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Sulodexide protects endothelial cells against 4-hydroxynonenal-induced oxidative stress and glutathione-dependent redox imbalance by modulation of sestrin2/nuclear factor erythroid 2-related factor 2 pathway. 舒洛地特通过调节雌三醇2/核因子红细胞2相关因子2通路,保护内皮细胞免受4-羟基壬烯醛诱导的氧化应激和谷胱甘肽依赖性氧化还原失衡的影响。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.03
K Bontor, B Gabryel

The lipid peroxidation product 4-hydroxynonenal (HNE) may be involved in vascular endothelial cell damage by induction of oxidative stress, apoptosis, and loss of redox homeostasis. There is evidence that stimulation of endothelial cells with 4-HNE induces the activation of the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap-1) pathway. Sestrin2 protein (SESN2) is one of the key regulators of Nrf2 and is involved in the cellular response to oxidative stress. However, the function of SESN2 in HNE-induced endothelial injury is not yet understood. Sulodexide (SDX) is a mixture of glycosaminoglycans used in clinical practice in the treatment of chronic venous and arterial diseases. While SDX has well-documented endothelial protective properties, little is known about its antioxidant effects. The aim of this study was to elucidate the molecular mechanisms activated by SDX in human umbilical endothelial cells (HUVECs) under HNE-induced oxidative stress. In this experimental model, we decided to evaluate the anti-apoptotic and antioxidant potential of SDX and its effect on the SESN2/Nrf2/GSH pathway. HUVECs were treated with 25 _M HNE or HNE combined with 0.5 LRU/mL SDX for 4 hours. Cell viability, apoptosis and intracellular reactive oxygen species (ROS) production were assessed by MTT assay and fluorescence microscopy. The expressions of Bax, cleaved caspase-3, Keap-1 and Nrf2 were determined by Western blot analysis. The intracellular concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG) were measured by colorimetric assay. SESN2, glutamate-cysteine ligase catalytic subunit (GCLc) and glutathione synthase (GSS) were assessed using ELISA. RT-qPCR was performed to detect Nrf2, GCLc and GSS mRNA levels. Transient Nrf2 silencing was obtained by short interfering RNA (siRNA). We have demonstrated that SDX can reduce the negative impact of HNE on HUVECs. SDX significantly protected HNE-treated HUVECs from apoptosis (p<0.001) and oxidative stress (p<0.001). SDX treatment significantly reduced Bax (p<0.05) and cleaved caspase-3 (p<0.01) expression. Co-administration of HNE and SDX increased GSH content (p<0.001) and GSH:GSSG ratio (p<0.001) as well as decreased SESN2 concentration (p<0.001) and Nrf2 (p<0.01), GCLc (p<0.05) and GSS (p<0.01) gene expression compared with the HNE group. Moreover, we revealed a negative correlation between SESN2 levels and GSH concentrations (p<0.001). Nrf2 silencing significantly decreased the effect of HNE and SDX on the induction of GCLc and GSS genes. SDX also significantly ameliorated the increase of nuclear Nrf2 in response to HNE (p<0.05). The results confirmed that SDX may protect against HNE-induced endothelial damage through its antioxidant effect and modulation of the SESN2/Nrf2/GSH signaling pathway.

