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Advances in nanoparticle-based drug delivery in cancer treatment 纳米颗粒给药在癌症治疗中的研究进展
Pub Date : 2023-07-12 DOI: 10.36922/gtm.0394
Pourya Sarvari, P. Sarvari
As a pathologically heterogeneous disease, cancer is one of the leading causes of global morbidity. According to the World Health Organization, approximately one in six deaths are caused by cancer. Fortunately, many cancers can be cured if diagnosed at early stages and treated efficiently. Despite the benefits of conventional cancer treatments such as surgery, chemotherapy, hormone therapy, and radiation therapy, they have several drawbacks, including cytotoxicity, inaccurate targeting of tumor cells, and multi-drug resistance, which underscore the importance of developing novel and effective strategies to improve diagnosis, prognosis, therapy, and patient survival. Recently, the advancement of nanotechnology has opened new horizons for cancer treatment thanks to the discovery of nanoparticles (NPs) and the small-sized molecules that revolutionized the drug delivery methods in cancerous tissues. The specific characteristics of NPs, such as reduced toxicity, improved permeability, and accurate targeting of tumor cells, provide a great advantage in cancer treatment and help to overcome the limitations and challenges of conventional cancer treatment methods. Besides, the role of NPs in immunotherapy has created a novel concept for cancer treatment. This review gives a brief overview regarding the importance of NPs and their targeting mechanism, as well as the challenges and limitations associated with their use in cancer treatment.
作为一种病理异质性疾病,癌症是全球发病率的主要原因之一。根据世界卫生组织的数据,大约六分之一的死亡是由癌症引起的。幸运的是,如果早期诊断和有效治疗,许多癌症是可以治愈的。尽管传统的癌症治疗方法如手术、化疗、激素治疗和放射治疗有好处,但它们也有一些缺点,包括细胞毒性、肿瘤细胞靶向不准确和多药耐药,这强调了开发新的有效策略来改善诊断、预后、治疗和患者生存的重要性。最近,纳米技术的进步为癌症治疗开辟了新的视野,这要归功于纳米粒子(NPs)和小分子的发现,这些小分子彻底改变了癌症组织中的药物输送方法。NPs具有降低毒性、提高通透性、准确靶向肿瘤细胞等特点,在癌症治疗中具有很大的优势,有助于克服传统癌症治疗方法的局限性和挑战。此外,NPs在免疫治疗中的作用为癌症治疗创造了一个新的概念。本文综述了NPs的重要性及其靶向机制,以及NPs在癌症治疗中的应用面临的挑战和局限性。
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引用次数: 1
Ultraviolet-induced mechanical augmentation of the degraded porcine aortic adventitia: Its significance for preventing aneurysmal rupture 紫外线诱导降解猪主动脉外膜的机械增强:对预防动脉瘤破裂的意义
Pub Date : 2023-07-05 DOI: 10.36922/gtm.0897
T. Chirila, Shuko Suzuki
In the previous studies, we have shown that the tunica adventitia of porcine abdominal aorta could be mechanically reinforced by irradiating it with ultraviolet A (UV-A) rays to promote the photocrosslinking of constitutive collagen, and we have proposed the method as a procedure to prevent or delay abdominal aortic aneurysm (AAA) ruptures. We have also demonstrated that UV irradiation-induced mechanical augmentation despite the degradation of the adventitia through collagenolysis in vitro. Considering that elastolysis is equally a relevant event in the pathogenesis of AAA, the degradation of elastin was also investigated in the present study. A total of 50 porcine aortas were used in the study. All processed samples were evaluated in a mechanical tester before and after degradation and/or irradiation. The adventitial layer was isolated and subjected to elastase for either 1 – 48 h. We found that both elastin and collagen were digested by elastase, with the former being completely digested after 48 h. The samples degraded for 1 h were subsequently irradiated with UV-A (365 nm) in the presence of riboflavin as a photoinitiator, a process that induced an enhancement of the strength and stiffness of the tissue. This is an indication that a partly degenerated aortic wall, like that in an aneurysmal region, can be reinforced mechanically by UV irradiation, possibly to the extent of delaying, or preventing altogether, the wall’s rupture. It appears important to irradiate the wall as early as possible.
