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Role of GPR81 in regulating intramuscular triglyceride storage during aerobic exercise in rats. 大鼠有氧运动时 GPR81 在调节肌肉内甘油三酯储存中的作用。
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-01-31 Print Date: 2024-03-21 DOI: 10.1556/2060.2023.00238
Yihan Ni, Xiangdeng Lai, Lin Li, Jingquan Sun, Yaqian Qu, Siyu Chen, Hao Zhang

Lactate, a metabolite of exercise, plays a crucial role in the body. In these studies, we aimed to investigate the role of G protein-coupled receptor 81 (GPR81), a specific receptor for lactate, in regulating lipid storage in the gastrocnemius muscle of rats. To achieve this, we measured the impact of sodium 3-hydroxybutyrate (3-OBA) concentration and time on the cAMP-PKA signaling pathway in the gastrocnemius muscles of rats. Our investigation involved determining the effects of administering 3-OBA at a concentration of 3 mmol L-1 just 15 min before exercise. As expected, exercise led to a notable increase in intramuscular lactate concentration in rats. However, injecting 3-OBA prior to exercise yielded intriguing results. It not only further augmented the cAMP-PKA signaling pathway but also boosted the expression of lipolysis-related proteins such as hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). Simultaneously, it decreased the expression of fat-synthesizing proteins, including acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS), while increasing the protein expression of cytochrome c oxidase subunit Ⅳ(COX Ⅳ) and the activity of citrate synthetase (CS). Unfortunately, there was no significant change observed in intramuscular triglyceride (IMTG) content. In summary, our findings shed light on the role of lactate in partially regulating intramuscular triglycerides during exercise.

乳酸盐是运动的代谢产物,在人体内起着至关重要的作用。在这些研究中,我们旨在研究乳酸的特异性受体 G 蛋白偶联受体 81(GPR81)在调节大鼠腓肠肌脂质储存中的作用。为此,我们测量了 3-羟基丁酸钠(3-OBA)浓度和时间对大鼠腓肠肌中 cAMP-PKA 信号通路的影响。我们的研究包括确定在运动前 15 分钟施用浓度为 3 mmol L-1 的 3-OBA 的影响。不出所料,运动会导致大鼠肌肉内乳酸浓度显著增加。然而,在运动前注射 3-OBA 却产生了耐人寻味的结果。它不仅进一步增强了 cAMP-PKA 信号通路,还促进了脂肪分解相关蛋白的表达,如激素敏感脂肪酶(HSL)和脂肪甘油三酯脂肪酶(ATGL)。同时,它降低了脂肪合成蛋白的表达,包括乙酰辅酶羧化酶(ACC)和脂肪酸合成酶(FAS),同时增加了细胞色素 c 氧化酶亚基Ⅳ(COX Ⅳ)的蛋白表达和柠檬酸合成酶(CS)的活性。遗憾的是,肌肉内甘油三酯(IMTG)含量没有明显变化。总之,我们的研究结果揭示了乳酸盐在运动过程中部分调节肌肉内甘油三酯的作用。
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引用次数: 0
Visually evoked local field potential changes in the caudate nucleus are remarkably more frequent in awake, behaving cats than in anaesthetized animals. 尾状核中视觉诱发的局部场电位变化在清醒状态下的行为猫中比在麻醉状态下的行为猫中更为频繁。
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-01-31 Print Date: 2024-03-21 DOI: 10.1556/2060.2023.00240
Diána Nyujtó, Ádám Kiss, Balázs Bodosi, Gabriella Eördegh, Kálmán Tót, András Kelemen, Attila Nagy

Previous results show that halothane gas anaesthesia has a suppressive effect on the visually evoked single-cell activities in the feline caudate nucleus (CN). In this study, we asked whether the low-frequency neuronal signals, the local field potentials (LFP) are also suppressed in the CN of anaesthetized animals.To answer this question, we compared the LFPs recorded from the CN of two halothane-anaesthetized (1.0%), paralyzed, and two awake, behaving cats during static and dynamic visual stimulation. The behaving animals were trained to perform a visual fixation task.Our results denoted a lower proportion of significant power changes to visual stimulation in the CN of the anesthetized cats in each frequency range (from delta to beta) of the LFPs, except gamma. These differences in power changes were more obvious in static visual stimulation, but still, remarkable differences were found in dynamic stimulation, too. The largest differences were found in the alpha and beta frequency bands for static stimulation. Concerning dynamic stimulation, the differences were the biggest in the theta, alpha and beta bands.Similar to the single-cell activities, remarkable differences were found between the visually evoked LFP changes in the CN of the anaesthetized, paralyzed and awake, behaving cats. The halothane gas anaesthesia and the immobilization suppressed the significant LFP power alterations in the CN to both static and dynamic stimulation. These results suggest the priority of the application of behaving animals even in the analysis of the visually evoked low-frequency electric signals, the LFPs recorded from the CN.