脂质过氧化产物 4-羟基壬烯醛(HNE)可能通过诱导氧化应激、细胞凋亡和氧化还原平衡的丧失而参与血管内皮细胞的损伤。有证据表明,4-HNE 对血管内皮细胞的刺激可诱导激活核因子红细胞 2 相关因子 2/Kelch 样 ECH 相关蛋白 1(Nrf2/Keap-1)通路。Sestrin2 蛋白(SESN2)是 Nrf2 的关键调节因子之一,参与细胞对氧化应激的反应。然而,SESN2 在 HNE 诱导的内皮损伤中的功能尚不清楚。舒洛地塞(SDX)是一种糖胺聚糖混合物,临床上用于治疗慢性静脉和动脉疾病。虽然 SDX 对内皮的保护作用已得到充分证实,但对其抗氧化作用却知之甚少。本研究旨在阐明在 HNE 诱导的氧化应激下,SDX 在人脐带内皮细胞(HUVECs)中激活的分子机制。在这一实验模型中,我们决定评估 SDX 的抗凋亡和抗氧化潜力及其对 SESN2/Nrf2/GSH 通路的影响。用 25 _M HNE 或 HNE 联合 0.5 LRU/mL SDX 处理 HUVEC 4 小时。细胞活力、细胞凋亡和细胞内活性氧(ROS)的产生通过 MTT 试验和荧光显微镜进行评估。通过 Western 印迹分析测定了 Bax、caspase-3、Keap-1 和 Nrf2 的表达。细胞内还原型谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)的浓度通过比色法测定。SESN2、谷氨酸-半胱氨酸连接酶催化亚基(GCLc)和谷胱甘肽合成酶(GSS)采用酶联免疫吸附法进行评估。采用 RT-qPCR 检测 Nrf2、GCLc 和 GSS mRNA 水平。通过短干扰 RNA(siRNA)获得瞬时 Nrf2 沉默。我们已经证明,SDX 可以减轻 HNE 对 HUVEC 的负面影响。SDX 能明显保护 HNE 处理的 HUVEC 免受细胞凋亡(p
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引用次数: 0
Myriad of factors involved in blood pressure control. Salt intake connects them all. 血压控制涉及众多因素。盐的摄入将它们全部联系在一起。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.01
M Kuczeriszka, L Dobrowolski

Long-lasting elevated blood pressure (BP), i.e. hypertension, is a major contributor to morbidity and mortality worldwide. As a multifactorial and systemic disease that involves multiple systems, hypertension remains a challenging disease to study. Models of hypertension are a basic source of knowledge to drive and support the discovery of the specific genetic, cellular, and molecular mechanisms underlying essential hypertension, as well as to discover and introduce new possible treatments to lower BP. Animal models of hypertension deliver a huge amount of information but it is important to choose the proper one for our scientific hypothesis. In this review, we discuss the physiological, and biochemical background of rodent models of hypertension through a systems approach and a myriad of mechanisms and pathways involved in blood pressure control. We also pay attention to how target organs and systems including the kidneys, vasculature, the sympathetic nervous system (SNS), and immunological system, interfere with each other, and their activity is differentially controlled by sodium delivery, which still remains a pivotal troublemaker.

长期血压(BP)升高,即高血压,是导致全球发病率和死亡率的一个主要因素。作为一种涉及多个系统的多因素系统性疾病,高血压仍然是一种极具挑战性的疾病。高血压模型是基本的知识来源,可推动和支持发现本质高血压的特定遗传、细胞和分子机制,以及发现和引入降低血压的新疗法。高血压动物模型提供了大量信息,但重要的是要为我们的科学假设选择合适的动物模型。在这篇综述中,我们将通过系统方法讨论高血压啮齿动物模型的生理和生化背景,以及参与血压控制的无数机制和途径。我们还关注包括肾脏、血管、交感神经系统(SNS)和免疫系统在内的目标器官和系统如何相互干扰,以及它们的活动如何受到钠输送的不同控制,而钠输送仍然是一个关键的麻烦制造者。
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引用次数: 0
The role of quantitative electroencephalography in diagnostic workup of mental disorders. 定量脑电图在精神障碍诊断工作中的作用。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.02
M Kopanska, D Ochojska, J Trojniak, I Sarzynska, J Szczygielski

Electroencephalography (EEG) is a non-invasive diagnostic tool, enabling us to assess the electrical activity of the brain and its disturbance in a great number of psychiatric conditions. This paper provides a narrative overview of the most recent advantages of EEG use in various psychiatric disorders that are associated. This article analyses selected psychiatric disorders. We discussed anxiety disorders characterized by chronic fear, dementia leading to cognitive decline, schizophrenia disrupting logical thinking, bipolar affective disorder with alternating episodes of mania and depression, and depression manifested by gradual loss of vital energy. We have shown that EEG testing, by monitoring the electrical activity of the brain, is a helpful tool in identifying specific brain wave patterns associated with these disorders. In the study of mental illness the EEG variant called quantitative EEG (QEEG) is of particular avail as to the spatial discrimination. QEEG is based on digital coding and transformation according to Fourier algorithm. Recently, even more complex methods of EEG data analysis have been implemented, including artificial intelligence (AI), deep learning (DL) and its branch: machine learning (ML). The use of sophisticated EEG postprocessing adds important information about the pathophysiology of mental disorders. More so, EEG/QEEG recording (in particular spectral analysis), if repeated over time may help to follow up the treatment results and to establish a prognosis as to the course of the given condition. Reliability, safety and availability of EEG makes it to be an indispensable tool in modern psychiatry. Use of EEG, QEEG may lead to faster and more precise differential diagnostic workup. Use of EEG/QEEG changes as an objective outcome measure in clinical trials may support the development of personalized pharmacotherapy or psychotherapy.

