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Quality of life and functional capacity in depressive patients on hemodialysis: a systematic review and meta-analysis. 血液透析抑郁症患者的生活质量和功能能力:系统回顾和荟萃分析。
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-12-18 eCollection Date: 2023-01-01 DOI: 10.1590/1414-431X2023e12850
M B Moreira, N P Cavalli, N C Righi, F B Schuch, L U Signori, A M V da Silva

Depression is a common disorder in patients with chronic kidney disease (CKD), and some data support its relationship with functional capacity and quality of life. However, to date, this has not been evaluated systematically or through meta-analysis. We sought to investigate the relationship of quality of life and functional capacity with depressive disorder in patients with CKD on hemodialysis. This systematic review considered studies published up to 2021 and included cross-sectional and cohort studies. PubMed, Embase, SPORTDiscus, Web of Science, and Cochrane (CENTRAL) databases were used to search for studies. The New Castle-Ottawa Quality Assessment scale was used to measure the quality of the studies. A total of 4,626 studies were found and, after applying the selection criteria, 16 studies (2,175 patients) remained for qualitative analysis and 10 for meta-analysis (1,484 patients). The physical component summary (MD=-6.563; 95%CI: -9.702 to -3.424) and mental component summary (MD=-18.760; 95%CI: -28.641 to -8.879) were lower in depressive patients, as in all Short Form Health Survey 36 (SF-36) domains. Only one study provided data regarding functional capacity, but it was not evaluated by the defined outcome measure. Twelve studies were classified as "moderate quality" (5 to 6 stars) and four were classified as "low-quality" (0 to 4 stars). This meta-analysis with CKD patients on hemodialysis showed a negative relationship between depression and quality of life, with worsening in all physical and mental domains of the SF-36 in depressed patients.

抑郁症是慢性肾脏病(CKD)患者的常见疾病,一些数据支持抑郁症与功能能力和生活质量的关系。然而,迄今为止,尚未对此进行过系统或荟萃分析评估。我们试图研究血液透析的 CKD 患者的生活质量和功能能力与抑郁障碍的关系。本系统综述考虑了截至 2021 年发表的研究,包括横断面研究和队列研究。研究采用 PubMed、Embase、SPORTDiscus、Web of Science 和 Cochrane (CENTRAL) 数据库进行检索。新堡-渥太华质量评估量表用于衡量研究的质量。共找到 4,626 项研究,在应用筛选标准后,剩下 16 项研究(2,175 名患者)用于定性分析,10 项研究(1,484 名患者)用于荟萃分析。抑郁症患者的躯体部分总结(MD=-6.563;95%CI:-9.702 至-3.424)和精神部分总结(MD=-18.760;95%CI:-28.641 至-8.879)与所有《健康调查简表 36》(SF-36)领域一样都较低。只有一项研究提供了有关功能能力的数据,但未通过定义的结果测量进行评估。12项研究被评为 "中等质量"(5至6星),4项被评为 "低质量"(0至4星)。这项针对接受血液透析的慢性肾脏病患者的荟萃分析表明,抑郁与生活质量之间存在负相关关系,抑郁患者在 SF-36 的所有身体和精神领域都会恶化。
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引用次数: 0
Sialic acid as the potential link between lipid metabolism and inflammation in the pathogenesis of atherosclerosis 唾液酸是动脉粥样硬化发病机制中脂质代谢和炎症之间的潜在联系
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-12-11 DOI: 10.1590/1414-431X2023e12972
A. Poznyak, D. Kashirskikh, A. Y. Postnov, 00 M.A, Popov, V. N. Sukhorukov, A. Orekhov
In the modern world, cardiovascular diseases have a special place among the most common causes of death. Naturally, this widespread problem cannot escape the attention of scientists and researchers. One of the main conditions preceding the development of fatal cardiovascular diseases is atherosclerosis. Despite extensive research into its pathogenesis and possible prevention and treatment strategies, many gaps remain in our understanding of this disease. For example, the concept of multiple low-density lipoprotein modifications was recently stated, in which desialylation is of special importance. Apart from this, sialic acids are known to be important contributors to processes such as endothelial dysfunction and inflammation, which in turn are major components of atherogenesis. In this review, we have collected information on sialic acid metabolism, analyzed various aspects of its implication in atherosclerosis at different stages, and provided an overview of the role of particular groups of enzymes responsible for sialic acid metabolism in the context of atherosclerosis.