在之前的研究中,我们已经证明,通过紫外线照射猪腹主动脉外膜,可以促进组成型胶原的光交联,从而对其进行机械强化,并提出了这种方法作为预防或延缓腹主动脉瘤(AAA)破裂的一种方法。我们还证明,尽管体外胶原溶解导致外膜降解,但紫外线照射诱导的机械增强。考虑到弹性分解在AAA的发病机制中同样是一个相关事件,本研究也对弹性蛋白的降解进行了研究。本研究共使用了50条猪主动脉。所有处理过的样品在降解和/或辐照前后在机械测试仪中进行评估。我们发现弹性蛋白和胶原蛋白都被弹性酶消化,前者在48小时后被完全消化。降解1小时的样品随后在核黄素作为光引发剂存在的情况下用UV-A (365 nm)照射,这一过程诱导了组织强度和刚度的增强。这表明部分退化的主动脉壁,如动脉瘤区,可以通过紫外线照射机械强化,可能在一定程度上延迟或完全防止主动脉壁的破裂。尽早照射胸壁显得很重要。
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引用次数: 1
Novel applications of manipulating gut microbiota for alleviating hematological disorders 控制肠道微生物群减轻血液系统疾病的新应用
Pub Date : 2023-06-30 DOI: 10.36922/gtm.0389
Sibusiso Luthuli, Lulama Luthuli
Investigations toward malignancies involving gut microbiota are still in their infancy, especially in hematology and oncology. There are approximately 1.2 million new hematological malignancy cases, resulting in more than 500,000 cases/year in mortality worldwide. It is through commendable advancements directed toward anticancer therapy in recent times that have significantly improved the survival rate among individuals; however, their cytotoxicity or side effects tend to be challenging for patients to tolerate, attributed to anticancer therapies such as chemotherapy and/or radiation therapy due to the aggressive nature in terms of their mechanism of action. Therefore, novel means, or treatments that could present less or non-toxic modalities are warranted, especially those that decrease unpleasant side effects. Studies indicate that the human body accommodates roughly 40 trillion microorganisms, also referred to as the human microbiota, and the abundance of this microbiota is predominantly found in the gastrointestinal tract. The microbiota is associated with various physiological roles, like immunology, digestive functions, and neural development. Therefore, the aim of this literature is to summarize current innovations (and achievements) in using gut microbiota to alleviate diseases and possible directions to explore toward curing malignancies or associated ailments. In addition, this type of publication seeks to encourage possible directions to be employed in establishing “possible biomarkers” which could be used in both the laboratory and clinical settings; this includes methodologies involving translational medicine through undertakings of improving cancer therapy.
对涉及肠道微生物群的恶性肿瘤的研究仍处于起步阶段,特别是在血液学和肿瘤学领域。大约有120万新的血液恶性肿瘤病例,导致全世界每年超过50万例死亡。近年来,抗癌治疗取得了令人称赞的进展,显著提高了个体的存活率;然而,它们的细胞毒性或副作用往往是患者难以忍受的,这归因于抗癌疗法,如化疗和/或放射治疗,因为它们的作用机制具有侵袭性。因此,有必要采用新的方法或治疗方法,以减少或无毒的方式,特别是那些减少令人不快的副作用。研究表明,人体容纳了大约40万亿个微生物,也被称为人体微生物群,这些微生物群的丰度主要存在于胃肠道中。微生物群与各种生理作用有关,如免疫、消化功能和神经发育。因此,本文献的目的是总结当前利用肠道微生物群缓解疾病的创新(和成就),并探索治疗恶性肿瘤或相关疾病的可能方向。此外,这种类型的出版物旨在鼓励在建立可在实验室和临床环境中使用的“可能的生物标志物”方面采用可能的方向;这包括通过改进癌症治疗的事业涉及转化医学的方法。
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引用次数: 0
Utility of cardiac biomarkers and biosensors for diagnosis of acute myocardial infarction 心脏生物标志物和生物传感器在急性心肌梗死诊断中的应用
Pub Date : 2023-06-27 DOI: 10.36922/gtm.0403
Rupali G. Shinde, Isha Juwarwala, V. Modi, Chandni V. Chandarana
