试管苗的微繁殖效率均得到提高,且对其生理条件无负面影响。因此,所使用的任何培养系统,包括生物反应器,都可以大规模地进行工业应用。
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引用次数: 2
Acknowledgment to the Reviewers of Physiologia in 2022 向2022年《生理学》审稿人致谢
Pub Date : 2023-01-17 DOI: 10.3390/physiologia3010005
High-quality academic publishing is built on rigorous peer review [...]
高质量的学术出版建立在严格的同行评审的基础上[…]
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引用次数: 0
Remodeling in Persistent Atrial Fibrillation: Pathophysiology and Therapeutic Targets—A Systematic Review 持续性心房颤动的重构:病理生理学和治疗靶点——系统综述
Pub Date : 2023-01-09 DOI: 10.3390/physiologia3010004
A. Roka, Isaac Burright
Atrial fibrillation (AF) is characterized by disorganized rapid atrial electrical activity, which leads to impaired atrial function, adverse hemodynamic effects, and increased thromboembolic risk. The paroxysmal forms of AF can be effectively treated with current pharmacological and non-pharmacological modalities by targeting the arrhythmia triggers. Persistent AF, however, is more difficult to treat due to remodeling processes which may become major factors in the maintenance of the arrhythmia, rendering trigger-targeting treatment options less effective. We will systematically review the recent findings of the development and maintenance of persistent AF, including genetic, cellular, organ level, and systemic processes. As AF remains the most common sustained arrhythmia with the ongoing need to find effective treatment, we will also discuss potential treatment options targeting the remodeling processes.
心房颤动(AF)以无序的快速心房电活动为特征,导致心房功能受损、不良血流动力学影响和血栓栓塞风险增加。阵发性房颤可以有效地治疗与当前的药物和非药物模式,通过针对心律失常的触发。然而,由于重构过程可能成为维持心律失常的主要因素,持续性房颤更难治疗,使得触发靶向治疗方案效果较差。我们将系统地回顾持续性房颤的发展和维持的最新发现,包括遗传、细胞、器官水平和系统过程。由于房颤仍然是最常见的持续性心律失常,需要持续寻找有效的治疗方法,我们也将讨论针对重构过程的潜在治疗方案。
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引用次数: 4
Bactericidal Effects of Snake Venom Phospholipases A2: A Systematic Review and Analysis of Minimum Inhibitory Concentration 蛇毒磷脂酶A2的杀菌作用:最小抑制浓度的系统评价和分析
Pub Date : 2023-01-09 DOI: 10.3390/physiologia3010003
Z. U. Abdullahi, S. Musa, Hammoda Abu-Odah, Ayman Ahmed, A. A. Lawan, U. Bello
Background: Infections caused by multi-drug resistance (MDR) strains are potentially fatal public health issues worldwide that need pressing attention. Previous reports suggested using snake venom fractions as an effective alternative mechanism to the already available antibacterial drugs. In this study, we conducted a systematic review to analyze the bactericidal effects of snake venom phospholipases (PLA2s). Methods: From the beginning through 30 March 2022, we searched the PubMed and Embase databases in accordance with the most recent PRISMA recommendations. We also conducted a manual search to identify relevant reports to improve literature coverage. Results: A total of 24 studies were included based on the selection criteria to compile this review. Of them, 16 studies were obtained from the abovementioned databases and eight through manual searches. The other 8 studies were obtained through the references of the included studies. According to the review, we reported that some PLA2s showed more vigorous bactericidal activity on some Gram-negative and a moderate effect on Gram-negative and Gram-positive. Furthermore, we reported that the presence of p-bromophenacyl bromide (p-BPP) showed a significant decrease in enzymatic and associated antibacterial activities. Moreover, we observed that about 80% of the PLA2s reported in our systematic review study were those from the Viperidae family, whereas 20% came from the Elapidae family. Moreover, some variations were revealed in the current study regarding the mechanism of actions of the snake venom PLA2s (svPLA2s). Conclusion: This systematic review provides a comprehensive overview of the bactericidal effect of snake venom PLA2s and the analysis of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PLA2s for bacterial strains. Varying bactericidal effects from various snake species and South American rattlesnakes were reported, presenting compelling concepts to the alternative search for therapies against bacterial resistance. Thus, further analysis of the bactericidal effects of other snake venoms PLA2s considering different strains is needed. Moreover, more data are needed to investigate other bacteria of public health priority using peptides and other purified snake toxins.