以前的研究结果表明,氟烷气体麻醉对猫尾状核(CN)中视觉诱发的单细胞活动有抑制作用。为了回答这个问题,我们比较了两只被氟烷麻醉(1.0%)的瘫痪猫和两只清醒的行为猫在静态和动态视觉刺激时从尾状核记录到的局部场电位(LFP)。我们的结果表明,在麻醉猫的神经中枢中,除伽马外,每个频率范围(从δ到β)的LFPs对视觉刺激的显著功率变化比例都较低。这些功率变化差异在静态视觉刺激中更为明显,但在动态刺激中也发现了显著差异。在静态刺激中,差异最大的是α和β频段。与单细胞活动类似,麻醉猫、瘫痪猫和清醒行为猫的视觉诱发 LFP 变化也存在显著差异。氟烷气体麻醉和固定抑制了中枢神经对静态和动态刺激的显著 LFP 功率变化。这些结果表明,即使在分析视觉诱发的低频电信号(即从神经中枢记录的 LFPs)时,也应优先使用行为动物。
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引用次数: 0
THAP9-AS1 promotes nasopharyngeal carcinoma progression through targeted regulation of the miR-185-5p/SOX13 axis. THAP9-AS1 通过靶向调控 miR-185-5p/SOX13 轴促进鼻咽癌的进展。
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-01-25 Print Date: 2024-03-21 DOI: 10.1556/2060.2023.00232
Jinhua Mo, Zengyi Gong, Hong Liu, Lian Zhou, Yanguang Zhao

Background: It has been reported that long non-coding RNA THAP9-AS1 exerts carcinogenic role by mediating miRNAs and target genes in various human cancers. However, whether THAP9-AS1 influences the progression of nasopharyngeal carcinoma (NPC) remains unknown.

Methods: The transcriptional levels of THAP9-AS1 and miR-185-5p were estimated via quantitative real time polymerase chain reaction (qRT-PCR) assay. The protein level of SOX13 was detected with western blotting assay. Additionally, methyl thiazolyl tetrazolium (MTT) assay as well as colony formation assay were utilized to measure cell growth. The apoptotic cells were observed by employing Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining analysis, and transwell assay was introduced to test cell migration in addition to invasion. Moreover, the relationship between miR-185-5p and THAP9-AS1 or SOX13 was estimated through dual-luciferase reporter gene assay.

Results: THAP9-AS1 was overexpressed in head and neck squamous cell carcinoma (HNSCC) tissues and NPC cells. Besides, silencing of THAP9-AS1 depressed the life processes of NPC cells including cell growth, migration as well as invasion but facilitated cell apoptosis. Further investigation proved that miR-185-5p was the direct target of THAP9-AS1. Besides, the knockdown of THAP9-AS1 notably reduced the transcriptional level of miR-185-5p. Furthermore, THAP9-AS1 served as a sponge of miR-185-5p to modulate the expression of SOX13, which regulated the development of NPC cells.

Conclusion: This work verified that THAP9-AS1 promoted NPC cell progression at least partly by mediating the miR-185-5p/SOX13 axis.

背景:有报道称,长非编码RNA THAP9-AS1在多种人类癌症中通过介导miRNA和靶基因发挥致癌作用。然而,THAP9-AS1 是否会影响鼻咽癌(NPC)的进展仍是未知数:方法:通过定量实时聚合酶链反应(qRT-PCR)测定 THAP9-AS1 和 miR-185-5p 的转录水平。SOX13的蛋白水平通过Western印迹法检测。此外,还利用甲基噻唑基四氮唑(MTT)检测法和菌落形成检测法测量细胞生长情况。采用末端脱氧核苷酸转移酶介导的尼克末端标记(TUNEL)染色分析法观察细胞凋亡情况,并采用透孔试验检测细胞迁移和侵袭情况。此外,还通过双荧光素酶报告基因检测法评估了 miR-185-5p 与 THAP9-AS1 或 SOX13 的关系:结果:THAP9-AS1在头颈部鳞状细胞癌(HNSCC)组织和鼻咽癌细胞中过表达。此外,沉默 THAP9-AS1 会抑制鼻咽癌细胞的生命过程,包括细胞生长、迁移和侵袭,但会促进细胞凋亡。进一步研究证明,miR-185-5p 是 THAP9-AS1 的直接靶标。此外,敲除 THAP9-AS1 会显著降低 miR-185-5p 的转录水平。此外,THAP9-AS1作为miR-185-5p的海绵,可调节SOX13的表达,从而调控鼻咽癌细胞的发育:这项研究证实,THAP9-AS1至少在一定程度上通过介导miR-185-5p/SOX13轴促进了鼻咽癌细胞的发展。
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引用次数: 0
RACGAP1 drives proliferation, migration and invasion and suppresses autophagy of gastric cancer cells via inhibiting SIRT1/Mfn2. RACGAP1 通过抑制 SIRT1/Mfn2 推动胃癌细胞的增殖、迁移和侵袭并抑制自噬。
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-01-22 Print Date: 2024-03-21 DOI: 10.1556/2060.2023.00235
Tingting Yan, Guangxin Lu, Rui Shang, Junhua Hu, Chaobei Zhu, Lingli Jin