Acute myocardial infarction (AMI) is the most prevalent condition that results in sickness and death worldwide. An early and accurate diagnosis of AMI is critical for prompt and appropriate treatment. Cardiac biomarkers, including myoglobin, creatinine phosphokinase (CK), and cardiac troponins, have been widely used for AMI diagnosis. More recently, new biomarkers such as heart-type fatty acid-binding protein and matrix metalloproteinases have shown promise in improving AMI diagnosis. At present, cardiac biomarkers and biosensors are used in the diagnosis and prognosis of AMI. This review article gives information on cardiac biomarkers specific to AMI and its diagnostic methods. These biomarkers have several advantages, including their high specificity for cardiac injury and their sensitivity to even small extent of cardiac damage. In addition, cardiac biomarkers can be used to assess the severity of AMI and predict the risk of complications or mortality. Recently, biosensors that can detect cardiac biomarkers in real time have been developed, allowing for an earlier and more accurate diagnosis of AMI. The utility of cardiac biomarkers and biosensors in the diagnosis of AMI underscores the importance of early and accurate diagnosis and treatment of this life-threatening condition.
急性心肌梗死(AMI)是全世界最常见的导致疾病和死亡的疾病。AMI的早期和准确诊断对于及时和适当的治疗至关重要。心脏生物标志物,包括肌红蛋白、肌酸酐磷酸激酶(CK)和心肌肌钙蛋白,已被广泛用于AMI的诊断。最近,新的生物标志物如心脏型脂肪酸结合蛋白和基质金属蛋白酶在改善AMI诊断方面显示出希望。目前,心脏生物标志物和生物传感器被用于AMI的诊断和预后。本文综述了AMI特异性的心脏生物标志物及其诊断方法。这些生物标志物有几个优点,包括它们对心脏损伤的高特异性和对小范围心脏损伤的敏感性。此外,心脏生物标志物可用于评估AMI的严重程度,并预测并发症或死亡的风险。最近,可以实时检测心脏生物标志物的生物传感器已经开发出来,可以更早、更准确地诊断AMI。心脏生物标志物和生物传感器在AMI诊断中的应用强调了早期准确诊断和治疗这种危及生命的疾病的重要性。
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引用次数: 1
Artificial intelligence algorithms for optimizing assisted reproductive technology programs: A systematic review 优化辅助生殖技术程序的人工智能算法:系统综述
Pub Date : 2023-05-29 DOI: 10.36922/gtm.0308
F. Bulletti, Marco Berrettini, R. Sciorio, C. Bulletti
Artificial intelligence (AI) has been experiencing rapid growth in recent years, and numerous applications are improving the single-step efficiency of the whole assisted reproductive technology (ART) procedure. In this review, we collected all the algorithms supplying ART and selected those supporting the clinical assistance to the procedure up to the successful attempt. Those with a clear role in improving ART performances were further selected. We found a questionnaire-based algorithm identifying patients at risk for endometriosis with early management and better fertility outcome. An algorithm can detect the values of simple gamete production (male) and reservoir (female) according to gradual scale allocation, and display themas normal or abnormal, spontaneousor stimulated gamete production. This can provide significant benefits for infertile couples undergoing diagnostic and therapeutic journeys. The calculators for the starting dose of gonadotropins and the trigger timing during controlled ovarian stimulation make clinical management more efficient. With the application of AI in ART, the ability to determine the optimal number of metaphase II oocytes required for blastocyst formation and number of oocytes needed for embryo production has been significantly improved. The calculation of the implantation rate as proposed in different calculators, using the ultrasound of endometrial vascularization or the age and euploidy of the embryo transferred, may provide further advancement in managing the ART procedure with more participation from the couples to increase the efficacy of the procedures. Finally, the calculator of presumptive success with an ART program based on couples or medical center profiling and efficiency is of tremendous comfort to couples. In conclusion, algorithms and machine learning development in human reproduction are growing daily with evident benefits. Infertility treatments by in vitro fertilization (IVF) are assisted by several algorithms that improve the efficiency of each procedure step, making IVF program’s management more effortless.