背景:多药耐药(MDR)菌株引起的感染是世界范围内潜在的致命公共卫生问题,需要迫切关注。以前的报告建议使用蛇毒提取物作为现有抗菌药物的有效替代机制。在本研究中,我们对蛇毒磷脂酶(PLA2s)的杀菌作用进行了系统的综述。方法:从开始到2022年3月30日,我们根据最新的PRISMA建议检索PubMed和Embase数据库。我们还进行了人工检索,以识别相关报告,以提高文献覆盖率。结果:根据入选标准共纳入24项研究。其中16项研究来自上述数据库,8项研究通过人工检索获得。另外8项研究通过纳入研究的参考文献获得。根据这篇综述,我们报道了一些PLA2s对某些革兰氏阴性菌具有较强的杀菌活性,对革兰氏阴性菌和革兰氏阳性菌具有中等的杀菌作用。此外,我们报道了对溴苯酰溴(p-BPP)的存在显着降低了酶和相关的抗菌活性。此外,我们观察到,在我们的系统综述研究中,大约80%的pla2来自毒蛇科,而20%来自Elapidae科。此外,在目前的研究中,蛇毒PLA2s (svPLA2s)的作用机制也出现了一些变化。结论:本系统综述了蛇毒PLA2s的杀菌作用,分析了PLA2s对菌株的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。据报道,不同种类的蛇和南美响尾蛇的不同杀菌效果,为寻找对抗细菌耐药性的替代疗法提供了令人信服的概念。因此,需要进一步分析不同毒株的其他蛇毒PLA2s的杀菌效果。此外,还需要更多的数据来利用肽和其他纯化的蛇毒素来研究其他公共卫生重点细菌。
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引用次数: 0
Proteogenomic Approaches to Understand Gene Mutations and Protein Structural Alterations in Colon Cancer 蛋白质基因组学方法了解结肠癌基因突变和蛋白质结构改变
Pub Date : 2023-01-04 DOI: 10.3390/physiologia3010002
S. Sarkar
With colon cancer being one of the deadliest and most common cancers, understanding the mechanisms behind colon cancer is crucial in improving therapies. One of the newest approaches in cancer research is the concept of proteogenomics. While genomic data is not sufficient to understand cancer, the integration of multi-omics data including proteomics in conjugation with protein modeling has a better potential to elucidate protein structural alterations and characterize tumors. This enables a more efficient diagnosis of cancer and improves remedial strategies. In this review, we aim to discuss the linkage between gene mutations and protein structural alterations that lead to colon cancer. Topics include alterations in the glycoproteome and structures of proteases that impact colon cancer development. Additionally, we highlight the importance of precision oncology with an emphasis on proteogenomic approaches, protein modeling, and the potential impact on colon cancer therapy.
由于癌症是最致命和最常见的癌症之一,了解癌症背后的机制对于改善治疗至关重要。癌症研究的最新方法之一是蛋白基因组学的概念。虽然基因组数据不足以理解癌症,但将包括蛋白质组学在内的多组学数据与蛋白质建模相结合,具有更好的潜力来阐明蛋白质结构变化和表征肿瘤。这使得能够更有效地诊断癌症并改进治疗策略。在这篇综述中,我们的目的是讨论基因突变和导致结肠癌的蛋白质结构改变之间的联系。主题包括影响癌症发展的糖蛋白质组和蛋白酶结构的改变。此外,我们强调了精确肿瘤学的重要性,强调了蛋白基因组方法、蛋白质建模以及对结肠癌癌症治疗的潜在影响。
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引用次数: 2
Assessing Asymmetry in Exercise Intensity Domains between Lower Limbs in Persons with Multiple Sclerosis: A Pilot Study 评估多发性硬化症患者下肢运动强度域的不对称性:一项初步研究
Pub Date : 2022-12-22 DOI: 10.3390/physiologia3010001
J. W. Farrell, Shelby R. Shipman, Christopher D. Black, C. Ade, Rebecca D. Larson
Persons with multiple sclerosis (PwMS) experience a variety of physical impairments that can present in an asymmetrical pattern, resulting in significant differences between contralateral limbs (i.e., >10%). Asymmetries in PwMS have been associated with walking impairment and postural instability. Exercise intensity has been shown to influence the degree of asymmetry outcomes in healthy populations, and may have an impact on appropriate exercise prescriptions. The purpose of the current pilot study was to investigate the potential presence of asymmetry in metabolic events demarcating exercise intensity domains during single-leg cycling in PwMS. Five PwMS (Expanded Disability Status Scale range 2.0 to 4.5) completed a single leg incremental cycling test (SLICT) and a series of single-leg constant power time-to-exhaustion trials to determine gas exchange threshold (GET), peak oxygen consumption (VO2peak), peak power output (PPO), critical power (CP), and W’ (exercise tolerance above CP) for both lower limbs. Statistical analysis revealed no significant between-limb differences for VO2peak, GET, CP, PPO, and W’. Only W’ asymmetry score was significantly (49.5 ± 28.7 vs. 10.0, p = 0.04) greater than 10%. No significant differences between asymmetry scores at the GET, CP, and PPO were observed. Results from the current pilot investigation suggest that exercise intensity may not influence asymmetry outcomes in PwMS. Future studies with larger sample sizes and those with higher disability levels are required to fully understand the influence of exercise intensity on asymmetry in PwMS.