Objective: Gastric cancer is the most frequent gastrointestinal malignancy with a poor prognosis. Rac GTPase activation protein 1 (RACGAP1) is a novel tumor promotor, whose detailed effect on gastric cancer remains to be further elucidated. Hence, this study identifies the action of RACGAP1 on gastric cancer and investigates the potential mechanism.

Methods: RACGAP1 expression in gastric cancer was analyzed based on the data of The Cancer Genome Atlas (TCGA) database. Cell proliferation was measured by CCK-8 and colony formation assay. Cell migration and invasion were evaluated by transwell assay. Cell apoptosis was assessed by flow cytometry. Cell autophagy was evaluated via determining LC3.

Results: RACGAP1 presented at high level in gastric cancer cells. Overexpressed RACGAP1 potentiated gastric cancer cell proliferation, migration, and invasion. Besides, silenced RACGAP1 induced cell apoptosis and autophagy. Furthermore, RACGAP1 suppressed the expression of SIRT1 and Mfn2.

Conclusion: RACGAP1 was overexpressed in gastric cancer. RACGAP1 potentiated aggressive behaviors of gastric cancer, and suppressed cell apoptosis and autophagy via modulating SIRT1/Mfn2. RACGAP1 may be a valuable target in the treatment of gastric cancer.

目的:胃癌是最常见的消化道恶性肿瘤,预后较差。Rac GTPase活化蛋白1(RACGAP1)是一种新型肿瘤促进因子,其对胃癌的详细作用仍有待进一步阐明。因此,本研究确定了 RACGAP1 对胃癌的作用,并探讨了其潜在机制:方法:根据癌症基因组图谱(TCGA)数据库的数据分析 RACGAP1 在胃癌中的表达。细胞增殖通过 CCK-8 和集落形成试验测定。细胞迁移和侵袭通过透孔试验进行评估。细胞凋亡通过流式细胞术进行评估。细胞自噬通过测定 LC3 进行评估:结果:RACGAP1在胃癌细胞中呈高水平表达。结果:RACGAP1 在胃癌细胞中呈高水平表达,过表达的 RACGAP1 可促进胃癌细胞的增殖、迁移和侵袭。此外,沉默的 RACGAP1 能诱导细胞凋亡和自噬。此外,RACGAP1 还能抑制 SIRT1 和 Mfn2 的表达:结论:RACGAP1在胃癌中过表达。结论:RACGAP1在胃癌中过表达,通过调节SIRT1/Mfn2,RACGAP1可增强胃癌的侵袭行为,抑制细胞凋亡和自噬。RACGAP1可能是治疗胃癌的一个有价值的靶点。
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引用次数: 0
Effect of folic acid on isoprenaline-induced myocardial injury in rats. 叶酸对异丙肾上腺素诱发的大鼠心肌损伤的影响
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2024-01-22 Print Date: 2024-03-21 DOI: 10.1556/2060.2023.00291
Tanja Sobot, Zorislava Bajic, Ranko Skrbic, Snezana Uletilovic, Nebojsa Mandic-Kovacevic, Tanja Cvjetkovic, Ugljesa Malicevic, Djordje Djukanovic, Milica Gajic Bojic, Sanja Jovicic, Maja Barudzija, Milos P Stojiljkovic, Dragan M Djuric

Background: Isoprenaline (ISO), a synthetic catecholamine and a β-adrenoceptor agonist, is widely used to develop an experimental model of myocardial injury (MI) in rats. The leading hypothesis for ISO-induced MI in rats is that it results from catecholamine overstimulation, oxidative stress, inflammatory responses, and development of cardiomyopathy during ISO administration. Folic acid (FA) reduces oxidative stress, improves endothelial function and prevents apoptosis, thereby contributing to cardiovascular protection. This study aimed to investigate the potentially protective effect of FA pretreatment on ISO-induced MI in rats.

Methods: For 7 days, adult male Wistar albino rats were pretreated with 5 mg/kg/day of FA. On the sixth and seventh days, MI in rats was induced by administering 85 mg/kg/day of ISO. Prooxidant markers in plasma samples, antioxidant capacity in erythrocyte lysates, cardiac damage markers, lipid profile, electrocardiography (ECG) and histopathological analysis were evaluated.