在现代世界,心血管疾病在最常见的死亡原因中占有特殊地位。自然,这个普遍存在的问题逃不过科学家和研究人员的注意。动脉粥样硬化是致死性心血管疾病发生前的主要条件之一。尽管对其发病机制和可能的预防和治疗策略进行了广泛的研究,但我们对这种疾病的了解仍有许多空白。例如,最近提出了多种低密度脂蛋白修饰的概念,其中去木质素化具有特别重要的意义。除此之外,已知唾液酸是内皮功能障碍和炎症等过程的重要贡献者,而内皮功能障碍和炎症又是动脉粥样硬化的主要组成部分。在这篇综述中,我们收集了有关唾液酸代谢的信息,分析了其在动脉粥样硬化不同阶段的含义,并概述了在动脉粥样硬化背景下负责唾液酸代谢的特定酶群的作用。
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引用次数: 0
Assessing multiple factors affecting the gut microbiome structure of very preterm infants 评估影响早产儿肠道微生物群结构的多种因素
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-12-11 DOI: 10.1590/1414-431X2023e13186
Wenlong Xiu, Jiajia Lin, Yanhua Hu, Heng Tang, Shuangchan Wu, Changyi Yang
The composition and diversity of the gut microbiota are essential for the health and development of the immune system of infants. However, there is limited information on factors that influence the gut microbiota of very preterm infants. In this study, we analyzed factors that affect the gut microbiota of very preterm infants. The stool samples from 64 very preterm infants with a gestational age less than 32 weeks were collected for 16S rRNA gene sequencing. The infants were divided according to the delivery mode, antibiotic use during pregnancy, and feeding methods. The abundance of Proteobacteria was high in both cesarean (92.7%) and spontaneous (55.5%) delivery groups and then shifted to Firmicutes after the first week of birth. In addition, Proteobacteria was also the dominant phylum of infant gut microbiome for mothers with antibiotic use, with more than 50% after the first week of birth. In comparison, the dominant phylum for mothers without antibiotic use was Firmicutes. Proteobacteria level was also high in breastfeeding and mixed-feeding groups, consisting of more than 90% of the community. By contrast, Proteobacteria was the dominant phylum at the first week of birth but then shifted to Firmicutes for the formula-fed group. The alterations of gut microbiota in infants can affect their health condition during growth. This study confirmed that the different feeding types, delivery modes, and use of antibiotics during pregnancy can significantly affect the composition of the gut microbiota of very preterm infants.