脑电图(EEG)是一种非侵入性诊断工具,能让我们评估大脑的电活动及其在大量精神疾病中的紊乱情况。本文概述了脑电图用于各种相关精神疾病的最新优势。本文分析了部分精神疾病。我们讨论了以长期恐惧为特征的焦虑症、导致认知能力下降的痴呆症、扰乱逻辑思维的精神分裂症、躁狂和抑郁交替发作的双相情感障碍以及以逐渐丧失活力为表现的抑郁症。我们已经证明,脑电图测试通过监测大脑的电活动,可以帮助识别与这些疾病相关的特定脑电波模式。在精神疾病的研究中,被称为定量脑电图(QEEG)的脑电图变体在空间辨别方面特别有用。QEEG 基于傅立叶算法进行数字编码和转换。近来,更复杂的脑电图数据分析方法已被采用,包括人工智能(AI)、深度学习(DL)及其分支:机器学习(ML)。使用复杂的脑电图后处理技术可以增加有关精神疾病病理生理学的重要信息。此外,脑电图/QEEG 记录(特别是频谱分析)如果能长期重复使用,还有助于跟踪治疗结果,并对特定病症的发展过程做出预后。脑电图的可靠性、安全性和可用性使其成为现代精神病学不可或缺的工具。使用脑电图和 QEEG 可以更快、更准确地进行鉴别诊断。在临床试验中使用脑电图/QEEG 变化作为客观的结果测量,可支持个性化药物疗法或心理疗法的开发。
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引用次数: 0
Adherence and acceptance of a new oral nutritional supplement in cancer patients - a pilot study in crossover design. 癌症患者对新型口服营养补充剂的依从性和接受度--交叉设计试验研究。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.07
L M Hardt, P C Konturek, H J Herrmann, D Reljic, L Kugler, J Meyer, M F Neurath, Y Zopf

Oral nutritional supplements (ONS) play a key role in the therapy of cancer-cachexia, but adherence to ONS-intake remains challenging. To improve adherence, a wide variety of ONS is crucial. We compared the acceptance and adherence of a commercial liquid ONS (LS) with a newly developed, energy- and protein-rich, semisolid, fruit-gum based product (FG) in oncological patients. Forty cancer patients with indication for artificial nutritional therapy were randomly assigned to LS and FG in crossover design for 4 weeks with a 1-week washout phase in-between. Adherence to ONS was recorded with MARS-D questionnaire. Sensory properties were evaluated and safety monitoring was performed. Energy and nutrient intake, nutrition and performance status and quality of life remained stable in both groups throughout the study (all p-values for the comparison between baseline and after 9 weeks were >0.05). Taste (p=0.004), smell (p=0.025) and enjoyment (p=0.027) of the LS were rated significantly better compared to FG and a higher adherence (p=0.005) for the LS was found. Nevertheless, patients were very interested about the new alternative of ONS, so that 16 of the study participants would buy it or strive for a medical prescription. The balanced, protein-rich ONS based on fruit gum is an innovative formulation that stabilizes nutritional status and might therefore extend the options for nutritional support in cancer patients in the future. However, the sensory properties must first be further improved to increase acceptance and adherence.