人工智能(AI)近年来发展迅速,许多应用正在提高整个辅助生殖技术(ART)过程的单步效率。在这篇综述中,我们收集了所有提供ART的算法,并选择了那些支持临床辅助的算法,直到成功尝试。进一步选择那些在改善ART表现方面有明确作用的项目。我们发现了一种基于问卷的算法,可以识别有子宫内膜异位症风险的患者,并进行早期治疗和更好的生育结果。该算法可以根据逐步的规模分配来检测简单配子产量(雄性)和储备配子产量(雌性)的值,并显示正常或异常、自发或受刺激配子产量的主题。这可以为正在进行诊断和治疗的不孕夫妇提供显著的好处。促性腺激素起始剂量的计算器和控制卵巢刺激时的触发时间使临床管理更有效。随着人工智能在ART中的应用,确定囊胚形成所需的中期II期卵母细胞的最佳数量和胚胎生成所需的卵母细胞数量的能力得到了显著提高。在不同的计算器中,使用子宫内膜血管形成的超声或移植胚胎的年龄和整倍体来计算着床率,可能会进一步提高ART手术的管理水平,让更多的夫妇参与其中,提高手术的疗效。最后,基于夫妇或医疗中心分析和效率的ART计划的推定成功计算器对夫妇来说是巨大的安慰。总之,算法和机器学习在人类生殖领域的发展日新月异,带来了明显的好处。通过体外受精(IVF)治疗不孕症有几种算法辅助,这些算法提高了每个程序步骤的效率,使体外受精程序的管理更加轻松。
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引用次数: 0
Diagnostic cardiac catheterization in a modified cardiac catheterization laboratory: The LASUTH experience 改良心导管实验室的诊断性心导管:LASUTH的经验
Pub Date : 2023-05-11 DOI: 10.36922/gtm.249
Alaba Busola Oladimeji, Oluwaseye Michael Oladimeji, Adeola Olubunmi Ajibare, Oluwafemi Tunde Ojo, Ramon Kolade Moronkola, A. Raheem, Abdulazeez Olanrewaju, Damilare Adewale Olusanya, Onomen Oluwaseyi Ehizojie, Oluwaseyi Ajimotokan, Abdulrahman Idris, Adenike Olufunke Akalakini, Moriam Omolola Lamina, Oluwaseun Oyeyemi Okunuga, Alaba Philips Adebola, Folashade Adeola Daniel, Oluwarotimi Ireti Akinola, Adetokunbo Olusegun Fabamwo
Cardiac catheterization is useful in the diagnosis and treatment of congenital and acquired cardiac diseases. However, it is rarely done in Nigeria because of the limited cardiac catheterization laboratories in the country. Transforming the existing operating theaters to modified catheterization laboratories may bridge the gap of limited cardiac catheterization. This study reviewed the procedures, outcomes, and challenges of a modified catheterization laboratory in Nigeria. A retrospective review of all diagnostic cardiac catheterizations at the modified catheterization laboratory of Lagos State University Teaching Hospital (LASUTH) between January and May 2022 was performed. A total of 8 adult and 4 pediatric patients had cardiac catheterization, and the mean age was 23.7 ± 16.9 (range: 2 – 52) years. The most common lesion was the ventricular septal defect. Complex congenital heart disease was seen in 16% of subjects, whereas pulmonary hypertension was found in 83% (10). The most common complication was transient bradycardia. Good surgical outcome was recorded in the patients who subsequently had corrective surgeries. A modified catheterization laboratory may be a suitable alternative to the standard catheterization laboratory in low-resourced countries.
