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Tumor Suppressor miR-27a-5p and Its Significance for Breast Cancer. 肿瘤抑制因子 miR-27a-5p 及其对乳腺癌的意义
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-17 DOI: 10.3390/biomedicines12112625
Paola Parrella, Raffaela Barbano, Katharina Jonas, Andrea Fontana, Serena Barile, Michelina Rendina, Antonio Lo Mele, Giuseppina Prencipe, Luigi Ciuffreda, Maria Grazia Morritti, Vanna Maria Valori, Paolo Graziano, Evaristo Maiello, Massimiliano Copetti, Martin Pichler, Barbara Pasculli

Background: MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. Objectives. Herein, we sought to investigate the putative involvement of miR-27a-5p in promoting a migratory phenotype of breast cancer cells, and establish whether miR-27a-5p is associated with patient clinicopathological characteristics. Methods: miR-27a-5p capability of inducing a metastasis-prone cell phenotype was analyzed in SUM159 and MDA-MB-231, both representing the triple negative BC subtype. miR-27a-5p expression profile was carried out in a cohort of 232 BC patients and normal breast tissues (NBTs) by RT-qPCR. Results: Transient miR-27a-5p inhibition did not affect cell proliferation but led to a significant increase of cell migration in knocked-down compared to control cells. Following quantification in the patient cohort, miR-27a-5p was found higher in NBTs (Median 2.28, IQR 1.50-5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68-4.32) compared to tumors. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03, IQR 0.83-1.58) or metachronous (Median 1.83, IQR 1.29-3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19-3.64), suggesting that miR-27a-5p expression is negatively correlated with breast pathology evolution (R = -0.13, p = 0.038). However, time-to-event analysis did not highlight significant associations with patient outcome in either our internal cohort or TCGA-BRCA dataset. Conclusions: Our study suggests a potential role of miR-27a-5p as tumor suppressor miRNA in breast cancer. Further investigations may help define its biomarker potential in each breast cancer subtype, and identify other molecular partners as targets for new interventions.

背景:微RNA是乳腺癌(BC)发生的主要调控因子和潜在的生物标记物。在一项初步研究中,我们从癌症基因组图谱乳腺浸润性癌(TCGA-BRCA)数据集中发现,miR-27a-5p 在实验衍生的乳腺球和乳腺癌患者中显著下调。研究目的在此,我们试图研究 miR-27a-5p 在促进乳腺癌细胞迁移表型中的假定参与,并确定 miR-27a-5p 是否与患者的临床病理特征相关。方法:在代表三阴性 BC 亚型的 SUM159 和 MDA-MB-231 中分析了 miR-27a-5p 诱导易转移细胞表型的能力,并通过 RT-qPCR 对 232 例 BC 患者和正常乳腺组织(NBTs)进行了 miR-27a-5p 表达谱分析。结果显示瞬时miR-27a-5p抑制不影响细胞增殖,但与对照细胞相比,被敲除的细胞迁移率显著增加。对患者群进行量化后发现,与肿瘤相比,miR-27a-5p在NBT(中位数为2.28,IQR为1.50-5.40)和浸润前乳腺病变(中位数为3.32,IQR为1.68-4.32)中的含量更高。特别是,在 5 年随访后,miR-27a-5p 在同步转移(中位数 1.03,IQR 0.83-1.58)或近同步转移(中位数 1.83,IQR 1.29-3.17)患者中的表达低于无转移患者(中位数 2.17,IQR 1.19-3.64),这表明 miR-27a-5p 的表达与乳腺病理演变呈负相关(R = -0.13,p = 0.038)。然而,在我们的内部队列或TCGA-BRCA数据集中,时间到事件分析并未突出显示与患者预后的显著关联。结论我们的研究表明,miR-27a-5p 在乳腺癌中可能起着肿瘤抑制 miRNA 的作用。进一步的研究可能有助于确定其在每种乳腺癌亚型中的生物标志物潜力,并确定其他分子伙伴作为新干预措施的靶点。
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引用次数: 0
Antithyroglobulin and Antiperoxidase Antibodies Can Negatively Influence Pregnancy Outcomes by Disturbing the Placentation Process and Triggering an Imbalance in Placental Angiogenic Factors. 抗甲状腺球蛋白抗体和抗过氧化物酶抗体会干扰胎盘形成过程并引发胎盘血管生成因子失衡,从而对妊娠结局产生负面影响。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-17 DOI: 10.3390/biomedicines12112628
Kamila Tańska, Piotr Glinicki, Beata Rebizant, Piotr Dudek, Wojciech Zgliczyński, Małgorzata Gietka-Czernel