多发性硬化症(PwMS)患者会经历各种各样的身体损伤,这些损伤可能以不对称的方式呈现,导致对侧肢体之间存在显著差异(即bbb10 %)。PwMS的不对称与行走障碍和姿势不稳定有关。运动强度已被证明会影响健康人群不对称结果的程度,并可能对适当的运动处方产生影响。目前的初步研究的目的是调查在PwMS单腿骑行期间划定运动强度域的代谢事件中可能存在的不对称性。5名PwMS(扩展残疾状态量表范围2.0至4.5)完成了单腿增量循环测试(SLICT)和一系列单腿恒定功率至衰竭时间试验,以确定双下肢的气体交换阈值(GET)、峰值耗氧量(VO2peak)、峰值输出功率(PPO)、临界功率(CP)和W ' (CP以上的运动耐量)。统计分析显示,VO2peak、GET、CP、PPO和W′在肢体间无显著差异。只有W′不对称评分显著(49.5±28.7∶10.0,p = 0.04)大于10%。GET、CP和PPO的不对称评分之间没有显著差异。目前的试点调查结果表明,运动强度可能不会影响PwMS的不对称性结果。未来需要更大样本量和更高残疾水平的研究来充分了解运动强度对PwMS不对称性的影响。
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引用次数: 0
The Impact of Wetsuit Use on Swimming Performance, Physiology and Biomechanics: A Systematic Review 潜水服使用对游泳成绩、生理和生物力学的影响:系统综述
Pub Date : 2022-12-12 DOI: 10.3390/physiologia2040016
A. Gay, J. Ruiz-Navarro, F. Cuenca-Fernández, Ó. López-Belmonte, J. Abraldes, R. Fernandes, R. Arellano
This systematic review aims to summarize the effects of wearing different types of wetsuits and swimsuits in front crawl swimming performance and physiological- and biomechanical-related variables. The Web of Science, PubMed, Scopus and the Proceedings of the International Symposium on Biomechanics and Medicine in Swimming databases were searched from inception to 25th March 2022. From the 1398 studies initially found, 26 studies were included in the review. The quality assessment and inter-rater reliability between researchers were conducted. The full body was the most studied wetsuit, with its use allowing 3.2–12.9% velocity increments in distances ranging from 25 to 1500 m, in incremental tests, in 5 and 30 min continuous swimming and in open water events. The sleeveless long vs. the full-body wetsuit led to a 400–800 m performance enhancement. Higher stroke rate, stroke length and stroke index were observed while using three different covered body part wetsuits vs. a regular swimsuit, with a lower energy cost being observed when swimming with the full-body wetsuit compared to a swimsuit. These findings provide useful information for coaches, swimmers and triathletes about the full-body and sleeveless long/short wetsuit use, since these three wetsuits allow improving swimming performance in different distances in diverse aquatic environments.
本系统综述旨在总结穿着不同类型的潜水服和泳衣对前爬行游泳性能以及生理和生物力学相关变量的影响。从成立到2022年3月25日,检索了科学网、PubMed、Scopus和国际游泳生物力学和医学研讨会论文集数据库。在最初发现的1398项研究中,26项研究被纳入审查。研究人员之间进行了质量评估和评分者间的可靠性。全身潜水服是研究最多的潜水服,在增量测试、5分钟和30分钟连续游泳以及公开水域项目中,全身潜水服的使用允许在25至1500米的距离内增加3.2–12.9%的速度。与全身潜水服相比,无袖长款潜水服的性能提高了400–800米。与普通泳衣相比,使用三种不同的覆盖身体部位的潜水服可以观察到更高的划水率、划水长度和划水指数,与泳衣相比,全身潜水服游泳的能量成本更低。这些发现为教练、游泳运动员和铁人三项运动员提供了关于全身和无袖长/短潜水服使用的有用信息,因为这三种潜水服可以在不同的水上环境中提高不同距离的游泳性能。
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引用次数: 1
Drought Stress Tolerance in Plants: Interplay of Molecular, Biochemical and Physiological Responses in Important Development Stages 植物抗旱性:重要发育阶段分子、生化和生理反应的相互作用
Pub Date : 2022-12-09 DOI: 10.3390/physiologia2040015
M. Ç. Oğuz, Murat Aycan, Ezgi Oğuz, Irem Poyraz, M. Yıldız
Drought is an important abiotic stress factor limiting crop productivity worldwide and its impact is increasing with climate change. Regardless of the plant growth period, drought has a deadly and yield-reducing effect on the plant at every stage of development. As with many environmental stressors, drought-exposed plants trigger a series of molecular, biochemical, and physiological responses to overcome the effect of drought stress. Currently, researchers are trying to determine the complex functioning of drought stress response in plants with different approaches. Plants are more sensitive to drought stress during certain critical stages like germination, seedling formation, flowering, fertilization, and grain formation periods. Plants have high success in reducing the effects of drought stress in vegetative development periods with the activity of tolerance mechanisms. On the other hand, drought stress during the generative period can cause irreversible losses in yield. This review focuses on the progression of molecular, biochemical, and physiological mechanisms involved in the drought stress tolerance in plants and the responses of field crops to drought stress at different development stages.