心导管插入术在先天性和后天性心脏病的诊断和治疗中是有用的。然而,由于尼日利亚的心导管实验室有限,在尼日利亚很少这样做。将现有的手术室改造为改良的导管室可以弥补有限心导管的空白。本研究回顾了尼日利亚一个改进的导尿实验室的程序、结果和挑战。对2022年1月至5月期间在拉各斯州立大学教学医院(LASUTH)改良导管实验室进行的所有诊断性心导管置入进行了回顾性审查。成人8例,儿童4例,平均年龄23.7±16.9岁(范围:2 ~ 52岁)。最常见的病变是室间隔缺损。复杂先天性心脏病见于16%的受试者,而肺动脉高压见于83%(10)。最常见的并发症是短暂性心动过缓。在随后进行矫正手术的患者中记录了良好的手术结果。在资源匮乏的国家,改良的导尿实验室可能是标准导尿实验室的合适替代方案。
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引用次数: 0
New insights into chronic pain management based on biopsychosocial model 基于生物心理社会模型的慢性疼痛管理新见解
Pub Date : 2023-04-19 DOI: 10.36922/gtm.312
Ekaterina Fedorovna Turovskaia, Lyudmila Ivanovna Alekseeva
The biopsychosocial model of pain dominates the scientific community’s understanding of chronic pain. Chronic pain is considered a different form of depression. In this study, pain relief was explored in chronic pain patients with different neurological disease, accompanied by comorbid symptoms, depression, and insomnia. Twenty-three chronic pain patients aged 26–79 years with comorbid symptoms were included in a prospective 12-week treatment using 10 mg vortioxetine. Different types of chronic pain were represented in this study: low back pain (13 patients), headache (four patients); neuropathic mechanism-induced pain (six patients) – spinal stenosis (two patients), radiculopathy (two patients), and trigeminal neuralgia (two patients). Efficacy of vortioxetine treatment was monitored after 1 week, 3 weeks, and 12 weeks. Visual analog scale (VAS) was used for pain intensity value. Dynamic of pain relief was assessed in accordance with comorbid depression and insomnia. Most patients with chronic pain actively reported depression (65%) and insomnia (74%). Depression was statistically rare in patients with neuropathic pain (33%) compared to patients with nociceptive pain (82%; P < 0.05). Incidence of insomnia was lower, although not statistically, in patients with neuropathic mechanism-induced pain (50%) compared to patients with nociceptive pain (82%, P = 0.129). Patients younger than 65 years reported pain reduction, according to VAS, after 1 week and 3 weeks vortioxetine therapy. The mean pain relief was 1.1 cm in young patients versus 0.16 cm in patients aged >65 years (P < 0.01) after 1-week treatment, and it was 2.35 cm in young patients versus 1.7 cm in patients aged >65 years (P < 0.05) after 3-week treatment. Vortioxetine therapy was effective in different types of chronic pain, accompanied by comorbid depression and insomnia. At early stage of treatment, pain relief was lower in old patients aged >65 years. Regardless of age, all patients had significant pain relief after the 12-week treatment.
疼痛的生物心理社会模型主导了科学界对慢性疼痛的理解。慢性疼痛被认为是抑郁症的另一种形式。在本研究中,探讨慢性疼痛患者的疼痛缓解不同的神经系统疾病,并伴有合并症,抑郁,失眠。23名年龄在26-79岁并伴有合并症的慢性疼痛患者被纳入前瞻性治疗,使用10mg沃替西汀12周。不同类型的慢性疼痛出现在本研究中:腰痛(13例),头痛(4例);神经性机制引起的疼痛(6例)-椎管狭窄(2例)、神经根病(2例)和三叉神经痛(2例)。沃替西汀治疗后1周、3周、12周监测疗效。疼痛强度评分采用视觉模拟评分法(VAS)。根据抑郁症和失眠的合并症评估疼痛缓解的动态。大多数慢性疼痛患者主动报告抑郁(65%)和失眠(74%)。神经性疼痛患者抑郁的发生率为33%,而痛觉性疼痛患者抑郁的发生率为82%;P < 0.05)。与痛觉性疼痛患者(82%,P = 0.129)相比,神经性机制性疼痛患者(50%)的失眠发生率较低,但没有统计学意义。根据VAS,年龄小于65岁的患者在沃替西汀治疗1周和3周后疼痛减轻。治疗1周后,年轻患者平均疼痛缓解1.1 cm, > ~ 65岁患者平均疼痛缓解0.16 cm (P < 0.01);治疗3周后,年轻患者平均疼痛缓解2.35 cm, > ~ 65岁患者平均疼痛缓解1.7 cm (P < 0.05)。沃替西汀治疗对不同类型的慢性疼痛,伴有抑郁症和失眠有效。在治疗早期,年龄在50 ~ 65岁的老年患者疼痛缓解程度较低。无论年龄大小,所有患者在12周的治疗后都有明显的疼痛缓解。
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引用次数: 0
Association between the FTO polymorphic variants and obesity in the Belarusian population 白俄罗斯人群中FTO多态性变异与肥胖之间的关系
Pub Date : 2023-04-10 DOI: 10.36922/gtm.352
M. Ameliyanovich, M. Lushchyk, I. Mosse, L. Danilova