Background/Objectives: Thyroid autoimmunity (TAI) affects about 15% of women of reproductive age and can negatively affect pregnancy outcomes. One possible mechanism for pregnancy complications can be attributed to a disturbed process of placentation caused by thyroid antibodies. To test this hypothesis, placental hormones and angiogenic factors in pregnant women with TAI were evaluated. Methods: Fifty-eight hypothyroid women positive for TPOAb/TgAb, thirty-three hypothyroid women negative for TPOAb/TgAb, and thirty-nine healthy controls were enrolled in this study. Maternal thyroid function tests were established every month throughout pregnancy, and angiogenic placental factors, pro-angiogenic placental growth factor (PlGF); two anti-angiogenic factors, soluble vascular endothelial growth factor receptor 1 (sFlt-1) and soluble endoglin (sEng); and placental hormones, estradiol, progesterone, and hCG, were determined during each trimester. Results: Obstetrical and neonatal outcomes did not differ between the groups. However, several detrimental effects of thyroid antibodies were observed. These included a positive correlation between TgAb and the sEng/PlGF ratio in the first trimester and positive correlations between TPOAb and sFlt-1 and between TgAb and the sFlt-1/PlGF ratio in the third trimester. TgAbs in the first trimester was a risk factor for gestational hypertension and preeclampsia. Conclusions: Our study indicates that TPOAbs and TgAbs can exert a direct harmful effect on placentation, leading to disturbances in the production of placental angiogenic factors and, consequently, to an increased risk of gestational hypertension and preeclampsia.

背景/目的:甲状腺自身免疫(TAI)影响着约 15%的育龄妇女,并可能对妊娠结果产生负面影响。妊娠并发症的一个可能机制是甲状腺抗体导致胎盘功能紊乱。为了验证这一假设,我们对患有 TAI 的孕妇的胎盘激素和血管生成因子进行了评估。研究方法58名TPOAb/TgAb阳性的甲状腺机能减退妇女、33名TPOAb/TgAb阴性的甲状腺机能减退妇女和39名健康对照者参加了这项研究。在整个妊娠期间,每月对母体进行甲状腺功能检测,并在每个孕期检测血管生成胎盘因子、促血管生成胎盘生长因子(PlGF)、两种抗血管生成因子、可溶性血管内皮生长因子受体 1(sFlt-1)和可溶性内皮素(sEng)以及胎盘激素、雌二醇、孕酮和 hCG。结果各组间的产科和新生儿结局无差异。但是,观察到甲状腺抗体有几种不利影响。其中包括妊娠头三个月甲状腺抗体与sEng/PlGF比率呈正相关,妊娠三个月TPOAb与sFlt-1呈正相关,TgAb与sFlt-1/PlGF比率呈正相关。妊娠头三个月的 TgAb 是妊娠高血压和子痫前期的风险因素。结论我们的研究表明,TPOAbs 和 TgAbs 可对胎盘产生直接的有害影响,导致胎盘血管生成因子的产生紊乱,从而增加妊娠高血压和子痫前期的风险。
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引用次数: 0
Chamomile Tincture and Lidocaine Hydrochloride Gel Ameliorates Periodontitis: A Preclinical Study. 洋甘菊酊剂和盐酸利多卡因凝胶可改善牙周炎:临床前研究
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-17 DOI: 10.3390/biomedicines12112629
Jiahui Sun, Huiyi Wang, Junhong Xiao, Qiudong Yang, Heyu Liu, Zhengkun Yang, Yuqi Liu, Xin Huang, Liu Yang, Li Ma, Zhengguo Cao