肠道菌群的组成和多样性对婴儿免疫系统的健康和发育至关重要。然而,关于影响极早产儿肠道微生物群的因素的信息有限。在这项研究中,我们分析了影响极早产儿肠道微生物群的因素。收集64例胎龄小于32周的极早产儿粪便样本进行16S rRNA基因测序。根据分娩方式、妊娠期间抗生素使用情况和喂养方式对婴儿进行分组。变形菌门的丰度在剖宫产组(92.7%)和自然分娩组(55.5%)均较高,然后在出生第一周后转移到厚壁菌门。此外,对于使用抗生素的母亲,变形菌门也是婴儿肠道微生物组的优势门,在出生第一周后超过50%。相比之下,没有使用抗生素的母亲的优势门是厚壁菌门。在母乳喂养组和混合喂养组中变形杆菌的水平也很高,占群落的90%以上。相比之下,变形菌门在出生的第一周是优势门,但随后在配方奶喂养组转移到厚壁菌门。婴儿肠道菌群的改变会影响其生长过程中的健康状况。本研究证实,妊娠期间不同的喂养方式、分娩方式和抗生素的使用会显著影响极早产儿肠道菌群的组成。
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引用次数: 0
Neuroblastoma with superficial soft tissue mass as the first symptom: case reports with atypical ultrasonic image and literature review 以浅表软组织肿块为首发症状的神经母细胞瘤:伴有非典型超声图像的病例报告和文献综述
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-12-11 DOI: 10.1590/1414-431X2023e12975
Jiale Hu, Bei Xia, Xiuli Yuan, Haixing Chen, Fuxiang Ou, Longlong Huang, Lei Xu, Xia Feng
Neuroblastoma is one of the most common tumors in children. Cases where an isolated soft-tissue metastasis mass is the initial symptom are rare, with only four such cases reported to date. We describe the imaging findings of ten cases of neuroblastoma patients in our hospital with superficial soft tissue mass (SSTM) as the primary symptom. The main ultrasound finding of SSTM was hypoechoic masses or scattered speck-like hyperechoic masses. However, when this type of SSTM is caused by soft tissue metastasis, the location is often atypical, and ultrasound findings are difficult to distinguish from other benign diseases. Therefore, this research should remind clinicians to recognize atypical presentations of this common childhood malignant tumor. Radiologists should also consider the possibility of neuroblastoma when finding this type of SSTM with atypical ultrasound features.
神经母细胞瘤是儿童最常见的肿瘤之一。以孤立的软组织转移肿块为首发症状的病例非常罕见,迄今为止仅报道了4例此类病例。本文报告我院10例以浅表软组织肿块(SSTM)为主要症状的神经母细胞瘤患者的影像学表现。超声主要表现为低回声肿块或散点样高回声肿块。然而,当这种类型的SSTM是由软组织转移引起时,其位置往往不典型,超声表现难以与其他良性疾病区分。因此,本研究应提醒临床医生认识到这种常见的儿童恶性肿瘤的非典型表现。当发现这种具有非典型超声特征的SSTM时,放射科医生也应考虑神经母细胞瘤的可能性。
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引用次数: 0
Rectangular method: a modified technique for sampling the ischemic border zone in a rat model of transient middle cerebral artery occlusion 矩形法:在大鼠一过性大脑中动脉闭塞模型中对缺血边界区取样的改良技术
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-12-11 DOI: 10.1590/1414-431X2023e13140
Sui-Yi Xu, Mao-mei Song, Xue Pan, Shi-na Song, Qi Zhang, Changpei Li
To date, there have been three common methods for sampling the cerebral ischemic border zone in a rat model of transient middle cerebral artery occlusion (tMCAO): the “two o'clock method”, the “diagonal method”, and the “parallel line method”. However, these methods have their own advantages and limitations. Here, we propose a modified technique (the “rectangular method“) for sampling the ischemic border zone. A rat tMCAO model was prepared under the support of a compact small animal anesthesia machine. Cerebral blood flow was monitored by high-resolution laser Doppler to control the quality of modeling, and 2,3,5-triphenyl tetrazolium chloride (TTC) staining was used for cerebral infarction location assessment. Superoxide dismutase 2 (SOD2), cysteinyl aspartate specific proteinase (caspase)-3, caspase-9, and heat shock protein 70 (HSP70) were used to verify the reliability and reproducibility of the rectangular method. The expression of biomarkers (SOD2, caspase-3, caspase-9, and HSP70) in the traditional (two o'clock method after TTC staining) and modified (rectangular method) groups were increased. There were no significant differences between the groups. The rectangular method proposed herein is based on a modification of the diagonal method and parallel line method, which could provide a directly observable infarct borderline and a sufficient sampling area for subsequent experimental operations regardless of the cerebral infarct location. The assessed biomarkers (SOD2, caspase-3, caspase-9, and HSP70) demonstrated the reliability and reproducibility of the rectangular method, which may facilitate inter-laboratory comparisons.