Results: FA pretreatment significantly alleviated changes induced by ISO; it decreased the homocysteine and high-sensitivity troponin I level. FA moderately decreased the reactive oxygen species (ROS) levels (superoxide anion radical, hydrogen peroxide and thiobarbituric acid reactive substances) and improved the antioxidant activities of catalase, superoxide dismutase and reduced glutathione. ISO reduced the nitrite level and FA significantly alleviated this change.

Conclusion: It can be concluded that FA, as a mild antioxidant, could be an appropriate cardioprotective substance in the rat model of ISO-induced MI.

背景:异丙肾上腺素(ISO)是一种人工合成的儿茶酚胺和β-肾上腺素受体激动剂,被广泛用于建立大鼠心肌损伤(MI)的实验模型。ISO 诱导大鼠心肌梗死的主要假说是,在服用 ISO 期间,儿茶酚胺过度刺激、氧化应激、炎症反应和心肌病的发展导致了心肌梗死。叶酸(FA)可降低氧化应激,改善内皮功能,防止细胞凋亡,从而有助于保护心血管。本研究旨在探讨叶酸预处理对 ISO 诱导的大鼠心肌梗死的潜在保护作用:方法:成年雄性 Wistar 白化大鼠接受为期 7 天、每公斤每天 5 毫克的 FA 预处理。第六天和第七天,给大鼠注射 85 毫克/千克/天的 ISO,诱发心肌梗死。对血浆样本中的前氧化标志物、红细胞裂解液中的抗氧化能力、心脏损伤标志物、血脂概况、心电图和组织病理学分析进行了评估:结果:FA 预处理明显缓解了 ISO 引起的变化;降低了同型半胱氨酸和高敏肌钙蛋白 I 的水平。脂肪酸适度降低了活性氧(ROS)水平(超氧阴离子自由基、过氧化氢和硫代巴比妥酸活性物质),提高了过氧化氢酶、超氧化物歧化酶和还原型谷胱甘肽的抗氧化活性。ISO 降低了亚硝酸盐水平,而 FA 则明显缓解了这一变化:可以得出结论,FA 作为一种温和的抗氧化剂,在 ISO 诱导的心肌梗死大鼠模型中可能是一种适当的心脏保护物质。
{"title":"Effect of folic acid on isoprenaline-induced myocardial injury in rats.","authors":"Tanja Sobot, Zorislava Bajic, Ranko Skrbic, Snezana Uletilovic, Nebojsa Mandic-Kovacevic, Tanja Cvjetkovic, Ugljesa Malicevic, Djordje Djukanovic, Milica Gajic Bojic, Sanja Jovicic, Maja Barudzija, Milos P Stojiljkovic, Dragan M Djuric","doi":"10.1556/2060.2023.00291","DOIUrl":"10.1556/2060.2023.00291","url":null,"abstract":"<p><strong>Background: </strong>Isoprenaline (ISO), a synthetic catecholamine and a β-adrenoceptor agonist, is widely used to develop an experimental model of myocardial injury (MI) in rats. The leading hypothesis for ISO-induced MI in rats is that it results from catecholamine overstimulation, oxidative stress, inflammatory responses, and development of cardiomyopathy during ISO administration. Folic acid (FA) reduces oxidative stress, improves endothelial function and prevents apoptosis, thereby contributing to cardiovascular protection. This study aimed to investigate the potentially protective effect of FA pretreatment on ISO-induced MI in rats.</p><p><strong>Methods: </strong>For 7 days, adult male Wistar albino rats were pretreated with 5 mg/kg/day of FA. On the sixth and seventh days, MI in rats was induced by administering 85 mg/kg/day of ISO. Prooxidant markers in plasma samples, antioxidant capacity in erythrocyte lysates, cardiac damage markers, lipid profile, electrocardiography (ECG) and histopathological analysis were evaluated.</p><p><strong>Results: </strong>FA pretreatment significantly alleviated changes induced by ISO; it decreased the homocysteine and high-sensitivity troponin I level. FA moderately decreased the reactive oxygen species (ROS) levels (superoxide anion radical, hydrogen peroxide and thiobarbituric acid reactive substances) and improved the antioxidant activities of catalase, superoxide dismutase and reduced glutathione. ISO reduced the nitrite level and FA significantly alleviated this change.</p><p><strong>Conclusion: </strong>It can be concluded that FA, as a mild antioxidant, could be an appropriate cardioprotective substance in the rat model of ISO-induced MI.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"80-96"},"PeriodicalIF":1.4,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
L-arginine supplementation attenuates ovarian oxidative stress in female rats subjected to chronic intermittent hypoxia. 补充l -精氨酸可减轻慢性间歇缺氧雌性大鼠卵巢氧化应激。
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2023-11-22 Print Date: 2023-12-18 DOI: 10.1556/2060.2023.00257
Amira Abdel-Rhman, Wessam Morsy, Nermeen Selim, Enas A Abdel-Hady

Background: Systemic and organ-specific oxidative stress triggered by hypoxia is suggested to play a key role in germ cell apoptosis and DNA damage. This study was designed to investigate the impact of chronic intermittent hypoxia (CIH) on female fertility and evaluate the potential antioxidant effect of L-arginine (L-Arg) supplementation.