Overweight and obesity refer to the abnormal and excessive deposition of adipose tissue in the human body causing significant harm to health. Unfortunately, there has always been a persisting upward trend in the number of overweight people. The development of obesity may be caused by a combination of excessive food intake, low physical activity, and a hereditary predisposition to it. Studies of the genotypes of obese individuals allowed identifying a number of polymorphic variants of genes that contribute to a genetic predisposition to an excessive weight gain. One of the most significant predictors of obesity is the FTO gene (a fat mass and obesity-associated gene). Genotyping of 655 representatives of the Republic of Belarus was carried out for 13 polymorphic variants of the FTO gene. Genomic DNA extraction was carried out from the peripheral venous blood samples. Real-time PCR was performed for the evaluation of polymorphic variants of the FTO gene. A significant association of the genotype with the body mass index was observed in eight polymorphic variants of the FTO gene: In the carriers of minor homozygotes of polymorphic variants rs11075990, rs1121980, rs1421085, rs17817449, rs3751812, rs9939609, rs9940128, and rs9941349, the body mass index (BMI) was much higher compared with the carriers of corresponding major homozygotes P = 0.0022 – 0.021. An analysis of the linkage disequilibrium of 13 polymorphic variants of the FTO gene was carried out. It was found that eight polymorphic variants of the FTO gene for which a statistically significant association with BMI was shown constitute one block of linkage disequilibrium (r2 = 0.82 – 1.0, P < 0.001) and form two most common haplotypes: A/G/T/T/G/T/G/C (51.9%) and G/A/C/G/T/A/A/T (42.8%). Therefore, to determine the risk for obesity development, it is sufficient to conduct genetic testing for one of these polymorphic variants. This greatly facilitates the process of determining a genetic predisposition to excess weight.
超重和肥胖是指人体脂肪组织的异常和过度沉积,对健康造成重大危害。不幸的是,超重人群的数量一直呈持续上升的趋势。肥胖的发展可能是由过多的食物摄入、低体力活动和遗传易感性共同引起的。通过对肥胖个体基因型的研究,我们可以识别出一些基因的多态性变异,这些变异会导致体重过度增加的遗传倾向。肥胖最重要的预测因子之一是FTO基因(一种脂肪量和肥胖相关基因)。对白俄罗斯共和国655名代表的FTO基因进行了13个多态性变异的基因分型。外周静脉血样本进行基因组DNA提取。实时荧光定量PCR检测FTO基因的多态性变异。FTO基因8个多态变异的基因型与体重指数存在显著相关性:多态变异rs11075990、rs1121980、rs1421085、rs17817449、rs3751812、rs9939609、rs9940128和rs9941349的小纯合子携带者的体重指数(BMI)显著高于相应的大纯合子携带者,P = 0.0022 ~ 0.021。对FTO基因13个多态性变异的连锁不平衡进行了分析。结果表明,8个FTO基因多态性变异与BMI呈显著相关,构成了1个连锁不平衡区(r2 = 0.82 ~ 1.0, P < 0.001),形成了a /G/T/T/G/ C(51.9%)和G/ a /C/G/T/ a / a /T(42.8%)两种最常见的单倍型。因此,为了确定肥胖发展的风险,对这些多态变异之一进行基因检测就足够了。这极大地促进了确定超重遗传倾向的过程。
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引用次数: 0
Chronic positive mass balance is the actual etiology of obesity: A living review 慢性正质量平衡是肥胖的真正病因:一个活生生的回顾
Pub Date : 2023-03-01 DOI: 10.36922/gtm.222
Anssi H Manninen
The fundamental cause of obesity is widely assumed to be an energy imbalance between calories consumed and calories expended (i.e., the energy balance theory). However, this century-old obesity paradigm is fallacious. According to known laws of physics, the actual etiology of obesity is chronic positive mass balance, not positive energy balance. Furthermore, the relevant physical law in body mass regulation is the Law of Conservation of Mass, not the Law of Conservation of Energy. It is important to understand that energy balance and mass balance are separate balances in the human body. Since calories simply represent the heat released on food oxidation, they have no impact on body mass. Body mass can only change as a result of net mass flow; thus, the only food property that can augment body mass is its nutrient mass, not its energy content. The recently proposed mass balance model describes the temporal evolution of body weight and body composition under a wide variety of feeding experiments, and it seems to provide a highly accurate description of the very best experimental human feeding data. By shifting to a mass balance paradigm of obesity, a deeper understanding of this condition may follow in the near future. The purpose of this living review is to present the core issues of the upcoming paradigm shift and some practical applications related to the subject.