干旱是限制全球作物生产力的一个重要非生物胁迫因素,其影响随着气候变化而加剧。无论植物生长期如何,干旱在植物发育的每个阶段都会对植物产生致命的减产影响。与许多环境胁迫源一样,干旱暴露的植物会引发一系列分子、生化和生理反应,以克服干旱胁迫的影响。目前,研究人员正试图通过不同的方法来确定植物干旱胁迫反应的复杂功能。植物在某些关键阶段对干旱胁迫更敏感,如发芽、幼苗形成、开花、施肥和籽粒形成期。植物通过耐受机制的活性,在营养发育期减少干旱胁迫的影响方面取得了很高的成功。另一方面,生育期的干旱胁迫会造成不可逆转的产量损失。本文综述了植物耐旱性的分子、生化和生理机制的进展,以及不同发育阶段田间作物对干旱胁迫的反应。
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引用次数: 26
RNA-Sequencing Muscle Plasticity to Resistance Exercise Training and Disuse in Youth and Older Age rna测序的肌肉可塑性抵抗运动训练和废弃在青年和老年
Pub Date : 2022-12-07 DOI: 10.3390/physiologia2040014
R. Fernandez-Gonzalo, C. Willis, T. Etheridge, C. Deane
Maintenance of skeletal muscle mass and function is critical to health and wellbeing throughout the lifespan. However, disuse through reduced physical activity (e.g., sedentarism), immobilisation, bed rest or microgravity has significant adverse effects on skeletal muscle health. Conversely, resistance exercise training (RET) induces positive muscle mass and strength adaptations. Several studies have employed microarray technology to understand the transcriptional basis of muscle atrophy and hypertrophy after disuse and RET, respectively, to devise fully effective therapeutic interventions. More recently, rapidly falling costs have seen RNA-sequencing (RNA-seq) increasingly applied in exploring muscle adaptations to RET and disuse. The aim of this review is to summarise the transcriptional responses to RET or disuse measured via RNA-seq in young and older adults. We also highlight analytical considerations to maximise the utility of RNA-seq in the context of skeletal muscle research. The limited number of muscle transcriptional signatures obtained thus far with RNA-seq are generally consistent with those obtained with microarrays. However, RNA-seq may provide additional molecular insight, particularly when combined with data-driven approaches such as correlation network analyses. In this context, it is essential to consider the most appropriate study design parameters as well as bioinformatic and statistical approaches. This will facilitate the use of RNA-seq to better understand the transcriptional regulators of skeletal muscle plasticity in response to increased or decreased use.
维持骨骼肌的质量和功能对整个生命周期的健康和幸福至关重要。然而,由于体力活动减少(如久坐不动)、固定不动、卧床休息或微重力而停用,会对骨骼肌健康产生重大不利影响。相反,阻力运动训练(RET)会诱导积极的肌肉质量和力量适应。一些研究利用微阵列技术分别了解废弃和RET后肌肉萎缩和肥大的转录基础,以设计完全有效的治疗干预措施。最近,随着成本的迅速下降,rna测序(RNA-seq)越来越多地应用于探索肌肉对RET和废用的适应。本综述的目的是总结通过RNA-seq测量的年轻人和老年人对RET或停用的转录反应。我们还强调了分析方面的考虑,以最大限度地发挥RNA-seq在骨骼肌研究中的效用。迄今为止,通过RNA-seq获得的有限数量的肌肉转录特征通常与微阵列获得的一致。然而,RNA-seq可以提供额外的分子洞察力,特别是当与数据驱动的方法(如相关网络分析)相结合时。在这种情况下,必须考虑最合适的研究设计参数以及生物信息学和统计学方法。这将有助于使用RNA-seq来更好地了解骨骼肌可塑性的转录调节因子对增加或减少使用的反应。
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引用次数: 0
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