Methods: Adult female rats were allocated into three groups: controls (normoxic), hypoxic and hypoxic supplemented with L-Arg. After 12 weeks; hematocrit value was determined, body weight (BW) and ovarian weight were measured for the calculation of the gonado-somatic index. Plasma levels of luteinizing hormone (LH) and progesterone were estimated. Ovarian tissue malondialdehyde (MDA) and catalase were assessed, and caspase-3 enzyme expression was detected by immunohistochemistry.

Results: Compared to controls, CIH resulted in increased oxidative stress in the ovarian tissue, decreased ovarian weight, and increased frequency of irregular cycles and higher plasma level of LH in rats with either regular or irregular ovarian cycles. Histological examination of ovarian sections revealed areas of degeneration, atretic follicles, interstitial edema, congested vessels and inflammatory cell infiltration. Immunohistochemistry confirmed the presence of apoptosis by increased caspase-3 expression. Hypoxic rats pre-treated with L-Arg showed increased BW and ovarian weight, decreased ovarian tissue MDA and plasma LH accompanied by a lower incidence of irregular cycles and mortality. The histological picture was improved and caspase-3 expression was reduced.

Conclusion: Oxidative stress caused by CIH is detrimental to the structure and function of the corpus luteum with an increased risk of reduced fertility. L-Arg supplementation increases antioxidant capacity and improves hypoxia-induced fertility disorders.

背景:缺氧引发的系统性和器官特异性氧化应激在生殖细胞凋亡和DNA损伤中起关键作用。本研究旨在探讨慢性间歇性缺氧(CIH)对女性生育能力的影响,并评估补充l -精氨酸(L-Arg)的潜在抗氧化作用。方法:将成年雌性大鼠分为正常对照组、低氧组和补充l -精氨酸低氧组。12周后;测定红细胞压积值,测定体重(BW)和卵巢重量,计算性腺-躯体指数。测定血浆黄体生成素(LH)和黄体酮水平。免疫组化检测卵巢组织丙二醛(MDA)、过氧化氢酶水平,caspase-3酶表达水平。结果:与对照组相比,在卵巢周期正常或不规则的大鼠中,CIH导致卵巢组织氧化应激增加,卵巢重量减轻,不规则周期频率增加,血浆LH水平升高。卵巢切片组织学检查显示变性、卵泡闭锁、间质水肿、血管充血及炎性细胞浸润。免疫组化通过增加caspase-3的表达证实了凋亡的存在。经l -精氨酸预处理的低氧大鼠体重和卵巢重量增加,卵巢组织MDA和血浆LH降低,月经周期不规律发生率和死亡率降低。组织学改变,caspase-3表达降低。结论:CIH引起的氧化应激损害了黄体的结构和功能,增加了生育能力下降的风险。补充l -精氨酸可提高抗氧化能力,改善缺氧诱导的生育障碍。
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引用次数: 0
Circulating apelin, IL22RA2 and VEGF in pre-capillary pulmonary hypertension. 毛细血管前肺动脉高压的循环apelin、IL22RA2和VEGF。
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2023-11-17 Print Date: 2023-12-18 DOI: 10.1556/2060.2023.00264
Györgyi Csósza, Gergő Szűcs, Zsolt Rozgonyi, Balázs Csoma, György Losonczy, Veronika Müller, Kristóf Karlócai, Zsófia Lázár

Cytokines can modulate vascular remodelling and the adaptation of the right ventricle in pre-capillary pulmonary hypertension (PH). However, detailed data on the circulating levels of cytokines in patients are limited. We measured blood cytokine concentration in 39 treatment-naïve patients (pulmonary arterial hypertension: N = 16, chronic thromboembolic PH: N = 15, PH due to lung disease: N = 8) and 12 control subjects using enzyme-linked immunoassays. Apelin concentration >1,261 ng/mL identified patients with PH (66% sensitivity and 82% specificity), and in patients it was related to systolic pulmonary arterial pressure (PAP) (r = 0.33, P = 0.04), right atrial pressure (r = 0.38, P = 0.02), cardiac index (r = -0.34, P = 0.04), and right ventricular stroke work index (r = -0.47, P = 0.003). IL22RA2 concentration correlated with mean PAP (r = -0.32, P = 0.04) and serum N-terminal pro B-type natriuretic peptide level (r = -0.42, P = 0.01). VEGF concentration increased in patients upon clinical improvement (N = 16, P = 0.02). Circulating apelin is a novel biomarker of pre-capillary PH. Apelin and IL22RA2 levels are related to right ventricular function upon diagnosis of PH.