Background/Objectives: Periodontitis is a common oral disease marked by gingival inflammation and alveolar bone loss. This study evaluated the efficacy of chamomile tincture and lidocaine hydrochloride (CLH) gel in mitigating periodontal inflammation and bone loss and uncovered the molecular mechanisms involved, both in vitro and in vivo. Methods: A periodontitis model was induced in Sprague Dawley rats by ligating the mandibular first molars. Sixty rats were divided into four groups: control (C), periodontitis (PD), periodontitis + CLH gel once daily (G1), and periodontitis + CLH gel thrice daily (G3). Clinical, micro-computed tomography (micro-CT), biological, and histological evaluations were performed, focusing on osteoclastogenesis, osteogenesis, and inflammatory cytokine production. The effect of CLH gel on inflammatory responses in RAW264.7 cells was also assessed through co-culture assays under Porphyromonas gingivalis (P. gingivalis) infection, with RNA-sequencing, qPCR, and Western blot analyses to explore underlying mechanisms. Results: CLH gel significantly reduced gingival and systemic inflammation and mitigated bone loss by enhancing the bone volume to tissue volume ratio and trabecular thickness via the RANKL/OPG axis in rats. The G3 group showed marked reductions in osteoclasts and increases in osterix-positive cells compared to other groups. In vitro, CLH gel reduced the inflammatory phenotype of macrophages in the periodontitis microenvironment by modulating Type II interferon (IFN-γ) networks. Conclusions: CLH gel reduced inflammation and bone loss in rat periodontitis, promoting osteogenesis and inhibiting osteoclastogenesis. It also suppressed macrophage inflammation via Type II interferon networks under P. gingivalis stimulation. These findings suggest that CLH gel has potential as an adjunctive therapy for periodontitis.

背景/目的:牙周炎是一种常见的口腔疾病,以牙龈发炎和牙槽骨流失为特征。本研究评估了洋甘菊酊和盐酸利多卡因(CLH)凝胶在减轻牙周炎症和骨质流失方面的疗效,并揭示了其中的体外和体内分子机制。研究方法通过结扎下颌第一磨牙诱导 Sprague Dawley 大鼠牙周炎模型。60 只大鼠被分为四组:对照组(C)、牙周炎组(PD)、牙周炎 + CLH 凝胶每日一次组(G1)和牙周炎 + CLH 凝胶每日三次组(G3)。对患者进行了临床、微型计算机断层扫描(micro-CT)、生物学和组织学评估,重点关注破骨细胞生成、骨生成和炎性细胞因子的产生。此外,还在牙龈卟啉单胞菌(P. gingivalis)感染的情况下,通过共培养试验评估了 CLH 凝胶对 RAW264.7 细胞炎症反应的影响,并通过 RNA 序列、qPCR 和 Western 印迹分析来探索其潜在机制。结果CLH凝胶通过RANKL/OPG轴提高大鼠的骨量与组织体积比和骨小梁厚度,从而明显减轻牙龈和全身炎症,缓解骨质流失。与其他组相比,G3 组的破骨细胞明显减少,而 osterix 阳性细胞则有所增加。在体外,CLH 凝胶通过调节 II 型干扰素(IFN-γ)网络,减少了牙周炎微环境中巨噬细胞的炎症表型。结论CLH凝胶可减少大鼠牙周炎的炎症和骨质流失,促进骨生成并抑制破骨细胞生成。它还能在牙龈脓疱刺激下通过 II 型干扰素网络抑制巨噬细胞炎症。这些研究结果表明,CLH凝胶具有辅助治疗牙周炎的潜力。
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引用次数: 0
Pancreatic Morphology, Immunology, and the Pathogenesis of Acute Pancreatitis. 胰腺形态学、免疫学和急性胰腺炎的发病机制。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-17 DOI: 10.3390/biomedicines12112627
Tudorel Mihoc, Silviu Constantin Latcu, Cosmin-Ciprian Secasan, Vlad Dema, Alin Adrian Cumpanas, Mircea Selaru, Catalin Alexandru Pirvu, Andrei Paul Valceanu, Flavia Zara, Cristina-Stefania Dumitru, Dorin Novacescu, Stelian Pantea