迄今为止,在大鼠短暂性大脑中动脉闭塞(tMCAO)模型中,常用的脑缺血边界区采样方法有三种:“两点法”、“对角线法”和“平行线法”。然而,这些方法都有各自的优点和局限性。在这里,我们提出了一种改进的技术(“矩形法”)来采样缺血边界区。在小型动物麻醉机的支持下制备大鼠tMCAO模型。采用高分辨率激光多普勒监测大鼠脑血流,控制模型质量;采用2,3,5-三苯四氯唑(TTC)染色评估脑梗死部位。采用超氧化物歧化酶2 (SOD2)、半胱氨酸天冬氨酸特异性蛋白酶(caspase)-3、caspase-9和热休克蛋白70 (HSP70)验证矩形法的可靠性和重复性。传统(TTC染色后两点钟方向法)组和改良(矩形法)组生物标志物SOD2、caspase-3、caspase-9、HSP70的表达均升高。两组之间没有显著差异。本文提出的矩形法是在对角线法和平行线法的基础上改进而成的,无论脑梗死的位置如何,矩形法都可以提供直接观察到的梗死边界和足够的采样区域,以便后续的实验操作。评估的生物标志物(SOD2、caspase-3、caspase-9和HSP70)证明了矩形方法的可靠性和重复性,这可以促进实验室间的比较。
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引用次数: 0
Respiratory oscillometry and functional analyses in patients with idiopathic scoliosis. 特发性脊柱侧凸患者的呼吸示波测定和功能分析。
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-11-03 eCollection Date: 2023-01-01 DOI: 10.1590/1414-431X2023e12898
C M S Sousa, A L C Pessoa, L E Carelli, C O Ribeiro, A J Lopes, P L Melo

Scoliosis is a condition that affects the spine and causes chest rotation and trunk distortion. Individuals with severe deformities may experience dyspnea on exertion and develop respiratory failure. Respiratory oscillometry is a simple and non-invasive method that provides detailed information on lung mechanics. This work aims to investigate the potential of oscillometry in the evaluation of respiratory mechanics in patients with scoliosis and its association with physical performance. We analyzed 32 volunteers in the control group and 32 in the scoliosis group. The volunteers underwent traditional pulmonary function tests, oscillometry, and the 6-minute walk test (6MWT). Oscillometric analysis showed increased values of resistance at 4 Hz (R4, P<0.01), 12 Hz (R12, P<0.0001), and 20 Hz (R20, P<0.01). Similar analysis showed reductions in dynamic compliance (Cdyn, P<0.001) and ventilation homogeneity, as evaluated by resonance frequency (fr, P<0.001) and reactance area (Ax, P<0.001). Respiratory work, described by the impedance modulus, also showed increased values (Z4, P<0.01). Functional capacity was reduced in the group with scoliosis (P<0.001). A significant direct correlation was found between Cobb angle and R12, AX, and Z4 (P=0.0237, P=0.0338, and P=0.0147, respectively), and an inverse correlation was found between Cdyn and Cobb angle (P=0.0190). These results provided new information on respiratory mechanics in scoliosis and are consistent with the involved pathophysiology, suggesting that oscillometry may improve lung function tests for patients with scoliosis.

