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.
{"title":"Role of GPR81 in regulating intramuscular triglyceride storage during aerobic exercise in rats.","authors":"Yihan Ni, Xiangdeng Lai, Lin Li, Jingquan Sun, Yaqian Qu, Siyu Chen, Hao Zhang","doi":"10.1556/2060.2023.00238","DOIUrl":"10.1556/2060.2023.00238","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"124-141"},"PeriodicalIF":1.4,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642760","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}
Pub Date : 2024-01-31Print Date: 2024-03-21DOI: 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.
{"title":"Visually evoked local field potential changes in the caudate nucleus are remarkably more frequent in awake, behaving cats than in anaesthetized animals.","authors":"Diána Nyujtó, Ádám Kiss, Balázs Bodosi, Gabriella Eördegh, Kálmán Tót, András Kelemen, Attila Nagy","doi":"10.1556/2060.2023.00240","DOIUrl":"10.1556/2060.2023.00240","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"47-62"},"PeriodicalIF":1.4,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642761","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}
Pub Date : 2024-01-25Print Date: 2024-03-21DOI: 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.
{"title":"THAP9-AS1 promotes nasopharyngeal carcinoma progression through targeted regulation of the miR-185-5p/SOX13 axis.","authors":"Jinhua Mo, Zengyi Gong, Hong Liu, Lian Zhou, Yanguang Zhao","doi":"10.1556/2060.2023.00232","DOIUrl":"10.1556/2060.2023.00232","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>This work verified that THAP9-AS1 promoted NPC cell progression at least partly by mediating the miR-185-5p/SOX13 axis.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"19-34"},"PeriodicalIF":1.4,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545781","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}
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.
{"title":"RACGAP1 drives proliferation, migration and invasion and suppresses autophagy of gastric cancer cells via inhibiting SIRT1/Mfn2.","authors":"Tingting Yan, Guangxin Lu, Rui Shang, Junhua Hu, Chaobei Zhu, Lingli Jin","doi":"10.1556/2060.2023.00235","DOIUrl":"10.1556/2060.2023.00235","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"35-46"},"PeriodicalIF":1.4,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521552","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}
Pub Date : 2024-01-22Print Date: 2024-03-21DOI: 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}
Pub Date : 2023-11-22Print Date: 2023-12-18DOI: 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.
{"title":"L-arginine supplementation attenuates ovarian oxidative stress in female rats subjected to chronic intermittent hypoxia.","authors":"Amira Abdel-Rhman, Wessam Morsy, Nermeen Selim, Enas A Abdel-Hady","doi":"10.1556/2060.2023.00257","DOIUrl":"10.1556/2060.2023.00257","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"326-341"},"PeriodicalIF":1.4,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291595","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}
Pub Date : 2023-11-17Print Date: 2023-12-18DOI: 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。
{"title":"Circulating apelin, IL22RA2 and VEGF in pre-capillary pulmonary hypertension.","authors":"Györgyi Csósza, Gergő Szűcs, Zsolt Rozgonyi, Balázs Csoma, György Losonczy, Veronika Müller, Kristóf Karlócai, Zsófia Lázár","doi":"10.1556/2060.2023.00264","DOIUrl":"10.1556/2060.2023.00264","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"356-370"},"PeriodicalIF":1.4,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398681","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}
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.
{"title":"Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems.","authors":"Nandini Bhattacharjee, Parantap Sarkar, Tania Sarkar","doi":"10.1556/2060.2023.00256","DOIUrl":"10.1556/2060.2023.00256","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20058,"journal":{"name":"Physiology international","volume":" ","pages":"291-310"},"PeriodicalIF":1.4,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71522261","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}
Pub Date : 2023-11-08Print Date: 2023-12-18DOI: 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.
{"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}
Pub Date : 2023-11-07Print Date: 2023-12-18DOI: 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.
{"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}