Acute pancreatitis is a complex inflammatory disorder with significant morbidity and mortality. This review aims to integrate the current knowledge of pancreatic morphology and immunology with the pathogenesis of acute pancreatitis, providing a comprehensive understanding of this critical condition. We conducted an extensive literature review, synthesizing data from recent studies and authoritative sources on pancreatic anatomy, histology, immunology, and the pathophysiology of acute pancreatitis. We also incorporated epidemiological data, clinical features, diagnostic criteria, and prognostic factors. The pancreas exhibits a complex morphology with intricate interactions between its exocrine and endocrine components. Its unique immunological landscape plays a crucial role in maintaining homeostasis and orchestrating responses to pathological conditions. In acute pancreatitis, the disruption of intracellular calcium signaling leads to premature enzyme activation, triggering a cascade of events including mitochondrial dysfunction, ATP depletion, and the release of proinflammatory mediators. This process can escalate from localized inflammation to systemic complications. The interplay between pancreatic morphology, immune responses, and pathophysiological mechanisms contributes to the varied clinical presentations and outcomes observed in acute pancreatitis. Understanding the intricate relationships between pancreatic morphology, immunology, and the pathogenesis of acute pancreatitis is crucial for developing more effective diagnostic and therapeutic strategies. This integrated approach provides new insights into the complex nature of acute pancreatitis and may guide future research directions in pancreatic disorders.

急性胰腺炎是一种复杂的炎症性疾病,发病率和死亡率都很高。本综述旨在将胰腺形态学和免疫学的现有知识与急性胰腺炎的发病机理结合起来,提供对这一危急病症的全面认识。我们进行了广泛的文献综述,综合了有关胰腺解剖学、组织学、免疫学和急性胰腺炎病理生理学的最新研究和权威资料。我们还纳入了流行病学数据、临床特征、诊断标准和预后因素。胰腺形态复杂,其外分泌和内分泌成分之间的相互作用错综复杂。其独特的免疫格局在维持体内平衡和协调对病理状态的反应方面发挥着至关重要的作用。在急性胰腺炎中,细胞内钙信号的中断会导致酶过早激活,引发一连串事件,包括线粒体功能障碍、ATP耗竭和促炎介质的释放。这一过程会从局部炎症升级到全身并发症。胰腺形态、免疫反应和病理生理机制之间的相互作用导致了急性胰腺炎的不同临床表现和结果。了解胰腺形态学、免疫学和急性胰腺炎发病机制之间错综复杂的关系,对于制定更有效的诊断和治疗策略至关重要。这种综合方法为了解急性胰腺炎的复杂性提供了新的视角,并可能为胰腺疾病的未来研究方向提供指导。
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引用次数: 0
Epigenetics of Hypertensive Nephropathy. 高血压肾病的表观遗传学。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-16 DOI: 10.3390/biomedicines12112622
Yize Zhang, Hamidreza Arzaghi, Zhehan Ma, Yasmin Roye, Samira Musah

Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), contributing to significant morbidity, mortality, and rising healthcare costs. In this review article, we explore the role of epigenetic mechanisms in HN progression and their potential therapeutic implications. We begin by examining key epigenetic modifications-DNA methylation, histone modifications, and non-coding RNAs-observed in kidney disease. Next, we discuss the underlying pathophysiology of HN and highlight current in vitro and in vivo models used to study the condition. Finally, we compare various types of HN-induced renal injury and their associated epigenetic mechanisms with those observed in other kidney injury models, drawing inferences on potential epigenetic therapies for HN. The information gathered in this work indicate that epigenetic mechanisms can drive the progression of HN by regulating key molecular signaling pathways involved in renal damage and fibrosis. The limitations of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors underscore the need for alternative treatments targeting epigenetic pathways. This review emphasizes the importance of further research into the epigenetic regulation of HN to develop more effective therapies and preventive strategies. Identifying novel epigenetic markers could provide new therapeutic opportunities for managing CKD and reducing the burden of ESRD.

高血压肾病(HN)是慢性肾脏病(CKD)和终末期肾脏病(ESRD)的主要病因,造成了严重的发病率、死亡率和医疗费用的上升。在这篇综述文章中,我们将探讨表观遗传机制在 HN 进展中的作用及其潜在的治疗意义。我们首先探讨了肾病中观察到的关键表观遗传修饰--DNA 甲基化、组蛋白修饰和非编码 RNA。接下来,我们讨论了 HN 的基本病理生理学,并重点介绍了目前用于研究该病症的体外和体内模型。最后,我们将 HN 诱导的各种肾损伤及其相关表观遗传学机制与在其他肾损伤模型中观察到的机制进行了比较,从而推断出治疗 HN 的潜在表观遗传学疗法。本研究收集的信息表明,表观遗传机制可通过调节参与肾损伤和纤维化的关键分子信号通路来推动 HN 的进展。肾素-血管紧张素-醛固酮系统(RAAS)抑制剂的局限性凸显了针对表观遗传通路的替代治疗的必要性。本综述强调了进一步研究 HN 的表观遗传调控以开发更有效的疗法和预防策略的重要性。确定新的表观遗传标记可为控制 CKD 和减轻 ESRD 负担提供新的治疗机会。
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引用次数: 0
Analysis of Circulating Catestatin in Early Pregnancy: A Preliminary Investigation. 妊娠早期循环睾酮分析:初步调查
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-16 DOI: 10.3390/biomedicines12112626
Zdenka Sunjic Lovric, Jasminka Resic Karara, Bianka Mimica, Marko Kumric, Daniela Supe-Domic, Roko Santic, Josko Bozic