细胞因子可以调节血管重构和右心室在毛细血管前肺动脉高压(PH)中的适应性。然而,关于患者循环细胞因子水平的详细数据是有限的。我们使用酶联免疫分析法测量了39例treatment-naïve患者(肺动脉高压:N = 16,慢性血栓栓塞PH: N = 15,肺部疾病引起的PH: N = 8)和12名对照组的血液细胞因子浓度。Apelin浓度>1,261 ng/mL鉴别患者的PH值(66%的敏感性和82%的特异性),在患者中,Apelin浓度与肺动脉收缩压(PAP) (r = 0.33, P = 0.04)、右心房压(r = 0.38, P = 0.02)、心脏指数(r = -0.34, P = 0.04)、右心室卒中工作指数(r = -0.47, P = 0.003)相关。IL22RA2浓度与平均PAP (r = -0.32, P = 0.04)和血清n端前b型利钠肽水平相关(r = -0.42, P = 0.01)。临床改善后患者VEGF浓度升高(N = 16, P = 0.02)。循环apelin是一种新的毛细管前PH生物标志物,apelin和IL22RA2水平与PH诊断时右心室功能有关。
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引用次数: 0
Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems. 超越急性疾病:探索长期新冠肺炎及其对多器官系统的影响。
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2023-11-09 Print Date: 2023-12-18 DOI: 10.1556/2060.2023.00256
Nandini Bhattacharjee, Parantap Sarkar, Tania Sarkar

Unprecedented worldwide health catastrophe due to the COVID-19 pandemic has ended up resulting in high morbidity and mortality rates. Even though many people recover from acute infection, there is rising concern regarding post-COVID-19 conditions (PCCs), often referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or "long COVID." The respiratory, cardiovascular, neurological, and endocrine systems are just a few of the many organ systems that can be impacted by this multifarious, complicated illness. The clinical manifestations of long COVID can vary among individuals and may include fatigue, dyspnea, chest pain, cognitive impairment, and new-onset diabetes, among others. Although the underlying processes of long COVID are not fully understood, they probably involve unregulated immune response, persistent generation of pro-inflammatory cytokines (chronic inflammation), autoimmune-like reactions, persistent viral replication, and micro-clot formation. To create successful treatments and care plans, it is essential to comprehend the immunological mechanisms causing these difficulties. The pathogenesis of long COVID should be clarified and potential biomarkers to help with diagnosis and treatment should be sought after. To reduce the burden of long COVID on people and healthcare systems around the world, the need for long-term monitoring and management of long COVID problems should be emphasized. It also underscores the significance of a multidisciplinary approach to patient care. The goal of this review is to carefully evaluate the clinical signs and symptoms of long COVID, their underlying causes, and any potential immunological implications.

新冠肺炎大流行造成的前所未有的全球卫生灾难最终导致高发病率和死亡率。尽管许多人从急性感染中康复,但人们越来越担心新冠肺炎后疾病(PCCs),通常被称为严重急性呼吸系统综合征冠状病毒2型感染(PASC)或“长期新冠肺炎”的急性后遗症。呼吸、心血管、神经和内分泌系统只是可能受到这种多种复杂疾病影响的众多器官系统中的一小部分。长期新冠肺炎的临床表现因个体而异,可能包括疲劳、呼吸困难、胸痛、认知障碍和新发糖尿病等。尽管长期新冠肺炎的潜在过程尚不完全清楚,但它们可能涉及不受调节的免疫反应、持续产生促炎细胞因子(慢性炎症)、自身免疫样反应、持续的病毒复制和微血栓形成。为了制定成功的治疗和护理计划,了解造成这些困难的免疫机制至关重要。应阐明长期新冠肺炎的发病机制,并寻求有助于诊断和治疗的潜在生物标志物。为了减轻长期新冠肺炎给世界各地的人们和医疗系统带来的负担,应该强调对长期新冠病毒问题进行长期监测和管理的必要性。它还强调了多学科方法对患者护理的重要性。这篇综述的目的是仔细评估长期新冠肺炎的临床体征和症状、其潜在原因以及任何潜在的免疫学意义。
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引用次数: 0
ATXN3 promotes proliferation, stemness and motility of clear cell renal cell carcinoma cells by regulating S100A8 ubiquitination. ATXN3通过调节S100A8泛素化促进透明细胞肾癌细胞的增殖、干性和运动性。
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2023-11-08 Print Date: 2023-12-18 DOI: 10.1556/2060.2023.00247
Jixiang Bai, Jieru Han, Jiayi Fan, Jing Song, Shuhui Wang

Background: Clear cell renal cell carcinoma (ccRCC) is a dominant subtype of kidney cancer with a dismal outcome at advanced stages. Ataxin 3 (ATXN3) has been proven to play a cancer-promoting role in several tumors and is upregulated in the patients with renal cell carcinoma. Thus, the objective of this research is to examine the biological roles and underlying mechanisms of ATXN3 in ccRCC.