人们普遍认为,肥胖的根本原因是摄入的卡路里和消耗的卡路里之间的能量不平衡(即能量平衡理论)。然而,这个有百年历史的肥胖范式是错误的。根据已知的物理定律,肥胖的真正病因是慢性正质量平衡,而不是正能量平衡。此外,与人体质量调节有关的物理定律是质量守恒定律,而不是能量守恒定律。重要的是要明白,能量平衡和质量平衡是人体内不同的平衡。由于卡路里仅仅代表食物氧化释放的热量,它们对体重没有影响。身体质量只能随着净质量流量而改变;因此,唯一能增加体重的食物属性是它的营养质量,而不是它的能量含量。最近提出的质量平衡模型描述了各种喂养实验下体重和身体成分的时间演变,它似乎提供了对人类喂养实验数据的高度准确描述。通过转向肥胖的质量平衡范式,在不久的将来可能会对这种情况有更深入的了解。这篇生活回顾的目的是提出即将到来的范式转变的核心问题以及与该主题相关的一些实际应用。
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引用次数: 0
Adenine base editing as a promising therapy for cardiovascular diseases 腺嘌呤碱基编辑作为一种有前途的治疗心血管疾病的方法
Pub Date : 2023-02-14 DOI: 10.36922/gtm.232
Lu-jia Yang, Zihao Tao, X. Ma, Xuanhui Zhang, Yuxuan Guo, Fei Gao
Cardiovascular diseases (CVDs) are the leading causes of human death worldwide. Genetic variants serve as the major risk factor for CVDs, with limited therapeutic interventions in clinical practice. The recent surge of genome editing technologies offers the hope to correct genetic variants and to cure genetic diseases. Among the diverse genome editing tools, adenine base editors (ABEs) exhibit high efficiency, high specificity, and low off-target effects, successfully entering a clinical trial and demonstrating the tremendous potential to transform modern cardiovascular therapy. In this review, we summarize the basic knowledge about ABE, showcase three hallmark studies using ABE to ameliorate or treat CVDs in experimental animals, and lastly discuss about the key technical concerns that should be addressed to achieve the full potential of ABEs in the future.
心血管疾病(cvd)是全世界人类死亡的主要原因。遗传变异是心血管疾病的主要危险因素,在临床实践中治疗干预有限。最近基因组编辑技术的激增为纠正基因变异和治愈遗传疾病带来了希望。在众多基因组编辑工具中,腺嘌呤碱基编辑器(adenine base editors, abe)以高效率、高特异性、低脱靶效应等特点,成功进入临床试验,展现出改变现代心血管治疗的巨大潜力。在本文中,我们总结了ABE的基本知识,展示了在实验动物中使用ABE改善或治疗心血管疾病的三个标志性研究,最后讨论了未来应该解决的关键技术问题,以充分发挥ABE的潜力。
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引用次数: 0
期刊
Global translational medicine
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