Background: During pregnancy, significant cardiovascular changes occur to accommodate fetal growth, and catestatin may play a role in these changes. Evidence suggests that catestatin, a pleiotropic sympathoinhibitory peptide, is involved in multiple cardiovascular pathologies, including hypertensive disorders. The objective of this study was to compare serum catestatin levels between first-trimester pregnant women and non-pregnant women, aiming to investigate catestatin's role in blood pressure regulation during early pregnancy. Methods: This cross-sectional study included 72 first-trimester pregnant women and 57 age-matched non-pregnant controls, all without known cardiovascular or metabolic disorders. Results: Serum catestatin concentrations were significantly higher in pregnant women compared to controls (12.4 (9.9-21.2) ng/mL vs. 7.1 (4.5-10.9) ng/mL, p < 0.001). However, there was no significant difference in serum catestatin levels between those with a normal and abnormal uterine artery pulsatility index (17.8 (8.3-22.3) ng/mL vs. 12.5 (9.9-22.4) ng/mL, p = 0.962). Similarly, catestatin concentrations did not significantly differ between primiparous and multiparous women (14.0 (11.5-22.4) ng/mL vs. 10.7 (8.8-19.0) ng/mL). A positive correlation was observed between systolic blood pressure and serum catestatin levels in the control group (r = 0.335, p = 0.011) but not in pregnant women. Conclusions: Research on catestatin in pregnancy is still in its early stages, necessitating further studies to fully elucidate its roles and potential therapeutic applications.

背景:在怀孕期间,心血管会发生重大变化以适应胎儿的生长,而催产素可能在这些变化中扮演了一定的角色。有证据表明,催产素是一种多效交感抑制肽,与包括高血压疾病在内的多种心血管病变有关。本研究的目的是比较妊娠初期孕妇和非孕妇的血清中催产素的水平,旨在研究催产素在妊娠初期血压调节中的作用。研究方法这项横断面研究包括 72 名怀孕初期的孕妇和 57 名年龄匹配的非孕妇对照组,她们都没有已知的心血管或代谢疾病。研究结果与对照组相比,孕妇血清中猫血素的浓度明显更高(12.4 (9.9-21.2) ng/mL vs. 7.1 (4.5-10.9) ng/mL,p < 0.001)。然而,子宫动脉搏动指数正常和异常者的血清促性腺激素水平没有明显差异(17.8 (8.3-22.3) ng/mL vs. 12.5 (9.9-22.4) ng/mL,p = 0.962)。同样,初产妇和多产妇的睾酮浓度也无明显差异(14.0 (11.5-22.4) 纳克/毫升 vs. 10.7 (8.8-19.0) 纳克/毫升)。在对照组中,收缩压与血清中的促睾酮水平呈正相关(r = 0.335,p = 0.011),但在孕妇中却没有发现。结论对妊娠期催产素的研究仍处于早期阶段,需要进一步研究以充分阐明其作用和潜在的治疗应用。
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引用次数: 0
p75NTR Modulation Reduces Oxidative Stress and the Expression of Pro-Inflammatory Mediators in a Cell Model of Rett Syndrome. p75NTR 调节可降低氧化应激和前炎症介质在雷特综合征细胞模型中的表达。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-16 DOI: 10.3390/biomedicines12112624
Michela Varone, Giuseppe Scavo, Mayra Colardo, Noemi Martella, Daniele Pensabene, Emanuele Bisesto, Andrea Del Busso, Marco Segatto