脊柱侧弯是一种影响脊柱的疾病,会导致胸部旋转和躯干扭曲。患有严重畸形的个体可能在用力时出现呼吸困难,并发展为呼吸衰竭。呼吸示波法是一种简单、无创的方法,可提供有关肺力学的详细信息。本工作旨在研究示波法在评估脊柱侧弯患者呼吸力学方面的潜力及其与身体表现的关系。我们分析了对照组和脊柱侧弯组的32名志愿者。志愿者接受了传统的肺功能测试、示波法和6分钟步行测试(6MWT)。示波分析显示,在4 Hz时电阻值增加(R4,P
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引用次数: 0
Effects of N-butanol extract of Amygdalus mongolica on rats with bleomycin-induced pulmonary fibrosis based on metabolomics. 基于代谢组学的蒙古苦杏仁正丁醇提取物对博莱霉素诱导的大鼠肺纤维化的影响。
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-11-03 eCollection Date: 2023-01-01 DOI: 10.1590/1414-431X2023e13045
Chen Gao, Yingchun Bai, Hongbing Zhou, Hongyu Meng, Tong Wu, Wanfu Bai, Jia Wang, Liya Fan, Yuxi Yang, Hong Chang, Songli Shi

Pulmonary fibrosis (PF) is a major public health issue with limited treatment options. As the active ingredient of the n-butanol extract of Amygdalus mongolica (BUT), amygdalin inhibits PF. However, its mechanisms of action are unclear and need further verification. Therefore, the purpose of the present studies was to investigate the anti-fibrotic effects of BUT on PF by serum metabolomics and the transforming growth factor β (TGF-β) pathway. Sixty male Sprague-Dawley rats were randomly divided into control, untreated PF, prednisone-treated (5 mg/kg), and BUT-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. The serum metabolomics profiles were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and metabolism network analysis. The expression of TGF-β1, Smad-3, Smad-7, and α-smooth muscle actin (α-SMA) was measured using a real-time polymerase chain reaction in the lung tissue. BUT significantly alleviated fibrosis by reducing the mRNA expressions of TGF-β1 (from 1.73 to 1.13), Smad-3 (from 2.01 to 1.19), and α-SMA (from 2.14 to 1.19) and increasing that of Smad7 (from 0.17 to 0.62). Twenty-eight potential biomarkers associated with PF were identified. In addition, four key biomarkers were restored to baseline levels following BUT treatment, with the lowest dose showing optimal effect. Furthermore, A. mongolica BUT was found to improve PF by the pentose phosphate pathway and by taurine, hypotaurine, and arachidonic acid metabolism. These findings revealed the mechanism of A. mongolica BUT antifibrotic effects and metabolic activity in PF rats and provided the experimental basis for its clinical application.

肺纤维化(PF)是一个主要的公共卫生问题,治疗选择有限。作为蒙古苦杏仁正丁醇提取物(BUT)的有效成分,苦杏仁苷对PF具有抑制作用,但其作用机制尚不清楚,有待进一步验证。因此,本研究的目的是通过血清代谢组学和转化生长因子β(TGF-β)途径研究BUT对PF的抗纤维化作用。将60只雄性Sprague-Dawley大鼠随机分为对照组、未治疗的PF组、泼尼松治疗组(5mg/kg)和BUT治疗组(1.75、1.25、0.75g/kg),并分别灌胃给药21天。通过超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF/MS)和代谢网络分析测定血清代谢组学图谱。采用实时聚合酶链反应测定肺组织中TGF-β1、Smad-3、Smad-7和α-平滑肌肌动蛋白(α-SMA)的表达。BUT通过降低TGF-β1(从1.73到1.13)、Smad-3(从2.01到1.19)和α-SMA(从2.14到1.19。此外,BUT治疗后,四种关键生物标志物恢复到基线水平,最低剂量显示最佳效果。此外,蒙古A.mongolica BUT通过磷酸戊糖途径以及牛磺酸、低牛磺酸和花生四烯酸代谢改善PF。这些发现揭示了沙冬青抗PF大鼠纤维化作用和代谢活性的机制,为其临床应用提供了实验依据。
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引用次数: 0
Dietary phytate induces subclinical mechanical allodynia in mice. 膳食植酸酶诱导小鼠亚临床机械性异常性疼痛。
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-11-03 eCollection Date: 2023-01-01 DOI: 10.1590/1414-431X2023e12955
D O Matias, T Sisnande, A F Martins, M J do Amaral, B L R Santos, A L P Miranda, L M T R Lima

Neuropathic pain is a condition with varying origins, including reduced dietary micronutrient intake. Phytate is a polyphosphate found in seeds and grains that can act as an antinutrient due to the ability of sequester essential divalent metals. Here we tested whether moderate dietary phytate intake could alter nociceptive pain. We subjected weaning mice to a chow supplemented with 1% phytate for eight weeks. Body weight gain, glycemic responses, food ingestion, water ingestion, and liver and adipose tissue weights were not altered compared to controls. We observed a decreased mechanical allodynia threshold in the intervention group, although there were no changes in heat- or cold-induced pain. Animals consuming phytate showed reduced spinal cord tumor necrosis factor (TNF), indicating altered inflammatory process. These data provide evidence for a subclinical induction of mechanical allodynia that is independent of phytate consumption in animals with otherwise normal phenotypic pattern.