Methods: Bioinformatics analysis was carried out to analyze ATXN3 expression in ccRCC tissues and patient survival. Gain- and loss-of-function assays were applied to explore the effect of ATXN3 on ccRCC cell malignant behavior in vitro. The effect of ATXN3 on the NF-κB pathway was assessed by Western blot and immunofluorescence staining. The binding between ATXN3 and S100A8 and the effect of ATXN3 on S100A8 ubiquitination were verified using coimmunoprecipitation.

Results: ATXN3 was upregulated in ccRCC tissues and correlated with adverse patient outcome. ATXN3 overexpression facilitated the proliferation, stemness, invasion and migratory capacity of ccRCC cells, whereas silencing had the opposite effect. ATXN3 enhanced the activity of the NF-κB pathway. Silencing ATXN3 facilitated S100A8 ubiquitination. Rescue experiments demonstrated that S100A8 downregulation reversed the promoting effect of ATXN3 on malignant behavior and NF-κB pathway activation in ccRCC cells.

Conclusion: ATXN3 exerts a cancer-promoting effect in ccRCC by regulating S100A8 ubiquitination. Therefore, targeting the ATXN3/S100A8/NF-κB axis may provide a novel underlying therapeutic strategy for ccRCC.

背景:肾透明细胞癌(ccRCC)是癌症的主要亚型,晚期预后极差。阿塔新3(ATXN3)已被证明在一些肿瘤中起着促进癌症的作用,并在肾细胞癌患者中上调。因此,本研究的目的是探讨ATXN3在ccRCC中的生物学作用和潜在机制。应用功能获得和丧失测定法探讨ATXN3对体外培养的ccRCC细胞恶性行为的影响。通过蛋白质印迹和免疫荧光染色评估ATXN3对NF-κB通路的影响。使用共免疫沉淀验证ATXN3和S100A8之间的结合以及ATXN3对S100A8泛素化的影响。结果:ATXN3在ccRCC组织中上调,并与不良患者结局相关。ATXN3过表达促进了ccRCC细胞的增殖、干性、侵袭和迁移能力,而沉默则具有相反的作用。ATXN3增强了NF-κB通路的活性。沉默ATXN3促进S100A8的泛素化。救援实验表明,S100A8下调逆转了ATXN3对ccRCC细胞恶性行为和NF-κB通路激活的促进作用。结论:ATXN3通过调节S100A8泛素化在ccRCC中发挥促癌作用。因此,靶向ATXN3/S100A8/NF-κB轴可能为ccRCC提供一种新的潜在治疗策略。
{"title":"ATXN3 promotes proliferation, stemness and motility of clear cell renal cell carcinoma cells by regulating S100A8 ubiquitination.","authors":"Jixiang Bai, Jieru Han, Jiayi Fan, Jing Song, Shuhui Wang","doi":"10.1556/2060.2023.00247","DOIUrl":"10.1556/2060.2023.00247","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) is a dominant subtype of kidney cancer with a dismal outcome at advanced stages. Ataxin 3 (ATXN3) has been proven to play a cancer-promoting role in several tumors and is upregulated in the patients with renal cell carcinoma. Thus, the objective of this research is to examine the biological roles and underlying mechanisms of ATXN3 in ccRCC.</p><p><strong>Methods: </strong>Bioinformatics analysis was carried out to analyze ATXN3 expression in ccRCC tissues and patient survival. Gain- and loss-of-function assays were applied to explore the effect of ATXN3 on ccRCC cell malignant behavior in vitro. The effect of ATXN3 on the NF-κB pathway was assessed by Western blot and immunofluorescence staining. The binding between ATXN3 and S100A8 and the effect of ATXN3 on S100A8 ubiquitination were verified using coimmunoprecipitation.</p><p><strong>Results: </strong>ATXN3 was upregulated in ccRCC tissues and correlated with adverse patient outcome. ATXN3 overexpression facilitated the proliferation, stemness, invasion and migratory capacity of ccRCC cells, whereas silencing had the opposite effect. ATXN3 enhanced the activity of the NF-κB pathway. Silencing ATXN3 facilitated S100A8 ubiquitination. Rescue experiments demonstrated that S100A8 downregulation reversed the promoting effect of ATXN3 on malignant behavior and NF-κB pathway activation in ccRCC cells.</p><p><strong>Conclusion: </strong>ATXN3 exerts a cancer-promoting effect in ccRCC by regulating S100A8 ubiquitination. Therefore, targeting the ATXN3/S100A8/NF-κB axis may provide a novel underlying therapeutic strategy for ccRCC.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"311-325"},"PeriodicalIF":1.4,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71484842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stent composition and immune response after long-term coronary angioplasty. 支架成分与长期冠状动脉血管成形术后的免疫反应。
IF 1.4 4区 医学 Q3 PHYSIOLOGY Pub Date : 2023-11-07 Print Date: 2023-12-18 DOI: 10.1556/2060.2023.00162
Viviane A R Sant'Anna, Adriano H P Barbosa, Rodrigo A Souza, José M A Sousa, Frederico Monfardini, Magnus Gidlund, Henrique A R Fonseca