Background: Rett syndrome (RTT) is an early-onset neurological disorder primarily affecting females, leading to severe cognitive and physical disabilities. Recent studies indicate that an imbalance of redox homeostasis and exacerbated inflammatory responses are key players in the clinical manifestations of the disease. Emerging evidence highlights that the p75 neurotrophin receptor (p75NTR) is implicated in the regulation of oxidative stress (OS) and inflammation. Thus, this study is aimed at investigating the effects of p75NTR modulation by LM11A-31 on fibroblasts derived from RTT donors. Methods: RTT cells were treated with 0.1 µM of LM11A-31 for 24 h, and results were obtained using qPCR, immunofluorescence, ELISA, and Western blot techniques. Results: Our findings demonstrate that LM11A-31 reduces OS markers in RTT fibroblasts. Specifically, p75NTR modulation by LM11A-31 restores protein glutathionylation and reduces the expression of the pro-oxidant enzyme NOX4. Additionally, LM11A-31 significantly decreases the expression of the pro-inflammatory mediators interleukin-6 and interleukin-8. Additionally, LM11A-31 normalizes the expression levels of transcription factors involved in the regulation of the antioxidant response and inflammation. Conclusions: Collectively, these data suggest that p75NTR modulation may represent an effective therapeutic target to improve redox balance and reduce inflammation in RTT.

背景介绍雷特综合征(RTT)是一种早发性神经系统疾病,主要影响女性,会导致严重的认知和身体残疾。最新研究表明,氧化还原平衡失衡和炎症反应加剧是该病临床表现的关键因素。新的证据表明,p75 神经营养素受体(p75NTR)与氧化应激(OS)和炎症的调节有关。因此,本研究旨在探讨 LM11A-31 对 p75NTR 的调节作用对来自 RTT 供体的成纤维细胞的影响。研究方法用 0.1 µM 的 LM11A-31 处理 RTT 细胞 24 小时,并使用 qPCR、免疫荧光、ELISA 和 Western 印迹技术得出结果。结果:我们的研究结果表明,LM11A-31能减少RTT成纤维细胞中的OS标记物。具体来说,LM11A-31 对 p75NTR 的调节可恢复蛋白质的谷胱甘肽化,并减少促氧化酶 NOX4 的表达。此外,LM11A-31 还能显著降低促炎介质白细胞介素-6 和白细胞介素-8 的表达。此外,LM11A-31 还能使参与调节抗氧化反应和炎症的转录因子的表达水平正常化。结论:这些数据共同表明,p75NTR调节可能是改善氧化还原平衡和减轻RTT炎症的有效治疗靶点。
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引用次数: 0
Effect of Comparable Carbon Chain Length Short- and Branched-Chain Fatty Acids on Adipokine Secretion from Normoxic and Hypoxic Lipopolysaccharide-Stimulated 3T3-L1 Adipocytes. 碳链长度相当的短链和支链脂肪酸对正常缺氧和缺氧脂多糖刺激的 3T3-L1 脂肪细胞分泌脂肪因子的影响
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-16 DOI: 10.3390/biomedicines12112621
Ala Alzubi, Jennifer M Monk

Background: Microbial fermentation of non-digestible carbohydrates and/or protein produces short-chain fatty acids (SCFA), whereas branched-chain fatty acids (BCFA) are produced from protein fermentation. The effects of individual SCFA and BCFA of comparable carbon chain length on adipocyte inflammation have not been investigated. Objective: To compare the effects of SCFA and BCFA on inflammatory mediator secretion in an adipocyte cell culture model designed to recapitulate obesity-associated adipocyte inflammation under normoxic and hypoxic conditions. Methods: The 3T3-L1 adipocytes were cultured (24 h) without (Control, Con) and with 1 mmol/L of SCFA (butyric acid (But) or valeric acid (Val)) or 1 mmol/L of BCFA (isobutyric acid (IsoBut) or isovaleric acid (IsoVal)) and were unstimulated (cells alone, n = 6/treatment), or stimulated with 10 ng/mL lipopolysaccharide (LPS, inflammatory stimulus, n = 8/treatment) or 10 ng/mL LPS + 100 µmol/L of the hypoxia memetic cobalt chloride (LPS/CC, inflammatory/hypoxic stimulus, n = 8/treatment). Results: Compared to Con + LPS, But + LPS reduced secreted protein levels of interleukin (IL)-1β, IL-6, macrophage chemoattractant protein (MCP)-1/chemokine ligand (CCL)2, MCP3/CCL7, macrophage inflammatory protein (MIP)-1α/CCL3 and regulated upon activation, normal T cell expressed, and secreted (RANTES)/CCL5 and decreased intracellular protein expression of the ratio of phosphorylated to total signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NFκB) p65 (p < 0.05). Val + LPS reduced IL-6 secretion and increased MCP-1/CCL2 secretion compared to Con + LPS and exhibited a different inflammatory mediator secretory profile from But + LPS (p < 0.05), indicating that individual SCFA exert individual effects. There were no differences in the secretory profile of the BCFA IsoBut + LPS and IsoVal + LPS (p > 0.05). Alternatively, under inflammatory hypoxic conditions (LPS/CC) Val, IsoVal, and IsoBut all increased secretion of IL-6, MCP-1/CCL2 and MIP-1α/CCL3 compared to Con (p < 0.05), whereas mediator secretion did not differ between But and Con (p > 0.05), indicating that the proinflammatory effects of SCFA and BCFA was attenuated by But. Interestingly, But + LPS/CC decreased STAT3 activation versus Con + LPS/CC (p < 0.05). Conclusions: The decreased secretion of inflammatory mediators that is attributable to But highlights the fact that individual SCFA and BCFA exert differential effects on adipocyte inflammation under normoxic and hypoxic conditions.