神经性疼痛是一种起源不同的疾病,包括膳食微量营养素摄入减少。Phytate是一种存在于种子和谷物中的多磷酸盐,由于能够螯合必需的二价金属,因此可以作为抗营养剂。在这里,我们测试了饮食中摄入适量的植酸酶是否可以改变伤害性疼痛。我们让断奶小鼠接受补充有1%植酸酶的食物八周。与对照组相比,体重增加、血糖反应、食物摄入、水分摄入以及肝脏和脂肪组织重量没有改变。我们观察到干预组的机械性异常性疼痛阈值降低,尽管热或冷引起的疼痛没有变化。摄入植酸酶的动物显示脊髓肿瘤坏死因子(TNF)降低,表明炎症过程改变。这些数据为具有正常表型模式的动物的机械性异常性疼痛的亚临床诱导提供了证据,该亚临床诱导与植酸酶的消耗无关。
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引用次数: 0
Evaluating the dissemination of evolutionary biology concepts in medicine. 评估进化生物学概念在医学中的传播。
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-10-27 eCollection Date: 2023-01-01 DOI: 10.1590/1414-431X2023e13052
C Mermelstein, M L Costa, C C Coutinho

Darwin's theory of evolution, which is based on variation, heredity, and selection, includes all biological fields and spreads to other areas such as philosophy. Medicine is an example of how the evolutionary perspective can greatly improve the understanding of concepts in an area, as human health and pathological conditions are under the effect of evolution. Evolutionary medicine is an emerging paradigm for understanding human heterogeneity, health, and diseases. Nevertheless, there are indications that medical research and practice are only marginally affected by these ideas. Here, we investigate how concepts of biological evolution are employed in medical research. We use a bibliometric approach to look for the presence and frequency of biological evolution-related concepts in medical articles. The distribution of these concepts over the years is analyzed according to the medical specialty and the impact of the journal. Our data showed that: i) only a small percentage of articles in medical journals have an evolutionary perspective; ii) medical journals where these evolution-based articles are published focus on basic science, theoretical medicine, and less frequently, on applied medicine; iii) these articles are mostly from the microbiology, immunology, neurology, psychology, behavior, and oncology fields; and iv) viruses are the most frequently covered microorganisms, followed by bacteria, fungi, and protozoans. The collection of our results, considering the importance of evolutionary medicine in the medical field, highlights the need for a decisive change in perspective in medical research.