口服营养补充剂(ONS)在治疗癌症腹痛症中发挥着关键作用,但坚持服用ONS仍是一项挑战。为了提高依从性,口服营养补充剂的多样性至关重要。我们比较了肿瘤患者对商用液体 ONS(LS)和新开发的富含能量和蛋白质的半固体果胶产品(FG)的接受度和依从性。40 名有人工营养疗法适应症的癌症患者被随机分配到液态营养补充剂和果胶营养补充剂中,交叉使用 4 周,中间有 1 周的清洗期。通过 MARS-D 问卷记录患者对 ONS 的依从性。对感官特性进行了评估,并进行了安全监测。在整个研究过程中,两组的能量和营养素摄入量、营养状况、表现状态和生活质量均保持稳定(基线与 9 周后的所有对比 p 值均大于 0.05)。与 FG 相比,LS 的口感(p=0.004)、气味(p=0.025)和享受(p=0.027)明显更好,LS 的依从性更高(p=0.005)。尽管如此,患者对新的替代性 ONS 非常感兴趣,因此研究参与者中有 16 人愿意购买或争取医生处方。以果胶为基础的均衡、富含蛋白质的 ONS 是一种创新配方,可稳定营养状况,因此未来可能会扩大癌症患者营养支持的选择范围。不过,首先必须进一步改进其感官特性,以提高接受度和依从性。
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引用次数: 0
Chromosomal analysis in pregnant women of advanced maternal age: indications for prenatal diagnosis. 高龄孕妇的染色体分析:产前诊断的适应症。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.08
F F Wang, Y Li, M M Liu, Y M Han, Z W Sun, C Wang, L L Wang, M Guo, P L Li

The demographic of women of advanced maternal age (AMA), defined as those over 35 years, is expanding in response to the liberalization of China's three-child policy. A significant proportion of these women are electing to undergo noninvasive prenatal testing (NIPT). Nonetheless, next-generation sequencing (NGS) is the recommended method for prenatal screening among women of AMA in the world. Consequently, the decision between opting for NIPT or NGS has emerged as topic of considerable debate and interest within the medical community. The objective was to explore which prenatal screening and diagnosis is suitable for women of AMA with different comorbidities. In this retrospective study, 326 pregnant women with AMA were divided into 9 groups to investigate clinically significant copy number variation (CNV) in different amniocentesis indications by amniocentesis and NGS. Clinically significant chromosomal abnormalities were identified in 84 cases (25.8%). Among the 119 detected segmental imbalances, 16 cases (13.4%) exhibited pathogenic or likely pathogenic microdeletions or micro-duplications. The incidence of pathogenic or likely pathogenic CNVs was significantly higher in the AMA with soft ultrasound markers group compared to the general AMA group (11.5% vs. 1.1%; P=0.016). Additionally, the incidence of pathogenic or likely pathogenic CNVs was significantly higher in the AMA with NIPT group compared to the general AMA group (48.7% vs. 1.1%; P<0.001). The incorporation of soft ultrasound markers and NIPT significantly enhanced the detection rate of clinically significant CNVs in women of AMA by 10.4% and 47.6%, respectively. Furthermore, the detection rate of clinically significant CNVs increased by 37% in women of AMA who underwent NIPT, when soft ultrasound markers were present. The positive predictive value of NIPT in detecting sex chromosome aneuploidy notably improved from 57.9% to 80% with the inclusion of soft ultrasound markers. Therefore, the combination of NIPT and soft ultrasound markers in women of AMA should be strongly considered and recommended for prenatal diagnosis.

随着中国三胎政策的放开,高龄产妇(AMA)(指 35 岁以上的妇女)的人数正在不断增加。这些妇女中有很大一部分选择接受无创产前检测(NIPT)。尽管如此,下一代测序(NGS)仍是世界上AMA妇女产前筛查的推荐方法。因此,选择 NIPT 还是 NGS 已成为医学界颇受争议和关注的话题。本研究旨在探讨哪种产前筛查和诊断方法适合患有不同合并症的 AMA 妇女。在这项回顾性研究中,326 名患有 AMA 的孕妇被分为 9 组,通过羊膜腔穿刺术和 NGS 研究不同羊膜腔穿刺适应症中具有临床意义的拷贝数变异(CNV)。结果发现 84 例(25.8%)有临床意义的染色体异常。在 119 例检测到的节段不平衡中,16 例(13.4%)表现为致病性或可能致病性微缺失或微重复。与普通 AMA 组相比,带有软超声标记物的 AMA 组致病性或可能致病性 CNV 的发生率明显更高(11.5% 对 1.1%;P=0.016)。此外,与普通 AMA 组相比,使用 NIPT 的 AMA 组致病性或可能致病性 CNV 的发生率明显更高(48.7% vs. 1.1%;P=0.016)。
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引用次数: 0
The efficacy of levosimendan and dobutamine on reducing peripheral blood interleukin-6 levels and improving cardiac function in patients with septic cardiomyopathy: a comparative study. 左西孟旦和多巴酚丁胺对降低脓毒性心肌病患者外周血白细胞介素-6水平和改善心功能的疗效:一项比较研究。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.05
T Sun, Q-L Sun, Y Liu, Y-Y Zhang, P Sheng, N Cui, N Zhang, S-H Wang, D Su