背景:微生物发酵非消化性碳水化合物和/或蛋白质会产生短链脂肪酸(SCFA),而支链脂肪酸(BCFA)则由蛋白质发酵产生。目前尚未研究碳链长度相当的单个 SCFA 和 BCFA 对脂肪细胞炎症的影响。目的:比较 SCFA 和 BCFA 对脂肪细胞炎症的影响:比较 SCFA 和 BCFA 在脂肪细胞培养模型中对炎症介质分泌的影响,该模型旨在再现肥胖相关的脂肪细胞炎症在常氧和缺氧条件下的情况。研究方法培养 3T3-L1 脂肪细胞(24 h),不添加(对照组,Con)和 1 mmol/L 的 SCFA(丁酸 (But) 或戊酸 (Val))或 1 mmol/L 的 BCFA(异丁酸 (IsoBut) 或异戊酸 (IsoVal)),不刺激(单独细胞、n = 6/处理),或用 10 ng/mL 脂多糖(LPS,炎症刺激,n = 8/处理)或 10 ng/mL LPS + 100 µmol/L 低氧记忆剂氯化钴(LPS/CC,炎症/缺氧刺激,n = 8/处理)刺激。结果与 Con + LPS 相比,But + LPS 可降低白细胞介素(IL)-1β、IL-6、巨噬细胞趋化蛋白(MCP)-1/趋化因子配体(CCL)2、MCP3/CCL7、巨噬细胞炎症蛋白(MIP)-1α/CCL3 的分泌蛋白水平,并在激活时进行调节、正常 T 细胞表达和分泌(RANTES)/CCL5,以及磷酸化与转录信号转导和激活因子 3(STAT3)和核因子卡巴 B(NFκB)p65 的细胞内蛋白表达量减少(p < 0.05).与 Con + LPS 相比,Val + LPS 减少了 IL-6 的分泌,增加了 MCP-1/CCL2 的分泌,并表现出与 But + LPS 不同的炎症介质分泌特征(p < 0.05),表明单个 SCFA 产生了单独的效应。BCFA IsoBut + LPS 和 IsoVal + LPS 的分泌概况没有差异(p > 0.05)。另外,在炎症缺氧条件下(LPS/CC),与 Con 相比,Val、IsoVal 和 IsoBut 都增加了 IL-6、MCP-1/CCL2 和 MIP-1α/CCL3 的分泌(p < 0.05),而 But 和 Con 的介质分泌没有差异(p > 0.有趣的是,与 Con + LPS/CC 相比,But + LPS/CC 降低了 STAT3 的激活(p < 0.05)。结论But可减少炎症介质的分泌,这突出表明在正常缺氧和缺氧条件下,单个SCFA和BCFA对脂肪细胞炎症的影响是不同的。
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引用次数: 0
Prognostic Value of Circulating Biomarkers of Fibrotic Remodeling in Arrhythmogenic Cardiomyopathy. 心律失常性心肌病纤维重塑循环生物标志物的预后价值
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-16 DOI: 10.3390/biomedicines12112623
Stephen P Chelko

Arrhythmogenic cardiomyopathy (ACM) is a nonischemic, familial heart disease with a high risk of sudden cardiac death (SCD) in the pediatric population and accounts for >20% of SCDs worldwide [...].