达尔文的进化论建立在变异、遗传和选择的基础上,涵盖了所有生物学领域,并传播到哲学等其他领域。医学就是一个例子,说明进化论视角可以极大地提高对一个领域概念的理解,因为人类的健康和病理状况都受到进化的影响。进化医学是理解人类异质性、健康和疾病的一种新兴范式。然而,有迹象表明,医学研究和实践只受到这些想法的轻微影响。在这里,我们研究了生物学进化的概念是如何应用于医学研究的。我们使用文献计量方法来寻找医学文章中与生物进化相关的概念的存在和频率。根据医学专业和期刊的影响,分析了这些概念多年来的分布情况。我们的数据表明:i)医学期刊上只有一小部分文章具有进化观点;ii)发表这些基于进化的文章的医学期刊侧重于基础科学、理论医学,而不太频繁地关注应用医学;iii)这些文章大多来自微生物学、免疫学、神经病学、心理学、行为学和肿瘤学领域;和iv)病毒是最常被覆盖的微生物,其次是细菌、真菌和原生动物。考虑到进化医学在医学领域的重要性,我们收集的结果突显了医学研究视角发生决定性变化的必要性。
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引用次数: 0
Telomerase inhibitors TMPyP4 and thymoquinone decreased cell proliferation and induced cell death in the non-small cell lung cancer cell line LC-HK2, modifying the pattern of focal adhesion. 端粒酶抑制剂TMPyP4和胸腺嘧啶醌降低了癌症细胞系LC-HK2的细胞增殖并诱导细胞死亡,改变了局灶性粘附模式。
IF 2.3 4区 医学 Q2 BIOLOGY Pub Date : 2023-10-27 eCollection Date: 2023-01-01 DOI: 10.1590/1414-431X2023e12897
A M B Garnique, P Rezende-Teixeira, G M Machado-Santelli

G-quadruplexes (G4) are structures formed at the ends of telomeres rich in guanines and stabilized by molecules that bind to specific sites. TMPyP4 and thymoquinone (TQ) are small molecules that bind to G4 and have drawn attention because of their role as telomerase inhibitors. The aim of this study was to evaluate the effects of telomerase inhibitors on cellular proliferation, senescence, and death. Two cell lines, LC-HK2 (non-small cell lung cancer - NSCLC) and RPE-1 (hTERT-immortalized), were treated with TMPyP4 (5 μM) and TQ (10 μM). Both inhibitors decreased telomerase activity. TMPyP4 increased the percentage of cells with membrane damage associated with cell death and decreased the frequency of cells in the S-phase. TMPyP4 reduced cell adhesion ability and modified the pattern of focal adhesion. TQ acted in a concentration-dependent manner, increasing the frequency of senescent cells and inducing cell cycle arrest in G1 phase. Thus, the present results showed that TMPyP4 and TQ, although acting as telomerase inhibitors, had a broader effect on other signaling pathways and processes in cells, differing from each other. However, they act both on malignant and immortalized cells, and further studies are needed before their anti-cancer potential can be considered.

G-四链体(G4)是在富含鸟嘌呤的端粒末端形成的结构,并通过与特定位点结合的分子稳定。TMPyP4和胸腺醌(TQ)是与G4结合的小分子,由于其作为端粒酶抑制剂的作用而引起关注。本研究的目的是评估端粒酶抑制剂对细胞增殖、衰老和死亡的影响。用TMPyP4(5μM)和TQ(10μM)处理两种细胞系,即LC-HK2(非小细胞肺癌癌症-NSCLC)和RPE-1(hTERT永生化)。两种抑制剂都降低了端粒酶活性。TMPyP4增加了与细胞死亡相关的膜损伤细胞的百分比,并降低了处于S期的细胞的频率。TMPyP4降低了细胞粘附能力并改变了局灶性粘附的模式。TQ以浓度依赖的方式发挥作用,增加衰老细胞的频率,并诱导细胞周期停滞在G1期。因此,目前的结果表明,TMPyP4和TQ虽然起到端粒酶抑制剂的作用,但对细胞中的其他信号通路和过程具有更广泛的影响,彼此不同。然而,它们同时作用于恶性细胞和永生细胞,在考虑它们的抗癌潜力之前,还需要进一步的研究。
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引用次数: 0
期刊
Brazilian Journal of Medical and Biological Research
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