In patients with severe septic cardiomyopathy, levosimendan has been found to improve myocardial contractility more effectively than dobutamine, although the underlying mechanisms remain unclear. This study aims to compare the effects of levosimendan and dobutamine on cardiac function and inflammatory markers in patients with septic cardiomyopathy, and to further investigate the advantages and disadvantages of both treatments. We included 40 patients with septic cardiomyopathy treated in the intensive care unit of our hospital from September 2020 to September 2023. The patients were randomly divided into a levosimendan group (n=20) and a dobutamine group (n=20). Plasma concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured by immunofluorescence at the start of treatment, 24 hours, and 48 hours. Cardiac troponin I (cTnI) concentrations were determined by chemiluminescence, and left ventricular ejection fraction (LVEF) was measured using the Simpson method. After 24 hours of treatment, there were no significant differences in IL-6, IL-1β, and TNFα levels between the two groups (P>0.05). However, at 48 hours, the IL-6 level in the levosimendan group was significantly lower than that in the dobutamine group (319.43±226.05 pg/ml vs. 504.57±315.20 pg/ml, P=0.039), while IL-1β and TNF-α levels showed no significant differences (P>0.05). Additionally, the cTnI level in the levosimendan group was significantly lower than that in the dobutamine group (1.01±0.54 ng/ml vs. 1.40±0.63 ng/ml, P=0.042), and LVEF was significantly higher in the levosimendan group (50.60±6.11% vs. 46.90±4.95%, P=0.042). These findings suggest that levosimendan may reduce plasma IL-6 levels, alleviate myocardial injury, and improve myocardial contractility in patients with septic cardiomyopathy compared to dobutamine.

在严重脓毒性心肌病患者中,研究发现左西孟旦比多巴酚丁胺能更有效地改善心肌收缩力,但其潜在机制仍不清楚。本研究旨在比较左西孟旦和多巴酚丁胺对脓毒性心肌病患者心功能和炎症指标的影响,并进一步探讨两种治疗方法的优缺点。我们纳入了 2020 年 9 月至 2023 年 9 月期间在我院重症监护室接受治疗的 40 例脓毒性心肌病患者。患者被随机分为左西孟旦组(20 人)和多巴酚丁胺组(20 人)。在治疗开始、24 小时和 48 小时时,用免疫荧光法测定血浆中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的浓度。心肌肌钙蛋白 I(cTnI)浓度采用化学发光法测定,左心室射血分数(LVEF)采用辛普森法测定。治疗 24 小时后,两组的 IL-6、IL-1β 和 TNFα 水平无明显差异(P>0.05)。但在 48 小时时,左西孟旦组的 IL-6 水平明显低于多巴酚丁胺组(319.43±226.05 pg/ml vs. 504.57±315.20 pg/ml,P=0.039),而 IL-1β 和 TNF-α 水平无明显差异(P>0.05)。此外,左西孟旦组 cTnI 水平显著低于多巴酚丁胺组(1.01±0.54 ng/ml vs. 1.40±0.63 ng/ml,P=0.042),左西孟旦组 LVEF 显著高于多巴酚丁胺组(50.60±6.11% vs. 46.90±4.95%,P=0.042)。这些研究结果表明,与多巴酚丁胺相比,左西孟旦可降低脓毒症心肌病患者的血浆IL-6水平,减轻心肌损伤,改善心肌收缩力。
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引用次数: 0
Determining the expression of vitamin D receptor, regulator of iron metabolism hepcidin and cathelicidin antimicrobial peptide genes for development of future diagnostic and therapeutic options in patients with inflammatory bowel disease. 确定维生素 D 受体、铁代谢调节剂肝磷脂素和 cathelicidin 抗菌肽基因的表达情况,以便为炎症性肠病患者开发未来的诊断和治疗方案。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.06
N Fabisiak, A Tarasiuk-Zawadzka, A Fabisiak, M Wlodarczyk, J Fichna

Patients with inflammatory bowel diseases (IBD) frequently experience malnutrition and develop nutrients deficiencies such as vitamin D or iron. Collectively, 39 patients were recruited to the study - 32 with IBD and 7 patients constituting the control group (CG). Quantitative real-time polymerase chain reaction was used to assess the expression of vitamin D receptor (VDR), hepcidin (HAMP) and cathelicidin antimicrobial peptide (CAMP) in colon mucosa. The mean expression of VDR and CAMP was higher in patients with ulcerative colitis than other groups (VDR vs. CG, p<0.05). However, the mean HAMP expression reached higher values in CG than in groups with IBD. Further research to understand the relationship between the VDR, HAMP and CAMP may constitute the way for development of future diagnostic and therapeutic options in patients with IBD.