Background: There are limited data about the influence of stent composition on immune responses after percutaneous coronary intervention (PCI).

Objective: The aim was to compare the effects of PCI with conventional cobalt-chromium bare metal stent (BMS) and drug-eluting stent (DES) implantation on the modulation of humoral and cellular immune responses.

Methods: A randomised, single-centre, open pilot study involving patients with stable coronary artery disease eligible for PCI was performed. Blood samples were collected from the peripheral artery (PA) and the coronary sinus (CS) at baseline and 40 weeks following PCI. IgM and IgG autoantibodies (Abs), anti-oxLDL and anti-ApoB-D, as well as cytokine levels were evaluated by enzyme-linked immunosorbent assay.

Results: A total of 30 patients of 60 years mean age were included, 68% of whom were men. At the nine-month follow-up, a modulation in the levels of cytokines and autoantibodies was observed in both stent type groups. However, no difference was observed in the modulation of these markers between stents.

Conclusion: The stent type promotes modulations in cellular and humoral immune responses in the long-term, with differences in the magnitude of effects in specific immune responses.

背景:关于支架成分对经皮冠状动脉介入治疗(PCI)后免疫反应的影响的数据有限。目的:比较PCI与传统钴铬裸金属支架(BMS)和药物洗脱支架(DES)植入对体液和细胞免疫反应的调节作用。方法:对符合PCI条件的稳定型冠状动脉疾病患者进行随机、单中心、开放性试点研究。在基线和PCI后40周从外周动脉(PA)和冠状窦(CS)采集血样。通过酶联免疫吸附试验评估IgM和IgG自身抗体(Abs)、抗oxLDL和抗ApoB-D以及细胞因子水平。结果:共纳入30名平均年龄为60岁的患者,其中68%为男性。在9个月的随访中,在两个支架型组中都观察到细胞因子和自身抗体水平的调节。然而,在支架之间这些标记物的调节没有观察到差异。结论:支架类型长期促进细胞和体液免疫反应的调节,在特异性免疫反应中的作用程度不同。
{"title":"Stent composition and immune response after long-term coronary angioplasty.","authors":"Viviane A R Sant'Anna, Adriano H P Barbosa, Rodrigo A Souza, José M A Sousa, Frederico Monfardini, Magnus Gidlund, Henrique A R Fonseca","doi":"10.1556/2060.2023.00162","DOIUrl":"10.1556/2060.2023.00162","url":null,"abstract":"<p><strong>Background: </strong>There are limited data about the influence of stent composition on immune responses after percutaneous coronary intervention (PCI).</p><p><strong>Objective: </strong>The aim was to compare the effects of PCI with conventional cobalt-chromium bare metal stent (BMS) and drug-eluting stent (DES) implantation on the modulation of humoral and cellular immune responses.</p><p><strong>Methods: </strong>A randomised, single-centre, open pilot study involving patients with stable coronary artery disease eligible for PCI was performed. Blood samples were collected from the peripheral artery (PA) and the coronary sinus (CS) at baseline and 40 weeks following PCI. IgM and IgG autoantibodies (Abs), anti-oxLDL and anti-ApoB-D, as well as cytokine levels were evaluated by enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>A total of 30 patients of 60 years mean age were included, 68% of whom were men. At the nine-month follow-up, a modulation in the levels of cytokines and autoantibodies was observed in both stent type groups. However, no difference was observed in the modulation of these markers between stents.</p><p><strong>Conclusion: </strong>The stent type promotes modulations in cellular and humoral immune responses in the long-term, with differences in the magnitude of effects in specific immune responses.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"371-384"},"PeriodicalIF":1.4,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71484843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Physiology international
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