致心律失常性心肌病(ACM)是一种非缺血性、家族性心脏病,在儿童人群中发生心脏性猝死(SCD)的风险很高,占全球 SCD 的 20% [...] 。
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引用次数: 0
Examining Erythrocytes as Potential Blood Biomarkers for Autism Spectrum Disorder: Their Relationship to Symptom Severity and Adaptive Behavior. 研究作为自闭症谱系障碍潜在血液生物标志物的红细胞:它们与症状严重程度和适应行为的关系。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-15 DOI: 10.3390/biomedicines12112619
Tomas Jasenovec, Dominika Radosinska, Ivan Belica, Barbara Raskova, Angelika Puzserova, Norbert Vrbjar, Jana Radosinska

Background: Multiple research teams have documented various abnormalities in erythrocyte properties in children with autism spectrum disorder (ASD) compared with neurotypical individuals. Reduced erythrocyte deformability, a crucial factor for microcirculation and oxygen delivery, may affect brain function. Other key factors like nitric oxide (NO) and Na,K-ATPase-regulated cation transport also play roles in both erythrocyte deformability and ASD, suggesting a possible relationship between erythrocyte parameters and autism severity. Thus, this study aims to describe these associations, exploring erythrocyte properties as potential biomarkers in ASD.

Methods: A total of 179 ASD children were enrolled in this study. Diagnosis was confirmed by the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Autism Diagnostic Interview-Revised. The Vineland Adaptive Behavior Scales, Third Edition (VABS-3), was used to assess adaptive behavior. RBC deformability was measured using a filtration technique, while NO production by RBCs was assessed via DAF-2DA fluorescence. Na,K-ATPase kinetics and RBC osmotic resistance were evaluated spectrophotometrically.

Results: Children with more severe ASD symptoms had more impaired deformability and osmotic resistance than children with mild symptoms. Higher RBC NO production was linked to better scores in some VABS-3 subdomains, and in the social affect domain of ADOS-2. Higher affinity of Na,K-ATPase for sodium negatively correlated with the occurrence of repetitive and restricted behavior-one of the core ASD symptoms.

Conclusions: This study identified potential links between ASD severity and RBC properties. While erythrocyte quality can influence ASD symptomatology, the observed relationships-such as those involving RBC deformability, NO production, Na,K-ATPase kinetics, and osmotic resistance-were not strong or consistent enough to be considered reliable diagnostic or prognostic biomarkers.

背景:多个研究小组记录了自闭症谱系障碍(ASD)儿童与神经畸形儿童相比在红细胞特性方面存在的各种异常。红细胞变形性降低是微循环和氧气输送的关键因素,可能会影响大脑功能。一氧化氮(NO)和 Na,K-ATPase 调节的阳离子转运等其他关键因素也在红细胞变形性和 ASD 中发挥作用,这表明红细胞参数与自闭症严重程度之间可能存在关系。因此,本研究旨在描述这些关联,探索红细胞特性作为 ASD 潜在生物标志物的可能性:本研究共招募了 179 名 ASD 儿童。自闭症诊断观察表-第二版(ADOS-2)和自闭症诊断访谈-修订版确认了诊断。维尼兰适应行为量表第三版(VABS-3)用于评估适应行为。采用过滤技术测量红细胞变形性,并通过 DAF-2DA 荧光评估红细胞产生的 NO。Na,K-ATP酶动力学和红细胞渗透阻力通过分光光度法进行评估:结果:与症状轻微的儿童相比,ASD 症状较重的儿童的变形能力和抗渗透能力受损更严重。较高的红细胞氮氧化物生成量与 VABS-3 的某些子域和 ADOS-2 的社会情感域的较高得分有关。Na,K-ATP酶对钠的亲和力较高与重复和受限行为的发生呈负相关,而重复和受限行为是ASD的核心症状之一:本研究发现了自闭症严重程度与红细胞特性之间的潜在联系。虽然红细胞质量会影响 ASD 症状,但观察到的关系(如涉及红细胞变形性、NO 生成、Na,K-ATP 酶动力学和抗渗透性的关系)并不牢固或不够一致,因此不能被视为可靠的诊断或预后生物标志物。
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引用次数: 0
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