炎症性肠病(IBD)患者经常会出现营养不良和维生素 D 或铁等营养素缺乏症。本研究共招募了 39 名患者--32 名 IBD 患者和 7 名对照组(CG)患者。研究采用定量实时聚合酶链反应评估结肠粘膜中维生素 D 受体(VDR)、肝素(HAMP)和柔毛素抗菌肽(CAMP)的表达。溃疡性结肠炎患者 VDR 和 CAMP 的平均表达量高于其他组别(VDR 与 CG 相比,p
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引用次数: 0
Strontium ranelate modulates circular RNA BACH1/microRNA-155-5p to ameliorate root resorption and tooth anchoring during orthodontic tooth movement. 雷尼酸锶能调节环状 RNA BACH1/microRNA-155-5p,从而在牙齿矫正过程中改善牙根吸收和牙齿固定。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.09
N N Wang, L Li, Z Q Gu

The tooth movement is a fundamental requirement during any orthodontic treatment. This study aimed to investigate the action and mechanism of strontium ranelate (SR) in orthodontic tooth movement (OTM). Rats were given SR by gavage daily, along with lentiviral vectors interfering with circBACH1 or miR-155-5p. Three weeks later, an OTM rat model was established. RANKL and osteoprotegerin (OpG) in serum were measured. The gap between the first and second molar and root resorption were examined. Osteoclast test was used; and root condition was examined. Detection of miR-155-5p, circBACH1, CLC7 and cathepsin K was performed. The binding of circBACH1 to miR-155-5p was verified. In OTM rats, circBACH1 was elevated (p<0.05) and miR-155-5p was silenced (p<0.05). SR reduced osteoclast activity (p<0.05) and improved root resorption (p<0.05) in OTM rats, which was enhanced by silenced circBACH1 (p<0.05) or elevated miR-155-5p (p<0.05). circBACH1 inhibited miR-155-5p expression (p<0.05). Silenced miR-155-5p reversed the ameliorative effect of circBACH1 on tooth root resorption in OTM rats (all p<0.05). SR modulates circBACH1/miR-155-5p to ameliorate root resorption and tooth fixation during OTM.

牙齿移动是任何正畸治疗的基本要求。本研究旨在探讨雷尼酸锶(SR)在正畸牙齿移动(OTM)中的作用和机制。研究人员每天给大鼠灌胃雷尼酸锶以及干扰 circBACH1 或 miR-155-5p 的慢病毒载体。三周后,建立了 OTM 大鼠模型。对血清中的 RANKL 和骨保护素(OpG)进行了测定。检查第一和第二磨牙之间的间隙以及牙根吸收情况。使用破骨细胞测试;并检查牙根状况。检测了 miR-155-5p、circBACH1、CLC7 和 cathepsin K。验证了 circBACH1 与 miR-155-5p 的结合。在 OTM 大鼠中,circBACH1 升高(p
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引用次数: 0
Expression patterns of interleukin-6 and microRNA-146A during orthodontic relapse in a rat model. 大鼠模型正畸复发期间白细胞介素-6 和 microRNA-146A 的表达模式。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.10
J-Y Dai, S-Q Li, X Jia, M-Y Wu, B Song, J-Y Li, Y Guo, R Gao

In this study, we established an experimental rat model to simulate orthodontic tooth movement relapse and a human periodontal ligament stem cell (PDLScs) model. Our aim was to explore the relationship between microRNA-146a (miR-146a) expression in periodontal tissue, the inflammatory factor interleukin-6 (IL-6), and orthodontic relapse subsequent to mechanical intervention. In the animal experiment, a total of 30 healthy male Wistar rats were randomly allocated to either the control group (n=6) or the model group (n=24). In the model group, the orthodontic appliance was removed 14 days after force application. Gingival crevicular fluid (GcF) and periodontal tissue samples were collected at intervals of days 0, 7, 14, and 21 following removal of the orthodontic appliance to assess alterations in miR-146a and IL-6 expressions. In the in vitro cell culture study, human premolar tooth tissue was isolated 24 hours following the addition of the transfection reagent to harvest PDLScs. Reverse transcription quantitative polymerase chain reaction was employed to evaluate the expression levels of the miRNA-146a gene, while Western blot analysis was utilized to assess the production of the IL-6 protein. As a result in comparison to the control group, the protein expression of IL-6 notably escalated to its peak value in the model-day 7 group (p<0.05). Subsequently, although experiencing a slight decline, the IL-6 expression in the model-day 14 group remained significantly elevated compared to control group (p<0.05). In the model-day 21 group, the protein expression of IL-6 approached that of the control group, with no significant difference observed (p>0.05). conversely, in relation to the control group, the gene expression of miR-146a drastically decreased to its lowest point in the model-day 7 group (p<0.05). While exhibiting a slight increase, the miR-146a expression in the model-day 14 group remained significantly diminished compared to control group (p<0.05). Following the identification of human periodontal ligament cells (hPDLcs) through immunofluorescence in the in vitro study, a subsequent experiment was conducted to specifically inhibit miR-146a expression. In comparison to the control group, the protein expression of IL-6 demonstrated a significant increase in the anti-miRNA oligodeoxyribonucleotide (AMO) group, where miR-146a expression was effectively suppressed (p<0.05). Throughout the process of orthodontic tooth movement relapse in rats, there was a notable reduction in the gene expression of miR-146a, accompanied by a significant increase in the expression of IL-6.

在这项研究中,我们建立了一个模拟正畸牙齿移动复发的实验大鼠模型和一个人类牙周韧带干细胞(PDLScs)模型。我们的目的是探索牙周组织中 microRNA-146a (miR-146a)的表达、炎症因子白细胞介素-6(IL-6)和机械干预后正畸复发之间的关系。在动物实验中,30 只健康雄性 Wistar 大鼠被随机分配到对照组(n=6)或模型组(n=24)。模型组在施力 14 天后取下正畸矫治器。在移除正畸装置后的第 0、7、14 和 21 天收集牙龈缝隙液(GcF)和牙周组织样本,以评估 miR-146a 和 IL-6 表达的变化。在体外细胞培养研究中,在加入转染试剂 24 小时后分离人类前磨牙组织,以收获 PDLScs。反转录定量聚合酶链反应用于评估 miRNA-146a 基因的表达水平,而 Western 印迹分析则用于评估 IL-6 蛋白的生成。结果显示,与对照组相比,IL-6 蛋白表达量在模型第 7 天组明显升高至峰值(p0.05)。
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引用次数: 0
Ginsenoside Rg1 induces ferroptosis by regulating the focal adhesion kinase/protein kinase B-forkhead box O3A signaling pathway and alleviates sepsis-induced myocardial damage. 人参皂苷Rg1通过调节局灶粘附激酶/蛋白激酶B-叉头盒O3A信号通路诱导铁变态反应,减轻败血症引起的心肌损伤
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-10-10 DOI: 10.26402/jpp.2024.4.04
L Q Lin, F K Mao, J Lin, L Guo, W R Yuan, B Y Wang

It is significant to note that 50% of patients with sepsis show cardiac insufficiency. Ginsenoside-Rg1 (G-Rg1) has been shown to have a cardiovascular protective effect. However, whether G-Rg1 is involved in the mechanism of action of sepsis-induced myocardial damage (SIMD) is unclear. This study aimed to investigate the protective effect of G-Rg1 on SIMD and to further investigate its mechanism and mechanisms of regulation of downstream pathways. An in vivo model of sepsis was established in mice by cecal ligation and puncture (CLP), and mice was administered intraperitoneally 35 or 70 mg/kg G-Rg1 after surgery. The damage to cardiac tissue was detected by hematoxylin and eosin (HE) staining. Forkhead transcription factor O subfamily member 3a (FOXO3A) in SIMD mice was detected by immunohistochemistry. Apoptosis in mouse myocardial tissue was determined by TUNEL staining. The effect of G-Rg1 on SIMD cardiomyocytes was evaluated by incubating the cells with lipopolysaccharide to induce inflammation as an in vitro model of SIMD. Cardiomyocyte viability and apoptosis were evaluated by cell counting kit-8 (CCK-8) and flow cytometry. Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and Fe2+ markers of heart damage were detected by the kit. The concentrations of tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) in heart tissue and H9c2 cells were determined by ELISA. The factors related to the focal adhesion kinase (FAK)/protein kinase B (AKT)-FOXO3A signaling pathway were determined by RT-qPCR and Western blot. High-dose G-Rg1 had a significant inhibitory effect on SIMD mouse model and lipopolysaccharide (LPS)-induced H9c2 cardiomyocytes, reducing serum levels of LDH, CK-MB, and cTnI concentrations, which effectively alleviated SIMD. G-Rg1 restored the abnormally elevated levels of TNF-α, IL-1β, and iron ions and promoted the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) expression, inhibiting apoptosis and inflammatory responses. In addition, G-Rg1 reversed the inhibitory effect of G-Rg1 on LPS-induced H9c2 cardiomyocyte injury through activation of the FAK/AKT signaling pathway and up-regulation of FOXO3A. G-Rg1 promoted the activation of the FAK/AKT signalling pathway and up-regulation of the protein expression levels of pathway-associated proteins, p-FAK and p-AKT. Therefore, G-Rg1 mediated the FAK/AKT-FOXO3A signaling pathway and played a role in the treatment of SIMD. We conclude that G-Rg1 inhibited apoptosis and inflammation of cardiomyocytes induced by sepsis and reduced iron ion levels by regulating FAK/AKT-FOXO3A signaling pathway.

值得注意的是,50% 的败血症患者会出现心功能不全。人参皂苷-Rg1(G-Rg1)已被证明具有保护心血管的作用。然而,G-Rg1 是否参与了败血症诱发心肌损伤(SIMD)的作用机制尚不清楚。本研究旨在探讨G-Rg1对SIMD的保护作用,并进一步研究其机制和下游通路的调控机制。通过盲肠结扎术(CLP)在小鼠体内建立败血症模型,术后给小鼠腹腔注射 35 或 70 mg/kg G-Rg1。通过苏木精和伊红(HE)染色检测心脏组织的损伤情况。免疫组化法检测了SIMD小鼠体内的叉头转录因子O亚家族成员3a(FOXO3A)。小鼠心肌组织的凋亡是通过 TUNEL 染色测定的。将细胞与脂多糖孵育以诱发炎症,作为 SIMD 的体外模型,从而评估 G-Rg1 对 SIMD 心肌细胞的影响。通过细胞计数试剂盒-8(CCK-8)和流式细胞术评估了心肌细胞的活力和凋亡。用试剂盒检测乳酸脱氢酶(LDH)、肌酸激酶-MB(CK-MB)、心肌肌钙蛋白 I(cTnI)和心脏损伤的 Fe2+ 标志物。用酶联免疫吸附法测定了心脏组织和 H9c2 细胞中肿瘤坏死因子α(TNF-α)和白细胞介素-1β(IL-1β)的浓度。用RT-qPCR和Western印迹法测定了与局灶粘附激酶(FAK)/蛋白激酶B(AKT)-FOXO3A信号通路相关的因子。大剂量G-Rg1对SIMD小鼠模型和脂多糖(LPS)诱导的H9c2心肌细胞有明显的抑制作用,可降低血清中LDH、CK-MB和cTnI的浓度,从而有效缓解SIMD。G-Rg1 恢复了异常升高的 TNF-α、IL-1β 和铁离子水平,促进了抗凋亡蛋白 B 细胞淋巴瘤 2(Bcl-2)的表达,抑制了细胞凋亡和炎症反应。此外,G-Rg1 通过激活 FAK/AKT 信号通路和上调 FOXO3A 逆转了 G-Rg1 对 LPS 诱导的 H9c2 心肌细胞损伤的抑制作用。G-Rg1促进了FAK/AKT信号通路的激活,并上调了通路相关蛋白p-FAK和p-AKT的蛋白表达水平。因此,G-Rg1介导了FAK/AKT-FOXO3A信号通路,并在治疗SIMD中发挥作用。我们得出结论:G-Rg1通过调节FAK/AKT-FOXO3A信号通路,抑制败血症诱导的心肌细胞凋亡和炎症反应,并降低铁离子水平。
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